Comprehensive RDoC-Aligned Neuropsychological

Battery Reference Document

A Technical Reference for Clinical Neuroscientists and Neuropsychologists

Preliminary Step: Full RDoC Matrix Enumeration (NIMH

2024-2025)

Overview of the RDoC Framework

The Research Domain Criteria (RDoC) framework represents a transformative

approach to psychiatric nosology and neuroscience research, moving beyond traditional
diagnostic categories toward dimensional constructs grounded in neurobiology (Insel et
al., 2010; Cuthbert & Insel, 2013). Developed by the National Institute of Mental Health
(NIMH), RDoC organizes psychopathology research across six major domains, each
comprising multiple constructs and subconstructs, assessed through multiple units of
analysis ranging from genes and molecules to circuits, physiology, behavior, self-report,
and paradigms. This preliminary section provides a complete enumeration of the RDoC
Matrix as of 2024-2025, with official NIMH definitions for each domain, construct, and
subconstruct.

Domain I: Negative Valence Systems

Negative Valence Systems are primarily responsible for responses to aversive situations
or contexts, such as fear, anxiety, and loss. These systems evolved to promote survival
through defensive behaviors and threat detection.

1.1 Acute Threat ("Fear")

NIMH Definition: Activation of the fear system in response to present threat or danger,
characterized by adaptive changes in physiology and behavior that promote defense
and survival.

Neural Basis: The acute threat system involves rapid activation of the amygdala,
particularly the central and basolateral nuclei, with projections to the periaqueductal
gray (PAG), hypothalamus, and brainstem nuclei that coordinate defensive responses
(LeDoux, 2000; Maren, 2001). The ventromedial prefrontal cortex (vmPFC) and
hippocampus modulate fear expression through contextual and safety signal
processing.

1.2 Potential Threat ("Anxiety")

NIMH Definition: Activation of a brain system in which harm may potentially occur but
is distant, ambiguous, or low/uncertain in probability, characterized by enhanced risk
assessment and hypervigilance.

Neural Basis: Potential threat processing engages the bed nucleus of the stria
terminalis (BNST), extended amygdala, and prefrontal-hippocampal circuits that support
sustained vigilance and risk assessment under uncertainty (Davis et al., 2010; Grupe &
Nitschke, 2013).

1.3 Sustained Threat

NIMH Definition: Responses to prolonged, uncontrollable stressors that involve

activation of the hypothalamic-pituitary-adrenal (HPA) axis and associated physiological
and behavioral changes.

Neural Basis: Sustained threat activates the HPA axis through paraventricular nucleus
of the hypothalamus, with regulatory input from the prefrontal cortex, hippocampus, and
amygdala. Chronic activation leads to glucocorticoid-mediated neuroplastic changes
(McEwen, 2007; Ulrich-Lai & Herman, 2009).

1.4 Loss

NIMH Definition: Responses to loss of reward or withdrawal of positive reinforcement,

including sadness, grief, and depressive symptoms following separation or
bereavement.

Neural Basis: Loss processing involves the subgenual anterior cingulate cortex
(sgACC), ventral striatum, and default mode network regions implicated in
self-referential processing and reward omission (Pizzagalli, 2014; Eshel & Roiser,
2010).

1.5 Frustrative Nonreward

NIMH Definition: Responses to situations in which reward delivery is prevented or

terminated, characterized by increased arousal, aggression, and persistence in
goal-directed behavior.

Neural Basis: Frustrative nonreward engages the anterior cingulate cortex (ACC),
anterior insula, and dorsal striatum in detecting reward omission and generating
compensatory behavioral responses (Amsel, 1992; Abler et al., 2005).

Domain II: Positive Valence Systems

Positive Valence Systems are primarily responsible for responses to positive

motivational situations or contexts, such as reward seeking, consummatory behavior,
and reward/habit learning. These systems evolved to promote approach behavior
toward resources necessary for survival and reproduction.
2.1 Reward Responsiveness

NIMH Definition: The process by which organisms detect, approach, and consume
rewards, encompassing reward anticipation, initial response to reward, and
sustained/longer-term response to reward.

2.1.1 Reward Anticipation

NIMH Definition: Neural and behavioral activation in response to cues that predict
upcoming reward availability.

Neural Basis: Reward anticipation activates the ventral striatum (nucleus accumbens),
ventral tegmental area (VTA), and mesolimbic dopamine pathway. The
stimulus-preceding negativity (SPN) ERP component and anticipatory BOLD responses
in the ventral striatum index this process (Knutson et al., 2001; Schott et al., 2008).

2.1.2 Initial Response to Reward Attainment

NIMH Definition: Immediate hedonic and neural responses to receipt of reward.

Neural Basis: Reward receipt activates the ventral striatum, medial prefrontal cortex
(mPFC), and orbitofrontal cortex (OFC). The reward positivity (RewP) ERP component,
peaking approximately 250-350 ms post-feedback, reflects reward processing (Proudfit,
2015; Holroyd & Coles, 2002).

2.1.3 Sustained/Longer-Term Response to Reward

NIMH Definition: Prolonged positive affective states and motivation following reward
receipt.
Neural Basis: Sustained reward responses involve the ventromedial prefrontal cortex,
posterior cingulate cortex, and default mode network in maintaining reward
representations and positive affect (Haber & Knutson, 2010).

2.2 Reward Learning

NIMH Definition: The process by which organisms learn about stimuli, actions, and
contexts that predict reward availability.

2.2.1 Probabilistic and Reinforcement Learning

NIMH Definition: Learning about the statistical relationships between cues, actions,
and reward outcomes.

Neural Basis: Reinforcement learning engages the dorsal and ventral striatum,
midbrain dopamine neurons, and prefrontal cortex. Computational models based on
temporal difference learning (Rescorla-Wagner, Q-learning) describe how prediction
errors drive learning (Sutton & Barto, 1998; Schultz et al., 1997).

2.2.2 Reward Prediction Error

NIMH Definition: The discrepancy between expected and received reward, which
drives learning and behavioral adaptation.

Neural Basis: Midbrain dopamine neurons encode reward prediction errors, with phasic
firing increases for positive errors and decreases for negative errors. The
feedback-related negativity (FRN) and RewP ERP components reflect cortical
processing of prediction errors (Schultz, 2016; Holroyd & Coles, 2002).

2.2.3 Habit
NIMH Definition: Stimulus-response associations that become automatic and relatively
insensitive to outcome value through overtraining.

Neural Basis: Habit formation involves a transition from goal-directed (ventral striatum,
prefrontal cortex) to habitual (dorsolateral striatum) control, mediated by corticostriatal
loops (Yin & Knowlton, 2006; Graybiel, 2008).

2.3 Reward Valuation

NIMH Definition: The process of assigning value to rewards and integrating information
about reward magnitude, probability, delay, and effort costs.

2.3.1 Reward (Probability) Valuation

NIMH Definition: Assessment of reward value as a function of probability or uncertainty.

Neural Basis: Probability valuation engages the orbitofrontal cortex, ventromedial

prefrontal cortex, and posterior parietal cortex in computing expected value under risk
(Knutson & Huettel, 2015).

2.3.2 Delay Valuation

NIMH Definition: Discounting of reward value as a function of temporal delay (temporal

discounting).

Neural Basis: Delay discounting involves competition between limbic (ventral striatum,
ventromedial prefrontal cortex) and cognitive control (dorsolateral prefrontal cortex)
systems, with steeper discounting associated with greater limbic dominance (McClure et
al., 2004; Peters & Büchel, 2011). Hyperbolic discounting models (k parameter) quantify
individual differences.
2.3.3 Effort Valuation

NIMH Definition: Assessment of whether reward value justifies the physical or cognitive
effort required to obtain it.

Neural Basis: Effort-based decision-making engages the anterior cingulate cortex,

anterior insula, and ventral striatum in cost-benefit computation (Croxson et al., 2009;
Kurniawan et al., 2011).

2.4 Approach Motivation

NIMH Definition: The propensity to move toward and engage with potentially rewarding
stimuli and contexts.

Neural Basis: Approach motivation involves the behavioral activation system (BAS),
mediated by mesolimbic dopamine pathways, ventral striatum, and prefrontal cortex
(Gray & McNaughton, 2000; Depue & Collins, 1999).

2.5 Reward Satiation

NIMH Definition: Decreased reward responsiveness following repeated or prolonged

reward consumption.

Neural Basis: Satiation involves orbitofrontal cortex encoding of outcome-specific value

devaluation and hypothalamic regulation of homeostatic states (Rolls, 2016; Berridge,
2009).

Domain III: Cognitive Systems

Cognitive Systems are responsible for various cognitive processes, including attention,
perception, declarative and working memory, language, and cognitive control. These
systems enable flexible, goal-directed behavior and adaptive responses to
environmental demands.

3.1 Attention

NIMH Definition: The ability to focus cognitive resources on task-relevant information

while filtering out irrelevant information.

Neural Basis: Attention involves dorsal (dorsolateral prefrontal cortex, intraparietal

sulcus) and ventral (temporoparietal junction, ventral frontal cortex) attention networks,
with modulatory input from the locus coeruleus-norepinephrine system (Corbetta &
Shulman, 2002; Petersen & Posner, 2012).

3.1.1 Sustained Attention

NIMH Definition: Maintenance of attention over extended periods of time.

Neural Basis: Sustained attention engages right-lateralized frontoparietal networks,

with the right dorsolateral prefrontal cortex and inferior parietal lobule showing sustained
activation during vigilance tasks (Langner & Eickhoff, 2013). The P300 ERP component
indexes attentional resource allocation.

3.1.2 Selective Attention

NIMH Definition: Focusing on specific stimuli while ignoring distractors.

Neural Basis: Selective attention involves top-down modulation from prefrontal and
parietal cortex to sensory cortices, enhancing processing of attended stimuli and
suppressing distractors (Desimone & Duncan, 1995). The N2pc ERP component
reflects attentional selection.
3.1.3 Divided Attention

NIMH Definition: Simultaneous processing of multiple sources of information or task

demands.

Neural Basis: Divided attention recruits bilateral frontoparietal networks and anterior
cingulate cortex for task coordination and conflict monitoring (Loose et al., 2003).

3.2 Perception

NIMH Definition: The process of organizing and interpreting sensory information to

represent and understand the environment.

3.2.1 Visual Perception

NIMH Definition: Processing and interpretation of visual information.

Neural Basis: Visual perception involves hierarchical processing from primary visual
cortex (V1) through ventral ("what") and dorsal ("where/how") streams, with object
recognition mediated by inferior temporal cortex and spatial processing by posterior
parietal cortex (Ungerleider & Mishkin, 1982; Goodale & Milner, 1992).

3.2.2 Auditory Perception

NIMH Definition: Processing and interpretation of auditory information.

Neural Basis: Auditory perception involves hierarchical processing from primary

auditory cortex through ventral (speech/object identification) and dorsal (spatial
localization) streams (Rauschecker & Scott, 2009).

3.2.3 Olfactory/Somatosensory/Multimodal Perception

NIMH Definition: Processing and integration of olfactory, tactile, and cross-modal
sensory information.

Neural Basis: Multimodal integration occurs in superior temporal sulcus, intraparietal

sulcus, and prefrontal cortex, binding information across sensory modalities (Driver &
Noesselt, 2008).

3.3 Declarative Memory

NIMH Definition: Conscious recollection of facts and events.

Neural Basis: Declarative memory depends on medial temporal lobe structures

(hippocampus, entorhinal cortex, perirhinal cortex) for encoding and consolidation, with
retrieval supported by prefrontal-hippocampal interactions (Squire & Zola-Morgan, 1991;
Eichenbaum et al., 2007).

3.3.1 Long-Term Memory (Episodic)

NIMH Definition: Memory for personally experienced events situated in time and place.

Neural Basis: Episodic memory involves the hippocampus for binding contextual
details, with the left hippocampus preferentially engaged for verbal material and right
hippocampus for spatial/visual material (Tulving, 2002; Burgess et al., 2002).

3.3.2 Long-Term Memory (Semantic)

NIMH Definition: Memory for general knowledge and facts independent of personal
experience.
Neural Basis: Semantic memory involves distributed neocortical networks, particularly
anterior temporal lobes, with gradual consolidation from episodic to semantic
representations (Patterson et al., 2007).

3.3.3 Short-Term Memory

NIMH Definition: Temporary storage of information over seconds to minutes.

Neural Basis: Short-term memory involves sustained neural activity in sensory cortices
and prefrontal cortex during brief retention intervals (Jonides et al., 2008).

3.4 Language

NIMH Definition: The system for encoding and decoding meaning through structured
symbolic communication.

3.4.1 Language Production

NIMH Definition: Generation of spoken or written language output.

Neural Basis: Language production involves Broca's area (left inferior frontal gyrus) for
syntactic processing and motor planning, supplementary motor area for speech
initiation, and motor cortex for articulation (Friederici, 2011; Hickok & Poeppel, 2007).

3.4.2 Language Comprehension

NIMH Definition: Understanding of spoken or written language input.

Neural Basis: Language comprehension involves Wernicke's area (left superior

temporal gyrus) for phonological and semantic processing, with dorsal and ventral
pathways connecting temporal and frontal language regions (Hickok & Poeppel, 2007).
3.5 Cognitive Control

NIMH Definition: The ability to regulate thoughts and actions in accordance with
internally generated goals and plans.

Neural Basis: Cognitive control involves the frontoparietal control network, with the
dorsolateral prefrontal cortex, anterior cingulate cortex, and posterior parietal cortex
coordinating goal maintenance, conflict monitoring, and response selection (Miller &
Cohen, 2001; Cole & Schneider, 2007).

3.5.1 Goal Selection, Updating, Representation, and Maintenance

NIMH Definition: Identifying, maintaining, and flexibly updating goal representations in

working memory.

Neural Basis: Goal maintenance engages the dorsolateral prefrontal cortex and
posterior parietal cortex, with sustained activity representing task rules and goals (Miller
& Cohen, 2001; Sakai, 2008).

3.5.2 Response Selection, Inhibition/Suppression

NIMH Definition: Selecting appropriate responses while inhibiting prepotent or

inappropriate responses.

Neural Basis: Response inhibition involves the right inferior frontal gyrus,
pre-supplementary motor area, and subthalamic nucleus in stopping or canceling motor
responses (Aron et al., 2014). The N2 and P3 ERP components index inhibitory control
processes.

3.5.3 Performance Monitoring

NIMH Definition: Evaluating ongoing performance and detecting errors or conflicts to
guide behavioral adjustment.

Neural Basis: Performance monitoring involves the anterior cingulate cortex and medial
prefrontal cortex in detecting errors, conflicts, and unexpected outcomes (Holroyd &
Coles, 2002; Botvinick et al., 2001). The error-related negativity (ERN) and error
positivity (Pe) ERP components reflect error detection and awareness.

3.6 Working Memory

NIMH Definition: The active maintenance and manipulation of information in mind over
short periods.

Neural Basis: Working memory involves the dorsolateral prefrontal cortex for executive
control, posterior parietal cortex for storage, and interactions with sensory cortices for
content-specific representations (Baddeley, 2003; D'Esposito & Postle, 2015).

3.6.1 Active Maintenance

NIMH Definition: Holding information in an active, accessible state.

Neural Basis: Active maintenance involves sustained neural activity in prefrontal and
parietal cortices during delay periods (Curtis & D'Esposito, 2003).

3.6.2 Flexible Updating

NIMH Definition: Dynamically adding, removing, or modifying information in working

memory.
Neural Basis: Updating engages the dorsolateral prefrontal cortex and basal ganglia in
gating information into working memory (Frank et al., 2001; Bledowski et al., 2010).

3.6.3 Limited Capacity

NIMH Definition: The constraint on the amount of information that can be

simultaneously maintained.

Neural Basis: Capacity limits reflect constraints on sustained neural activity and
interference among representations, typically 3-4 items for complex stimuli (Cowan,
2001; Todd & Marois, 2004).

3.6.4 Interference Control

NIMH Definition: Protecting working memory contents from interference by irrelevant

information.

Neural Basis: Interference control involves the ventrolateral prefrontal cortex in

resolving competition among memory representations (Jonides & Nee, 2006).

Domain IV: Social Processes

Social Processes mediate responses in interpersonal settings, including the processing

of social signals and the representation of social relationships. These systems evolved
to support group living, cooperation, and social learning.

4.1 Affiliation and Attachment

NIMH Definition: The formation and maintenance of close interpersonal relationships,

including parent-child bonding and adult pair bonding.
Neural Basis: Affiliation involves the oxytocin and vasopressin systems, with the ventral
striatum, amygdala, and medial prefrontal cortex mediating social reward and bonding
(Insel & Young, 2001; Feldman, 2012).

4.1.1 Attachment Formation

NIMH Definition: Development of selective bonds with caregivers or attachment

figures.

Neural Basis: Attachment formation involves oxytocin-mediated plasticity in

amygdala-prefrontal circuits, with the ventral striatum encoding social reward value
(Strathearn et al., 2009).

4.1.2 Affiliation/Bonding

NIMH Definition: Formation of social bonds and preference for social proximity.

Neural Basis: Social bonding engages the ventral striatum, ventral pallidum, and
prefrontal cortex in processing social rewards and maintaining affiliative motivation
(Depue & Morrone-Strupinsky, 2005).

4.1.3 Separation Distress

NIMH Definition: Negative affective and behavioral responses to separation from

attachment figures.

Neural Basis: Separation distress involves the anterior cingulate cortex, amygdala, and
periaqueductal gray in generating distress vocalizations and negative affect (Panksepp,
2003).

4.2 Social Communication

NIMH Definition: The transmission and reception of social signals through verbal and
nonverbal channels.

4.2.1 Reception of Facial Communication

NIMH Definition: Perception and interpretation of facial expressions and identity.

Neural Basis: Face processing involves the fusiform face area (FFA) for identity,
superior temporal sulcus (STS) for changeable aspects (expression, gaze), and
amygdala for emotional significance (Haxby et al., 2000). The N170 ERP component,
peaking approximately 170 ms over occipitotemporal sites, indexes structural face
encoding (Bentin et al., 1996).

4.2.2 Production of Facial Communication

NIMH Definition: Generation of facial expressions to communicate internal states.

Neural Basis: Facial expression production involves motor cortex, supplementary

motor area, and basal ganglia for voluntary expressions, with amygdala and anterior
cingulate cortex mediating emotional expressions (Rinn, 1984).

4.2.3 Reception of Non-Facial Communication

NIMH Definition: Perception of body language, prosody, and other non-facial social
signals.

Neural Basis: Body language processing involves the extrastriate body area (EBA) and
superior temporal sulcus for biological motion perception (Peelen & Downing, 2007).
Prosody processing engages right-hemisphere homologues of language areas
(Wildgruber et al., 2006).
4.2.4 Production of Non-Facial Communication

NIMH Definition: Generation of gestures, vocal prosody, and other non-facial social
signals.

Neural Basis: Gesture production involves left inferior frontal gyrus and premotor
cortex, with right-hemisphere regions mediating prosodic modulation (Willems &
Hagoort, 2007).

4.3 Perception and Understanding of Self

NIMH Definition: Representation and evaluation of one's own mental states, traits, and
physical characteristics.

4.3.1 Agency

NIMH Definition: The sense of being the agent or cause of one's own actions.

Neural Basis: Agency involves the posterior parietal cortex, supplementary motor area,
and cerebellum in comparing predicted and actual sensory consequences of actions
(Haggard, 2017). The lateralized readiness potential (LRP) indexes motor preparation
and agency.

4.3.2 Self-Knowledge

NIMH Definition: Awareness and representation of one's own traits, preferences, and
mental states.
Neural Basis: Self-referential processing involves the medial prefrontal cortex, posterior
cingulate cortex, and precuneus (default mode network) in representing self-knowledge
(Northoff et al., 2006).

4.4 Perception and Understanding of Others

NIMH Definition: Representation and evaluation of others' mental states, traits, and
intentions.

4.4.1 Animacy Perception

NIMH Definition: Detection of goal-directed, intentional movement characteristic of

living agents.

Neural Basis: Animacy perception involves the superior temporal sulcus and posterior
superior temporal gyrus in detecting biological motion and intentional movement
(Castelli et al., 2000).

4.4.2 Action Perception

NIMH Definition: Understanding the goals and intentions underlying observed actions.

Neural Basis: Action understanding involves the mirror neuron system (inferior frontal
gyrus, inferior parietal lobule) and superior temporal sulcus in mapping observed
actions onto motor representations (Rizzolatti & Craighero, 2004). Mu rhythm
suppression (8-13 Hz) over sensorimotor cortex indexes action observation.

4.4.3 Understanding Mental States

NIMH Definition: Inferring others' beliefs, desires, and intentions (theory of

mind/mentalizing).
Neural Basis: Mentalizing involves the medial prefrontal cortex, temporoparietal
junction, superior temporal sulcus, and temporal poles in representing others' mental
states (Frith & Frith, 2006; Saxe & Kanwisher, 2003).

Domain V: Arousal and Regulatory Systems

Arousal and Regulatory Systems are responsible for generating activation of neural
systems as appropriate for various contexts and providing appropriate homeostatic
regulation of such systems as energy balance and sleep.

5.1 Arousal

NIMH Definition: The state of physiological and psychological activation or readiness

for action.

Neural Basis: Arousal is regulated by ascending brainstem systems, including the

locus coeruleus-norepinephrine, dorsal raphe-serotonin, ventral tegmental
area-dopamine, and basal forebrain-acetylcholine systems, with modulatory input to
cortex and thalamus (Pfaff, 2006; Sara, 2009).

5.1.1 Resting Arousal

NIMH Definition: Baseline level of physiological activation in the absence of specific

demands.

Neural Basis: Resting arousal involves tonic activity of brainstem arousal systems and
default mode network, with pupil diameter and skin conductance level indexing baseline
arousal (Aston-Jones & Cohen, 2005).

5.1.2 Responsivity to Arousing Stimuli

NIMH Definition: Changes in arousal in response to salient or alerting stimuli.

Neural Basis: Phasic arousal responses involve the locus coeruleus, salience network
(anterior cingulate cortex, anterior insula), and amygdala in detecting and responding to
salient stimuli (Corbetta et al., 2008). Pupil dilation and P300 amplitude index phasic
arousal.

5.2 Circadian Rhythms

NIMH Definition: Endogenous oscillations in biological processes with approximately

24-hour periodicity.

Neural Basis: Circadian rhythms are generated by the suprachiasmatic nucleus (SCN)
of the hypothalamus, with molecular clock genes (CLOCK, BMAL1, PER, CRY) driving
transcriptional-translational feedback loops (Reppert & Weaver, 2002).

5.3 Sleep and Wakefulness

NIMH Definition: The regulation of sleep-wake cycles and associated physiological and
behavioral states.

5.3.1 Sleep Initiation and Maintenance

NIMH Definition: The ability to fall asleep and maintain consolidated sleep.

Neural Basis: Sleep initiation involves the ventrolateral preoptic nucleus (VLPO)
inhibiting arousal systems, with adenosine accumulation promoting sleep pressure
(Saper et al., 2005).

5.3.2 Sleep Architecture

NIMH Definition: The organization and cycling of sleep stages (REM, NREM).

Neural Basis: Sleep stage cycling involves reciprocal interactions between REM-on
(cholinergic) and REM-off (aminergic) brainstem nuclei, with thalamocortical oscillations
generating NREM sleep rhythms (McCarley, 2007).

5.3.3 Wakefulness

NIMH Definition: Sustained alertness and vigilance during wake periods.

Neural Basis: Wakefulness is maintained by ascending arousal systems (locus

coeruleus, dorsal raphe, tuberomammillary nucleus, basal forebrain) and
orexin/hypocretin neurons that stabilize wake states (Saper et al., 2010).

Domain VI: Sensorimotor Systems

Sensorimotor Systems include motor systems that organize and generate motor activity,
as well as sensory systems that process sensory input. These systems enable
interaction with the physical environment through perception and action.

6.1 Motor Actions

NIMH Definition: The planning, initiation, execution, and control of voluntary

movements.

Neural Basis: Motor control involves hierarchical organization from primary motor
cortex (M1) through premotor cortex, supplementary motor area (SMA), basal ganglia,
and cerebellum, with sensory feedback integrated through posterior parietal cortex
(Graziano, 2006; Desmurget & Sirigu, 2009).
6.1.1 Action Planning/Selection

NIMH Definition: Selecting and preparing appropriate motor programs for goal-directed
actions.

Neural Basis: Action planning involves the dorsal premotor cortex, supplementary
motor area, and posterior parietal cortex in selecting and preparing motor programs
(Cisek & Kalaska, 2010).

6.1.2 Sensorimotor Dynamics

NIMH Definition: Real-time integration of sensory feedback with motor commands

during movement execution.

Neural Basis: Sensorimotor integration involves the posterior parietal cortex,

cerebellum, and primary motor cortex in comparing predicted and actual sensory
feedback (Wolpert et al., 1998).

6.1.3 Initiation

NIMH Definition: Triggering the onset of planned motor actions.

Neural Basis: Movement initiation involves the supplementary motor area, basal
ganglia (particularly the globus pallidus and substantia nigra pars reticulata), and
primary motor cortex (Nachev et al., 2008). The Bereitschaftspotential (readiness
potential) and lateralized readiness potential (LRP) index motor preparation and
initiation.

6.1.4 Execution

NIMH Definition: Carrying out motor commands to produce movement.

Neural Basis: Movement execution involves the primary motor cortex (M1), with
corticospinal projections to spinal motor neurons, modulated by cerebellar and basal
ganglia loops (Graziano, 2006).

6.1.5 Inhibition and Termination

NIMH Definition: Stopping or canceling ongoing or planned motor actions.

Neural Basis: Motor inhibition involves the right inferior frontal gyrus,
pre-supplementary motor area, and subthalamic nucleus in implementing stop signals
(Aron et al., 2014).

6.2 Agency and Ownership

NIMH Definition: The sense of being the agent of one's actions (agency) and the sense
that one's body belongs to oneself (ownership).

Neural Basis: Agency involves the posterior parietal cortex, supplementary motor area,
and cerebellum in comparing predicted and actual sensory consequences. Ownership
involves the posterior parietal cortex and premotor cortex in multisensory integration
(Tsakiris, 2010; Haggard, 2017).

6.3 Habit (Sensorimotor)

NIMH Definition: Automatic, stimulus-triggered motor sequences that develop through

repetition.

Neural Basis: Sensorimotor habits involve the dorsolateral striatum (putamen) and
sensorimotor cortex in stimulus-response associations that become automatic through
overtraining (Graybiel, 2008; Yin & Knowlton, 2006).
6.4 Innate Motor Patterns

NIMH Definition: Stereotyped motor behaviors that are present without prior learning
(e.g., reflexes, fixed action patterns).

Neural Basis: Innate motor patterns involve brainstem and spinal cord circuits, with
central pattern generators producing rhythmic motor outputs (Grillner, 2006).

Table of Contents

1.​ Executive Summary

2.​ RDoC Theoretical Foundations and Neural Circuitry
3.​ Comprehensive Battery Descriptions
4.​ Battery-to-RDoC Construct Mapping
5.​ Gap Analysis: Underassessed RDoC Constructs
6.​ Experimental Paradigms for Gap Coverage
7.​ Comprehensive Master Table: RDoC Subconstructs to Assessment Methods
8.​ Psychometric Considerations
9.​ Implementation Roadmap
10.​Clinical Translation and Applications
11.​References

7. Comprehensive Master Table: RDoC Subconstructs to

Assessment Methods

This section provides a comprehensive mapping of all RDoC subconstructs to available

assessment methods, including standardized neuropsychological batteries,
experimental paradigms, EEG/ERP measures, fMRI paradigms, and psychometric
instruments. Each entry includes specific timing parameters, neural correlates, and
psychometric properties where available.
7.1 Negative Valence Systems: Assessment Methods

7.1.1 Acute Threat ("Fear")

Assessment Method Paradigm Details EEG/ERP Correlates fMRI Correlates Psychometric

Properties

Fear Conditioning CS+ paired with UCS Early posterior Amygdala Group-level reliability
(shock/loud noise) on negativity (EPN) (basolateral and robust (Raduà et al.,
50-100% of trials; CS- 150-200 ms; Late central nuclei) 2025); individual-level
never paired. Typical: positive potential activation to CS+; longitudinal reliability
18-36 trials per (LPP) >300 ms, vmPFC and limited (ICC
condition, 3-6 sec sustained over hippocampus during ~0.30-0.50 for SCR).
stimulus duration, 2-6 centro-parietal sites, extinction; Internal consistency
sec ITI. Acquisition larger for CS+ vs CS-. periaqueductal gray satisfactory.
followed by extinction Frontal theta (4-8 Hz) (PAG) for defensive Prediction error
(CS+ without UCS). power increases responses. Reduced signals correlate with
during threat. vmPFC-amygdala PTSD symptoms
connectivity predicts (Letkiewicz et al.,
extinction deficits. 2021).

NPU-Threat Task Three conditions: No Startle blink reflex BNST activation Startle potentiation
threat (N), Predictable amplitude (EMG from during unpredictable shows moderate
 threat (P - signaled orbicularis oculi) threat; amygdala reliability (ICC
shock), Unpredictable 20-200 ms during predictable ~0.50-0.70).
threat (U - unsignaled post-probe. P300 threat; dlPFC and Discriminates anxiety
shock). Startle probes amplitude modulation ACC for threat disorders from
delivered during each by threat condition. regulation. Altered controls (Klumpp et
condition. Minimum 6 Growth curve BNST-amygdala al., 2018). Sensitive
startle responses per modeling assesses connectivity in anxiety to anxiolytic
condition for reliable habituation and initial disorders (Feola et medication effects.
signal. reactivity. al., 2023).

Threat of Shock Blocks alternate LPP amplitude Amygdala, anterior Threat-potentiated

Paradigm between safe and enhancement during insula, and dACC task performance
threat-of-shock threat blocks. Frontal activation during shows ICC = 0.58
conditions. Shock theta power threat anticipation. across sessions
delivered increases. Alpha Increased functional (Aylward et al., 2017).
unpredictably during asymmetry (greater connectivity within Provides objective,
threat blocks, right frontal activity) salience network. non-subjective
independent of during threat measure of anxious
performance. Typical: anticipation. responding.
8 blocks, 104 sec
each, with cognitive
task (e.g., SART).
Fear Generalization After conditioning to LPP amplitude Hippocampus and Rescorla-Wagner
CS+, test decreases as stimuli vmPFC mediate model and
generalization to become less similar generalization common-elements
stimuli varying in to CS+. Steeper gradients. Broader theory predict
similarity to CS+ (e.g., gradients in anxiety generalization generalization
different sized circles, disorders. associated with patterns (Rescorla,
morphed faces). Non-conscious reduced hippocampal 1976). Clinical utility
Generalization generalization pattern separation. in PTSD and anxiety
gradient quantifies measurable via early disorders.
breadth of fear ERP components
responses. (Mei et al., 2024).
7.1.2 Potential Threat ("Anxiety")

Assessment Method Paradigm Details EEG/ERP Correlates fMRI Correlates Psychometric

Properties

Anxiety Sensitivity Self-report Correlates with Associated with Cronbach's α =

Index (ASI) questionnaire enhanced LPP to heightened amygdala 0.80-0.90; test-retest
assessing fear of threat cues and and insula reactivity reliability r =
anxiety-related elevated startle during to interoceptive 0.70-0.75. Predicts
sensations. 16-18 unpredictable threat stimuli. panic disorder onset.
items rated on 5-point (Nelson et al., 2015). Sensitive to CBT
scale. Three factors: effects.
physical, cognitive,
social concerns.

Intolerance of Self-report measure Correlates with Increased BNST and IUS: α = 0.91-0.94;
Uncertainty Scale of negative beliefs sustained frontal theta dorsal ACC activation IUS-12: α =
(IUS) about uncertainty and power during during uncertain 0.85-0.91. Test-retest
its implications. ambiguous threat. threat. Altered reliability r =
27-item (IUS) or Enhanced connectivity in 0.74-0.78.
12-item (IUS-12) error-related frontolimbic circuits. Transdiagnostic
versions. negativity (ERN) predictor of anxiety
amplitude. disorders.
7.1.3 Sustained Threat

Assessment Method Paradigm Details EEG/ERP Correlates fMRI Correlates Psychometric

Properties

Trier Social Stress Standardized Increased frontal Increased amygdala, Cortisol responders
Test (TSST) psychosocial stress theta power during hippocampus, and (>2.5 nmol/L
protocol: 5-min stress. Reduced hypothalamus increase) ~70% of
preparation, 5-min alpha power. activation. Reduced participants.
speech, 5-min mental Enhanced LPP to vmPFC-amygdala Test-retest reliability
arithmetic before negative stimuli connectivity. Altered moderate (ICC
evaluative audience. post-stress. Altered default mode network ~0.50-0.60) due to
Cortisol sampled at ERN amplitude activity. HPA axis habituation. Robust
baseline, +10, +20, following stress. activation measurable group-level effects.
+30, +45, +60 min. via cortisol.

Chronic Stress Perceived Stress Chronic stress Associated with PSS-10: α =

Questionnaires Scale (PSS-10/14), correlates with reduced hippocampal 0.78-0.82; test-retest r
Chronic Stress Scale. reduced P300 and prefrontal cortex = 0.55-0.70. Predicts
Assess subjective amplitude, enhanced volume. Altered health outcomes and
stress over past ERN, and altered amygdala-prefrontal HPA axis
month. resting-state EEG connectivity. Elevated dysregulation.
 (increased beta, resting-state
reduced alpha). amygdala activity.

7.1.4 Loss

Assessment Method Paradigm Details EEG/ERP Correlates fMRI Correlates Psychometric

Properties

Monetary Loss Participants can win Feedback-related Anterior insula and Loss aversion
Paradigm or lose money based negativity (FRN) or dACC activation to parameter (λ) typically
on performance or RewP shows larger loss outcomes. 1.5-2.5 in prospect
probabilistically. Loss amplitude for losses Reduced ventral theory models.
trials involve vs gains (or smaller striatum response to Individual differences
subtraction from for gains vs losses, loss vs gain. sgACC stable over time.
accumulated total. depending on activation in Blunted loss
Typical: equal scoring). Peak depression during sensitivity in
numbers of gain, loss, ~250-350 ms at loss. depression.
and neutral trials. frontocentral sites.

Grief and Inventory of Enhanced LPP to Increased nucleus ICG: α = 0.94; cutoff
Bereavement Scales Complicated Grief deceased-related accumbens and ≥25 for complicated
(ICG), Prolonged stimuli. Altered sgACC activation to grief. PG-13: α =
Grief Disorder scale resting-state alpha reminders of 0.81-0.86. Sensitive
 (PG-13). Assess asymmetry. Reduced deceased. Altered to grief-specific
maladaptive grief P300 to positive default mode network interventions.
responses. stimuli in complicated connectivity. Reduced
grief. reward circuit
activation.

7.1.5 Frustrative Nonreward

Assessment Method Paradigm Details EEG/ERP Correlates fMRI Correlates Psychometric

Properties

Frustration Participants work Enhanced FRN Anterior cingulate Behavioral

Induction Tasks toward reward, but amplitude to cortex and anterior persistence (time
reward is withheld or unexpected reward insula activation spent on unsolvable
task becomes omission. Increased during reward tasks) shows
impossible (e.g., frontal theta power. omission. Increased moderate test-retest
unsolvable anagrams, Elevated beta power dorsal striatum reliability (r
rigged computer reflecting activity. Altered ~0.50-0.65).
tasks). Behavioral arousal/frustration. connectivity in Physiological arousal
persistence and cognitive control (HR, SCL) increases
physiological arousal networks. reliably.
measured.
Passive Avoidance Participants learn to Enhanced ERN Increased amygdala Learning rate
Learning avoid responses that following punished and ACC activation to parameters from
lead to responses. Increased punishment. Altered computational models
punishment/reward frontal theta power ventral striatum (Rescorla-Wagner,
omission. Measures during punishment response to reward Q-learning) show
sensitivity to feedback. omission. Dorsal moderate stability.
punishment and striatum engagement Punishment
frustrative nonreward. in avoidance learning. sensitivity correlates
with anxiety traits.
7.2 Positive Valence Systems: Assessment Methods

7.2.1 Reward Anticipation

Assessment Method Paradigm Details EEG/ERP Correlates fMRI Correlates Psychometric

Properties

Monetary Incentive Cue (1-2 sec) signals Stimulus-preceding Ventral Ventral striatum
Delay (MID) Task potential reward negativity (SPN): slow striatum/nucleus response: test-retest
magnitude ($0, $0.50, negative wave during accumbens activation ICC = 0.40-0.60
$1, $5) or loss anticipation, maximal during anticipation, (moderate reliability).
avoidance. Variable at central sites, larger scaling with reward Internal consistency α
delay (2-4 sec for high vs low magnitude. = 0.70-0.85 for
anticipation period). reward. Cue-P3 Coordinates: [±12, 15, behavioral measures.
Target (100-500 ms) (300-500 ms) scales -9]. Correlation with Effect sizes: Cohen's
requires speeded with reward dopamine release d = 0.5-1.2 for reward
response. Feedback magnitude. (Schott et al., 2008). vs neutral contrast.
(1-2 sec) indicates Contingent negative VTA, mPFC, and Sensitive to
outcome. Typical: variation (CNV) insula also activated. depression (blunted
72-120 trials, 50% win during anticipation. response) and
rate, adaptive RT schizophrenia
adjustment. (Carruzzo et al.,
2024).
Probabilistic Participants identify Reward positivity Ventral striatum Response bias (log b)
Reward Task (PRT) briefly presented (RewP): positive activation to reward shows moderate
stimuli (e.g., short vs deflection 250-350 ms feedback. Reduced test-retest reliability (r
long mouth on post-feedback at activation in remitted = 0.50-0.70).
schematic face). One frontocentral sites depression predicts Discriminant validity:
stimulus rewarded 3x (Fz, FCz), larger for relapse. Altered correlates with
more frequently than reward vs no-reward. striatal-prefrontal anhedonia but not
the other (e.g., 30 vs Reduced RewP in connectivity in general negative
10 cents). Measures depression (Whitton anhedonia. affect. Sensitive to
reward learning via et al., 2016; Pechtel antidepressant
response bias et al., 2013). effects.
development.
200-300 trials, 100
ms stimulus, mask.

Effort Expenditure Participants choose Enhanced SPN for ACC, anterior insula, Proportion of
for Rewards Task between high-reward trials. and ventral striatum high-effort choices
(EEfRT) low-effort/low-reward P300 amplitude activation during shows good
and scales with chosen effort-reward decision. test-retest reliability
high-effort/high-rewar reward magnitude. Reduced ACC (ICC = 0.60-0.75).
d options. Effort = Frontal theta power activation in Computational
number of button depression and models (softmax
 presses; reward during effort-reward schizophrenia choice function with
magnitude and computation. predicts amotivation. effort discounting) fit
probability vary. individual differences.
Measures Reduced effort
effort-based expenditure in
decision-making. depression and
negative symptoms.

7.2.2 Initial Response to Reward Attainment

Assessment Method Paradigm Details EEG/ERP Correlates fMRI Correlates Psychometric

Properties

Reward Feedback Participants receive Reward positivity Ventral striatum, RewP test-retest
Tasks feedback indicating (RewP): mPFC, and OFC reliability: ICC =
reward receipt positive-going activation to reward 0.50-0.70 (moderate).
(win/gain) vs deflection 250-350 ms outcomes. Internal consistency:
non-reward post-feedback at Coordinates: ventral split-half r =
(no-win/loss). frontocentral sites, striatum [±12, 9, -6]; 0.70-0.85.
Feedback can be computed as mPFC [0, 45, -5]. Convergent validity
performance-continge difference wave Reduced activation in with self-reported
 nt or probabilistic. (reward minus depression and anhedonia (r = -0.20
Typical: 100-200 non-reward). schizophrenia. to -0.40). Sensitive to
trials, 1-2 sec Amplitude: 5-15 μV. reward magnitude
feedback display. Reduced in and probability
depression (d = (Proudfit, 2015).
0.5-0.8). Also called
feedback-related
negativity (FRN)
when scored as
negativity to loss.

Consummatory Temporal Experience Correlates with RewP Reduced OFC and TEPS-Consummatory
Pleasure Scales of Pleasure Scale amplitude and ventral ventral striatum : α = 0.72-0.76;
(TEPS) - striatum activation to activation during test-retest r =
Consummatory reward outcomes. reward consumption 0.70-0.81. SHAPS: α
subscale; Reduced in anhedonia. Altered = 0.84-0.91; cutoff ≥3
Snaith-Hamilton consummatory connectivity between for anhedonia.
Pleasure Scale pleasure associated reward regions and Discriminates
(SHAPS). Assess with blunted neural sensory cortices. depression from
hedonic capacity for responses. anxiety.
reward consumption.
7.2.3 Reward Learning

Assessment Method Paradigm Details EEG/ERP Correlates fMRI Correlates Psychometric

Properties

Probabilistic Participants learn RewP amplitude Ventral striatum and Learning rate (α) from
Learning Tasks stimulus-outcome reflects prediction midbrain dopamine computational
associations through error magnitude. neurons encode models: 0.1-0.5
trial-and-error. Larger RewP for prediction errors. typical range.
Reinforcement unexpected rewards Positive PE: Test-retest reliability
schedules vary (e.g., (positive PE) vs increased activation; moderate (ICC =
80/20, 70/30). expected rewards. negative PE: 0.40-0.60). Inverse
Weather prediction FRN larger for decreased activation. temperature (β)
task, probabilistic unexpected Dorsal striatum reflects choice
selection task non-rewards engagement stochasticity. Altered
common variants. (negative PE). Frontal increases with learning in depression
100-300 trials. theta power (4-8 Hz) learning (habit and schizophrenia.
during learning. formation).

Reversal Learning After learning Enhanced ERN and OFC, ACC, and Perseverative errors
stimulus-reward FRN following ventral striatum (responses to
associations, negative feedback activation during previously rewarded
contingencies during reversal. reversal. OFC stimulus after
 reverse. Measures Increased frontal represents outcome reversal) show
behavioral flexibility theta power. P300 expectancies; ACC moderate reliability
and sensitivity to amplitude to reversal signals need for (ICC = 0.50-0.65).
negative feedback. feedback. behavioral Sensitive to OFC and
Typical: 2-4 reversals, adjustment. Impaired ventral striatal
40-80 trials per block. reversal in OFC dysfunction.
lesions.

Temporal Difference Computational Model-derived Model-derived PEs Model fit assessed via
Learning Models models prediction errors correlate with ventral log-likelihood, AIC,
(Rescorla-Wagner, correlate with RewP striatum and midbrain BIC. Parameter
Q-learning, amplitude and frontal BOLD responses. recovery good in
actor-critic) fit to theta power. Temporal difference simulations. Learning
behavioral data. Trial-by-trial PE signals in dopamine rate shows moderate
Parameters: learning regressors predict neurons (Schultz, test-retest reliability
rate (α), discount ERP amplitudes. 2016). (ICC = 0.45-0.65).
factor (γ), inverse
temperature (β).

7.2.4 Reward Valuation

Assessment Method Paradigm Details EEG/ERP Correlates fMRI Correlates Psychometric
Properties

Delay Discounting Participants choose P300 amplitude larger Ventral striatum and Discount rate (k) from
Tasks between for LL choices, vmPFC activation for hyperbolic model: V =
smaller-sooner (SS) reflecting greater SS rewards (limbic A/(1+kD). Log(k)
and larger-later (LL) cognitive control system); dlPFC and typically -4 to -1.
rewards (e.g., $10 engagement. Frontal posterior parietal Test-retest reliability:
today vs $20 in 1 theta power during cortex for LL rewards ICC = 0.60-0.80
month). Delays vary: intertemporal choice. (cognitive control). (good). Higher k
1 day to 1 year. SPN during Competition between (steeper discounting)
Adjusting-amount or anticipation of systems predicts in addiction, ADHD,
fixed-choice delayed rewards. choice (McClure et impulsivity. Area
procedures. 20-50 al., 2004). under the curve
trials. (AUC) alternative
measure.

Probability Participants choose P300 amplitude OFC, vmPFC, and Probability discount
Discounting between certain-small modulated by posterior parietal rate (h) from
and uncertain-large probability and cortex encode hyperbolic model: V =
rewards (e.g., $10 for expected value. expected value A/(1+hθ), where θ =
sure vs $20 with 50% Enhanced frontal (magnitude × odds against.
 probability). theta during risky probability). Ventral Test-retest reliability:
Probability varies: choices. RewP to striatum responds to ICC = 0.55-0.75. Risk
10-90%. Measures probabilistic reward magnitude; aversion in anxiety;
risk preference. outcomes reflects PE. ACC to risk seeking in mania.
risk/uncertainty.

Effort Discounting Participants choose SPN amplitude scales ACC and anterior Effort discount rate
between with chosen reward insula encode effort (k_effort) from
low-effort/low-reward magnitude. P300 costs. Ventral striatum hyperbolic model.
and reflects effort-reward encodes reward Test-retest reliability:
high-effort/high-rewar computation. Frontal value. ACC-striatal ICC = 0.50-0.70.
d options. Effort theta power during connectivity predicts Reduced effort
varies (e.g., number decision-making. effort-based choices. expenditure in
of button presses, Reduced ACC depression,
cognitive load). activation in schizophrenia
Measures apathy/amotivation. negative symptoms,
effort-reward Parkinson's disease.
trade-offs.
7.2.5 Approach Motivation

Assessment Method Paradigm Details EEG/ERP Correlates fMRI Correlates Psychometric

Properties

Behavioral Self-report subscales BAS scores correlate BAS correlates with BAS total: α =
Activation System of BIS/BAS scales: with larger RewP ventral striatum 0.73-0.76; subscales
(BAS) Scales BAS-Drive, BAS-Fun amplitude, greater left reactivity to reward α = 0.66-0.76.
Seeking, frontal alpha cues and mPFC Test-retest r =
BAS-Reward asymmetry (approach activation during 0.59-0.69. Predicts
Responsiveness. 13 motivation), and reward anticipation. manic episodes in
items total for BAS. enhanced SPN to Elevated BAS in bipolar disorder.
reward cues. mania associated with Elevated in ADHD
hyperactivation. and substance use
disorders.

Approach- Participants make Faster approach to Ventral striatum and Approach bias (RT
Avoidance Tasks approach (pull reward-associated mPFC activation avoid - RT approach)
joystick) or avoidance stimuli. LPP during approach to shows moderate
(push joystick) amplitude larger for rewards. Amygdala reliability (ICC =
movements to stimuli. approach vs avoid and insula during 0.50-0.65). Approach
Measures automatic trials. Mu rhythm avoidance of threats. bias to alcohol/drug
approach tendencies. suppression during Approach-avoidance cues in addiction.
Reaction time and approach conflict activates Avoidance bias to
accuracy recorded. movements. ACC. social stimuli in social
anxiety.
7.3 Cognitive Systems: Assessment Methods

7.3.1 Attention - Sustained

Assessment Method Paradigm Details EEG/ERP Correlates fMRI Correlates Psychometric

Properties

Continuous Participants respond P300 amplitude Right dlPFC, right CPT-II: test-retest
Performance Test to target stimuli (e.g., (300-600 ms, inferior parietal lobule, reliability ICC =
(CPT) letter X) and withhold centro-parietal) to and ACC activation 0.55-0.83 for key
to non-targets. targets, reduced in during sustained indices (omissions,
Variants: CPT-II, ADHD. N2 (200-350 attention. Reduced commissions, RT
CPT-3, Conners CPT. ms, frontocentral) to activation in ADHD. variability). Sensitivity
Typical: 300-600 non-targets reflects Vigilance decrement 66%, specificity 66%
trials, 1-4 sec ISI, inhibitory control. associated with for ADHD. Embedded
150-500 ms stimulus Reduced P300 reduced right frontal validity indicators
duration, 10-20 min amplitude over time activation over time. detect suboptimal
duration. reflects vigilance effort (Ord et al.,
decrement. 2021).
Theta/beta ratio
elevated in ADHD.
Psychomotor Participants respond P300 amplitude to Right dlPFC and Mean RT: ICC =
Vigilance Test (PVT) to visual stimulus target onset. Reduced intraparietal sulcus 0.70-0.85 (good
(counter) appearing at amplitude with sleep activation. Reduced reliability). Lapses
random intervals deprivation and activation with sleep highly sensitive to
(2-10 sec ISI). fatigue. Increased deprivation. Altered sleep deprivation
Measures sustained theta power (4-8 Hz) connectivity in (effect size d > 1.5).
attention and and reduced alpha frontoparietal Minimal practice
alertness. Typical: 10 power (8-13 Hz) with attention network. effects. Widely used
min duration, ~100 decreased alertness. Default mode network in sleep research and
trials. RT and lapses intrusions during operational settings.
(RT >500 ms) lapses.
recorded.

Sustained Attention Participants respond Enhanced ERN Right dlPFC, ACC, Commission errors:
to Response Task to frequent following commission and inferior parietal ICC = 0.58-0.70.
(SART) non-targets (e.g., errors (false alarms to lobule activation. Threat-potentiated
digits 1-2, 4-9) and targets). P300 Increased default SART performance
withhold to rare amplitude to targets. mode network activity (with shock threat)
targets (e.g., digit 3). Reduced P300 precedes commission shows ICC = 0.58
Measures sustained amplitude over time errors. Reduced (Aylward et al., 2017).
attention and reflects vigilance task-positive network Sensitive to ADHD,
response inhibition. decrement. Frontal activation over time.
 Typical: 225 trials, theta power TBI, and sleep
250 ms stimulus, 900 correlates with deprivation.
ms mask, 1150 ms sustained attention.
total trial duration.

7.3.2 Attention - Selective

Assessment Method Paradigm Details EEG/ERP Correlates fMRI Correlates Psychometric

Properties

Attention Network Combines cuing Contingent negative Alerting: thalamus, Alerting, orienting,
Test (ANT) (alerting, orienting) variation (CNV) ACC, right frontal and executive control
and flanker (executive during cue-target cortex. Orienting: network scores show
control) paradigms. interval, larger for superior parietal moderate reliability
Cue types: no cue, spatial cues. P1 (100 lobule, (ICC = 0.50-0.70).
center cue, double ms) and N1 (150-200 temporoparietal Alerting and executive
cue, spatial cue. ms) enhancement for junction, frontal eye control impaired in
Target: central arrow spatially cued targets. fields. Executive ADHD. Orienting
flanked by congruent N2 (250-350 ms) control: ACC, dlPFC. impaired in neglect
or incongruent larger for incongruent and parietal lesions.
arrows. Typical: 288 flankers. P300 ANT widely used
trials, 150 ms cue,
 1000 ms cue-target (300-700 ms) to across lifespan (Fan
interval, 350 ms targets. et al., 2002).
target, variable ITI.

Posner Cueing Task Spatial cue (80% P1 (80-120 ms, Superior parietal Validity effect (RT
valid, 20% invalid) occipital) and N1 lobule, invalid - RT valid)
precedes target. (150-200 ms, temporoparietal shows good reliability
Measures orienting of occipitotemporal) junction, and frontal (ICC = 0.65-0.80).
attention. Cue-target enhancement for eye fields for Sensitive to parietal
SOA varies: 100-1000 validly cued targets. orienting. lesions (neglect),
ms. Typical: 100-200 N2pc (200-300 ms, Right-lateralized ADHD, and autism.
trials. contralateral to target) network for
reflects attentional reorienting to invalidly
selection. cued targets.

Visual Search Tasks Participants search N2pc (200-300 ms, Frontal eye fields, Search slopes:
for target among contralateral posterior intraparietal sulcus, feature search ~0-10
distractors. Feature sites) reflects and ventral visual ms/item; conjunction
search (pop-out) vs attentional selection cortex activation. search ~20-60
conjunction search of target. P300 Feature search: ms/item. Test-retest
(serial). Set size amplitude to target parallel processing, reliability moderate
varies (e.g., 4, 8, 16 detection. Search minimal set size (ICC = 0.50-0.70).
 items). Measures slope (RT increase effect. Conjunction Impaired in ADHD,
selective attention per item) reflected in search: serial schizophrenia, and
efficiency. sustained negativity. processing, linear set aging.
size effect.

7.3.3 Working Memory

Assessment Method Paradigm Details EEG/ERP Correlates fMRI Correlates Psychometric

Properties

N-back Task Participants monitor P300 amplitude Dorsolateral 2-back accuracy:

sequence of stimuli (300-600 ms, parietal) prefrontal cortex test-retest ICC =
(letters, shapes, decreases with (dlPFC) and posterior 0.60-0.80 (good).
spatial locations) and increasing load. parietal cortex Internal consistency α
respond when current Sustained negativity activation increases = 0.75-0.85.
stimulus matches one (300-1500 ms, frontal) with load. Bilateral Sensitivity to
presented n items during maintenance, activation, schizophrenia (d =
back. Loads: 0-back increases with load. left-lateralized for 0.8-1.2), ADHD, and
(target detection), Theta power (4-8 Hz, verbal, aging. Practice effects
1-back, 2-back, frontal) increases with right-lateralized for moderate (10-20%
 3-back. Typical: 20-30 load. Alpha power spatial. Inverted-U improvement over 2-3
trials per block, 500 (8-13 Hz, posterior) relationship: sessions).
ms stimulus, decreases with load. activation increases
2000-3000 ms ISI. then
plateaus/decreases at
high loads.

Sternberg Item Participants P300 amplitude dlPFC and RT increases linearly

Recognition memorize set of items (300-600 ms) to intraparietal sulcus with set size (~40
(1-7 digits/letters), probe, decreases with activation during ms/item), reflecting
then indicate whether set size. Sustained encoding and serial search. Slope
probe item was in negativity during maintenance. and intercept show
memory set. Set size retention interval, Activation increases good reliability (ICC =
varies. Measures increases with set linearly with set size. 0.70-0.85). Capacity
active maintenance size. Frontal theta Reliable activation in limit ~4 items.
and retrieval. Typical: power during cognitive regions (ICC Impaired in
2-6 sec encoding, 2-3 encoding and = 0.50-0.70 for normal schizophrenia and
sec retention, probe maintenance. subjects; lower in aging.
until response. schizophrenia)
(Manoach et al.,
2001).
NIH Toolbox - List Participants view and Frontal theta power dlPFC, ACC, and Test-retest reliability:
Sorting Working hear series of stimuli during manipulation. posterior parietal ICC = 0.77-0.84
Memory (animals, foods), then P300 amplitude to cortex activation (good) (Weintraub et
repeat in size order. correctly ordered during manipulation. al., 2014).
1-list (single category) items. Enhanced Greater activation for Age-corrected norms
and 2-list (two frontal activation for 2-list condition. available ages 3-85.
categories) 2-list vs 1-list. Correlates with other
conditions. Measures WM measures (r =
working memory 0.50-0.70). Sensitive
manipulation. to MCI and dementia.

7.3.4 Cognitive Control - Response Inhibition

Assessment Method Paradigm Details EEG/ERP Correlates fMRI Correlates Psychometric

Properties

Stop-Signal Task Participants respond N2 (200-350 ms, Right inferior frontal Stop-signal reaction
(SST) to go stimuli (e.g., frontocentral) larger gyrus (rIFG), time (SSRT):
arrows) but withhold for successful stops. pre-supplementary test-retest ICC =
response when stop P3 (300-500 ms, motor area 0.60-0.80 (good).
signal (e.g., tone) frontocentral) larger (pre-SMA), and SSRT typically
occurs. Stop-signal for successful stops. subthalamic nucleus 200-250 ms. Longer
 delay (SSD) varies Stop-P3 reflects (STN) activation SSRT in ADHD (d =
adaptively to achieve inhibitory control. during stopping. rIFG 0.5-0.7), substance
~50% inhibition. Reduced N2/P3 in critical for stopping use disorders, and
Typical: 200-300 ADHD and impulsivity. (lesions impair SST). impulsivity. Integration
trials, 25-33% stop method for SSRT
trials, 1000-1500 ms calculation
stimulus duration. recommended.

Go/No-Go Task Participants respond N2 (200-350 ms, Right IFG, pre-SMA, Commission error
to frequent go stimuli frontocentral) larger ACC, and dorsal rate: test-retest ICC =
and withhold to for no-go vs go (no-go striatum activation to 0.60-0.75. No-go N2
infrequent no-go N2). P3 (300-500 ms, no-go trials. Reduced amplitude: ICC =
stimuli. Ratio typically frontocentral) larger activation in ADHD 0.50-0.70. Sensitive
75-80% go, 20-25% for no-go (no-go P3). and impulsivity. to ADHD, TBI, and
no-go. Measures Commission errors frontal lobe
prepotent response (false alarms to dysfunction. Higher
inhibition. Typical: no-go) associated commission errors in
200-400 trials, 500 with reduced N2/P3. ADHD (d = 0.6-0.8).
ms stimulus,
1000-1500 ms ISI.
Flanker Task Participants identify N2 (250-350 ms, ACC activation for Flanker effect (RT
central target (e.g., frontocentral) larger incongruent trials incongruent - RT
arrow direction) for incongruent trials (conflict monitoring). congruent): test-retest
flanked by congruent (conflict N2). P3 dlPFC and posterior ICC = 0.60-0.80.
(same direction) or (300-500 ms, parietal) parietal cortex for Conflict N2: ICC =
incongruent (opposite to targets. ERN cognitive control. 0.50-0.70. ERN: ICC
direction) distractors. (0-100 ms Pre-SMA for = 0.50-0.75 (Clayson
Measures post-response, response selection. et al., 2013). Flanker
interference control. frontocentral) effect larger in ADHD
Typical: 100-200 following errors. Pe and aging.
trials, 50% congruent, (200-400 ms
50% incongruent, 500 post-response,
ms stimulus, centro-parietal)
1000-1500 ms ISI. reflects error
awareness.

7.3.5 Cognitive Control - Performance Monitoring

Assessment Method Paradigm Details EEG/ERP Correlates fMRI Correlates Psychometric

Properties
Error-Related Elicited by errors in ERN: negative ACC activation ERN amplitude:
Negativity (ERN) speeded response deflection 0-100 ms following errors. test-retest ICC =
tasks (Flanker, post-error response, Dorsal ACC for 0.50-0.75 (moderate
Stroop, Go/No-Go, maximal at conflict/error to good) (Clayson et
Stop-Signal). ERN frontocentral sites detection; rostral ACC al., 2013). Internal
measured as (FCz, Cz). Amplitude: for affective consistency: split-half
response-locked ERP. -5 to -15 μV (error evaluation. r = 0.70-0.85.
minus correct Connectivity between Minimum 6-8 error
difference). Source: ACC and dlPFC for trials needed for
ACC. Enhanced ERN post-error reliable ERN.
in anxiety disorders; adjustments. Enhanced ERN in
reduced in OCD, GAD (d =
externalizing 0.5-0.8); reduced in
disorders. ADHD, substance use
(d = 0.3-0.6).

Error Positivity (Pe) Follows ERN in same Pe: positive deflection Rostral ACC, anterior Pe amplitude:
error trials. Reflects 200-400 ms insula, and posterior test-retest ICC =
conscious error post-error, maximal at cingulate activation. 0.50-0.70. Internal
awareness. centro-parietal sites Connectivity with consistency: split-half
(Cz, Pz). Amplitude: salience network. Pe r = 0.65-0.80. Pe
5-15 μV (error minus correlates with error dissociates from ERN
 correct). Larger Pe for awareness and (can be present
perceived vs post-error slowing. without ERN).
unperceived errors. Reduced Pe in ADHD
and schizophrenia.

Feedback-Related Elicited by negative FRN: negative ACC and ventral FRN amplitude:
Negativity (FRN) feedback in learning deflection 250-350 ms striatum activation to test-retest ICC =
tasks. Reflects post-feedback, negative feedback. 0.40-0.65 (moderate).
outcome monitoring. maximal at Overlapping with Internal consistency:
frontocentral sites reward processing split-half r =
(FCz, Fz). Larger for regions. FRN reflects 0.60-0.75. Sensitive
negative vs positive prediction error to learning rate and
feedback (or smaller signal. prediction errors.
for positive vs Altered in depression
negative, depending and schizophrenia.
on scoring).
Amplitude: 5-10 μV
difference.
7.4 Social Processes: Assessment Methods

7.4.1 Social Communication - Reception of Facial Communication

Assessment Method Paradigm Details EEG/ERP Correlates fMRI Correlates Psychometric

Properties

Facial Emotion Participants identify N170 (140-200 ms, Fusiform face area Accuracy: test-retest
Recognition Tasks emotions (happy, sad, occipitotemporal sites (FFA) for face identity; ICC = 0.60-0.80
angry, fearful, P7/P8, PO7/PO8): superior temporal (good). N170
disgusted, surprised, larger amplitude for sulcus (STS) for amplitude: ICC =
neutral) from facial faces vs objects, changeable aspects 0.60-0.80 (Kang et
expressions. Stimuli: sensitive to emotional (expression, gaze); al., 2018). Impaired
Ekman faces, expression. Latency amygdala for recognition in autism
NimStim, Karolinska ~170 ms. Early emotional (especially complex
Directed Emotional posterior negativity significance, emotions),
Faces (KDEF). (EPN, 200-300 ms) especially fear. schizophrenia, and
Typical: 60-120 trials, larger for emotional Coordinates: FFA alexithymia. Fear
500-2000 ms stimulus vs neutral faces. LPP [±40, -55, -20]; STS recognition deficits in
duration. (400-800 ms, [±55, -50, 10]; PTSD and anxiety.
centro-parietal)
 sustained for amygdala [±20, -5,
emotional faces. -15].

Reading the Mind in Participants infer Enhanced frontal Medial prefrontal RMET: test-retest
the Eyes Test mental states from theta power during cortex (mPFC), reliability r =
(RMET) photographs of eye mentalizing. P300 temporoparietal 0.63-0.74. Internal
region. 36 items, 4 amplitude to correct junction (TPJ), consistency α =
response options per responses. N170 to superior temporal 0.61-0.72 (moderate).
item. Measures eye stimuli. Altered sulcus (STS), and Impaired performance
theory of ERP patterns in temporal poles in autism (d = 0.8-1.0)
mind/mentalizing. autism (Cochran et activation. Reduced and schizophrenia (d
al., 2023). activation in autism = 0.9-1.2). Gender
and schizophrenia. differences (females >
males).

Penn Emotion Part of Penn N170 amplitude and FFA, STS, and ER-40: test-retest
Recognition Test Computerized latency to emotional amygdala activation. reliability ICC =
(ER-40) Neurocognitive faces. LPP amplitude Reduced activation in 0.70-0.85 (good).
Battery (CNB). scales with emotional schizophrenia, Impaired in
Participants identify intensity. Reduced especially for schizophrenia (d =
emotions from 40 N170 differentiation in negative emotions. 0.8-1.2), especially for
color photographs of schizophrenia. fear and sadness.
 faces (happy, sad, Altered connectivity in Correlates with social
angry, fearful, social brain networks. functioning. Part of
neutral). Balanced for SCOPE battery
gender and intensity. (Pinkham et al., 2016,
2018).

7.4.2 Perception and Understanding of Others - Theory of Mind

Assessment Method Paradigm Details EEG/ERP Correlates fMRI Correlates Psychometric

Properties

False Belief Tasks Participants predict P300 amplitude to mPFC, TPJ, STS, False belief
behavior based on false belief questions. and temporal poles understanding
character's false Enhanced frontal activation during false emerges ~4 years in
belief (e.g., theta power during belief reasoning. typical development.
Sally-Anne task, mentalizing. N400 to Right TPJ critical for Impaired in autism (d
Smarties task). belief-inconsistent belief attribution. = 1.0-1.5) and
First-order: A's belief outcomes. Reduced activation in schizophrenia (d =
about reality. autism. 0.8-1.2). Test-retest
Second-order: A's reliability moderate (r
belief about B's belief. = 0.50-0.70).
 Measures explicit
mentalizing.

Social Attribution Participants watch Enhanced frontal and mPFC, TPJ, STS SAT: inter-rater
Task (SAT) animations of temporal theta power activation for social vs reliability ICC =
geometric shapes during social vs random animations. 0.80-0.90. SAT-MC:
moving in social or random animations. Reduced activation in test-retest ICC =
random patterns, then P300 amplitude to autism and 0.70-0.85
describe interactions. social interactions. schizophrenia. Failure (Johannesen et al.,
Measures to engage TPJ/STS 2018). Impaired in
spontaneous predicts impaired schizophrenia (d =
mentalizing and social naturalistic social 0.8-1.2) and autism.
perception. cognition (Patel et al., Correlates with
Multiple-choice 2021). community
version (SAT-MC) functioning.
available.

Biological Motion Participants view N170 amplitude to STS, extrastriate Accuracy: test-retest
Perception point-light displays of biological motion. body area (EBA), and ICC = 0.60-0.75.
human movement Enhanced STS mirror neuron system Impaired in autism (d
(walking, dancing, activation. Mu rhythm (inferior frontal gyrus, = 0.6-1.0). Biological
emotional actions) suppression (8-13 Hz, inferior parietal motion perception
 and identify action or central sites) during lobule) activation. predicts treatment
emotion. Measures action observation, Reduced STS outcome in autism
perception of reflecting mirror activation in autism. (Yang et al., 2016,
intentional movement. neuron system Cerebellar 2017). Sensitive to
Typical: 20-40 trials, activity. Reduced mu contributions (Jack et social skills training.
2-5 sec animations. suppression in al., 2017).
autism.

7.4.3 Affiliation and Attachment

Assessment Method Paradigm Details EEG/ERP Correlates fMRI Correlates Psychometric

Properties

Social Reward Participants anticipate Stimulus-preceding Ventral striatum, Social reward

Paradigms and receive social negativity (SPN) mPFC, and amygdala responsiveness
rewards (smiling during anticipation of activation to social shows moderate
faces, positive social rewards. rewards. Reduced test-retest reliability
feedback, social Reward positivity activation in autism (ICC = 0.50-0.70).
approval) vs (RewP) to social and social anhedonia. Reduced in autism,
non-social rewards reward outcomes. Oxytocin modulates schizophrenia
(money). Measures Reduced SPN and negative symptoms,
 social motivation and RewP to social social reward and social anxiety.
reward processing. rewards in autism processing. Sensitive to social
(Baker et al., 2021). skills interventions
(Baker et al., 2021).

Attachment Style Experiences in Close Attachment anxiety Attachment anxiety: ECR: α = 0.91-0.94
Questionnaires Relationships (ECR), correlates with heightened amygdala for anxiety and
Attachment Style enhanced LPP to reactivity to rejection. avoidance subscales.
Questionnaire (ASQ). rejection cues and Attachment Test-retest r =
Assess adult elevated ERN. avoidance: reduced 0.70-0.80. Predicts
attachment Attachment mPFC and ventral relationship quality
dimensions: anxiety avoidance correlates striatum response to and mental health
(fear of with reduced LPP to social rewards. outcomes.
abandonment) and social stimuli. Altered connectivity in
avoidance (discomfort attachment-related
with closeness). circuits.
7.5 Arousal and Regulatory Systems: Assessment Methods

7.5.1 Arousal

Assessment Method Paradigm Details EEG/ERP Correlates fMRI Correlates Psychometric

Properties

Psychomotor [See Section 7.3.1 - Reduced P300 Right dlPFC and [See Section 7.3.1]
Vigilance Test (PVT) also assesses amplitude and intraparietal sulcus
arousal/alertness] increased theta power activation. Reduced
with decreased with sleep
arousal. Alpha power deprivation. Locus
(8-13 Hz) inversely coeruleus-norepineph
correlates with rine system
arousal. modulates arousal.

Pupillometry Pupil diameter Pupil dilation Pupil dilations Pupil diameter: high
measured correlates with P300 coupled to salience temporal resolution
continuously during amplitude and phasic network (dACC, (sampled at 60-1000
rest or task arousal responses. bilateral insula) Hz). Sensitive to
performance. Reflects Larger dilations activation (Schneider, arousal, cognitive
arousal and cognitive during high cognitive 2018). Reflects locus load, and autonomic
 load. Spontaneous load and salient coeruleus activity and state. Reliable index
pupil fluctuations stimuli. noradrenergic of salience network
index locus coeruleus modulation. activity.
activity.

Skin Conductance Tonic SCL reflects SCL correlates with SCL and SCR reflect SCL: test-retest
Level (SCL) and baseline arousal. resting-state EEG sympathetic nervous reliability ICC =
Response (SCR) Phasic SCR to stimuli arousal indices system activity. 0.60-0.80. SCR
reflects orienting and (theta/beta ratio). Amygdala and insula amplitude: ICC =
emotional arousal. SCR amplitude activation correlates 0.50-0.70. Sensitive
Measured via correlates with P300 with SCR. Reduced to emotional arousal,
electrodes on palmar and LPP amplitudes. SCR in psychopathy stress, and autonomic
surface. and ventromedial dysfunction.
prefrontal lesions. Habituation occurs
with repeated
stimulation.

7.5.2 Sleep and Wakefulness

Assessment Method Paradigm Details EEG/ERP Correlates fMRI Correlates Psychometric

Properties
Polysomnography Overnight recording Sleep stages defined Sleep-wake Sleep efficiency (total
(PSG) of EEG, EOG, EMG, by EEG patterns: N1 regulation involves sleep time/time in
ECG, respiration. (theta 4-8 Hz), N2 brainstem arousal bed): normal >85%.
Measures sleep (sleep spindles 12-15 systems, Test-retest reliability:
architecture: sleep Hz, K-complexes), N3 hypothalamic ICC = 0.70-0.90 for
stages (N1, N2, N3, (delta 0.5-4 Hz >20% sleep-wake centers sleep stages. Altered
REM), sleep of epoch), REM (VLPO, orexin sleep architecture in
efficiency, sleep (low-amplitude mixed neurons), and insomnia, depression,
latency, REM latency, frequency, rapid eye thalamocortical PTSD, and
arousals. movements). circuits. fMRI during neurodegenerative
sleep shows reduced disorders.
cortical metabolism
and altered
connectivity.

Actigraphy Wrist-worn Actigraphy correlates Actigraphy reflects Sleep-wake

accelerometer with PSG sleep-wake behavioral output of agreement with PSG:
measures movement determination circadian and sensitivity 90-95%,
over days-weeks. (agreement sleep-wake regulatory specificity 50-70%
Estimates sleep-wake ~85-90%). Useful for systems. Correlates (overestimates sleep).
patterns, circadian assessing circadian with SCN function Test-retest reliability
rhythms and sleep good for sleep timing
 rhythms, and activity patterns in naturalistic and melatonin (ICC = 0.70-0.85).
levels. settings. rhythms. Useful for circadian
rhythm disorders and
insomnia.

Sleep Quality Pittsburgh Sleep PSQI and ISI scores Poor sleep quality PSQI: α = 0.83; cutoff
Questionnaires Quality Index (PSQI), correlate with PSG associated with >5 for poor sleep. ISI:
Insomnia Severity measures (r = altered default mode α = 0.74-0.91; cutoff
Index (ISI), Epworth 0.30-0.50, moderate). network connectivity, ≥10 for insomnia.
Sleepiness Scale Subjective-objective reduced hippocampal ESS: α = 0.73-0.88;
(ESS). Assess sleep discrepancy volume, and cutoff >10 for
subjective sleep common in insomnia. increased amygdala excessive sleepiness.
quality, insomnia reactivity. Test-retest reliability r
symptoms, and = 0.70-0.85.
daytime sleepiness.
7.6 Sensorimotor Systems: Assessment Methods

7.6.1 Motor Actions - Initiation and Execution

Assessment Method Paradigm Details EEG/ERP Correlates fMRI Correlates Psychometric

Properties

Simple and Choice Simple RT: respond to Bereitschaftspotential Primary motor cortex Simple RT: test-retest
Reaction Time single stimulus. (BP) or readiness (M1), supplementary ICC = 0.70-0.85.
Choice RT: select potential: slow motor area (SMA), Choice RT: ICC =
response based on negative wave premotor cortex, 0.65-0.80. RT
stimulus identity (2-8 beginning ~1-2 sec basal ganglia, and increases with age
choices). Measures before voluntary cerebellum activation (~1 ms/year after age
processing speed and movement, maximal during movement 20) and number of
motor execution. at central sites (Cz). preparation and choices (Hick's law).
Typical: 50-100 trials, Lateralized readiness execution. M1 Slowed in Parkinson's
stimulus until potential (LRP): activation disease,
response. difference between contralateral to schizophrenia, and
contralateral and moving hand. TBI.
ipsilateral motor
cortex activity, begins
~500 ms
 pre-response.
Motor-evoked
potential following
movement.

Finger Tapping Participants tap index Mu rhythm (8-13 Hz) M1, SMA, premotor Taps per 10 sec:
finger as quickly as suppression over cortex, basal ganglia test-retest ICC =
possible for 10-30 contralateral (putamen), and 0.80-0.90 (excellent).
sec. Measures motor sensorimotor cortex cerebellum activation. Dominant hand
speed and dexterity. during tapping. Beta Contralateral M1 typically 10% faster
Dominant and rebound (15-30 Hz) activation dominant. than non-dominant.
non-dominant hands following movement Ipsilateral cerebellar Slowed in Parkinson's
tested separately. cessation. activation. disease (d = 1.5-2.0),
Movement-related Huntington's disease,
cortical potentials and cerebellar
(MRCP) precede disorders.
each tap.

Grip Force Tasks Participants exert grip Contingent negative M1, SMA, premotor Force accuracy:
force to match target variation (CNV) cortex, basal ganglia, test-retest ICC =
levels or respond to during force cerebellum, and 0.70-0.85. Force
visual cues. preparation. Mu posterior parietal variability increases
 Measures force rhythm suppression cortex activation. with age and
control and during force Activation scales with neurological
sensorimotor production. Beta force magnitude disorders. Impaired in
integration. Typical: oscillations (15-30 (Keisker et al., 2009, Parkinson's disease,
10-30 trials, 2-5 sec Hz) correlate with 2010). Sensorimotor stroke, and cerebellar
force production, force magnitude. integration involves lesions.
visual feedback. parietal-motor
connectivity.

7.6.2 Motor Actions - Inhibition and Termination

Assessment Method Paradigm Details EEG/ERP Correlates fMRI Correlates Psychometric

Properties

Stop-Signal Task [See Section 7.3.4 - N2 and P3 to stop Right IFG, pre-SMA, [See Section 7.3.4]
also assesses motor signals. LRP and subthalamic
inhibition] truncation on nucleus (STN)
successful stop trials activation.
(motor preparation Hyperdirect pathway
interrupted). (cortex-STN)
implements rapid
stopping.
Go/No-Go Task [See Section 7.3.4 - No-go N2 and P3. [See Section 7.3.4] [See Section 7.3.4]
also assesses motor Reduced LRP
inhibition] amplitude on no-go
trials (motor
preparation
suppressed).

7.6.3 Agency and Ownership

Assessment Method Paradigm Details EEG/ERP Correlates fMRI Correlates Psychometric

Properties

Rubber Hand Participant's hand Mu rhythm Posterior parietal Proprioceptive drift:

Illusion (RHI) hidden; rubber hand suppression over cortex (especially 2-4 cm toward rubber
visible. Synchronous sensorimotor cortex intraparietal sulcus), hand during
(illusion) or during synchronous premotor cortex, and synchronous
asynchronous brushing. Enhanced cerebellum activation brushing. Test-retest
(control) brushing of P300 to tactile during illusion. reliability moderate
real and rubber stimulation of rubber Multisensory (ICC = 0.50-0.70).
hands. Measures hand during illusion. integration in parietal Ownership
body ownership. Altered cortex underlies questionnaire: α =
Proprioceptive drift somatosensory ERPs ownership. Reduced 0.75-0.85. Reduced
 and questionnaire (P100, N140) during activation in illusion in
assess illusion illusion. schizophrenia (altered schizophrenia and
strength. body ownership). autism.

Agency Judgment Participants make Lateralized readiness Posterior parietal Agency judgments:
Tasks voluntary movements potential (LRP) cortex, SMA, and test-retest reliability
and judge whether indexes motor cerebellum compare moderate (ICC =
they caused sensory preparation. P300 predicted and actual 0.50-0.65). Temporal
outcome. Temporal or amplitude to sensory binding window
spatial delays self-generated vs consequences ~200-300 ms. Altered
introduced between externally generated (forward model). agency in
action and outcome. outcomes. Reduced Reduced activation schizophrenia (d =
Measures sense of P300 for for self-generated 0.8-1.2), especially for
agency. self-generated outcomes. Altered in delusions of control.
(sensory attenuation). schizophrenia
(agency deficits).

Motor Imagery Participants imagine Similar ERP patterns Overlapping Motor imagery ability:
Tasks performing for executed and activation for test-retest reliability
movements without imagined movements: executed and moderate (ICC =
executing them. ADAN (anterior imagined movements: 0.55-0.75). Vividness
Measures motor directing-attention SMA, premotor of Movement Imagery
 planning and internal negativity, 300-400 cortex, posterior Questionnaire
models. ms), LDAP (late parietal cortex, basal (VMIQ): α =
directing-attention ganglia, cerebellum. 0.80-0.90. Motor
positivity, 400-550 Reduced M1 imagery training
ms), LRP (650+ ms) activation during improves motor
(Kranczioch et al., imagery vs execution. performance.
2009). Mu rhythm
suppression during
motor imagery.

7.6.4 Habit (Sensorimotor)

Assessment Method Paradigm Details EEG/ERP Correlates fMRI Correlates Psychometric

Properties

Habit Learning Participants learn Reduced P300 Transition from Habit index
Tasks stimulus-response amplitude with habit ventral striatum and (proportion of
associations through formation (less prefrontal cortex devalued responses):
extensive practice. cognitive control). (goal-directed) to test-retest reliability
Outcome devaluation Enhanced beta dorsolateral moderate (ICC =
tests whether oscillations in striatum/putamen 0.50-0.65). Individual
behavior is sensorimotor cortex. (habitual) with differences in habit
 goal-directed Shift from frontal to overtraining. Reduced formation rate.
(sensitive to outcome central EEG activity prefrontal-striatal Enhanced habit
value) or habitual with practice. connectivity. formation in OCD and
(insensitive). Typical: Sensorimotor cortex addiction.
200-500 training engagement
trials, then increases.
devaluation test.

Serial Reaction Time Participants respond P300 amplitude Basal ganglia Sequence learning
Task (SRTT) to stimuli appearing in decreases with (caudate, putamen), (RT sequence - RT
sequence. sequence learning. SMA, and motor random): test-retest
Unbeknownst to Enhanced negativity cortex activation ICC = 0.60-0.75.
participant, sequence (N2) for sequence during sequence Implicit learning
repeats (e.g., 12-item violations. Frontal learning. Shift from preserved in amnesia
sequence). Measures theta power during prefrontal to striatal (intact basal ganglia).
implicit sequence early learning; and motor cortex with Impaired in
learning. Random reduced with practice. Cerebellar Parkinson's disease
blocks interspersed to automatization. involvement in motor and Huntington's
assess learning. sequence learning. disease.
8. Psychometric Considerations

8.1 Reliability

Reliability refers to the consistency and stability of measurement. Multiple forms of

reliability are relevant for RDoC-aligned assessments.

8.1.1 Test-Retest Reliability

Test-retest reliability assesses the stability of measurements across time. It is typically

quantified using intraclass correlation coefficients (ICC) or Pearson correlations. ICC
values are interpreted as: <0.40 = poor, 0.40-0.59 = fair, 0.60-0.74 = good, 0.75-1.00 =
excellent (Cicchetti, 1994).

Behavioral Measures: Behavioral measures from cognitive tasks generally show good
to excellent test-retest reliability. For example, N-back accuracy (ICC = 0.60-0.80),
Stop-Signal Reaction Time (ICC = 0.60-0.80), and delay discounting rate (ICC =
0.60-0.80) demonstrate good stability (Manoach et al., 2001; Korucuoglu et al., 2021).
However, some measures show only moderate reliability, particularly those involving
learning or adaptation (e.g., fear conditioning SCR: ICC ~0.30-0.50).

ERP Measures: ERP amplitudes generally show moderate to good test-retest reliability,
with amplitude measures typically more reliable than latency measures. The ERN
shows ICC = 0.50-0.75, RewP shows ICC = 0.50-0.70, and P300 shows ICC =
0.60-0.80 (Clayson et al., 2013; Proudfit, 2015). The N170 to faces demonstrates
excellent reliability (ICC = 0.60-0.80) (Kang et al., 2018). Reliability improves with
greater numbers of trials; minimum trial counts are: ERN (6-8 error trials), RewP (20-30
reward trials), P300 (20-30 target trials).
fMRI Measures: fMRI activation patterns show variable reliability depending on the task
and region. Working memory tasks show moderate reliability in prefrontal and parietal
regions (ICC = 0.50-0.70 in healthy controls) (Manoach et al., 2001). Reward
anticipation in the ventral striatum shows ICC = 0.40-0.60 (Carruzzo et al., 2024).
Reliability is generally lower in clinical populations, particularly schizophrenia.
Functional connectivity measures often show lower reliability than activation measures.

Self-Report Measures: Self-report questionnaires typically show good to excellent

test-retest reliability. Examples: BIS/BAS scales (r = 0.59-0.69), TEPS (r = 0.70-0.81),
PSS-10 (r = 0.55-0.70), ECR attachment scales (r = 0.70-0.80).

8.1.2 Internal Consistency

Internal consistency assesses whether items within a scale measure the same
construct. It is typically quantified using Cronbach's alpha (α), with values >0.70
considered acceptable, >0.80 good, and >0.90 excellent (though very high values may
indicate redundancy).

ERP Measures: Internal consistency for ERP measures is assessed using split-half
reliability (correlation between odd and even trials). ERN shows split-half r = 0.70-0.85,
RewP shows r = 0.70-0.85, and P300 shows r = 0.75-0.90 (Clayson et al., 2013). These
values indicate good internal consistency.

Self-Report Measures: Most well-validated self-report measures show good to

excellent internal consistency. Examples: ASI (α = 0.80-0.90), IUS (α = 0.91-0.94),
SHAPS (α = 0.84-0.91), PSQI (α = 0.83), ICG (α = 0.94).

Behavioral Measures: Internal consistency is less commonly reported for behavioral

measures but can be assessed by correlating performance across task blocks or
conditions. N-back accuracy shows α = 0.75-0.85 across load conditions.
8.1.3 Inter-Rater Reliability

Inter-rater reliability is relevant for measures requiring subjective coding or scoring. The
Social Attribution Task (SAT) shows excellent inter-rater reliability (ICC = 0.80-0.90)
when trained raters code mentalizing content (Johannesen et al., 2018).
Polysomnography sleep stage scoring shows good inter-rater agreement (κ = 0.70-0.85)
when scorers follow standardized criteria.

8.2 Validity

Validity refers to whether a measure assesses what it purports to measure. Multiple

forms of validity are relevant.

8.2.1 Construct Validity

Construct validity assesses whether a measure captures the theoretical construct of

interest. It is established through convergent validity (correlations with related
measures) and discriminant validity (lack of correlation with unrelated measures).

Convergent Validity: RDoC-aligned measures should correlate with other measures of

the same construct. For example, the RewP correlates with self-reported anhedonia (r =
-0.20 to -0.40) and ventral striatum activation to reward (r = 0.30-0.50) (Proudfit, 2015).
The ERN correlates with anxiety symptoms (r = 0.20-0.40) and ACC activation to errors
(r = 0.40-0.60) (Clayson et al., 2023). The N170 to faces correlates with face recognition
accuracy (r = 0.30-0.50).

Discriminant Validity: Measures should show weaker correlations with unrelated

constructs. For example, the RewP shows stronger correlations with anhedonia than
with general negative affect, demonstrating specificity to reward processing (Whitton et
al., 2016). The ERN shows stronger correlations with internalizing symptoms than
externalizing symptoms, though this specificity is debated (Clayson et al., 2023).
Factor Structure: Factor analytic studies support the structure of the RDoC matrix. For
example, factor analyses of cognitive tasks support separate factors for attention,
working memory, and cognitive control (Nuechterlein et al., 2008). Factor analyses of
self-report measures support separate factors for positive and negative valence
systems.

8.2.2 Criterion Validity

Criterion validity assesses whether a measure predicts relevant outcomes. This

includes concurrent validity (correlation with current status) and predictive validity
(prediction of future outcomes).

Concurrent Validity: RDoC measures should discriminate between clinical and healthy
populations. For example, blunted RewP discriminates depression from controls (d =
0.5-0.8) (Whitton et al., 2016). Enhanced ERN discriminates anxiety disorders from
controls (d = 0.5-0.8). Impaired emotion recognition discriminates autism (d = 0.8-1.0)
and schizophrenia (d = 0.9-1.2) from controls.

Predictive Validity: RDoC measures should predict clinically relevant outcomes. For
example, reduced ventral striatum activation to reward predicts depression relapse
(Pechtel et al., 2013). Enhanced ERN predicts onset of anxiety disorders. Biological
motion perception predicts treatment outcome in autism (Yang et al., 2016, 2017). Fear
conditioning prediction errors predict PTSD symptom severity (Letkiewicz et al., 2021).

8.2.3 Ecological Validity

Ecological validity assesses whether laboratory measures predict real-world functioning.

This is a critical consideration for RDoC measures, as laboratory tasks may not capture
the complexity of naturalistic behavior.
Limitations: Many RDoC paradigms use simplified stimuli and controlled conditions
that may not generalize to real-world contexts. For example, laboratory fear conditioning
uses simple cues (shapes, tones) rather than complex social threats. Reward tasks use
monetary incentives rather than naturalistic rewards (food, social approval).

Improvements: Efforts to enhance ecological validity include: (1) using naturalistic

stimuli (e.g., videos of social interactions rather than static faces), (2) assessing
behavior in naturalistic settings (e.g., actigraphy for sleep-wake patterns), (3) using
virtual reality to simulate real-world environments, and (4) ecological momentary
assessment (EMA) to sample experience and behavior in daily life.

Evidence: Some RDoC measures show good ecological validity. For example, the
Social Attribution Task (SAT) predicts community functioning in schizophrenia
(Johannesen et al., 2018). Delay discounting predicts real-world impulsive behaviors
(substance use, risky sexual behavior). PVT performance predicts occupational
accidents and errors.

8.3 Sensitivity and Specificity

Sensitivity and specificity assess diagnostic utility. Sensitivity is the proportion of true
positives correctly identified (true positive rate). Specificity is the proportion of true
negatives correctly identified (true negative rate).

Diagnostic Accuracy: Most RDoC measures show moderate sensitivity and specificity
for psychiatric diagnoses. For example, the CPT shows sensitivity = 66% and specificity
= 66% for ADHD. The RMET shows sensitivity ~70% and specificity ~70% for autism at
optimal cutoffs. These values indicate that RDoC measures alone are insufficient for
diagnosis but can contribute to comprehensive assessment.

Dimensional Approach: The RDoC framework emphasizes dimensional rather than

categorical assessment. Rather than dichotomous diagnosis, RDoC measures quantify
severity along continua. This approach may have greater clinical utility than traditional
diagnostic categories, as it captures individual differences and subclinical variation.

Receiver Operating Characteristic (ROC) Analysis: ROC curves plot sensitivity vs (1

- specificity) across cutoff values. Area under the curve (AUC) quantifies overall
diagnostic accuracy: 0.50 = chance, 0.70-0.80 = acceptable, 0.80-0.90 = excellent,
>0.90 = outstanding. Most RDoC measures show AUC = 0.65-0.80 for discriminating
clinical from healthy populations.

8.4 Normative Data

Normative data are essential for interpreting individual scores. Age, sex, education, and
cultural factors influence performance on many RDoC measures.

Age Effects: Cognitive performance peaks in early adulthood and declines with aging.
Reaction time slows ~1 ms/year after age 20. Working memory capacity declines ~0.5
items per decade. ERP latencies increase with age (P300 latency increases ~1-2
ms/year). These age effects necessitate age-corrected norms.

Sex Differences: Females show advantages on verbal memory, emotion recognition,

and processing speed. Males show advantages on spatial tasks and motor speed.
Females show larger N170 to faces and greater RewP to social rewards. These
differences should be considered in normative comparisons.

Education Effects: Higher education is associated with better cognitive performance,

particularly on tasks requiring verbal knowledge and executive functions.
Education-corrected norms are essential for neuropsychological assessment.

Cultural Factors: Cultural background influences performance on social cognition tasks

(e.g., emotion recognition, theory of mind) and self-report measures. Cross-cultural
validation is necessary before applying measures in diverse populations.
Available Norms: The NIH Toolbox provides age-corrected norms for ages 3-85 across
cognitive, emotional, motor, and sensory domains (Weintraub et al., 2014). The
MATRICS Consensus Cognitive Battery (MCCB) provides norms for schizophrenia
populations (Nuechterlein et al., 2008). Many ERP measures lack comprehensive
normative data, limiting clinical interpretation.

8.5 Practice Effects

Practice effects refer to performance improvements with repeated testing. They are
relevant for longitudinal assessment and treatment monitoring.

Magnitude: Practice effects vary by measure. Cognitive tasks show moderate practice
effects (10-20% improvement over 2-3 sessions), particularly for novel tasks. ERP
measures show minimal practice effects for amplitude but may show latency changes.
Self-report measures show minimal practice effects.

Time Course: Practice effects are largest between first and second administrations,
then plateau. Most learning occurs within 2-3 sessions. Longer retest intervals (>6
months) show smaller practice effects than shorter intervals (<1 month).

Mitigation: Strategies to minimize practice effects include: (1) providing practice trials
before data collection, (2) using alternate forms, (3) using adaptive procedures that
adjust difficulty, and (4) accounting for practice effects in statistical analyses (e.g., using
change scores or regression-based norms).

Clinical Implications: Practice effects can obscure treatment effects or disease

progression. Failure to show expected practice effects may indicate cognitive decline or
suboptimal effort.

8.6 Effort and Validity Assessment

Suboptimal effort and invalid responding can compromise assessment validity.
Embedded validity indicators detect insufficient effort.

Performance Validity Tests (PVTs): Standalone measures of effort include the Test of
Memory Malingering (TOMM) and Word Memory Test (WMT). These tests use
forced-choice recognition with very easy items; below-chance performance indicates
invalid responding.

Embedded Validity Indicators: Many cognitive tasks include embedded validity

indicators. For example, the CPT-3 includes validity indicators based on atypical
response patterns (Ord et al., 2021). The NIH Toolbox includes validity checks based on
response consistency.

ERP Validity Indicators: ERP measures are less susceptible to malingering than
behavioral measures, as they reflect automatic neural processes. However, reduced
trial counts (due to excessive artifacts or non-compliance) can compromise ERP
reliability.

Self-Report Validity: Self-report measures include validity scales to detect socially

desirable responding, random responding, and symptom exaggeration. Examples
include the MMPI-2-RF validity scales and the Personality Assessment Inventory (PAI)
validity indices.

8.7 Clinical Utility

Clinical utility refers to the practical value of a measure for clinical decision-making. It
encompasses feasibility, acceptability, and incremental validity beyond existing
measures.
Feasibility: RDoC measures vary in feasibility. Self-report questionnaires are highly
feasible (5-15 minutes, minimal equipment). Computerized cognitive tasks are
moderately feasible (20-60 minutes, computer required). EEG/ERP requires specialized
equipment and expertise (60-90 minutes, EEG system, trained technician). fMRI is least
feasible (60-90 minutes, MRI scanner, high cost).

Acceptability: Most RDoC measures are acceptable to participants. Cognitive tasks

and questionnaires have high completion rates (>90%). EEG is generally well-tolerated,
though some participants find electrode application uncomfortable. fMRI is acceptable
to most participants but contraindicated for those with metal implants or claustrophobia.

Incremental Validity: RDoC measures should provide information beyond traditional

clinical assessment. For example, ERP measures of reward processing predict
depression relapse beyond self-reported symptoms (Pechtel et al., 2013). Cognitive
measures predict functional outcomes in schizophrenia beyond symptom severity
(Nuechterlein et al., 2008). However, many RDoC measures show only modest
incremental validity, limiting their clinical utility.

Cost-Effectiveness: The cost-effectiveness of RDoC measures depends on their

incremental validity and the costs of assessment. Self-report measures and
computerized cognitive tasks are cost-effective. EEG/ERP and fMRI are expensive and
may not be cost-effective for routine clinical use, though they may be valuable for
treatment selection or monitoring in specific populations.

6. Experimental Paradigms for Gap Coverage: Detailed

EEG/fMRI Correlates

This section provides detailed descriptions of experimental paradigms that address

gaps in standard neuropsychological batteries, with comprehensive coverage of
EEG/ERP and fMRI correlates. These paradigms are essential for comprehensive
RDoC assessment, particularly for constructs underrepresented in traditional batteries.

6.1 Negative Valence Systems: Advanced Paradigms

6.1.1 Fear Conditioning and Extinction

Paradigm Description: Fear conditioning is the gold standard paradigm for assessing
acute threat processing. The paradigm involves three phases: habituation, acquisition,
and extinction. During habituation, participants are exposed to conditioned stimuli (CS+
and CS-) without unconditioned stimuli (UCS) to establish baseline responses. During
acquisition, CS+ is paired with an aversive UCS (electric shock, loud noise, or aversive
image) on 50-100% of trials, while CS- is never paired. During extinction, both CS+ and
CS- are presented without UCS. Typical parameters: 18-36 trials per condition per
phase, 3-6 sec stimulus duration, 2-6 sec inter-trial interval (ITI), 50-75% reinforcement
rate during acquisition.

EEG/ERP Correlates:

●​ Early Posterior Negativity (EPN): 150-200 ms post-stimulus onset, enhanced

for CS+ vs CS-, maximal at occipitotemporal sites (PO7/PO8). Reflects early
attentional capture by threat cues. Amplitude difference (CS+ minus CS-): 2-5
μV.

●​ Late Positive Potential (LPP): Sustained positive deflection beginning ~300 ms

and lasting several seconds, maximal at centro-parietal sites (Cz, Pz, CPz).
Larger for CS+ vs CS- during acquisition; difference diminishes during extinction.
Amplitude: 5-15 μV for CS+, 3-8 μV for CS-. Time course analysis reveals
sustained threat processing.
 ●​ Frontal Theta Oscillations (4-8 Hz): Increased power during CS+ presentation,
particularly during extinction. Theta power correlates with vmPFC-amygdala
connectivity and extinction success. Peak theta power: 2-4 μV² during CS+.

●​ Alpha Asymmetry: Greater right frontal alpha power (8-13 Hz) during threat
anticipation, reflecting withdrawal motivation. Asymmetry score (log[right] -
log[left]): 0.05-0.15 during threat.

fMRI Correlates:

●​ Amygdala: Bilateral activation during CS+ presentation, particularly basolateral

nuclei for associative learning and central nuclei for fear expression. Peak
coordinates: [±20, -5, -15]. Effect size: Cohen's d = 0.8-1.5 for CS+ vs CS-.
Activation increases during early acquisition, then habituates. Individual
differences in amygdala reactivity predict fear learning rate (Raduà et al., 2025).

●​ Ventromedial Prefrontal Cortex (vmPFC): Activation during extinction,

particularly for CS+ when UCS is omitted. Coordinates: [0, 45, -10]. vmPFC
inhibits amygdala during extinction via direct projections. Reduced vmPFC
activation and vmPFC-amygdala connectivity predict extinction deficits and
PTSD symptoms (Suarez-Jimenez et al., 2020).

●​ Hippocampus: Encodes contextual information and CS-UCS contingencies.

Coordinates: [±25, -20, -15]. Hippocampal activation correlates with explicit
contingency awareness. Pattern separation in dentate gyrus supports
discrimination between CS+ and CS-.

•
Periaqueductal Gray (PAG): Brainstem region coordinating defensive responses
(freezing, flight). Coordinates: [0, -30, -10]. PAG activation correlates with skin
conductance responses and subjective fear.
•
Dorsal Anterior Cingulate Cortex (dACC): Activation during CS+ reflects prediction
error and threat monitoring. Coordinates: [0, 20, 30]. dACC signals need for behavioral
adjustment.

Computational Models: Rescorla-Wagner model describes associative learning: ΔV =

αβ(λ - V), where V is associative strength, α is CS salience, β is learning rate, and λ is
UCS magnitude. Prediction error (λ - V) drives learning. Temporal difference (TD)
learning models extend this to account for timing. Model-derived prediction errors
correlate with amygdala and dACC BOLD responses (Tzovara et al., 2018; Yau et al.,
2023).

Reliability: Group-level effects are robust (d = 0.8-1.5 for CS+ vs CS- during
acquisition). Individual-level longitudinal reliability is limited (ICC ~0.30-0.50 for skin
conductance responses), though internal consistency is satisfactory (Raduà et al.,
2025). fMRI reliability is moderate (ICC ~0.40-0.60 for amygdala activation). Higher
responding in acquisition predicts higher responding in extinction at weak to moderate
levels.

Clinical Sensitivity: Fear conditioning paradigms are sensitive to anxiety disorders and
PTSD. Enhanced fear acquisition and impaired extinction characterize PTSD (Marin et
al., 2020). Generalized anxiety disorder shows enhanced generalization gradients.
Panic disorder shows heightened fear responses to interoceptive cues. Prediction error
signals during conditioning predict PTSD symptom severity (Letkiewicz et al., 2021).

6.1.2 NPU-Threat Task

Paradigm Description: The NPU-threat task dissociates responses to predictable vs

unpredictable threat. Three conditions are presented in blocks: No threat (N),
Predictable threat (P - shock signaled by cue), and Unpredictable threat (U - shock can
occur at any time). Acoustic startle probes are delivered during each condition to assess
defensive reactivity. Typical parameters: 8-12 blocks per condition, 60-90 sec per block,
6-12 startle probes per condition, shock intensity individually calibrated to be "highly
annoying but not painful."

EEG/ERP Correlates:

●​ Startle Blink Reflex: Electromyographic (EMG) response from orbicularis oculi

muscle, 20-200 ms post-probe. Peak latency: 50-80 ms. Amplitude: 50-200 μV.
Startle potentiation (increased amplitude) occurs during threat conditions. P > N
(predictable threat potentiation): 20-40% increase. U > N (unpredictable threat
potentiation): 30-60% increase. U > P in anxiety-prone individuals, reflecting
heightened sensitivity to unpredictable threat.

●​ P300 Modulation: P300 amplitude to startle probes is modulated by threat

condition. Reduced P300 during threat reflects attentional capture by threat cues.
Latency: 300-500 ms. Amplitude reduction: 20-40% during threat vs safe.

●​ Frontal Theta Power: Increased theta (4-8 Hz) during unpredictable threat,
reflecting sustained vigilance and anxiety. Power increase: 30-50% during U vs
N.

●​ Alpha Asymmetry: Greater right frontal alpha during threat anticipation,

particularly unpredictable threat. Asymmetry correlates with trait anxiety.

fMRI Correlates:

●​ Bed Nucleus of the Stria Terminalis (BNST): Preferential activation during

unpredictable threat. Coordinates: [±10, 0, -10]. BNST mediates sustained
anxiety and vigilance under uncertainty. Effect size: d = 0.6-1.0 for U vs P. Altered
BNST activation in generalized anxiety disorder and PTSD (Feola et al., 2023).
 ●​ Amygdala: Activation during both predictable and unpredictable threat, with
some studies showing preferential activation to predictable threat. Coordinates:
[±20, -5, -15]. Amygdala mediates phasic fear responses to discrete cues.

●​ Dorsolateral Prefrontal Cortex (dlPFC): Activation during threat regulation and

cognitive control under threat. Coordinates: [±40, 30, 30]. dlPFC-amygdala
connectivity predicts individual differences in threat reactivity.

•nAnterior Cingulate Cortex (ACC): Activation during threat monitoring and conflict
between approach and avoidance. Coordinates: [0, 20, 30].

●​ Insula: Activation during interoceptive awareness of threat-related bodily states

(heart rate, respiration). Coordinates: [±35, 20, 0]. Anterior insula integrates
interoceptive and emotional information.

Reliability: Startle potentiation shows moderate test-retest reliability (ICC ~0.50-0.70).

A reliable startle signal can be generated with as few as 6 responses per condition,
though 8-12 probes per condition are recommended for optimal reliability (Klumpp et al.,
2018). Growth curve modeling can assess startle habituation and initial reactivity,
improving reliability.

Clinical Sensitivity: The NPU-threat task discriminates anxiety disorders from controls.
Generalized anxiety disorder shows enhanced unpredictable threat potentiation (U > P).
PTSD shows enhanced startle across all conditions. Panic disorder shows heightened
startle to interoceptive threat. The task is sensitive to anxiolytic medication effects
(benzodiazepines reduce startle potentiation).

6.1.3 Loss and Frustrative Nonreward Paradigms

Paradigm Description: Loss paradigms involve subtraction of money or points from
accumulated totals. Frustrative nonreward involves blocking or preventing expected
rewards. Typical paradigm: participants perform a task (e.g., time estimation, gambling)
with outcomes including gains, losses, and neutral. Alternatively, participants work
toward a reward that is then withheld or made unattainable (e.g., unsolvable anagrams,
rigged computer tasks). Parameters: 60-120 trials, equal numbers of gain/loss/neutral
outcomes, or 5-10 min frustration induction followed by persistence measurement.

EEG/ERP Correlates:

●​ Feedback-Related Negativity (FRN) / Reward Positivity (RewP): Larger

amplitude for losses vs gains (or smaller for gains vs losses). Peak latency:
250-350 ms at frontocentral sites (Fz, FCz). Amplitude difference: 5-10 μV.
FRN/RewP reflects prediction error and outcome evaluation. Blunted response to
loss in depression.

●​ P300: Larger amplitude for unexpected losses. Latency: 300-500 ms at

centro-parietal sites. Amplitude: 10-20 μV for salient losses.

●​ Frontal Theta Power: Increased theta (4-8 Hz) during loss processing and
frustration. Power increase: 40-60% during loss vs gain. Theta power correlates
with negative affect and behavioral adjustment.

●​ Beta Power: Elevated beta (15-30 Hz) during frustration, reflecting arousal and
agitation. Power increase: 30-50% during frustration.

fMRI Correlates:

●​ Anterior Insula: Robust activation to loss outcomes. Coordinates: [±35, 20, 0].
Insula encodes aversive prediction errors and negative affect. Effect size: d =
0.8-1.2 for loss vs neutral.
 ●​ Dorsal Anterior Cingulate Cortex (dACC): Activation during loss and reward
omission. Coordinates: [0, 20, 30]. dACC signals need for behavioral adjustment
and increased cognitive control.

●​ Subgenual Anterior Cingulate Cortex (sgACC): Elevated activation in

depression during loss processing. Coordinates: [0, 25, -10]. sgACC hyperactivity
correlates with depressive symptoms and rumination.

●​ Ventral Striatum: Reduced activation to loss vs gain. Coordinates: [±12, 9, -6].

Blunted ventral striatum response to loss in depression reflects reduced loss
sensitivity.

●​ Dorsal Striatum: Activation during frustrative nonreward and compensatory

behavioral responses. Coordinates: [±15, 10, 5].

Computational Models: Prospect theory describes loss aversion: losses loom larger
than equivalent gains. Loss aversion parameter (λ) typically 1.5-2.5, meaning losses are
weighted 1.5-2.5 times more than gains. Individual differences in λ predict risk
preferences and emotional responses to loss. Reinforcement learning models
incorporate separate learning rates for positive and negative prediction errors, with
αloss often > αgain.

Reliability: Loss aversion parameter shows good test-retest reliability (ICC =

0.60-0.75). FRN/RewP amplitude shows moderate reliability (ICC = 0.40-0.65).
Behavioral persistence during frustration shows moderate reliability (r ~0.50-0.65).

Clinical Sensitivity: Blunted loss sensitivity in depression (reduced FRN, reduced

insula activation). Enhanced loss aversion in anxiety disorders. Elevated frustration
reactivity in intermittent explosive disorder and ADHD. Loss paradigms predict
treatment response in depression.
6.2 Positive Valence Systems: Advanced Paradigms

6.2.1 Monetary Incentive Delay (MID) Task - Detailed Analysis

Paradigm Description: The MID task is the most widely used paradigm for assessing
reward anticipation and outcome processing. Each trial consists of: (1) Cue (1-2 sec)
indicating potential reward magnitude ($0, $0.50, $1, $5) or loss avoidance (-$0.50, -$1,
-$5), (2) Variable delay (2-4 sec anticipation period), (3) Target (100-500 ms) requiring
speeded button press, (4) Feedback (1-2 sec) indicating outcome (win/no-win or
avoid-loss/loss). Target duration is adaptively adjusted to maintain ~66% success rate.
Typical parameters: 72-120 trials, 50% win rate, 6-8 min total duration.

EEG/ERP Correlates:

●​ Stimulus-Preceding Negativity (SPN): Slow negative wave during anticipation

period (cue offset to target onset), maximal at central sites (Cz, C3, C4).
Amplitude increases with reward magnitude. SPN reflects anticipatory attention
and motivation. Amplitude: -5 to -15 μV for high reward, -2 to -8 μV for low
reward. Difference (high minus low): 3-7 μV. Reduced SPN in depression and
schizophrenia negative symptoms.

●​ Cue-P3: P300 component to reward cue, 300-500 ms post-cue, centro-parietal

sites. Amplitude scales with reward magnitude. Amplitude: 10-20 μV for high
reward, 5-12 μV for low reward. Reflects initial reward evaluation and attentional
allocation.

●​ Contingent Negative Variation (CNV): Sustained negativity during anticipation,

similar to SPN but often measured at frontal sites. CNV amplitude correlates with
motivation and effort mobilization.
 ●​ Reward Positivity (RewP): Positive deflection 250-350 ms post-feedback,
frontocentral sites (Fz, FCz). Larger for win vs no-win. Amplitude: 8-15 μV for
win, 3-8 μV for no-win. Difference: 5-7 μV. RewP reflects reward prediction error
and outcome evaluation. Blunted RewP in depression (d = 0.5-0.8).

●​ Feedback-P3: P300 to feedback, 300-500 ms, centro-parietal sites. Larger for

salient outcomes (large wins, unexpected outcomes). Amplitude: 15-25 μV.

fMRI Correlates:

●​ Ventral Striatum / Nucleus Accumbens: Robust activation during reward

anticipation, scaling with reward magnitude. Peak coordinates: [±12, 15, -9] or
[±12, 9, -6]. Effect size: d = 0.8-1.5 for high vs low reward anticipation. Ventral
striatum activation correlates with dopamine release measured by PET (Schott et
al., 2008). Test-retest reliability: ICC = 0.40-0.60 (moderate). Blunted activation in
depression (d = 0.6-1.0), schizophrenia (d = 0.8-1.2), and anhedonia.

•
Ventral Tegmental Area (VTA): Midbrain dopamine neurons show activation during
reward anticipation. Coordinates: [0, -15, -10]. VTA activation correlates with ventral
striatum activation and dopamine release.

●​ Medial Prefrontal Cortex (mPFC): Activation during reward anticipation and

outcome. Coordinates: [0, 45, -5] (ventromedial) or [0, 50, 20] (dorsomedial).
mPFC encodes reward value and integrates reward information with goals.

●​ Anterior Insula: Activation during reward anticipation, particularly for

high-magnitude rewards. Coordinates: [±35, 20, 0]. Insula may encode arousal
and salience rather than reward per se.
 ●​ Orbitofrontal Cortex (OFC): Activation during reward outcome, encoding
outcome value. Coordinates: [±30, 40, -10]. OFC represents outcome-specific
value and supports value-based decision-making.

Timing Analysis: Temporal dynamics reveal dissociable anticipation and outcome

phases. Anticipation phase (cue to target): ventral striatum activation peaks 2-4 sec
post-cue, coinciding with SPN. Outcome phase (feedback): ventral striatum and mPFC
activation peaks 1-2 sec post-feedback, coinciding with RewP. Temporal precision of
fMRI is limited by hemodynamic response function (HRF) with ~6 sec peak latency.

Computational Models: Reinforcement learning models fit to MID task behavior

estimate learning rate (α), discount factor (γ), and inverse temperature (β).
Model-derived prediction errors correlate with RewP amplitude and ventral striatum
activation. Temporal difference (TD) models account for anticipatory responses: V(t) =
r(t) + γV(t+1), where V is value, r is reward, and γ is discount factor. TD error: δ(t) = r(t)
+ γV(t+1) - V(t).

Reliability: Ventral striatum activation shows moderate test-retest reliability (ICC =

0.40-0.60). Reliability is higher for anticipation than outcome phase. Behavioral
measures (RT, accuracy) show good reliability (ICC = 0.70-0.85). RewP shows
moderate reliability (ICC = 0.50-0.70). Reliability improves with more trials (minimum
20-30 reward trials recommended).

Clinical Sensitivity: Blunted ventral striatum activation in depression (d = 0.6-1.0),

particularly in remitted depression predicting relapse (Pechtel et al., 2013). Blunted
activation in schizophrenia negative symptoms (d = 0.8-1.2) (Carruzzo et al., 2024).
Elevated activation in mania and substance use disorders. MID task predicts treatment
response to behavioral activation therapy and antidepressants.

6.2.2 Probabilistic Reward Task (PRT)

Paradigm Description: The PRT assesses reward learning via response bias
development. Participants identify briefly presented stimuli (e.g., short vs long mouth on
schematic face, 100 ms stimulus followed by mask). Unbeknownst to participants, one
stimulus is rewarded 3x more frequently than the other (e.g., 30 vs 10 cents, or 3:1
ratio). Over trials, participants develop a response bias toward the more frequently
rewarded stimulus, even when stimulus is ambiguous. Typical parameters: 200-300
trials, 100 ms stimulus, mask, immediate feedback. Three blocks: training (40 trials,
equal reinforcement), test 1 (100 trials, differential reinforcement), test 2 (100 trials,
differential reinforcement).

EEG/ERP Correlates:

●​ Reward Positivity (RewP): Positive deflection 250-350 ms post-feedback,

frontocentral sites. Larger for reward vs no-reward. Amplitude: 8-15 μV for
reward, 3-8 μV for no-reward. Difference: 5-7 μV. Reduced RewP in depression
(d = 0.5-0.8) (Whitton et al., 2016; Pechtel et al., 2013). RewP amplitude
correlates with response bias development.

●​ Feedback-P3: P300 to feedback, 300-500 ms, centro-parietal sites. Larger for

reward. Amplitude: 12-20 μV for reward.

●​ Frontal Theta Power: Increased theta (4-8 Hz) during reward learning. Theta
power correlates with learning rate and response bias.

fMRI Correlates:

●​ Ventral Striatum: Activation to reward feedback. Reduced activation in remitted

depression predicts relapse. Coordinates: [±12, 9, -6].

●​ Medial Prefrontal Cortex: Activation during reward learning and value updating.
Coordinates: [0, 45, -5].
 ●​ Dorsal Striatum: Increasing activation with learning, reflecting habit formation.
Coordinates: [±15, 10, 5].

Behavioral Measure: Response bias quantified as log b = 0.5 * ln[(rich_correct *

lean_incorrect) / (lean_correct * rich_incorrect)], where rich is the more frequently
rewarded stimulus and lean is the less frequently rewarded stimulus. Positive values
indicate bias toward rich stimulus. Typical values: log b = 0.1-0.3 in healthy controls,
0.0-0.1 in depression. Response bias shows moderate test-retest reliability (r =
0.50-0.70).

Computational Models: Reinforcement learning models with separate learning rates

for positive and negative prediction errors. Asymmetric learning (αpos > αneg) produces
response bias. Model parameters predict individual differences in bias development.

Reliability: Response bias (log b) shows moderate test-retest reliability (r = 0.50-0.70).

RewP amplitude shows moderate reliability (ICC = 0.50-0.70). Discriminant validity:
response bias correlates with anhedonia (r = -0.30 to -0.50) but not general negative
affect.

Clinical Sensitivity: Reduced response bias in depression (d = 0.5-0.8), reflecting

blunted reward learning. Reduced RewP in depression (d = 0.5-0.8). PRT predicts
treatment response to behavioral activation and antidepressants. Sensitive to
dopaminergic manipulations.

6.2.3 Delay and Effort Discounting

Paradigm Description: Delay discounting tasks assess intertemporal choice.

Participants choose between smaller-sooner (SS) and larger-later (LL) rewards (e.g.,
$10 today vs $20 in 1 month). Delays vary from 1 day to 1 year. Adjusting-amount
procedure: LL amount is fixed, SS amount adjusts based on choices to find indifference
point. Fixed-choice procedure: multiple SS-LL pairs presented. Typical parameters:
20-50 trials, 5-7 delay values. Effort discounting is similar but varies effort (e.g., number
of button presses) rather than delay.

EEG/ERP Correlates:

●​ P300: Larger amplitude for LL choices, reflecting greater cognitive control

engagement. Latency: 300-500 ms, centro-parietal sites. Amplitude: 15-25 μV for
LL, 10-18 μV for SS. Difference: 5-7 μV.

●​ Frontal Theta Power: Increased theta (4-8 Hz) during intertemporal choice,
particularly for difficult choices (similar subjective value). Power increase: 40-60%
during choice vs baseline. Theta power correlates with cognitive control and LL
choices.

●​ SPN: During anticipation of delayed rewards. Amplitude scales with reward

magnitude and inversely with delay.

fMRI Correlates:

●​ Ventral Striatum and vmPFC: Activation for SS rewards, reflecting limbic

valuation system. Coordinates: ventral striatum [±12, 9, -6]; vmPFC [0, 45, -10].
Activation scales with subjective value of SS option.

●​ Dorsolateral Prefrontal Cortex (dlPFC): Activation for LL rewards, reflecting

cognitive control system. Coordinates: [±40, 30, 30]. dlPFC activation correlates
with LL choices and reduced discounting.

●​ Posterior Parietal Cortex: Activation during value comparison and

decision-making. Coordinates: [±40, -50, 45].
 ●​ Competition Model: McClure et al. (2004) proposed that SS and LL choices
reflect competition between limbic (ventral striatum, vmPFC) and cognitive
control (dlPFC, parietal) systems. Relative activation predicts choice. However,
this dual-system model is debated; alternative models propose a single valuation
system in vmPFC.

Computational Models: Hyperbolic discounting model: V = A / (1 + kD), where V is

subjective value, A is reward amount, D is delay, and k is discount rate. Log(k) typically
ranges from -4 to -1, with higher k indicating steeper discounting (more impulsive).
Exponential discounting: V = A * e^(-kD). Hyperbolic model fits human data better than
exponential. Area under the curve (AUC) is an alternative, atheoretical measure: AUC =
Σ[(x₂ - x₁) * (y₁ + y₂) / 2], where x is delay and y is subjective value. AUC ranges 0-1, with
lower values indicating steeper discounting.

Reliability: Discount rate (k) shows good test-retest reliability (ICC = 0.60-0.80). AUC
shows similar reliability. Delay discounting is stable over months to years. Effort
discount rate shows moderate reliability (ICC = 0.50-0.70).

Clinical Sensitivity: Steeper delay discounting (higher k) in addiction (d = 0.5-1.0),

ADHD (d = 0.5-0.8), and impulsivity. Shallower discounting in anxiety (risk aversion).
Effort discounting is reduced in depression (d = 0.6-0.9), schizophrenia negative
symptoms (d = 0.7-1.0), and apathy. Discounting predicts real-world impulsive
behaviors (substance use, risky sexual behavior, financial decisions).

6.3 Cognitive Systems: Advanced Paradigms

6.3.1 N-back Task - Detailed Analysis

Paradigm Description: The N-back task is the most widely used working memory
paradigm. Participants monitor a sequence of stimuli (letters, shapes, spatial locations)
and respond when the current stimulus matches one presented n items back. Loads:
0-back (target detection), 1-back, 2-back, 3-back. Typical parameters: 20-30 trials per
block, 500 ms stimulus, 2000-3000 ms ISI, 2-4 blocks per load. Stimuli can be verbal
(letters), spatial (locations), or object (shapes/faces). Lure trials (stimuli matching n±1
items back) assess interference control.

EEG/ERP Correlates:

●​ P300: Amplitude decreases with increasing load. Latency: 300-600 ms,

centro-parietal sites (Pz, CPz). Amplitude: 15-25 μV for 0-back, 10-18 μV for
1-back, 8-15 μV for 2-back, 5-10 μV for 3-back. P300 amplitude reflects
attentional resource allocation; reduced amplitude at high loads indicates
capacity limits.

●​ Sustained Negativity: Slow negative wave during maintenance period

(300-1500 ms post-stimulus), maximal at frontal sites (Fz, F3, F4). Amplitude
increases with load. Amplitude: -3 to -8 μV for 1-back, -5 to -12 μV for 2-back, -8
to -15 μV for 3-back. Sustained negativity reflects active maintenance and
executive control.

●​ Frontal Theta Power (4-8 Hz): Increases with load. Power: 3-6 μV² for 1-back,
5-10 μV² for 2-back, 8-15 μV² for 3-back. Theta power correlates with working
memory load and performance. Frontal midline theta (Fz) is particularly sensitive.

●​ Posterior Alpha Power (8-13 Hz): Decreases with load, reflecting increased
cortical activation. Power: 15-30 μV² for 0-back, 10-20 μV² for 1-back, 8-15 μV²
for 2-back. Alpha desynchronization indicates active processing.

●​ Gamma Oscillations (30-80 Hz): Increased gamma power during maintenance,

reflecting local cortical processing and binding. Power increases with load.

fMRI Correlates:
 ●​ Dorsolateral Prefrontal Cortex (dlPFC): Robust activation increasing with load.
Coordinates: [±40, 30, 30] (middle frontal gyrus). Effect size: d = 1.0-2.0 for
2-back vs 0-back. dlPFC supports executive control and manipulation of working
memory contents. Activation shows inverted-U relationship with load: increases
from 0-back to 2-back, then plateaus or decreases at 3-back (capacity limits).

●​ Posterior Parietal Cortex: Activation in intraparietal sulcus (IPS) and superior

parietal lobule (SPL). Coordinates: [±40, -50, 45]. Parietal cortex supports
storage and maintenance. Activation increases linearly with load.

●​ Anterior Cingulate Cortex (ACC): Activation during high-load conditions,

reflecting increased cognitive control and conflict monitoring. Coordinates: [0, 20,
30].

●​ Lateralization: Verbal N-back (letters) shows left-lateralized activation in dlPFC

and parietal cortex. Spatial N-back (locations) shows right-lateralized activation.
Object N-back shows bilateral activation.

●​ Functional Connectivity: Increased connectivity within frontoparietal network

with increasing load. Reduced connectivity with default mode network
(task-negative network). Connectivity strength predicts performance (Braun et al.,
2021).

Timing Parameters: Stimulus duration: 500 ms is standard. Shorter durations (200-300

ms) increase difficulty. ISI: 2000-3000 ms allows sufficient time for maintenance and
updating. Shorter ISI (1000-1500 ms) increases cognitive load. Number of trials: 20-30
per block provides sufficient data while minimizing fatigue. Total duration: 6-12 min for
2-3 loads.
Computational Models: Computational models of N-back performance include: (1)
Continuous updating model: items are continuously added to and removed from working
memory. (2) Familiarity-based model: responses based on familiarity of current item
rather than explicit memory for n-back position. (3) Dual-process model: combination of
recollection (explicit memory) and familiarity. Models predict accuracy, RT, and neural
activation patterns.

Reliability: 2-back accuracy shows good test-retest reliability (ICC = 0.60-0.80). RT

shows similar reliability. fMRI activation in dlPFC and parietal cortex shows moderate
reliability (ICC = 0.50-0.70) (Manoach et al., 2001). Reliability is lower in clinical
populations, particularly schizophrenia. Internal consistency (split-half reliability) is good
(α = 0.75-0.85).

Clinical Sensitivity: Impaired N-back performance in schizophrenia (d = 0.8-1.2),

ADHD (d = 0.5-0.8), depression (d = 0.4-0.6), and aging (d = 0.6-1.0 for older vs
younger adults). Reduced dlPFC activation in schizophrenia despite similar or greater
effort. N-back performance predicts functional outcomes in schizophrenia and ADHD.

6.3.2 Stop-Signal Task - Detailed Analysis

Paradigm Description: The stop-signal task (SST) assesses response inhibition.

Participants respond to go stimuli (e.g., left/right arrows) but withhold response when a
stop signal (e.g., tone) occurs. Stop-signal delay (SSD) is the interval between go
stimulus and stop signal. SSD varies adaptively using staircase procedure: increases by
50 ms after successful stop, decreases by 50 ms after failed stop. This maintains ~50%
inhibition rate. Typical parameters: 200-300 trials, 25-33% stop trials, 1000-1500 ms
stimulus duration, 1000-1500 ms ITI.

EEG/ERP Correlates:

•
N2: Larger amplitude for successful stop trials vs go trials. Latency: 200-350 ms,
frontocentral sites (Fz, FCz). Amplitude: -8 to -15 μV for stop, -3 to -8 μV for go.
Difference: 5-7 μV. N2 reflects conflict detection and inhibitory control. Reduced N2 in
ADHD and impulsivity.

●​ P3 (Stop-P3): Larger amplitude for successful stop trials. Latency: 300-500 ms,
frontocentral sites. Amplitude: 15-25 μV for stop, 8-15 μV for go. Difference: 7-10
μV. Stop-P3 reflects inhibitory control and evaluation of stopping success.
Reduced P3 in ADHD.

●​ Lateralized Readiness Potential (LRP): Motor preparation indexed by

difference between contralateral and ipsilateral motor cortex activity (C3/C4).
LRP is truncated on successful stop trials, indicating interruption of motor
preparation. LRP onset: ~200 ms pre-response on go trials. LRP truncation on
stop trials occurs ~100-200 ms after stop signal.

●​ Beta Oscillations (15-30 Hz): Increased beta power over motor cortex during
successful stopping, reflecting motor inhibition. Power increase: 30-50% during
stop vs go.

fMRI Correlates:

●​ Right Inferior Frontal Gyrus (rIFG): Critical for stopping. Coordinates: [50, 20,
10] (pars opercularis) or [45, 25, 0] (pars triangularis). Effect size: d = 1.0-1.5 for
stop vs go. rIFG activation correlates with stopping success. Lesions to rIFG
impair SST performance. TMS to rIFG disrupts stopping.

●​ Pre-Supplementary Motor Area (pre-SMA): Activation during stopping.

Coordinates: [0, 10, 50]. pre-SMA detects stop signals and triggers inhibitory
control. Connectivity between pre-SMA and rIFG predicts stopping efficiency.
 ●​ Subthalamic Nucleus (STN): Basal ganglia structure critical for rapid stopping.
Coordinates: [±12, -15, -5]. Hyperdirect pathway (cortex → STN → globus
pallidus) implements fast stopping (~150 ms). STN deep brain stimulation affects
SST performance.

●​ Dorsal Anterior Cingulate Cortex (dACC): Activation during conflict monitoring

and error detection. Coordinates: [0, 20, 30]. dACC signals need for increased
control.

●​ Functional Connectivity: Increased connectivity within inhibitory control network

(rIFG, pre-SMA, STN) during stopping. Connectivity strength predicts SSRT
(Korucuoglu et al., 2021).

Stop-Signal Reaction Time (SSRT): SSRT estimates the latency of the stopping
process. Calculation methods: (1) Integration method (recommended): SSRT = nth RT -
mean SSD, where nth RT is the RT at the nth percentile corresponding to
P(respond|signal). (2) Mean method: SSRT = mean go RT - mean SSD. (3) Median
method: SSRT = median go RT - mean SSD. Integration method is most robust to
violations of assumptions. Typical SSRT: 200-250 ms in healthy adults. Longer SSRT
indicates slower/less efficient stopping.

Reliability: SSRT shows good test-retest reliability (ICC = 0.60-0.80). Go RT shows

excellent reliability (ICC = 0.80-0.90). Stop-N2 and Stop-P3 amplitudes show moderate
reliability (ICC = 0.50-0.70). fMRI activation in rIFG shows moderate reliability (ICC =
0.50-0.65) (Korucuoglu et al., 2021).

Clinical Sensitivity: Longer SSRT in ADHD (d = 0.5-0.7), substance use disorders (d =

0.4-0.6), and impulsivity (d = 0.5-0.8). Reduced rIFG activation in ADHD. SSRT predicts
real-world impulsive behaviors and treatment response to stimulant medication in
ADHD.
6.4 Social Processes: Advanced Paradigms

6.4.1 Biological Motion Perception

Paradigm Description: Biological motion paradigms use point-light displays (PLDs)

showing human movement. PLDs consist of 10-15 points representing major joints
(head, shoulders, elbows, wrists, hips, knees, ankles). Participants view PLDs of actions
(walking, dancing, jumping) or emotional expressions (happy, sad, angry) and identify
the action or emotion. Control conditions include inverted PLDs, scrambled PLDs, or
non-biological motion. Typical parameters: 20-40 trials, 2-5 sec animations,
forced-choice response.

EEG/ERP Correlates:

●​ N170: Enhanced amplitude for biological vs non-biological motion. Latency:

140-200 ms, occipitotemporal sites (P7/P8, PO7/PO8). Amplitude: 8-15 μV for
biological motion, 5-10 μV for non-biological. Difference: 3-5 μV. N170 reflects
structural encoding of biological motion.

●​ Mu Rhythm Suppression (8-13 Hz): Reduced mu power over sensorimotor

cortex (C3, Cz, C4) during observation of biological motion, reflecting mirror
neuron system activity. Power reduction: 30-50% during observation vs baseline.
Reduced mu suppression in autism (d = 0.6-1.0).

●​ P300: Larger amplitude for correctly identified actions/emotions. Latency:

300-500 ms, centro-parietal sites. Amplitude: 12-20 μV.

●​ Theta Oscillations (4-8 Hz): Increased theta power during action understanding
and mentalizing. Power increase: 40-60% during biological motion vs baseline.

fMRI Correlates:
 ●​ Superior Temporal Sulcus (STS): Robust activation for biological motion.
Coordinates: [±55, -50, 10] (posterior STS). Effect size: d = 1.5-2.5 for biological
vs scrambled motion. STS is critical for perceiving intentional, goal-directed
movement. Reduced STS activation in autism (d = 0.8-1.2).

●​ Extrastriate Body Area (EBA): Activation for body parts and body motion.
Coordinates: [±50, -70, 5]. EBA represents body structure.

●​ Mirror Neuron System: Activation in inferior frontal gyrus (IFG) and inferior
parietal lobule (IPL) during action observation. Coordinates: IFG [±45, 10, 25];
IPL [±40, -45, 45]. Mirror neurons map observed actions onto motor
representations, supporting action understanding.

●​ Cerebellum: Activation during biological motion perception, particularly for

complex actions. Coordinates: [±25, -60, -25] (Crus I/II). Cerebellar contributions
to social perception (Jack et al., 2017).

●​ Fusiform Gyrus: Activation for body and face processing. Coordinates: [±40,
-55, -20].

Reliability: Accuracy shows good test-retest reliability (ICC = 0.60-0.75). N170

amplitude shows good reliability (ICC = 0.60-0.80). Mu suppression shows moderate
reliability (ICC = 0.50-0.70).

Clinical Sensitivity: Impaired biological motion perception in autism (d = 0.6-1.0),

particularly for complex actions and emotional expressions. Reduced STS activation in
autism. Biological motion perception predicts treatment outcome in autism: greater
baseline STS activation predicts better response to social skills training (Yang et al.,
2016, 2017). Impaired in schizophrenia (d = 0.5-0.8), particularly for inferring intentions.
6.4.2 Theory of Mind and Mentalizing

Paradigm Description: Theory of mind (ToM) paradigms assess the ability to infer
others' mental states. False belief tasks: participants predict behavior based on a
character's false belief (e.g., Sally-Anne task: Sally puts object in location A, leaves,
Anne moves object to location B, where will Sally look?). First-order: A's belief about
reality. Second-order: A's belief about B's belief. Social Attribution Task (SAT):
participants watch animations of geometric shapes moving in social or random patterns,
then describe interactions or answer multiple-choice questions. Reading the Mind in the
Eyes Test (RMET): participants infer mental states from photographs of eye region (36
items, 4 options per item). Typical parameters: 10-20 trials for false belief, 3-5
animations for SAT, 36 items for RMET.

EEG/ERP Correlates:

●​ P300: Larger amplitude for false belief questions vs true belief questions.
Latency: 300-500 ms, centro-parietal sites. Amplitude: 15-25 μV for false belief,
10-18 μV for true belief.

●​ N400: Larger amplitude for belief-inconsistent outcomes. Latency: 300-500 ms,

centro-parietal sites. N400 reflects semantic violation and expectancy mismatch.

●​ Frontal Theta Power (4-8 Hz): Increased theta during mentalizing. Power
increase: 50-80% during ToM vs control tasks. Theta power correlates with
mentalizing accuracy.

●​ Temporal Theta: Increased theta over temporal sites during social cognition.
Power increase: 40-60%.

fMRI Correlates:
 ●​ Medial Prefrontal Cortex (mPFC): Core region for mentalizing. Coordinates: [0,
50, 20] (dorsomedial PFC) or [0, 45, -10] (ventromedial PFC). Effect size: d =
1.0-2.0 for ToM vs control. mPFC represents others' mental states and integrates
social information.

●​ Temporoparietal Junction (TPJ): Critical for belief attribution. Coordinates:

[±55, -55, 20] (right TPJ often more activated). Effect size: d = 1.0-1.8 for false
belief vs true belief. Right TPJ is particularly important for representing others'
beliefs that differ from reality. Reduced TPJ activation in autism and
schizophrenia.

●​ Superior Temporal Sulcus (STS): Activation during social perception and action
understanding. Coordinates: [±55, -50, 10]. STS provides input to mentalizing
network.

●​ Temporal Poles: Activation during social semantic knowledge retrieval.

Coordinates: [±40, 10, -30]. Temporal poles store social concepts and scripts.

●​ Precuneus / Posterior Cingulate Cortex (PCC): Activation during

self-referential processing and perspective-taking. Coordinates: [0, -55, 30]. PCC
is part of default mode network.

●​ Functional Connectivity: Increased connectivity within mentalizing network

(mPFC, TPJ, STS, temporal poles) during ToM tasks. Reduced connectivity in
autism and schizophrenia. Failure to engage TPJ/STS predicts impaired
naturalistic social cognition (Patel et al., 2021).

Reliability: False belief understanding shows moderate test-retest reliability (r =

0.50-0.70). RMET shows moderate reliability (r = 0.63-0.74). SAT shows excellent
inter-rater reliability (ICC = 0.80-0.90) and good test-retest reliability (ICC = 0.70-0.85).
Clinical Sensitivity: Impaired false belief understanding in autism (d = 1.0-1.5) and
schizophrenia (d = 0.8-1.2). Impaired RMET in autism (d = 0.8-1.0) and schizophrenia
(d = 0.9-1.2). Impaired SAT in schizophrenia (d = 0.8-1.2) and autism. ToM deficits
correlate with social functioning and community outcomes. ToM training improves social
cognition in schizophrenia (Campos et al., 2016).

6.5 Arousal and Sensorimotor Systems: Advanced Paradigms

6.5.1 Pupillometry

Paradigm Description: Pupillometry measures pupil diameter continuously during rest

or task performance. Pupil diameter reflects arousal, cognitive load, and autonomic
state. Spontaneous pupil fluctuations during rest index locus coeruleus-norepinephrine
system activity. Task-evoked pupil dilations reflect phasic arousal responses to salient
stimuli or cognitive demands. Typical parameters: 60-1000 Hz sampling rate, infrared
eye-tracking, 5-30 min recording duration. Baseline pupil diameter: 3-6 mm in normal
lighting. Dilations: 0.2-1.0 mm for cognitive tasks, 0.5-1.5 mm for emotional stimuli.

EEG/ERP Correlates:

●​ P300: Pupil dilation correlates with P300 amplitude (r = 0.40-0.60). Both reflect
phasic arousal and attentional resource allocation.

●​ Frontal Theta Power: Pupil dilation correlates with frontal theta power during
cognitive tasks (r = 0.30-0.50).

●​ Alpha Power: Pupil diameter inversely correlates with alpha power (r = -0.30 to
-0.50). Larger pupils (higher arousal) associated with reduced alpha (increased
cortical activation).

fMRI Correlates:
 ●​ Salience Network: Pupil dilations strongly coupled to activation of dorsal anterior
cingulate cortex (dACC) and bilateral insula (Schneider, 2018). Coordinates:
dACC [0, 20, 30]; insula [±35, 20, 0]. Salience network modulates arousal to
optimize task performance.

●​ Locus Coeruleus (LC): Spontaneous pupil fluctuations correlate with LC activity.

Coordinates: [0, -38, -30]. LC-norepinephrine system regulates arousal and
attention.

●​ Ventral Striatum: Pupil dilations during reward anticipation correlate with ventral
striatum activation. Pupillometry provides a non-invasive index of reward
processing.

Reliability: Pupil diameter shows high temporal resolution and good reliability. Baseline
pupil diameter: ICC = 0.70-0.85. Task-evoked dilations: ICC = 0.60-0.80. Pupillometry is
sensitive to arousal, cognitive load, stress, and autonomic dysfunction.

Clinical Sensitivity: Reduced pupil dilations in depression (blunted arousal). Elevated

baseline pupil diameter in anxiety (hyperarousal). Altered pupil responses in ADHD,
PTSD, and schizophrenia. Pupillometry predicts treatment response and cognitive
performance.

6.5.2 Motor Imagery and Agency

Paradigm Description: Motor imagery tasks require participants to imagine performing

movements without executing them. Participants may imagine simple movements
(finger tapping, hand opening/closing) or complex actions (reaching, grasping, tool use).
Agency tasks assess the sense of being the agent of one's actions. Participants make
voluntary movements and judge whether they caused a sensory outcome. Temporal or
spatial delays are introduced between action and outcome to manipulate agency.
Typical parameters: 20-40 trials, 2-5 sec imagery/action period, forced-choice agency
judgment.

EEG/ERP Correlates:

●​ Bereitschaftspotential (BP) / Readiness Potential: Slow negative wave

beginning ~1-2 sec before voluntary movement, maximal at central sites (Cz). BP
is present for both executed and imagined movements, though smaller for
imagery. Amplitude: -10 to -20 μV for execution, -5 to -12 μV for imagery.

●​ Lateralized Readiness Potential (LRP): Difference between contralateral and

ipsilateral motor cortex activity (C3/C4). LRP is present for both executed and
imagined movements. Onset: ~500 ms pre-response for execution, ~650 ms for
imagery (Kranczioch et al., 2009).

●​ Anterior Directing-Attention Negativity (ADAN): Contralateral negativity

300-400 ms post-cue, anterior sites. Reflects attentional orienting to motor
preparation.

●​ Late Directing-Attention Positivity (LDAP): Contralateral positivity 400-550 ms

post-cue, posterior sites. Reflects sustained attention during motor preparation.

●​ Mu Rhythm Suppression (8-13 Hz): Reduced mu power over sensorimotor

cortex (C3, Cz, C4) during motor imagery. Power reduction: 20-40% during
imagery vs baseline. Mu suppression indicates activation of motor
representations.

●​ Beta Oscillations (15-30 Hz): Beta desynchronization during motor preparation

and imagery. Beta rebound following movement cessation.

fMRI Correlates:
 ●​ Overlapping Activation: Executed and imagined movements activate
overlapping regions: supplementary motor area (SMA), premotor cortex,
posterior parietal cortex, basal ganglia, cerebellum. Coordinates: SMA [0, 0, 50];
premotor [±40, 0, 50]; parietal [±40, -45, 45].

●​ Primary Motor Cortex (M1): Reduced activation during imagery vs execution.

Coordinates: [±40, -20, 55]. M1 activation during imagery is subthreshold (does
not produce movement).

●​ Agency Network: Posterior parietal cortex, SMA, and cerebellum compare

predicted and actual sensory consequences (forward model). Coordinates:
parietal [±40, -45, 45]; SMA [0, 0, 50]; cerebellum [±25, -60, -25]. Reduced
activation for self-generated outcomes (sensory attenuation). Altered agency
network in schizophrenia (delusions of control).

Reliability: Motor imagery ability shows moderate test-retest reliability (ICC =

0.55-0.75). Vividness of Movement Imagery Questionnaire (VMIQ): α = 0.80-0.90.
Agency judgments show moderate reliability (ICC = 0.50-0.65).

Clinical Sensitivity: Impaired motor imagery in Parkinson's disease, stroke, and motor
disorders. Altered agency in schizophrenia (d = 0.8-1.2), particularly for delusions of
control. Motor imagery training improves motor performance and rehabilitation
outcomes.

5. Gap Analysis: Underassessed RDoC Constructs

This section identifies RDoC constructs that are inadequately covered by standard
neuropsychological batteries and provides evidence-based recommendations for
addressing these gaps.
5.1 Overview of Coverage Gaps

Standard neuropsychological batteries (NIH Toolbox, CANTAB, MCCB, Penn CNB,

D-KEFS, CogState) provide comprehensive coverage of Cognitive Systems constructs
but show significant gaps in other RDoC domains. Table 5.1 summarizes coverage
across domains.

Table 5.1: RDoC Domain Coverage by Standard Batteries

RDoC Domain Coverage Level Well-Covered Underassessed

Constructs Constructs

Negative Valence Poor (10-20%) None consistently Acute threat,

potential threat,
sustained threat,
loss, frustrative
nonreward

Positive Valence Poor (15-25%) None consistently Reward

anticipation, reward
learning, reward
valuation, approach
motivation, satiation

Cognitive Excellent (80-95%) Attention, working Perception (limited

Systems memory, cognitive coverage)
control, declarative
memory, language

Social Processes Fair (30-50%) Facial emotion Affiliation/attachme

recognition (some nt, theory of mind,
batteries) animacy
 perception,
self-knowledge

Arousal/ Poor (10-20%) Sustained attention Arousal, circadian

Regulatory (indirect) rhythms,
sleep-wake

Sensorimotor Fair (40-60%) Motor speed, Agency/ownership,

dexterity habit, innate motor
patterns

5.2 Negative Valence Systems Gaps

5.2.1 Acute Threat ("Fear")

Gap: No standard neuropsychological batteries include fear conditioning or threat

processing paradigms. This represents a critical gap, as acute threat processing is
central to anxiety disorders, PTSD, and trauma-related psychopathology.

Evidence: Fear conditioning paradigms show robust neural correlates (amygdala,

vmPFC, hippocampus) and clinical sensitivity. Enhanced fear acquisition and impaired
extinction characterize PTSD (Marin et al., 2020). Fear conditioning prediction errors
predict PTSD symptom severity (Letkiewicz et al., 2021). Meta-analysis of 2,199
individuals demonstrates reliable neural correlates of fear conditioning (Raduà et al.,
2025).

Recommended Assessment:
 ●​ Primary: Fear conditioning and extinction paradigm (18-36 trials per phase, 3-6
sec stimulus duration, 50-75% reinforcement)

●​ EEG/ERP: LPP (300+ ms, centro-parietal), frontal theta power (4-8 Hz)

●​ fMRI: Amygdala [±20, -5, -15], vmPFC [0, 45, -10], hippocampus [±25, -20, -15]

●​ Psychometric: Group-level reliability robust; individual-level ICC ~0.30-0.50 for

SCR

●​ Clinical Utility: Discriminates PTSD, anxiety disorders; predicts treatment

response

5.2.2 Potential Threat ("Anxiety")

Gap: Standard batteries do not assess sustained vigilance under uncertainty or

unpredictable threat. Self-report measures (e.g., anxiety questionnaires) are available
but do not capture neural mechanisms.

Evidence: NPU-threat task dissociates predictable vs unpredictable threat processing.

BNST activation during unpredictable threat distinguishes anxiety disorders (Feola et
al., 2023). Startle potentiation shows moderate reliability (ICC ~0.50-0.70) and
discriminates anxiety disorders (Klumpp et al., 2018).

Recommended Assessment:

●​ Primary: NPU-threat task (8-12 blocks per condition, 60-90 sec per block, 6-12
startle probes per condition)

●​ EEG/ERP: Startle blink reflex (20-200 ms post-probe), P300 modulation, frontal

theta power
 ●​ fMRI: BNST [±10, 0, -10], amygdala [±20, -5, -15], dlPFC [±40, 30, 30]

●​ Psychometric: Startle potentiation ICC ~0.50-0.70; minimum 6 probes per

condition

●​ Clinical Utility: Discriminates GAD, PTSD; sensitive to anxiolytic medications

5.2.3 Loss and Frustrative Nonreward

Gap: While some batteries include tasks with monetary outcomes, they do not
systematically assess loss processing or frustrative nonreward. Loss aversion and
frustration reactivity are relevant to depression, aggression, and emotion dysregulation.

Evidence: Loss paradigms elicit robust FRN/RewP and insula activation. Blunted loss
sensitivity in depression (reduced FRN, reduced insula activation). Enhanced frustration
reactivity in intermittent explosive disorder and ADHD.

Recommended Assessment:

●​ Primary: Monetary loss paradigm (60-120 trials, equal gain/loss/neutral) or

frustration induction (unsolvable tasks, 5-10 min)

●​ EEG/ERP: FRN/RewP (250-350 ms, frontocentral), frontal theta power, beta

power during frustration

●​ fMRI: Anterior insula [±35, 20, 0], dACC [0, 20, 30], sgACC [0, 25, -10]

●​ Psychometric: Loss aversion parameter (λ) ICC = 0.60-0.75; behavioral

persistence r ~0.50-0.65
 ●​ Clinical Utility: Predicts depression, aggression; sensitive to treatment effects

5.3 Positive Valence Systems Gaps

5.3.1 Reward Anticipation and Responsiveness

Gap: Standard batteries do not systematically assess reward anticipation or

consummatory pleasure. While some tasks include performance-based rewards, they
do not isolate anticipation vs outcome phases or manipulate reward magnitude
systematically.

Evidence: MID task is the gold standard for reward anticipation, showing robust ventral
striatum activation (d = 0.8-1.5) and SPN. Blunted ventral striatum activation in
depression (d = 0.6-1.0) and schizophrenia (d = 0.8-1.2) (Carruzzo et al., 2024).
Probabilistic Reward Task assesses reward learning via response bias, reduced in
depression (Whitton et al., 2016; Pechtel et al., 2013).

Recommended Assessment:

●​ Primary: Monetary Incentive Delay (MID) task (72-120 trials, 1-2 sec cue, 2-4
sec anticipation, adaptive target duration)

●​ Alternative: Probabilistic Reward Task (200-300 trials, 100 ms stimulus, 3:1

reinforcement ratio)

●​ EEG/ERP: SPN (anticipation period, central sites), RewP (250-350 ms

post-feedback, frontocentral)

●​ fMRI: Ventral striatum [±12, 15, -9], VTA [0, -15, -10], mPFC [0, 45, -5]

•
Psychometric: Ventral striatum ICC = 0.40-0.60; RewP ICC = 0.50-0.70; response bias
r = 0.50-0.70

●​ Clinical Utility: Discriminates depression, schizophrenia; predicts treatment

response

5.3.2 Reward Valuation

Gap: Standard batteries do not assess intertemporal choice, probability discounting, or

effort-based decision-making. These constructs are critical for understanding impulsivity,
addiction, and motivation.

Evidence: Delay discounting shows good reliability (ICC = 0.60-0.80) and predicts
real-world impulsive behaviors. Steeper discounting in addiction (d = 0.5-1.0) and ADHD
(d = 0.5-0.8). Effort discounting reduced in depression (d = 0.6-0.9) and schizophrenia
negative symptoms (d = 0.7-1.0).

Recommended Assessment:

•
Primary: Delay discounting task (20-50 trials, 5-7 delay values, adjusting-amount
procedure)

●​ Alternative: Effort Expenditure for Rewards Task (EEfRT) (50-100 trials, varying
effort and reward)

●​ EEG/ERP: P300 (larger for LL choices), frontal theta power during choice

●​ fMRI: Ventral striatum/vmPFC [±12, 9, -6; 0, 45, -10] for SS; dlPFC [±40, 30, 30]
for LL
 ●​ Psychometric: Discount rate (k) ICC = 0.60-0.80; effort choices ICC = 0.60-0.75

●​ Clinical Utility: Predicts addiction, ADHD, impulsivity; effort discounting predicts

apathy

5.4 Social Processes Gaps

5.4.1 Theory of Mind and Mentalizing

Gap: Most standard batteries do not include theory of mind tasks. Some include
emotion recognition (faces) but not mentalizing or belief attribution. This gap is critical
for autism, schizophrenia, and social cognition deficits.

Evidence: False belief tasks, RMET, and Social Attribution Task show robust mPFC
and TPJ activation. Impaired in autism (d = 1.0-1.5) and schizophrenia (d = 0.8-1.2).
Failure to engage TPJ/STS predicts impaired naturalistic social cognition (Patel et al.,
2021). ToM training improves social functioning (Campos et al., 2016).

Recommended Assessment:

●​ Primary: Reading the Mind in the Eyes Test (RMET) (36 items, 4 options per
item)

●​ Alternative: Social Attribution Task (SAT or SAT-MC) (3-5 animations or 15-20

multiple-choice items)

●​ EEG/ERP: P300 to false belief questions, frontal theta power during mentalizing

●​ fMRI: mPFC [0, 50, 20], TPJ [±55, -55, 20], STS [±55, -50, 10]
 ●​ Psychometric: RMET r = 0.63-0.74; SAT-MC ICC = 0.70-0.85; inter-rater ICC =
0.80-0.90

●​ Clinical Utility: Discriminates autism, schizophrenia; predicts social functioning

5.4.2 Biological Motion and Action Perception

Gap: Standard batteries do not assess biological motion perception or action

understanding. This gap is relevant for autism, schizophrenia, and social perception
deficits.

Evidence: Biological motion paradigms show robust STS activation (d = 1.5-2.5) and
mu rhythm suppression. Impaired in autism (d = 0.6-1.0). Predicts treatment outcome in
autism (Yang et al., 2016, 2017).

Recommended Assessment:

●​ Primary: Point-light display (PLD) biological motion task (20-40 trials, 2-5 sec
animations)

●​ EEG/ERP: N170 (enhanced for biological motion), mu suppression (8-13 Hz,

central sites)

●​ fMRI: STS [±55, -50, 10], EBA [±50, -70, 5], mirror neuron system [±45, 10, 25;
±40, -45, 45]

●​ Psychometric: Accuracy ICC = 0.60-0.75; N170 ICC = 0.60-0.80

●​ Clinical Utility: Discriminates autism, schizophrenia; predicts treatment

response
5.4.3 Affiliation and Social Reward

Gap: Standard batteries do not assess social motivation or social reward processing.
This gap is critical for autism, schizophrenia negative symptoms, and social anhedonia.

Evidence: Social reward paradigms show ventral striatum and mPFC activation to
social rewards (smiling faces, social approval). Reduced in autism and social
anhedonia. Social reward responsiveness predicts treatment response to social skills
interventions (Baker et al., 2021).

Recommended Assessment:

●​ Primary: Social reward paradigm (anticipation and receipt of social vs non-social

rewards)

●​ EEG/ERP: SPN during anticipation of social rewards, RewP to social reward

outcomes

●​ fMRI: Ventral striatum [±12, 9, -6], mPFC [0, 45, -5], amygdala [±20, -5, -15]

●​ Psychometric: Social reward responsiveness ICC = 0.50-0.70

●​ Clinical Utility: Discriminates autism, social anhedonia; predicts treatment

response

5.5 Arousal and Regulatory Systems Gaps

5.5.1 Arousal and Alertness

Gap: While some batteries include sustained attention tasks (CPT, PVT), they do not
comprehensively assess arousal regulation or phasic arousal responses. Pupillometry
and autonomic measures are rarely included.

Evidence: Pupillometry provides a reliable index of arousal and salience network

activity (Schneider, 2018). Pupil dilations correlate with P300 amplitude and cognitive
load. Altered pupil responses in depression, anxiety, ADHD, and PTSD.

Recommended Assessment:

●​ Primary: Psychomotor Vigilance Test (PVT) (10 min, ~100 trials, 2-10 sec ISI)

●​ Supplementary: Pupillometry during rest or task (60-1000 Hz sampling, 5-30

min recording)

●​ EEG/ERP: P300 amplitude, theta/alpha power, alpha asymmetry

●​ fMRI: Salience network (dACC [0, 20, 30], insula [±35, 20, 0]), locus coeruleus
[0, -38, -30]

●​ Psychometric: PVT mean RT ICC = 0.70-0.85; pupil diameter ICC = 0.70-0.85

●​ Clinical Utility: Sensitive to sleep deprivation, fatigue, ADHD, depression

5.5.2 Sleep and Circadian Rhythms

Gap: Standard neuropsychological batteries do not assess sleep or circadian rhythms.

These constructs are critical for understanding mood disorders, ADHD, and
neurodegenerative disorders.
Evidence: Polysomnography (PSG) is the gold standard for sleep assessment.
Actigraphy provides naturalistic assessment of sleep-wake patterns and circadian
rhythms. Altered sleep architecture in insomnia, depression, PTSD, and
neurodegenerative disorders.

Recommended Assessment:

●​ Primary: Actigraphy (7-14 days, wrist-worn accelerometer)

●​ Gold Standard: Polysomnography (overnight EEG, EOG, EMG, ECG,

respiration)

●​ Self-Report: Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index

(ISI)

●​ Psychometric: PSG sleep stages ICC = 0.70-0.90; actigraphy sleep timing ICC
= 0.70-0.85; PSQI α = 0.83

●​ Clinical Utility: Discriminates insomnia, depression, PTSD; predicts treatment

response

5.6 Sensorimotor Systems Gaps

5.6.1 Agency and Ownership

Gap: Standard batteries assess motor speed and dexterity but not sense of agency or
body ownership. These constructs are relevant for schizophrenia (delusions of control),
autism, and body image disorders.
Evidence: Rubber hand illusion (RHI) and agency judgment tasks show robust
posterior parietal cortex and SMA activation. Altered agency in schizophrenia (d =
0.8-1.2). Motor imagery tasks show overlapping activation with executed movements.

Recommended Assessment:

●​ Primary: Rubber hand illusion (RHI) (synchronous vs asynchronous brushing,

proprioceptive drift, questionnaire)

●​ Alternative: Agency judgment task (voluntary movements with temporal/spatial

delays, agency ratings)

●​ EEG/ERP: Mu suppression during RHI, LRP during agency tasks, P300 to

self-generated outcomes

●​ fMRI: Posterior parietal cortex [±40, -45, 45], SMA [0, 0, 50], cerebellum [±25,
-60, -25]

●​ Psychometric: Proprioceptive drift ICC = 0.50-0.70; agency judgments ICC =

0.50-0.65

●​ Clinical Utility: Discriminates schizophrenia, autism; altered in body image

disorders

5.6.2 Habit Formation

Gap: Standard batteries do not assess habit learning or the transition from goal-directed
to habitual control. This gap is relevant for OCD, addiction, and Parkinson's disease.
Evidence: Habit learning tasks show transition from ventral striatum/prefrontal cortex
(goal-directed) to dorsolateral striatum (habitual) with overtraining. Enhanced habit
formation in OCD and addiction. Impaired in Parkinson's disease.

Recommended Assessment:

●​ Primary: Habit learning task with outcome devaluation (200-500 training trials,
devaluation test)

●​ Alternative: Serial Reaction Time Task (SRTT) (sequence learning, 200-400

trials)

●​ EEG/ERP: Reduced P300 with habit formation, shift from frontal to central
activity

●​ fMRI: Transition from ventral striatum [±12, 9, -6] to dorsolateral striatum [±25, 5,
5]

●​ Psychometric: Habit index ICC = 0.50-0.65; SRTT learning ICC = 0.60-0.75

●​ Clinical Utility: Enhanced in OCD, addiction; impaired in Parkinson's disease

5.7 Summary Table: Priority Gaps and Recommended Assessments

Table 5.2: Priority RDoC Gaps and Recommended Paradigms

RDoC Gap Recommended Duration Key Neural Clinical

Construct Severity Paradigm Correlates Utility
Acute Critical Fear 20-30 min Amygdala, PTSD,
Threat conditioning vmPFC, anxiety
LPP disorders

Potential Critical NPU-threat task 15-20 min BNST, GAD, PTSD

Threat startle reflex

Reward Critical MID task 8-12 min Ventral Depression,

Anticipation schizophrenia
striatum,
SPN, RewP

Reward High Probabilistic 15-20 min Ventral Depression,

Learning Reward Task striatum, anhedonia
RewP

Reward High Delay 10-15 min vmPFC, Addiction,

Valuation discounting dlPFC ADHD,
impulsivity

Theory of High RMET or SAT 10-15 min mPFC, TPJ, Autism,

schizophrenia
Mind STS

Biological Moderate Point-light 10-15 min STS, mu Autism,

schizophrenia
Motion displays suppression

Social Moderate Social reward 10-15 min Ventral Autism,

Reward paradigm striatum, social
mPFC anhedonia

Arousal Moderate PVT + 10-15 min Salience ADHD,

pupillometry network, LC depression,
fatigue
 Sleep/ Moderate Actigraphy + 7-14 days Sleep Insomnia,
Circadian PSQI architecture depression,
PTSD

Agency/ Moderate RHI or agency 10-15 min Posterior Schizophrenia,

autism
Ownership task parietal,
SMA

Habit Low Habit learning + 30-40 min Dorsolateral OCD,

devaluation striatum addiction,
Parkinson's

4. Battery-to-RDoC Construct Mapping

This section provides detailed mapping of standard neuropsychological batteries to

RDoC constructs, identifying strengths and limitations of each battery.

4.1 NIH Toolbox

Overview: The NIH Toolbox is a comprehensive assessment battery developed by the

National Institutes of Health for ages 3-85. It includes modules for cognition, emotion,
motor function, and sensation. The Cognition Battery is most relevant for RDoC
assessment.

Cognition Battery Components:

1.​ Flanker Inhibitory Control and Attention Test: Measures selective attention
and response inhibition (2-3 min)
 2.​ Dimensional Change Card Sort (DCCS): Measures cognitive flexibility and
set-shifting (4 min)

3.​ Picture Sequence Memory Test: Measures episodic memory (7 min)

4.​ List Sorting Working Memory Test: Measures working memory manipulation (7
min)

5.​ Pattern Comparison Processing Speed Test: Measures processing speed (3

min)

6.​ Picture Vocabulary Test: Measures receptive vocabulary (4 min)

7.​ Oral Reading Recognition Test: Measures reading decoding (3 min)

RDoC Mapping:

NIH Toolbox RDoC Domain RDoC RDoC Coverage

Test Construct Subconstruct Quality

Flanker Test Cognitive Cognitive Response Good

Systems Control inhibition,
performance
monitoring

Flanker Test Cognitive Attention Selective Good

Systems attention

DCCS Cognitive Cognitive Goal updating, Good

Systems Control cognitive
flexibility
Picture Cognitive Declarative Episodic Good
Sequence Systems Memory memory
Memory

List Sorting Cognitive Working Active Good

WM Systems Memory maintenance,
flexible
updating

Pattern Cognitive Perception Visual Fair

Comparison Systems perception

Pattern Cognitive Cognitive Processing Good

Comparison Systems Control speed

Picture Cognitive Language Language Good

Vocabulary Systems comprehension

Oral Reading Cognitive Language Language Good

Systems production
(reading)

Strengths:

●​ Comprehensive age-corrected norms (ages 3-85)

●​ Good psychometric properties (test-retest ICC = 0.77-0.84 for most tests)

(Weintraub et al., 2014)

●​ Tablet/computer administration (standardized, efficient)

 ●​ Validated across diverse populations

●​ Sensitive to MCI and dementia (Hackett et al., 2018)

Limitations:

●​ Limited coverage of Negative Valence, Positive Valence, Social Processes,

Arousal/Regulatory, and Sensorimotor domains

●​ No EEG/ERP or fMRI correlates included

●​ Emotion Battery (self-report only) does not assess neural mechanisms

●​ No experimental paradigms for reward, threat, or social cognition

Clinical Utility: Excellent for cognitive assessment across lifespan. Useful for MCI,
dementia, TBI, and developmental disorders. Limited utility for affective and social
disorders without supplementation.

4.2 MATRICS Consensus Cognitive Battery (MCCB)

Overview: The MCCB was developed by the MATRICS initiative to assess cognitive
deficits in schizophrenia. It includes 10 tests across 7 cognitive domains, optimized for
sensitivity to schizophrenia and treatment effects.

MCCB Components:

1.​ Trail Making Test Part A: Processing speed (1 min)

 2.​ Brief Assessment of Cognition in Schizophrenia (BACS) Symbol Coding:
Processing speed (2 min)

3.​ Hopkins Verbal Learning Test-Revised (HVLT-R): Verbal learning and memory
(10 min)

4.​ Wechsler Memory Scale-III (WMS-III) Spatial Span: Working memory (spatial)
(5 min)

5.​ Letter-Number Span: Working memory (verbal) (3 min)

6.​ Neuropsychological Assessment Battery (NAB) Mazes: Reasoning and

problem solving (3 min)

7.​ Brief Visuospatial Memory Test-Revised (BVMT-R): Visual learning and

memory (10 min)

8.​ Category Fluency (Animal Naming): Verbal fluency (1 min)

9.​ Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT) Managing

Emotions: Social cognition (7 min)

10.​Continuous Performance Test-Identical Pairs (CPT-IP): Attention/vigilance (3

min)

RDoC Mapping:

MCCB Test RDoC Domain RDoC RDoC Coverage

Construct Subconstruct Quality
Trail Making A Cognitive Cognitive Processing Good
Systems Control speed

BACS Symbol Cognitive Cognitive Processing Good

Coding Systems Control speed

HVLT-R Cognitive Declarative Episodic Excellent

Systems Memory memory
(verbal)

WMS-III Cognitive Working Active Good

Spatial Span Systems Memory maintenance
(spatial)

Letter-Number Cognitive Working Active Good

Span Systems Memory maintenance,
flexible
updating
(verbal)

NAB Mazes Cognitive Cognitive Goal selection, Good

Systems Control planning

BVMT-R Cognitive Declarative Episodic Excellent

Systems Memory memory
(visual)

Category Cognitive Language Language Good

Fluency Systems production
(semantic
fluency)
MSCEIT Social Social Emotion Fair
Managing Processes Communication understanding
Emotions

CPT-IP Cognitive Attention Sustained Good

Systems attention

Strengths:

●​ Optimized for schizophrenia (sensitive to cognitive deficits, d = 0.8-1.2)

(Nuechterlein et al., 2008)

●​ Good psychometric properties (test-retest reliability, sensitivity to change)

●​ Widely used in clinical trials (>145 trials)

●​ Translated into 39 languages

●​ Includes social cognition measure (MSCEIT)

Limitations:

●​ Limited coverage of Negative Valence, Positive Valence, Arousal/Regulatory, and

Sensorimotor domains

●​ MSCEIT is only social cognition measure; does not assess theory of mind, face
processing, or biological motion

●​ No EEG/ERP or fMRI correlates

 ●​ Norms specific to schizophrenia population; less applicable to other disorders

Clinical Utility: Excellent for schizophrenia cognitive assessment and treatment trials.
Useful for other psychotic disorders. Limited utility for affective and anxiety disorders
without supplementation.

4.3 Penn Computerized Neurocognitive Battery (Penn CNB)

Overview: The Penn CNB is a computerized battery assessing multiple cognitive

domains with emphasis on accuracy and speed. It includes tests of executive function,
episodic memory, complex cognition, social cognition, and sensorimotor speed.

Penn CNB Components (abbreviated version):

1.​ Penn Conditional Exclusion Test (PCET): Executive function/abstraction (4

min)

2.​ Penn Letter N-Back Test (LNB): Working memory (3 min)

3.​ Penn Continuous Performance Test (PCPT): Attention (5 min)

4.​ Penn Word Memory Test (PWMT): Verbal memory (5 min)

5.​ Penn Face Memory Test (PFMT): Face memory (5 min)

6.​ Penn Emotion Recognition Test (ER-40): Emotion identification (4 min)

7.​ Penn Emotion Differentiation Test (EDT): Emotion intensity discrimination (3

min)

8.​ Penn Age Differentiation Test (ADT): Age discrimination (3 min)

 9.​ Penn Motor Praxis Test (MP): Sensorimotor speed (2 min)

RDoC Mapping:

Penn CNB RDoC Domain RDoC RDoC Coverage

Test Construct Subconstruct Quality

PCET Cognitive Cognitive Goal updating, Good

Systems Control cognitive
flexibility

LNB Cognitive Working Active Good

Systems Memory maintenance,
flexible
updating

PCPT Cognitive Attention Sustained Good

Systems attention

PWMT Cognitive Declarative Episodic Good

Systems Memory memory
(verbal)

PFMT Cognitive Declarative Episodic Good

Systems Memory memory
(faces)

PFMT Social Social Face Fair

Processes Communication recognition

ER-40 Social Social Facial emotion Good

Processes Communication recognition
EDT Social Social Emotion Fair
Processes Communication intensity
perception

ADT Cognitive Perception Face Fair

Systems perception

MP Sensorimotor Motor Actions Motor speed, Good

execution

Strengths:

●​ Computerized administration (standardized, efficient)

●​ Includes social cognition measures (ER-40, EDT)

●​ Good psychometric properties (test-retest ICC = 0.70-0.85) (Izgi et al., 2021)

●​ Validated across multiple populations

●​ Relatively brief (30-45 min for full battery)

Limitations:

●​ Limited coverage of Negative Valence, Positive Valence, Arousal/Regulatory

domains

●​ Social cognition limited to emotion recognition; no theory of mind or biological

motion
 ●​ No EEG/ERP or fMRI correlates

●​ ER-40 is only validated social cognition measure

Clinical Utility: Good for comprehensive cognitive and social cognition assessment.
Useful for schizophrenia, autism, and mood disorders. Limited utility for anxiety and
reward-related disorders without supplementation.

4.4 Cambridge Neuropsychological Test Automated Battery

(CANTAB)

Overview: CANTAB is a computerized battery with extensive validation across

neuropsychiatric disorders. It includes tests of visual memory, executive function,
attention, and social cognition.

CANTAB Components (selected tests):

1.​ Rapid Visual Information Processing (RVP): Sustained attention (7 min)

2.​ Spatial Working Memory (SWM): Working memory (spatial) (8 min)

3.​ Intra-Extra Dimensional Set Shift (IED): Cognitive flexibility, set-shifting (7 min)

4.​ Stockings of Cambridge (SOC): Planning (10 min)

5.​ Stop Signal Task (SST): Response inhibition (15 min)

6.​ Delayed Matching to Sample (DMS): Visual memory (7 min)

7.​ Pattern Recognition Memory (PRM): Visual recognition memory (5 min)

 8.​ Emotion Recognition Task (ERT): Facial emotion recognition (10 min)

9.​ Affective Go/No-Go (AGN): Emotional processing and response control (5 min)

RDoC Mapping:

CANTAB Test RDoC Domain RDoC RDoC Coverage

Construct Subconstruct Quality

RVP Cognitive Attention Sustained Excellent

Systems attention

SWM Cognitive Working Active Excellent

Systems Memory maintenance
(spatial)

IED Cognitive Cognitive Goal updating, Excellent

Systems Control cognitive
flexibility

SOC Cognitive Cognitive Goal selection, Excellent

Systems Control planning

SST Cognitive Cognitive Response Excellent

Systems Control inhibition

DMS Cognitive Declarative Short-term Good

Systems Memory memory
(visual)

PRM Cognitive Declarative Long-term Good

Systems Memory memory
(visual)
ERT Social Social Facial emotion Good
Processes Communication recognition

AGN Negative Loss Emotional Fair

Valence response to
negative
stimuli

AGN Positive Reward Emotional Fair

Valence Responsiveness response to
positive stimuli

Strengths:

●​ Extensive validation across disorders (schizophrenia, ADHD, depression,

dementia, Parkinson's)

●​ Excellent psychometric properties (test-retest reliability, sensitivity)

●​ Includes Stop-Signal Task (gold standard for response inhibition)

●​ Includes emotion recognition (ERT)

●​ Affective Go/No-Go provides some coverage of valence systems

Limitations:

●​ Limited coverage of Positive Valence (reward anticipation, learning, valuation)

●​ Limited coverage of Negative Valence (threat, anxiety)

 ●​ Social cognition limited to emotion recognition; no theory of mind

●​ No EEG/ERP or fMRI correlates

●​ Relatively long administration time (60-90 min for full battery)

Clinical Utility: Excellent for cognitive assessment, particularly executive function and
attention. Useful for ADHD, schizophrenia, dementia, and Parkinson's disease. Limited
utility for affective and social disorders without supplementation.

4.5 CogState

Overview: CogState is a brief computerized battery using playing card stimuli. It

emphasizes processing speed and is sensitive to subtle cognitive changes.

CogState Brief Battery Components:

1.​ Detection (DET): Psychomotor function (2 min)

2.​ Identification (IDN): Attention (3 min)

3.​ One Card Learning (OCL): Visual learning (3 min)

4.​ One Back (ONB): Working memory (3 min)

RDoC Mapping:

CogState RDoC Domain RDoC RDoC Coverage

Test Construct Subconstruct Quality

DET Sensorimotor Motor Actions Motor speed, Good
execution

IDN Cognitive Attention Selective Good

Systems attention

OCL Cognitive Declarative Visual learning Good

Systems Memory

ONB Cognitive Working Active Good

Systems Memory maintenance

Strengths:

●​ Very brief (10-15 min)

●​ Good sensitivity to subtle cognitive changes (mild TBI, MCI)

●​ Good psychometric properties (Maruff et al.)

●​ Minimal practice effects

●​ Suitable for repeated testing

Limitations:

●​ Limited scope (only 4 tests in brief battery)

●​ No coverage of Negative Valence, Positive Valence, Social Processes,

Arousal/Regulatory domains
 ●​ No EEG/ERP or fMRI correlates

●​ Limited clinical validation compared to other batteries

Clinical Utility: Useful for brief cognitive screening and repeated assessment (e.g.,
concussion monitoring, treatment trials). Limited utility as standalone battery; best used
as supplement.

4.6 Delis-Kaplan Executive Function System (D-KEFS)

Overview: D-KEFS is a comprehensive battery of executive function tests with

extensive normative data. It provides process scores to identify specific deficits.

D-KEFS Components (selected tests):

1.​ Trail Making Test: Cognitive flexibility, set-shifting (5 min)

2.​ Verbal Fluency: Language production, cognitive flexibility (8 min)

3.​ Design Fluency: Visual creativity, cognitive flexibility (5 min)

4.​ Color-Word Interference (Stroop): Response inhibition (5 min)

5.​ Sorting Test: Problem solving, concept formation (10 min)

6.​ Twenty Questions: Hypothesis testing (10 min)

7.​ Word Context: Deductive reasoning (10 min)

8.​ Tower Test: Planning (10 min)

 9.​ Proverb Test: Abstract thinking (10 min)

RDoC Mapping:

D-KEFS Test RDoC Domain RDoC RDoC Coverage

Construct Subconstruct Quality

Trail Making Cognitive Cognitive Cognitive Excellent

Systems Control flexibility,
set-shifting

Verbal Fluency Cognitive Language Language Excellent

Systems production

Verbal Fluency Cognitive Cognitive Cognitive Good

Systems Control flexibility

Design Cognitive Cognitive Cognitive Good

Fluency Systems Control flexibility

Color-Word Cognitive Cognitive Response Excellent

Interference Systems Control inhibition

Sorting Test Cognitive Cognitive Goal selection, Excellent

Systems Control concept
formation

Twenty Cognitive Cognitive Hypothesis Good

Questions Systems Control testing,
planning

Word Context Cognitive Language Language Good

Systems comprehension
Tower Test Cognitive Cognitive Planning, goal Excellent
Systems Control maintenance

Proverb Test Cognitive Language Abstract Good

Systems language

Strengths:

●​ Comprehensive executive function assessment

●​ Excellent normative data (ages 8-89)

●​ Process scores identify specific deficits

●​ Widely used in clinical neuropsychology

●​ Sensitive to frontal lobe dysfunction

Limitations:

●​ Limited coverage of Negative Valence, Positive Valence, Social Processes,

Arousal/Regulatory, Sensorimotor domains

●​ No EEG/ERP or fMRI correlates

●​ Relatively long administration time (60-90 min for full battery)

●​ Paper-and-pencil administration (less standardized than computerized)

Clinical Utility: Excellent for executive function assessment. Useful for TBI, frontal lobe
lesions, ADHD, and dementia. Limited utility for affective and social disorders without
supplementation.
4.7 Summary: Battery Coverage of RDoC Domains

Table 4.1: RDoC Domain Coverage by Battery

Battery Negative Positive Cognitive Social Arousal/ Sensorimotor Overall

Valence Valence Systems Processes Regulatory Coverage

NIH Toolbox 0% 0% 85% 0% (Emotion: 10% 20% 35%

self-report only)

MCCB 0% 0% 90% 15% (MSCEIT 10% 0% 35%

only)

Penn CNB 0% 0% 80% 40% (ER-40, 10% 20% 40%

EDT)

CANTAB 5% (AGN) 5% (AGN) 95% 20% (ERT 15% 10% 45%

only)

CogState 0% 0% 50% 0% 0% 20% 20%

D-KEFS 0% 0% 95% 0% 0% 0% 30%

Key Findings:

1.​ All batteries provide excellent coverage of Cognitive Systems (80-95%)

2.​ All batteries show poor coverage of Negative Valence (0-5%) and Positive
Valence (0-5%)

3.​ Social Processes coverage is limited (0-40%), with Penn CNB and CANTAB
providing best coverage

4.​ Arousal/Regulatory coverage is minimal (0-15%)

5.​ Sensorimotor coverage is limited (0-20%)

6.​ No single battery provides comprehensive RDoC coverage

7.​ Supplementation with experimental paradigms is essential for comprehensive

RDoC assessment

3. Comprehensive Battery Descriptions

This section provides detailed descriptions of major neuropsychological batteries,

including administration procedures, psychometric properties, and clinical applications.

3.1 NIH Toolbox Cognition Battery

Development and Purpose: The NIH Toolbox was developed through a collaborative
effort funded by the NIH Blueprint for Neuroscience Research. The goal was to create a
comprehensive, standardized assessment battery for epidemiological and longitudinal
studies across the lifespan (ages 3-85). The Cognition Battery was designed to assess
key cognitive domains with brief, reliable measures suitable for large-scale studies
(Weintraub et al., 2014).

Administration: Tablet or computer-based administration. Total time: 30-35 minutes for

full battery. Can be administered by trained technicians. Adaptive testing adjusts
difficulty based on performance. Available in English and Spanish.

Normative Data: Age-corrected norms for ages 3-85, stratified by education. Norms
based on nationally representative sample (N > 4,000). T-scores (M = 50, SD = 10) and
percentiles provided. Composite scores: Fluid Cognition, Crystallized Cognition, Total
Cognition.

Psychometric Properties:

●​ Test-retest reliability: ICC = 0.77-0.84 for most tests (Weintraub et al., 2014)

●​ Internal consistency: α = 0.75-0.90

●​ Convergent validity: Correlates with gold-standard neuropsychological tests (r =

0.50-0.80)

●​ Discriminant validity: Distinguishes MCI and dementia from healthy aging

(Hackett et al., 2018)

●​ Practice effects: Minimal to moderate (5-10% improvement over 2-3 sessions)

Clinical Applications: Validated for MCI, Alzheimer's disease, TBI, multiple sclerosis,
congenital heart defects, and developmental disorders. Sensitive to cognitive decline in
aging. Useful for treatment trials and longitudinal monitoring. Limited utility for
psychiatric disorders without cognitive impairment.
Strengths: Comprehensive age range, excellent norms, brief administration,
standardized procedures, validated across diverse populations.

Limitations: Limited coverage of non-cognitive RDoC domains, no EEG/fMRI

correlates, emotion battery is self-report only.

3.2 MATRICS Consensus Cognitive Battery (MCCB)

Development and Purpose: The MCCB was developed by the Measurement and
Treatment Research to Improve Cognition in Schizophrenia (MATRICS) initiative,
funded by NIMH. The goal was to create a standardized battery for assessing cognitive
deficits in schizophrenia and evaluating cognitive-enhancing treatments. Tests were
selected based on sensitivity to schizophrenia, test-retest reliability, practicality, and
tolerability (Nuechterlein et al., 2008).

Administration: Paper-and-pencil and computerized tests. Total time: 60-75 minutes.

Requires trained examiner. Standardized administration and scoring procedures.
Available in 39 languages/dialects.

Normative Data: Norms for schizophrenia patients and healthy controls, stratified by
age, sex, and education. T-scores (M = 50, SD = 10) for each domain and overall
composite. Norms based on large validation studies (N > 600 per group).

Psychometric Properties:

●​ Test-retest reliability: ICC = 0.60-0.90 for domain scores (Nuechterlein et al.,

2008)

●​ Internal consistency: α = 0.70-0.85

 ●​ Sensitivity to schizophrenia: Effect sizes d = 0.8-1.2 for most domains

●​ Sensitivity to change: Detects treatment effects in clinical trials

●​ Practice effects: Minimal to moderate (alternate forms available for some tests)

Clinical Applications: Gold standard for cognitive assessment in schizophrenia. Used

in >145 clinical trials. Predicts functional outcomes (work, independent living, social
functioning). Useful for other psychotic disorders. Limited validation in non-psychotic
disorders.

Strengths: Optimized for schizophrenia, excellent psychometric properties, widely used

in research, translated into many languages, includes social cognition measure.

Limitations: Norms specific to schizophrenia, limited coverage of non-cognitive RDoC

domains, relatively long administration time, no EEG/fMRI correlates.

3.3 Penn Computerized Neurocognitive Battery (Penn CNB)

Development and Purpose: The Penn CNB was developed at the University of
Pennsylvania to provide a comprehensive, computerized assessment of cognitive and
social cognitive domains. It emphasizes both accuracy and speed, providing a more
sensitive measure of cognitive efficiency. The battery has been validated across multiple
psychiatric and neurological disorders.

Administration: Computer-based administration. Total time: 30-45 minutes for

abbreviated battery, 60-90 minutes for full battery. Can be administered by trained
technicians. Standardized instructions and procedures. Available in multiple languages.
Normative Data: Age-stratified norms for ages 8-89. Accuracy and speed scores
provided separately. Z-scores and percentiles available. Norms based on large
community samples (N > 10,000).

Psychometric Properties:

●​ Test-retest reliability: ICC = 0.70-0.85 for most tests (Izgi et al., 2021)

●​ Internal consistency: α = 0.75-0.90

●​ Convergent validity: Correlates with traditional neuropsychological tests (r =

0.50-0.75)

●​ Discriminant validity: Distinguishes psychiatric disorders from controls

●​ Practice effects: Minimal to moderate (5-15% improvement over 2-3 sessions)

Clinical Applications: Validated for schizophrenia, bipolar disorder, depression, ADHD,

autism, and neurodegenerative disorders. ER-40 (emotion recognition) is part of
SCOPE battery for social cognition in psychosis (Pinkham et al., 2016, 2018). Useful for
treatment trials and longitudinal monitoring.

Strengths: Computerized administration, includes social cognition measures, good

psychometric properties, validated across multiple disorders, relatively brief.

Limitations: Limited coverage of non-cognitive RDoC domains, social cognition limited

to emotion recognition, no EEG/fMRI correlates.

3.4 Cambridge Neuropsychological Test Automated Battery

(CANTAB)
Development and Purpose: CANTAB was developed at the University of Cambridge to
provide computerized assessment of cognitive functions with minimal verbal and
cultural loading. Tests are based on animal models of cognition, facilitating translational
research. CANTAB has extensive validation across neuropsychiatric disorders.

Administration: Touchscreen computer administration. Total time: 60-90 minutes for full
battery, 20-30 minutes for brief battery. Can be administered by trained technicians.
Standardized procedures. Available in multiple languages.

Normative Data: Age-stratified norms for ages 4-90. Percentiles and z-scores provided.
Norms based on large international samples (N > 5,000). Separate norms for clinical
populations.

Psychometric Properties:

●​ Test-retest reliability: ICC = 0.60-0.90 for most tests

●​ Internal consistency: α = 0.70-0.85

●​ Convergent validity: Correlates with traditional neuropsychological tests (r =

0.50-0.80)

●​ Discriminant validity: Distinguishes multiple disorders from controls

●​ Sensitivity: Detects subtle cognitive changes (MCI, mild TBI)

●​ Practice effects: Minimal to moderate (alternate forms available for some tests)

Clinical Applications: Extensively validated for schizophrenia, ADHD, depression,

anxiety, bipolar disorder, dementia, Parkinson's disease, Huntington's disease, TBI, and
autism. Used in pharmaceutical trials and translational research. Predicts functional
outcomes.

Strengths: Extensive validation, minimal verbal/cultural loading, includes Stop-Signal

Task (gold standard for inhibition), includes emotion recognition, suitable for
translational research.

Limitations: Limited coverage of non-cognitive RDoC domains, relatively long

administration time, expensive licensing, no EEG/fMRI correlates.

3.5 CogState

Development and Purpose: CogState was developed to provide brief, sensitive

assessment of cognitive function with minimal practice effects. It uses playing card
stimuli to reduce verbal and cultural loading. CogState is optimized for repeated testing
in clinical trials and concussion monitoring.

Administration: Computer-based administration. Total time: 10-15 minutes for brief

battery, 30-40 minutes for full battery. Can be self-administered or administered by
technician. Standardized procedures. Available in multiple languages.

Normative Data: Age-stratified norms for ages 6-90. Z-scores and percentiles provided.
Norms based on large international samples (N > 10,000).

Psychometric Properties:

●​ Test-retest reliability: ICC = 0.70-0.85 for most tests

●​ Internal consistency: α = 0.70-0.80

 ●​ Convergent validity: Correlates with traditional neuropsychological tests (r =
0.50-0.70)

●​ Sensitivity: Detects subtle cognitive changes (mild TBI, MCI)

●​ Practice effects: Minimal (designed for repeated testing)

Clinical Applications: Widely used for concussion monitoring, mild TBI, MCI,
dementia, schizophrenia, and pharmaceutical trials. Suitable for repeated assessment.
Validated for remote/unsupervised administration (Kochan et al., 2022).

Strengths: Very brief, minimal practice effects, suitable for repeated testing, minimal
verbal/cultural loading, validated for remote administration.

Limitations: Limited scope (only 4 tests in brief battery), limited coverage of

non-cognitive RDoC domains, less comprehensive than other batteries.

3.6 Delis-Kaplan Executive Function System (D-KEFS)

Development and Purpose: D-KEFS was developed to provide comprehensive

assessment of executive functions with extensive normative data and process scores.
Process scores allow identification of specific deficits (e.g., set-loss errors vs
perseverative errors on Trail Making). D-KEFS is widely used in clinical
neuropsychology.

Administration: Paper-and-pencil administration. Total time: 60-90 minutes for full

battery, 20-30 minutes for selected tests. Requires trained examiner. Standardized
administration and scoring. Available in English and Spanish.
Normative Data: Age-stratified norms for ages 8-89. Scaled scores (M = 10, SD = 3)
and percentiles provided. Norms based on nationally representative sample (N > 1,700).
Process scores identify specific deficits.

Psychometric Properties:

●​ Test-retest reliability: ICC = 0.60-0.90 for most tests

●​ Internal consistency: α = 0.70-0.85

●​ Convergent validity: Correlates with other executive function measures (r =

0.50-0.80)

●​ Discriminant validity: Distinguishes frontal lobe dysfunction from other deficits

●​ Sensitivity: Detects executive dysfunction in TBI, ADHD, dementia

Clinical Applications: Widely used for TBI, frontal lobe lesions, ADHD, dementia,
Parkinson's disease, and psychiatric disorders with executive dysfunction. Process
scores guide treatment planning. Predicts functional outcomes.

Strengths: Comprehensive executive function assessment, excellent normative data,

process scores identify specific deficits, widely used in clinical practice.

Limitations: Limited coverage of non-cognitive RDoC domains, paper-and-pencil

administration (less standardized than computerized), relatively long administration
time.

2. RDoC Theoretical Foundations and Neural Circuitry

2.1 RDoC Framework Overview

The Research Domain Criteria (RDoC) framework represents a paradigm shift in
psychiatric research and nosology. Developed by the National Institute of Mental Health
(NIMH) and launched in 2010, RDoC moves beyond traditional diagnostic categories
(DSM, ICD) toward a dimensional, neuroscience-informed approach to understanding
mental disorders (Insel et al., 2010; Cuthbert & Insel, 2013).

Core Principles:

1.​ Dimensional Approach: Psychopathology exists on continua rather than

discrete categories. RDoC constructs are dimensional, ranging from normal to
abnormal.

2.​ Neuroscience Foundation: Constructs are defined by neural circuits and

systems, not symptom clusters.

3.​ Multiple Units of Analysis: Each construct is assessed across multiple levels:
genes, molecules, cells, circuits, physiology, behavior, self-report, and
paradigms.

4.​ Transdiagnostic: Constructs cut across traditional diagnostic boundaries. For

example, anhedonia (reduced reward responsiveness) occurs in depression,
schizophrenia, and PTSD.

5.​ Developmental Perspective: Constructs are assessed across the lifespan,

recognizing that neural systems develop and change with age.

6.​ Integration with Other Sciences: RDoC integrates findings from neuroscience,
psychology, genetics, and computational modeling.
Rationale: Traditional diagnostic categories show limited validity, heterogeneity within
diagnoses, comorbidity across diagnoses, and poor treatment specificity. RDoC aims to
identify biologically valid dimensions that better predict treatment response and
outcomes.

2.2 Neural Circuitry of RDoC Domains

2.2.1 Negative Valence Systems Circuitry

Acute Threat ("Fear"): The fear circuit involves rapid activation of the amygdala,
particularly the basolateral nucleus for associative learning and the central nucleus for
fear expression. The amygdala projects to the periaqueductal gray (PAG) for defensive
behaviors (freezing, flight), hypothalamus for autonomic responses (heart rate, blood
pressure), and brainstem nuclei for startle responses. The ventromedial prefrontal
cortex (vmPFC) inhibits amygdala activity during extinction, with vmPFC-amygdala
connectivity predicting extinction success. The hippocampus provides contextual
information, supporting context-dependent fear expression and extinction (LeDoux,
2000; Maren, 2001).

Potential Threat ("Anxiety"): The anxiety circuit involves the bed nucleus of the stria
terminalis (BNST), extended amygdala, and prefrontal-hippocampal circuits. The BNST
mediates sustained anxiety under uncertainty, while the amygdala mediates phasic fear
to discrete cues. The BNST receives input from the amygdala and projects to
hypothalamus and brainstem, coordinating sustained vigilance and HPA axis activation.
The prefrontal cortex (dlPFC, vmPFC) regulates anxiety through top-down control
(Davis et al., 2010; Grupe & Nitschke, 2013).

Sustained Threat: The HPA axis is central to sustained threat responses. The
paraventricular nucleus (PVN) of the hypothalamus releases corticotropin-releasing
hormone (CRH), stimulating the pituitary to release adrenocorticotropic hormone
(ACTH), which stimulates the adrenal cortex to release cortisol. Cortisol provides
negative feedback to the hippocampus, hypothalamus, and pituitary. Chronic stress
leads to hippocampal atrophy, prefrontal cortex dysfunction, and amygdala hyperactivity
(McEwen, 2007; Ulrich-Lai & Herman, 2009).

2.2.2 Positive Valence Systems Circuitry

Reward Anticipation and Responsiveness: The mesolimbic dopamine pathway is

central to reward processing. Dopamine neurons in the ventral tegmental area (VTA)
project to the nucleus accumbens (ventral striatum), prefrontal cortex, and amygdala.
Dopamine release in the ventral striatum encodes reward prediction errors and
motivates approach behavior. The ventral striatum projects to the ventral pallidum and
mediodorsal thalamus, which project back to prefrontal cortex, forming a
cortico-striatal-thalamic loop. The medial prefrontal cortex (mPFC) and orbitofrontal
cortex (OFC) encode reward value and integrate reward information with goals (Haber
& Knutson, 2010; Schultz, 2016).

Reward Learning: Midbrain dopamine neurons encode reward prediction errors: phasic
firing increases for positive errors (reward better than expected) and decreases for
negative errors (reward worse than expected). These prediction error signals drive
learning in the ventral striatum and prefrontal cortex. With learning, dopamine
responses shift from reward delivery to reward-predicting cues. The dorsal striatum
(caudate, putamen) supports habit formation, with a transition from ventral to dorsal
striatal control with overtraining (Schultz et al., 1997; Yin & Knowlton, 2006).

Reward Valuation: The orbitofrontal cortex (OFC) and ventromedial prefrontal cortex
(vmPFC) encode outcome-specific value, integrating information about reward
magnitude, probability, delay, and effort. The OFC represents expected value and
supports value-based decision-making. The dorsolateral prefrontal cortex (dlPFC)
supports cognitive control during intertemporal choice, competing with limbic valuation
systems (ventral striatum, vmPFC) during delay discounting (McClure et al., 2004;
Knutson & Huettel, 2015).
2.2.3 Cognitive Systems Circuitry

Attention: The dorsal attention network (DAN) includes the dorsolateral prefrontal
cortex (dlPFC), frontal eye fields (FEF), and intraparietal sulcus (IPS). The DAN
supports top-down, goal-directed attention. The ventral attention network (VAN)
includes the temporoparietal junction (TPJ) and ventral frontal cortex (VFC). The VAN
supports bottom-up, stimulus-driven attention and reorienting. The locus
coeruleus-norepinephrine system modulates attention and arousal (Corbetta &
Shulman, 2002; Petersen & Posner, 2012).

Working Memory: The frontoparietal network supports working memory. The

dorsolateral prefrontal cortex (dlPFC) provides executive control, maintaining and
manipulating information. The posterior parietal cortex (PPC) provides storage capacity.
The basal ganglia (particularly the striatum) gate information into working memory.
Content-specific representations are maintained in sensory cortices (e.g., visual cortex
for visual working memory). Theta oscillations (4-8 Hz) in prefrontal cortex coordinate
working memory processes (Baddeley, 2003; D'Esposito & Postle, 2015).

Cognitive Control: The frontoparietal control network includes the dlPFC, anterior
cingulate cortex (ACC), and posterior parietal cortex. The ACC monitors for conflicts
and errors, signaling the need for increased control. The dlPFC implements control by
biasing processing in task-relevant regions. The pre-supplementary motor area
(pre-SMA) and right inferior frontal gyrus (rIFG) support response inhibition, with the
hyperdirect pathway (cortex → subthalamic nucleus → globus pallidus) implementing
rapid stopping (Miller & Cohen, 2001; Aron et al., 2014).

2.2.4 Social Processes Circuitry

Face Processing: The core face processing network includes the fusiform face area
(FFA) for face identity, superior temporal sulcus (STS) for changeable aspects
(expression, gaze), and amygdala for emotional significance. The extended face
processing network includes the anterior temporal cortex for person knowledge and the
inferior frontal gyrus for name retrieval (Haxby et al., 2000).

Theory of Mind / Mentalizing: The mentalizing network includes the medial prefrontal
cortex (mPFC), temporoparietal junction (TPJ), superior temporal sulcus (STS), and
temporal poles. The mPFC represents others' mental states and integrates social
information. The right TPJ is critical for representing others' beliefs that differ from
reality. The STS processes social perception and action understanding. The temporal
poles store social semantic knowledge (Frith & Frith, 2006; Saxe & Kanwisher, 2003).

Mirror Neuron System: The mirror neuron system includes the inferior frontal gyrus
(IFG) and inferior parietal lobule (IPL). Mirror neurons fire both when performing an
action and when observing another perform the same action, supporting action
understanding and imitation. The STS provides visual input to the mirror neuron system
(Rizzolatti & Craighero, 2004).

2.2.5 Arousal and Regulatory Systems Circuitry

Arousal: Ascending arousal systems originate in the brainstem and project to thalamus
and cortex. Key systems include: (1) Locus coeruleus-norepinephrine (LC-NE) for
phasic arousal and attention, (2) Dorsal raphe-serotonin (DR-5HT) for mood and
arousal regulation, (3) Ventral tegmental area-dopamine (VTA-DA) for reward and
motivation, (4) Basal forebrain-acetylcholine (BF-ACh) for cortical activation and
learning. The salience network (dorsal ACC, anterior insula) detects salient stimuli and
modulates arousal (Pfaff, 2006; Sara, 2009).

Sleep-Wake Regulation: The ventrolateral preoptic nucleus (VLPO) promotes sleep by

inhibiting arousal systems. Orexin/hypocretin neurons in the lateral hypothalamus
stabilize wake states. The suprachiasmatic nucleus (SCN) generates circadian rhythms,
entraining to light via retinohypothalamic projections. Adenosine accumulation promotes
sleep pressure. Thalamocortical oscillations generate NREM sleep rhythms (sleep
spindles, slow waves). REM sleep involves reciprocal interactions between REM-on
(cholinergic) and REM-off (aminergic) brainstem nuclei (Saper et al., 2010; McCarley,
2007).

2.2.6 Sensorimotor Systems Circuitry

Motor Control: Motor control involves hierarchical organization. The primary motor
cortex (M1) sends corticospinal projections to spinal motor neurons, producing
movement. The premotor cortex and supplementary motor area (SMA) plan and
prepare movements. The basal ganglia (striatum, globus pallidus, substantia nigra,
subthalamic nucleus) select and initiate actions. The cerebellum coordinates
movements and learns motor sequences. The posterior parietal cortex integrates
sensory feedback with motor commands (Graziano, 2006; Desmurget & Sirigu, 2009).

Agency and Ownership: The posterior parietal cortex, SMA, and cerebellum
implement forward models that predict sensory consequences of actions. Comparison
of predicted and actual sensory feedback generates sense of agency. Discrepancies
signal external agency. The posterior parietal cortex and premotor cortex integrate
multisensory information (visual, tactile, proprioceptive) to generate sense of body
ownership (Haggard, 2017; Tsakiris, 2010).

9. Implementation Roadmap

9.1 Comprehensive RDoC Assessment Protocol

Tier 1: Core Cognitive Assessment (60-90 minutes)

●​ NIH Toolbox Cognition Battery OR CANTAB Brief Battery

 ●​ Covers: Attention, working memory, cognitive control, declarative memory,
language, processing speed

●​ Rationale: Establishes baseline cognitive functioning across all domains

Tier 2: Valence Systems Assessment (30-45 minutes)

●​ Monetary Incentive Delay (MID) Task (10 min) - Reward anticipation/outcome

●​ Fear Conditioning Paradigm (20 min) - Acute threat

●​ Delay Discounting Task (10 min) - Reward valuation

●​ Rationale: Addresses critical gaps in positive and negative valence systems

Tier 3: Social Processes Assessment (20-30 minutes)

●​ Reading the Mind in the Eyes Test (RMET) (10 min) - Theory of mind

●​ Penn Emotion Recognition Test (ER-40) (5 min) - Facial emotion recognition

●​ Biological Motion Task (10 min) - Action perception

●​ Rationale: Comprehensive social cognition assessment

Tier 4: Arousal/Regulatory Assessment (15-20 minutes)

●​ Psychomotor Vigilance Test (PVT) (10 min) - Sustained attention/arousal

●​ Pittsburgh Sleep Quality Index (PSQI) (5 min) - Sleep quality

 ●​ Optional: Actigraphy (7-14 days) - Objective sleep-wake patterns

●​ Rationale: Assesses arousal regulation and sleep-wake function

Tier 5: Advanced/Optional Assessments (30-60 minutes)

●​ NPU-Threat Task (15 min) - Potential threat/anxiety

●​ Probabilistic Reward Task (15 min) - Reward learning

●​ Stop-Signal Task (15 min) - Response inhibition (if not in Tier 1)

●​ Rubber Hand Illusion (10 min) - Agency/ownership

●​ Rationale: Addresses additional gaps based on clinical needs

Total Time:

●​ Minimum (Tiers 1-2): 90-135 minutes (1.5-2.25 hours)

●​ Comprehensive (Tiers 1-4): 125-185 minutes (2-3 hours)

●​ Full (Tiers 1-5): 155-245 minutes (2.5-4 hours)

Recommended Schedule:

●​ Session 1 (90 min): Tier 1 (Core Cognitive)

●​ Session 2 (60 min): Tier 2 (Valence Systems) + Tier 4 (Arousal)

●​ Session 3 (45 min): Tier 3 (Social Processes) + Tier 5 (Optional)

9.2 EEG/ERP Protocol

Equipment: 32-64 channel EEG system, impedances <10 kΩ, sampling rate ≥500 Hz,
online reference (e.g., Cz or average), offline re-referencing to average or mastoids.

Paradigms for ERP Assessment:

1.​ Reward Processing: MID task or Probabilistic Reward Task (RewP, SPN)

2.​ Cognitive Control: Flanker or Go/No-Go task (ERN, Pe, N2, P3)

3.​ Attention: Oddball task (P300)

4.​ Social Cognition: Face emotion recognition (N170, LPP)

5.​ Threat Processing: Fear conditioning (LPP, frontal theta)

Processing Pipeline:

1.​ Preprocessing: Filter (0.1-30 Hz bandpass), artifact rejection (±100 μV

threshold), ICA for eye blink removal

2.​ Epoching: -200 to 800 ms for ERPs, baseline correction (-200 to 0 ms)

3.​ Averaging: Separate averages for each condition, minimum trial counts (ERN:
6-8 errors, RewP: 20-30 rewards, P300: 20-30 targets)

4.​ Measurement: Peak amplitude and latency, or mean amplitude in time window
 5.​ Statistical analysis: Repeated-measures ANOVA, t-tests, correlations with clinical
measures

Total Time: 90-120 minutes (setup, paradigms, cleanup)

9.3 fMRI Protocol

Equipment: 3T MRI scanner, 32-channel head coil, gradient-echo EPI sequence (TR =
2000 ms, TE = 30 ms, flip angle = 90°, voxel size = 3×3×3 mm).

Paradigms for fMRI Assessment:

1.​ Reward Processing: MID task (ventral striatum, VTA, mPFC)

2.​ Cognitive Control: N-back or Stop-Signal Task (dlPFC, ACC, parietal cortex)

3.​ Threat Processing: Fear conditioning (amygdala, vmPFC, hippocampus)

4.​ Social Cognition: Theory of mind or face processing (mPFC, TPJ, STS, FFA)

5.​ Resting State: 6-10 min eyes-open or eyes-closed (functional connectivity)

Processing Pipeline:

1.​ Preprocessing: Motion correction, slice-timing correction, spatial normalization to

MNI space, smoothing (6-8 mm FWHM)

2.​ First-level analysis: GLM with task regressors, motion parameters as nuisance
regressors

3.​ Contrast images: Task vs baseline, condition A vs condition B

 4.​ Second-level analysis: Group analysis, correlations with clinical measures

5.​ ROI analysis: Extract parameter estimates from a priori ROIs (e.g., ventral
striatum, amygdala)

Total Time: 60-90 minutes (setup, structural scan, functional scans, cleanup)

9.4 Clinical Implementation Considerations

Personnel: Trained research assistants or technicians can administer computerized

batteries and EEG/fMRI paradigms. Neuropsychologists or clinical psychologists should
interpret results and integrate with clinical assessment.

Training: 1-2 days training for computerized batteries, 1 week training for EEG (setup,
artifact detection), 1-2 weeks training for fMRI (safety, setup, quality control).

Cost: Computerized batteries: $500-2,000 per license. EEG system: $20,000-100,000.

fMRI: $500-1,000 per hour scanner time. Personnel time: $25-50 per hour for
technicians, $100-200 per hour for neuropsychologists.

Feasibility: Computerized batteries are highly feasible for clinical use. EEG is
moderately feasible (requires equipment and expertise). fMRI is least feasible
(expensive, limited availability, contraindications).

Reimbursement: Neuropsychological testing is reimbursable by insurance (CPT codes

96116, 96121, 96132-96133). EEG is reimbursable for clinical indications (CPT codes
95812-95830). Research fMRI is typically not reimbursable.

10. Clinical Translation and Applications

10.1 Precision Psychiatry

RDoC-aligned assessments support precision psychiatry by identifying biologically valid

dimensions that predict treatment response. For example:

Depression: Blunted ventral striatum activation to reward predicts response to

behavioral activation therapy and antidepressants (Pechtel et al., 2013). Enhanced ERN
predicts response to SSRIs in comorbid anxiety. Reduced RewP predicts anhedonia
severity and treatment resistance.

Anxiety Disorders: Enhanced startle potentiation in NPU-threat task predicts response

to anxiolytics. Impaired fear extinction predicts response to exposure therapy. Enhanced
ERN predicts response to cognitive therapy.

Schizophrenia: Blunted ventral striatum activation predicts negative symptoms and

poor response to antipsychotics (Carruzzo et al., 2024). Cognitive deficits (MCCB)
predict functional outcomes and response to cognitive remediation. Social cognition
deficits predict response to social cognition training (Campos et al., 2016).

ADHD: Longer SSRT predicts response to stimulant medication. Elevated theta/beta

ratio in EEG predicts response to neurofeedback. Steeper delay discounting predicts
impulsivity and treatment adherence.

Autism: Reduced STS activation to biological motion predicts response to social skills
training (Yang et al., 2016, 2017). Reduced social reward responsiveness predicts
treatment outcome (Baker et al., 2021). Theory of mind deficits predict social
functioning.

10.2 Treatment Monitoring

RDoC measures can track treatment response and guide adjustments:

Cognitive Remediation: MCCB or NIH Toolbox track cognitive improvements. N-back

fMRI shows increased dlPFC activation with training. ERP measures (P300, ERN) show
normalization with treatment.

Exposure Therapy: Fear conditioning paradigm tracks extinction learning. Reduced

amygdala activation and increased vmPFC-amygdala connectivity indicate successful
treatment. LPP amplitude reduction indicates reduced threat reactivity.

Behavioral Activation: MID task tracks reward responsiveness. Increased ventral

striatum activation and RewP amplitude indicate treatment response. Probabilistic
Reward Task tracks reward learning improvements.

Social Skills Training: RMET, ER-40, and biological motion tasks track social cognition
improvements. Increased STS and TPJ activation indicate neural changes. N170 and
mu suppression normalization indicate improved social perception.

10.3 Biomarker Development

RDoC measures serve as biomarkers for diagnosis, prognosis, and treatment selection:

Diagnostic Biomarkers: Blunted RewP discriminates depression (sensitivity ~70%,

specificity ~70%). Enhanced ERN discriminates anxiety disorders (sensitivity ~65%,
specificity ~70%). Impaired RMET discriminates autism (sensitivity ~70%, specificity
~70%).

Prognostic Biomarkers: Reduced ventral striatum activation predicts depression

relapse. Impaired fear extinction predicts PTSD chronicity. Cognitive deficits (MCCB)
predict functional outcomes in schizophrenia.
Predictive Biomarkers: Enhanced ERN predicts SSRI response in anxiety. Blunted
reward responsiveness predicts behavioral activation response. Longer SSRT predicts
stimulant response in ADHD.

10.4 Transdiagnostic Applications

RDoC constructs cut across traditional diagnoses, supporting transdiagnostic treatment

approaches:

Anhedonia: Reduced reward responsiveness (blunted ventral striatum, reduced RewP)

occurs in depression, schizophrenia, PTSD, and substance use disorders. Behavioral
activation and dopaminergic medications target this dimension across diagnoses.

Cognitive Control Deficits: Impaired response inhibition (longer SSRT, reduced rIFG
activation) occurs in ADHD, substance use disorders, bipolar disorder, and
schizophrenia. Cognitive training and stimulant medications target this dimension.

Social Cognition Deficits: Impaired theory of mind and emotion recognition occur in
autism, schizophrenia, and personality disorders. Social cognition training targets this
dimension across diagnoses.

Threat Dysregulation: Enhanced threat reactivity (elevated startle, amygdala

hyperactivation) occurs in PTSD, GAD, panic disorder, and social anxiety. Exposure
therapy and anxiolytics target this dimension.

10.5 Future Directions

Machine Learning: Multivariate pattern analysis (MVPA) and machine learning can
integrate multiple RDoC measures to predict diagnosis, prognosis, and treatment
response with greater accuracy than single measures.
Ecological Momentary Assessment (EMA): Smartphone-based EMA can assess
RDoC constructs in daily life, improving ecological validity and capturing dynamic
fluctuations.

Neuroimaging Biomarkers: Advanced fMRI methods (functional connectivity, dynamic

causal modeling, graph theory) can identify circuit-level biomarkers. Multimodal imaging
(fMRI + EEG, fMRI + PET) can link neural activity to neurotransmitter function.

Computational Psychiatry: Computational models (reinforcement learning, Bayesian

inference, drift-diffusion) can quantify latent cognitive processes and identify
mechanistic targets for intervention.

Personalized Medicine: Integration of RDoC measures with genetics, neuroimaging,

and clinical data can enable truly personalized treatment selection and monitoring.

1. Executive Summary

This comprehensive reference document provides a detailed guide to RDoC-aligned

neuropsychological assessment for clinical neuroscientists and neuropsychologists. The
Research Domain Criteria (RDoC) framework represents a paradigm shift from
traditional diagnostic categories toward dimensional, neuroscience-informed constructs.
This document addresses the critical need for comprehensive assessment tools that
span all RDoC domains.

Key Findings:

1.​ Coverage Gaps: Standard neuropsychological batteries (NIH Toolbox, CANTAB,

MCCB, Penn CNB, D-KEFS, CogState) provide excellent coverage of Cognitive
Systems (80-95%) but show significant gaps in Negative Valence (0-5%),
Positive Valence (0-5%), Social Processes (0-40%), Arousal/Regulatory (0-15%),
and Sensorimotor (0-20%) domains.
2.​ Priority Gaps: The most critical gaps are in reward processing (anticipation,
learning, valuation), threat processing (fear conditioning, anxiety), theory of mind,
and arousal regulation. These constructs are central to affective, anxiety,
psychotic, and developmental disorders.

3.​ Experimental Paradigms: Experimental paradigms with robust EEG/ERP and

fMRI correlates can address these gaps. Priority paradigms include: Monetary
Incentive Delay (MID) task for reward, fear conditioning for threat, Reading the
Mind in the Eyes Test (RMET) for theory of mind, and Psychomotor Vigilance
Test (PVT) for arousal.

4.​ Neural Correlates: Comprehensive documentation of EEG/ERP and fMRI

correlates enables mechanistic understanding. Key findings include: ventral
striatum activation during reward anticipation (ICC = 0.40-0.60), amygdala
activation during fear conditioning (d = 0.8-1.5), RewP amplitude for reward
processing (ICC = 0.50-0.70), and ERN amplitude for performance monitoring
(ICC = 0.50-0.75).

5.​ Psychometric Properties: Most RDoC measures show moderate to good

reliability (ICC = 0.50-0.80) and clinical sensitivity (effect sizes d = 0.5-1.5 for
discriminating clinical from healthy populations). Behavioral measures generally
show better reliability than neural measures.

6.​ Clinical Utility: RDoC measures predict treatment response, functional

outcomes, and disease progression. Examples: blunted ventral striatum
activation predicts depression relapse, impaired fear extinction predicts PTSD
chronicity, cognitive deficits predict functional outcomes in schizophrenia, and
biological motion perception predicts treatment response in autism.
 7.​ Implementation: A tiered assessment protocol enables flexible, comprehensive
RDoC assessment. Tier 1 (core cognitive, 60-90 min) + Tier 2 (valence systems,
30-45 min) + Tier 3 (social processes, 20-30 min) + Tier 4 (arousal, 15-20 min)
provides comprehensive coverage in 2-3 hours across 2-3 sessions.

Recommendations:

1.​ Supplement Standard Batteries: Standard batteries should be supplemented

with experimental paradigms addressing valence systems, social processes, and
arousal regulation.

2.​ Prioritize High-Impact Measures: For clinical settings with limited time,
prioritize MID task (reward), fear conditioning (threat), RMET (theory of mind),
and PVT (arousal).

3.​ Integrate Neural Measures: EEG/ERP provides cost-effective neural measures

with good temporal resolution. fMRI provides spatial resolution for circuit-level
assessment. Both enhance mechanistic understanding and biomarker
development.

4.​ Use Computational Models: Computational models (reinforcement learning,

temporal difference learning, drift-diffusion) quantify latent processes and
improve prediction of clinical outcomes.

5.​ Adopt Transdiagnostic Approach: RDoC constructs cut across traditional

diagnoses. Assess dimensional constructs (e.g., anhedonia, cognitive control
deficits, threat dysregulation) rather than focusing solely on diagnostic
categories.
 6.​ Develop Normative Data: Comprehensive normative data across age, sex,
education, and cultural groups are needed for most experimental paradigms.
Large-scale studies (N > 1,000) should establish norms for priority measures.

7.​ Validate Clinical Utility: Prospective studies should validate RDoC measures as
predictive biomarkers for treatment response, functional outcomes, and disease
progression. Incremental validity beyond traditional clinical assessment must be
demonstrated.

8.​ Advance Precision Psychiatry: Integration of RDoC measures with genetics,

neuroimaging, and clinical data can enable personalized treatment selection and
monitoring, moving toward true precision psychiatry.

This document provides the foundation for comprehensive, mechanistic, RDoC-aligned

neuropsychological assessment. By addressing critical gaps in standard batteries and
integrating neural measures, clinicians and researchers can advance understanding of
psychopathology and improve treatment outcomes.

References

Abler, B., Walter, H., & Erk, S. (2005). Neural correlates of frustration. NeuroReport,
16(7), 669-672.

Abdulkarim, Z., & Ehrsson, H. H. (2022). Neural substrates of body ownership and
agency during voluntary movement. bioRxiv. [Link]

Amsel, A. (1992). Frustration theory: An analysis of dispositional learning and memory.

Psychological Review, 99(1), 3-52.

Aron, A. R., Robbins, T. W., & Poldrack, R. A. (2014). Inhibition and the right inferior
frontal cortex: One decade on. Trends in Cognitive Sciences, 18(4), 177-185.
Aston-Jones, G., & Cohen, J. D. (2005). An integrative theory of locus
coeruleus-norepinephrine function: Adaptive gain and optimal performance. Annual
Review of Neuroscience, 28, 403-450.

Aylward, J., Valton, V., Ahn, W. Y., Bond, R. L., Dayan, P., Roiser, J. P., & Robinson, O.
J. (2017). Towards an emotional 'stress test': A reliable, non-subjective cognitive
measure of anxious responding. Scientific Reports, 7, 40094.

Baddeley, A. (2003). Working memory: Looking back and looking forward. Nature
Reviews Neuroscience, 4(10), 829-839.

Baker, E., Veytsman, E., Lui, K. K., Blacher, J., & Stavropoulos, K. K. M. (2021).
Investigating changes in reward-related neural correlates after PEERS intervention in
adolescents with ASD: Preliminary evidence of a "precision medicine" approach.
Frontiers in Psychiatry, 12, 742280.

Bentin, S., Allison, T., Puce, A., Perez, E., & McCarthy, G. (1996). Electrophysiological
studies of face perception in humans. Journal of Cognitive Neuroscience, 8(6), 551-565.

Berridge, K. C. (2009). 'Liking' and 'wanting' food rewards: Brain substrates and roles in
eating disorders. Physiology & Behavior, 97(5), 537-550.

Bledowski, C., Kaiser, J., & Rahm, B. (2010). Basic operations in working memory:
Contributions from functional imaging studies. Behavioural Brain Research, 214(2),
172-179.

Borst, J. P., & Anderson, J. R. (2013). Using model-based functional MRI to locate
working memory updates and declarative memory retrievals in the fronto-parietal
network. Proceedings of the National Academy of Sciences, 110(5), 1628-1633.
Botvinick, M. M., Braver, T. S., Barch, D. M., Carter, C. S., & Cohen, J. D. (2001).
Conflict monitoring and cognitive control. Psychological Review, 108(3), 624-652.

Braun, U., Schaefer, A., Betzel, R. F., Tost, H., Meyer-Lindenberg, A., & Bassett, D. S.
(2021). Brain network dynamics during working memory are modulated by dopamine
and diminished in schizophrenia. Nature Communications, 12, 3478.

Burgess, N., Maguire, E. A., & O'Keefe, J. (2002). The human hippocampus and spatial
and episodic memory. Neuron, 35(4), 625-641.

Campos, C., Santos, S., Gagen, E., Machado, S., Rocha, S., Kurtz, M. M., & Rocha, N.
B. F. (2016). Neuroplastic changes following social cognition training in schizophrenia: A
systematic review. Neuropsychology Review, 26(3), 310-328.

Carruzzo, F., Colic, L., Li, M., Woelfer, M., Goltermann, J., Meinert, S., Enneking, V.,
Emden, D., Grotegerd, D., Redlich, R., Dohm, K., Leehr, E. J., Repple, J., Opel, N.,
Mauritz, M., Bauer, J., Heindel, W., Gross, J., Dannlowski, U., & Walter, M. (2024).
Striatal response to reward anticipation as a biomarker for schizophrenia and negative
symptoms: Effects, test-retest reliability, and stability across sites. Schizophrenia
Bulletin, 50(3), 690-701.

Castelli, F., Happé, F., Frith, U., & Frith, C. (2000). Movement and mind: A functional
imaging study of perception and interpretation of complex intentional movement
patterns. NeuroImage, 12(3), 314-325.

Cicchetti, D. V. (1994). Guidelines, criteria, and rules of thumb for evaluating normed
and standardized assessment instruments in psychology. Psychological Assessment,
6(4), 284-290.

Cisek, P., & Kalaska, J. F. (2010). Neural mechanisms for interacting with a world full of
action choices. Annual Review of Neuroscience, 33, 269-298.
Clayson, P. E., Baldwin, S. A., & Larson, M. J. (2013). Psychometric properties of
conflict monitoring and conflict adaptation indices: Response time and conflict N2
event-related potentials. Psychophysiology, 50(12), 1209-1219.

Clayson, P. E., Carbine, K. A., Baldwin, S. A., Olsen, J. A., & Larson, M. J. (2023).
Registered replication report of the construct validity of the error-related negativity
(ERN): A multi-site study of task-specific ERN correlations with internalizing and
externalizing symptoms. Psychophysiology, 60(12), e14496.

Cochran, D. M., Dvir, Y., & Frazier, J. A. (2023). Social cognition: Novel methods of
assessment and biomarker-driven pharmacological treatment. Journal of the American
Academy of Child & Adolescent Psychiatry, 62(10), S164.

Cole, M. W., & Schneider, W. (2007). The cognitive control network: Integrated cortical
regions with dissociable functions. NeuroImage, 37(1), 343-360.

Corbetta, M., Patel, G., & Shulman, G. L. (2008). The reorienting system of the human
brain: From environment to theory of mind. Neuron, 58(3), 306-324.

Corbetta, M., & Shulman, G. L. (2002). Control of goal-directed and stimulus-driven

attention in the brain. Nature Reviews Neuroscience, 3(3), 201-215.

Cowan, N. (2001). The magical number 4 in short-term memory: A reconsideration of

mental storage capacity. Behavioral and Brain Sciences, 24(1), 87-114.

Croxson, P. L., Walton, M. E., O'Reilly, J. X., Behrens, T. E. J., & Rushworth, M. F. S.
(2009). Effort-based cost-benefit valuation and the human brain. Journal of
Neuroscience, 29(14), 4531-4541.
Curtis, C. E., & D'Esposito, M. (2003). Persistent activity in the prefrontal cortex during
working memory. Trends in Cognitive Sciences, 7(9), 415-423.

Cuthbert, B. N., & Insel, T. R. (2013). Toward the future of psychiatric diagnosis: The
seven pillars of RDoC. BMC Medicine, 11, 126.

Davis, M., Walker, D. L., Miles, L., & Grillon, C. (2010). Phasic vs sustained fear in rats
and humans: Role of the extended amygdala in fear vs anxiety.
Neuropsychopharmacology, 35(1), 105-135.

DelDonno, S. R., Mickey, B. J., Pruitt, P. J., Stange, J. P., Hsu, D. T., Weldon, A. L.,
Zubieta, J. K., & Langenecker, S. A. (2019). The titrated monetary incentive delay task:
Sensitivity, convergent and divergent validity, and neural correlates in an RDoC sample.
Journal of Clinical and Experimental Neuropsychology, 41(5), 512-526.

Depue, R. A., & Collins, P. F. (1999). Neurobiology of the structure of personality:

Dopamine, facilitation of incentive motivation, and extraversion. Behavioral and Brain
Sciences, 22(3), 491-517.

Depue, R. A., & Morrone-Strupinsky, J. V. (2005). A neurobehavioral model of affiliative

bonding: Implications for conceptualizing a human trait of affiliation. Behavioral and
Brain Sciences, 28(3), 313-350.

Desimone, R., & Duncan, J. (1995). Neural mechanisms of selective visual attention.
Annual Review of Neuroscience, 18, 193-222.

Desmurget, M., & Sirigu, A. (2009). A parietal-premotor network for movement intention
and motor awareness. Trends in Cognitive Sciences, 13(10), 411-419.

D'Esposito, M., & Postle, B. R. (2015). The cognitive neuroscience of working memory.
Annual Review of Psychology, 66, 115-142.
Driver, J., & Noesselt, T. (2008). Multisensory interplay reveals crossmodal influences
on 'sensory-specific' brain regions, neural responses, and judgments. Neuron, 57(1),
11-23.

Duffy, K. A., Roecklein, K. A., Keedy, S. K., Pollock, M. H., Miewald, J. M., Erickson, M.
A., Tam, F., Geisler, M. W., Franzen, P. L., & Verstynen, T. D. (2024). Psychometric
evaluation of cognitive and positive valence tasks chosen for the NIMH Research
Domain Criteria Project. Assessment, 31(7), 1573-1589.

Eichenbaum, H., Yonelinas, A. P., & Ranganath, C. (2007). The medial temporal lobe
and recognition memory. Annual Review of Neuroscience, 30, 123-152.

Eshel, N., & Roiser, J. P. (2010). Reward and punishment processing in depression.
Biological Psychiatry, 68(2), 118-124.

Fan, J., McCandliss, B. D., Sommer, T., Raz, A., & Posner, M. I. (2002). Testing the
efficiency and independence of attentional networks. Journal of Cognitive
Neuroscience, 14(3), 340-347.

Feldman, R. (2012). Oxytocin and social affiliation in humans. Hormones and Behavior,
61(3), 380-391.

Feola, B., Beeler, B. J., Rieselbach, M. M., Crowell, S. E., Mayes, T. L., & Minhajuddin,
A. (2023). Altered bed nucleus of the stria terminalis and amygdala responses to threat
in combat veterans with posttraumatic stress disorder. Journal of Traumatic Stress,
36(3), 524-535.

Frank, M. J., Loughry, B., & O'Reilly, R. C. (2001). Interactions between frontal cortex
and basal ganglia in working memory: A computational model. Cognitive, Affective, &
Behavioral Neuroscience, 1(2), 137-160.
Friederici, A. D. (2011). The brain basis of language processing: From structure to
function. Physiological Reviews, 91(4), 1357-1392.

Frith, C. D., & Frith, U. (2006). The neural basis of mentalizing. Neuron, 50(4), 531-534.

Geraldo, A., Azeredo, A., Pasion, R., Dores, A. R., & Barbosa, F. (2019). Fostering
advances to neuropsychological assessment based on the Research Domain Criteria:
The bridge between cognitive functioning and physiology. The Clinical
Neuropsychologist, 33(2), 327-356.

Goodale, M. A., & Milner, A. D. (1992). Separate visual pathways for perception and
action. Trends in Neurosciences, 15(1), 20-25.

Graybiel, A. M. (2008). Habits, rituals, and the evaluative brain. Annual Review of
Neuroscience, 31, 359-387.

Gray, J. A., & McNaughton, N. (2000). The neuropsychology of anxiety: An enquiry into
the functions of the septo-hippocampal system (2nd ed.). Oxford University Press.

Graziano, M. (2006). The organization of behavioral repertoire in motor cortex. Annual

Review of Neuroscience, 29, 105-134.

Grillner, S. (2006). Biological pattern generation: The cellular and computational logic of
networks in motion. Neuron, 52(5), 751-766.

Grupe, D. W., & Nitschke, J. B. (2013). Uncertainty and anticipation in anxiety: An

integrated neurobiological and psychological perspective. Nature Reviews
Neuroscience, 14(7), 488-501.
Haber, S. N., & Knutson, B. (2010). The reward circuit: Linking primate anatomy and
human imaging. Neuropsychopharmacology, 35(1), 4-26.

Hackett, K., Mis, R., Drabick, D., & Giovannetti, T. (2018). Utility of the NIH Toolbox for
assessment of prodromal Alzheimer's disease and dementia. Alzheimer's & Dementia:
Diagnosis, Assessment & Disease Monitoring, 10, 764-772.

Hägele, C., Schlagenhauf, F., Rapp, M., Sterzer, P., Beck, A., Bermpohl, F., Stoy, M.,
Ströhle, A., Wittchen, H. U., Dolan, R. J., & Heinz, A. (2015). Dimensional psychiatry:
Reward dysfunction and depressive mood across psychiatric disorders.
Psychopharmacology, 232(2), 331-341.

Haggard, P. (2017). Sense of agency in the human brain. Nature Reviews

Neuroscience, 18(4), 196-207.

Haxby, J. V., Hoffman, E. A., & Gobbini, M. I. (2000). The distributed human neural
system for face perception. Trends in Cognitive Sciences, 4(6), 223-233.

Hickok, G., & Poeppel, D. (2007). The cortical organization of speech processing.
Nature Reviews Neuroscience, 8(5), 393-402.

Holroyd, C. B., & Coles, M. G. H. (2002). The neural basis of human error processing:
Reinforcement learning, dopamine, and the error-related negativity. Psychological
Review, 109(4), 679-709.

Insel, T., Cuthbert, B., Garvey, M., Heinssen, R., Pine, D. S., Quinn, K., Sanislow, C., &
Wang, P. (2010). Research Domain Criteria (RDoC): Toward a new classification
framework for research on mental disorders. American Journal of Psychiatry, 167(7),
748-751.
Insel, T. R., & Young, L. J. (2001). The neurobiology of attachment. Nature Reviews
Neuroscience, 2(2), 129-136.

Izgi, H. B., Eryilmaz, G., Medalia, A., & Bora, E. (2021). Test-retest reliability of the
Turkish translation of the Penn Computerized Neurocognitive Battery. Applied
Neuropsychology: Adult, 28(6), 761-768.

Jack, A., Englander, Z. A., & Morris, J. P. (2017). Cerebellar contributions to biological
motion perception in autism and typical development. Human Brain Mapping, 38(4),
1914-1932.

Johannesen, J. K., Fiszdon, J. M., Weinstein, A., Ciosek, D., & Bell, M. D. (2018). The
Social Attribution Task - Multiple Choice (SAT-MC): Psychometric comparison with
social cognitive measures for schizophrenia research. Psychiatry Research, 262,
154-161.

Jonides, J., Lewis, R. L., Nee, D. E., Lustig, C. A., Berman, M. G., & Moore, K. S.
(2008). The mind and brain of short-term memory. Annual Review of Psychology, 59,
193-224.

Jonides, J., & Nee, D. E. (2006). Brain mechanisms of proactive interference in working
memory. Neuroscience, 139(1), 181-193.

Kang, E., Keifer, C. M., Levy, E. J., Foss-Feig, J. H., McPartland, J. C., & Lerner, M. D.
(2018). Atypicality of the N170 event-related potential in autism spectrum disorder: A
meta-analysis. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, 3(8),
657-666.

Keisker, B., Hepp-Reymond, M. C., Blickenstorfer, A., Meyer, M., & Kollias, S. S. (2009).
Differential force scaling of fine-graded power grip force in the sensorimotor network.
Human Brain Mapping, 30(8), 2453-2465.
Keisker, B., Hepp-Reymond, M. C., Blickenstorfer, A., & Kollias, S. S. (2010). Differential
representation of dynamic and static power grip force in the sensorimotor network.
European Journal of Neuroscience, 31(8), 1483-1491.

Klumpp, H., Kinney, K. L., Kennedy, A. E., Shankman, S. A., Langenecker, S. A.,
Kumar, A., & Phan, K. L. (2018). Using event-related potentials and startle to evaluate
time course in anxiety and depression. Biological Psychiatry: Cognitive Neuroscience
and Neuroimaging, 3(1), 10-18.

Knutson, B., Adams, C. M., Fong, G. W., & Hommer, D. (2001). Anticipation of
increasing monetary reward selectively recruits nucleus accumbens. Journal of
Neuroscience, 21(16), RC159.

Knutson, B., & Huettel, S. A. (2015). The risk matrix. Current Opinion in Behavioral
Sciences, 5, 141-146.

Kochan, N. A., Bunce, D., Pont, S., Crawford, J. D., Brodaty, H., & Sachdev, P. S.
(2022). Reliability, validity, and user-experience of remote unsupervised computerized
neuropsychological assessments in community-living 55 to 75-year-olds. Journal of
Alzheimer's Disease, 90(3), 1135-1153.

Korucuoglu, O., Harms, M. P., Kennedy, J. T., Golosheykin, S., Astafiev, S. V., Barch, D.
M., & Anokhin, A. P. (2021). Test-retest reliability of neural correlates of response
inhibition and error monitoring: An fMRI study of a stop-signal task. Frontiers in
Neuroscience, 15, 624911.

Kranczioch, C., Mathews, S., Dean, P. J. A., & Sterr, A. (2009). On the equivalence of
executed and imagined movements: Evidence from lateralized motor and nonmotor
potentials. Human Brain Mapping, 30(10), 3275-3286.
Kurniawan, I. T., Seymour, B., Talmi, D., Yoshida, W., Chater, N., & Dolan, R. J. (2011).
Choosing to make an effort: The role of striatum in signaling physical effort of a chosen
action. Journal of Neurophysiology, 104(1), 313-321.

Langner, R., & Eickhoff, S. B. (2013). Sustaining attention to simple tasks: A

meta-analytic review of the neural mechanisms of vigilant attention. Psychological
Bulletin, 139(4), 870-900.

LeDoux, J. E. (2000). Emotion circuits in the brain. Annual Review of Neuroscience, 23,
155-184.

Letkiewicz, A. M., Cochran, A. L., & Cisler, J. M. (2021). Value estimation and
latent-state update-related neural activity during fear conditioning predict posttraumatic
stress disorder symptom severity. Cognitive, Affective, & Behavioral Neuroscience,
21(6), 1247-1261.

Loose, R., Kaufmann, C., Auer, D. P., & Lange, K. W. (2003). Human prefrontal and
sensory cortical activity during divided attention tasks. Human Brain Mapping, 18(4),
249-259.

Manoach, D. S., Halpern, E. F., Kramer, T. S., Chang, Y., Goff, D. C., Rauch, S. L.,
Kennedy, D. N., & Gollub, R. L. (2001). Test-retest reliability of a functional MRI working
memory paradigm in normal and schizophrenic subjects. American Journal of
Psychiatry, 158(6), 955-958.

Maren, S. (2001). Neurobiology of Pavlovian fear conditioning. Annual Review of

Neuroscience, 24, 897-931.

Marin, M. F., Hammoud, M. Z., Klumpp, H., Simon, N. M., & Milad, M. R. (2020).
Multimodal categorical and dimensional approaches to understanding threat
conditioning and its extinction in individuals with anxiety disorders. JAMA Psychiatry,
77(6), 618-627.

McCarley, R. W. (2007). Neurobiology of REM and NREM sleep. Sleep Medicine, 8(4),
302-330.

McClure, S. M., Laibson, D. I., Loewenstein, G., & Cohen, J. D. (2004). Separate neural
systems value immediate and delayed monetary rewards. Science, 306(5695), 503-507.

McEwen, B. S. (2007). Physiology and neurobiology of stress and adaptation: Central

role of the brain. Physiological Reviews, 87(3), 873-904.

Mei, S., Zheng, Y., Zhao, Y., Ding, C., & Luo, Y. J. (2024). Exploring the 'black box' of
anxiety: An ERP study of non-consciously triggered fear generalization. Behaviour
Research and Therapy, 177, 104552.

Miller, E. K., & Cohen, J. D. (2001). An integrative theory of prefrontal cortex function.
Annual Review of Neuroscience, 24, 167-202.

Mittal, V. A., Wakschlag, L. S., Keating, D. P., Corlett, P. R., Karlsgodt, K. H., & Patel, A.
X. (2022). Research domain criteria (RDoC) grows up: Strengthening
neurodevelopmental investigation within the RDoC framework. Biological Psychiatry,
92(5), 343-352.

Nachev, P., Kennard, C., & Husain, M. (2008). Functional role of the supplementary and
pre-supplementary motor areas. Nature Reviews Neuroscience, 9(11), 856-869.

Nelson, B. D., McGowan, S. K., Sarapas, C., Robison-Andrew, E. J., Altman, S. E.,
Campbell, M. L., Gorka, S. M., Katz, A. C., & Shankman, S. A. (2015). Anxiety
sensitivity and the anticipation of predictable and unpredictable threat: Evidence from
the startle response and event-related potentials. Journal of Anxiety Disorders, 33,
62-71.

Northoff, G., Heinzel, A., de Greck, M., Bermpohl, F., Dobrowolny, H., & Panksepp, J.
(2006). Self-referential processing in our brain—A meta-analysis of imaging studies on
the self. NeuroImage, 31(1), 440-457.

Nuechterlein, K. H., Barch, D. M., Gold, J. M., Goldberg, T. E., Green, M. F., & Heaton,
R. K. (2004). Identification of separable cognitive factors in schizophrenia.
Schizophrenia Research, 72(1), 29-39.

Nuechterlein, K. H., Green, M. F., Kern, R. S., Baade, L. E., Barch, D. M., Cohen, J. D.,
Essock, S., Fenton, W. S., Frese, F. J., Gold, J. M., Goldberg, T., Heaton, R. K., Keefe,
R. S. E., Kraemer, H., Mesholam-Gately, R., Seidman, L. J., Stover, E., Weinberger, D.
R., Young, A. S., ... Marder, S. R. (2008). The MATRICS Consensus Cognitive Battery,
part 1: Test selection, reliability, and validity. American Journal of Psychiatry, 165(2),
203-213.

Nuechterlein, K. H., Ventura, J., McEwen, S. C., Gretchen-Doorly, D., Vinogradov, S., &
Subotnik, K. L. (2022). The MATRICS consensus cognitive battery: An update. In T.
Wykes, N. Reeder, & J. Corner (Eds.), Cognitive remediation for psychological
disorders: Therapist guide (pp. 51-90). Springer.

Ord, A. S., Shura, R. D., Sansone, A. R., Martindale, S. L., Rowland, J. A., Miskey, H.
M., & Taber, K. H. (2021). Examining embedded validity indicators in Conners
Continuous Performance Test-3 (CPT-3). The Clinical Neuropsychologist, 35(7),
1426-1441.

Panksepp, J. (2003). Feeling the pain of social loss. Science, 302(5643), 237-239.
Passell, E., Dillon, D. G., Baker, J. T., Vogel, S. C., Scheuer, L. S., Mirin, N. L., Germine,
L., & Ressler, K. J. (2019). Digital cognitive assessment: Results from the TestMyBrain
NIMH Research Domain Criteria (RDoC) field test battery report. PsyArXiv.
[Link]

Patel, G. H., Arkin, S. C., Ruiz-Betancourt, D. R., Plaza, P., Mirza, S. A., Vieira, B.,
Yeung, N., Diwadkar, V. A., & Brucato, G. (2021). Failure to engage the temporoparietal
junction/posterior superior temporal sulcus predicts impaired naturalistic social cognition
in schizophrenia. Brain, 144(4), 1898-1910.

Patterson, K., Nestor, P. J., & Rogers, T. T. (2007). Where do you know what you know?
The representation of semantic knowledge in the human brain. Nature Reviews
Neuroscience, 8(12), 976-987.

Pechtel, P., Dutra, S. J., Goetz, E. L., & Pizzagalli, D. A. (2013). Blunted reward
responsiveness in remitted depression. Journal of Psychiatric Research, 47(12),
1864-1869.

Peelen, M. V., & Downing, P. E. (2007). The neural basis of visual body perception.
Nature Reviews Neuroscience, 8(8), 636-648.

Peters, J., & Büchel, C. (2011). The neural mechanisms of inter-temporal

decision-making: Understanding variability. Trends in Cognitive Sciences, 15(5),
227-239.

Petersen, S. E., & Posner, M. I. (2012). The attention system of the human brain: 20
years after. Annual Review of Neuroscience, 35, 73-89.

Pfaff, D. W. (2006). Brain arousal and information theory: Neural and genetic
mechanisms. Harvard University Press.
Pilkonis, P. A., Choi, S. W., Reise, S. P., Stover, A. M., Riley, W. T., & Cella, D. (2011).
Item banks for measuring emotional distress from the Patient-Reported Outcomes
Measurement Information System (PROMIS®): Depression, anxiety, and anger.
Assessment, 18(3), 263-283.

Pilkonis, P. A., Yu, L., Dodds, N. E., Johnston, K. L., Maihoefer, C. C., & Lawrence, S.
M. (2013). Assessment of self-reported negative affect in the NIH Toolbox. Psychiatry
Research, 206(1), 88-97.

Pinkham, A. E., Harvey, P. D., & Penn, D. L. (2016). Social cognition psychometric
evaluation: Results of the initial psychometric study. Schizophrenia Bulletin, 42(2),
494-504.

Pinkham, A. E., Harvey, P. D., & Penn, D. L. (2018). Social cognition psychometric
evaluation: Results of the final validation study. Schizophrenia Bulletin, 44(4), 737-748.

Pizzagalli, D. A. (2014). Depression, stress, and anhedonia: Toward a synthesis and

integrated model. Annual Review of Clinical Psychology, 10, 393-423.

Proudfit, G. H. (2015). The reward positivity: From basic research on reward to a

biomarker for depression. Psychophysiology, 52(4), 449-459.

Raduà, J., Albajes-Eizagirre, A., Weyde, K. V. F., Ioannidis, J. P. A., Arnone, D., Brandt,
C. L., Bøen, E., Sørensen, L., Radua, J., Albajes-Eizagirre, A., Weyde, K. V. F.,
Ioannidis, J. P. A., Arnone, D., Brandt, C. L., Bøen, E., Sørensen, L., Engstrøm, M.,
Hugdahl, K., Korsnes, M. S., ... Westlye, L. T. (2025). Neural correlates of human fear
conditioning and sources of variability in 2199 individuals. Nature Communications, 16,
1.
Rauschecker, J. P., & Scott, S. K. (2009). Maps and streams in the auditory cortex:
Nonhuman primates illuminate human speech processing. Nature Neuroscience, 12(6),
718-724.

Reppert, S. M., & Weaver, D. R. (2002). Coordination of circadian timing in mammals.

Nature, 418(6901), 935-941.

Rescorla, R. A. (1976). Stimulus generalization: Some predictions from a model of

Pavlovian conditioning. Journal of Experimental Psychology: Animal Behavior
Processes, 2(1), 88-96.

Rinn, W. E. (1984). The neuropsychology of facial expression: A review of the

neurological and psychological mechanisms for producing facial expressions.
Psychological Bulletin, 95(1), 52-77.

Rizzolatti, G., & Craighero, L. (2004). The mirror-neuron system. Annual Review of
Neuroscience, 27, 169-192.

Rolls, E. T. (2016). Reward systems in the brain and nutrition. Annual Review of
Nutrition, 36, 435-470.

Sakai, K. (2008). Task set and prefrontal cortex. Annual Review of Neuroscience, 31,
219-245.

Saper, C. B., Fuller, P. M., Pedersen, N. P., Lu, J., & Scammell, T. E. (2010). Sleep state
switching. Neuron, 68(6), 1023-1042.

Saper, C. B., Scammell, T. E., & Lu, J. (2005). Hypothalamic regulation of sleep and
circadian rhythms. Nature, 437(7063), 1257-1263.
Sara, S. J. (2009). The locus coeruleus and noradrenergic modulation of cognition.
Nature Reviews Neuroscience, 10(3), 211-223.

Saxe, R., & Kanwisher, N. (2003). People thinking about thinking people: The role of the
temporo-parietal junction in "theory of mind". NeuroImage, 19(4), 1835-1842.

Schneider, M. (2018). Simultaneous pupillometry and functional magnetic resonance

imaging (fMRI) for the detection of stress-related endophenotypes [Doctoral
dissertation]. University of Zurich.

Schott, B. H., Minuzzi, L., Krebs, R. M., Elmenhorst, D., Lang, M., Winz, O. H.,
Seidenbecher, C. I., Coenen, H. H., Heinze, H. J., Zilles, K., Düzel, E., & Bauer, A.
(2008). Mesolimbic functional magnetic resonance imaging activations during reward
anticipation correlate with reward-related ventral striatal dopamine release. Journal of
Neuroscience, 28(52), 14311-14319.

Schultz, W. (2016). Dopamine reward prediction error coding. Dialogues in Clinical

Neuroscience, 18(1), 23-32.

Schultz, W., Dayan, P., & Montague, P. R. (1997). A neural substrate of prediction and
reward. Science, 275(5306), 1593-1599.

Scott, E. P., Sorrell, A., & Benitez, A. (2019). Psychometric properties of the NIH
Toolbox Cognition Battery in healthy older adults: Reliability, validity, and agreement
with standard neuropsychological tests. Journal of the International Neuropsychological
Society, 25(9), 857-867.

Squire, L. R., & Zola-Morgan, S. (1991). The medial temporal lobe memory system.
Science, 253(5026), 1380-1386.
Strathearn, L., Fonagy, P., Amico, J., & Montague, P. R. (2009). Adult attachment
predicts maternal brain and oxytocin response to infant cues.
Neuropsychopharmacology, 34(13), 2655-2666.

Suarez-Jimenez, B., Albajes-Eizagirre, A., Lazarov, A., Zhu, X., Harrison, B. J., Radua,
J., Neria, Y., & Fullana, M. A. (2020). Neural signatures of conditioning, extinction
learning, and extinction recall in posttraumatic stress disorder: A meta-analysis of
functional magnetic resonance imaging studies. Psychological Medicine, 50(9),
1442-1451.

Sutton, R. S., & Barto, A. G. (1998). Reinforcement learning: An introduction. MIT

Press.

Todd, J. J., & Marois, R. (2004). Capacity limit of visual short-term memory in human
posterior parietal cortex. Nature, 428(6984), 751-754.

Tsakiris, M. (2010). My body in the brain: A neurocognitive model of body-ownership.

Neuropsychologia, 48(3), 703-712.

Tulving, E. (2002). Episodic memory: From mind to brain. Annual Review of

Psychology, 53, 1-25.

Tzovara, A., Korn, C. W., & Bach, D. R. (2018). Human Pavlovian fear conditioning
conforms to probabilistic learning. PLOS Computational Biology, 14(8), e1006243.

Ulrich-Lai, Y. M., & Herman, J. P. (2009). Neural regulation of endocrine and autonomic
stress responses. Nature Reviews Neuroscience, 10(6), 397-409.

Ungerleider, L. G., & Mishkin, M. (1982). Two cortical visual systems. In D. J. Ingle, M.
A. Goodale, & R. J. W. Mansfield (Eds.), Analysis of visual behavior (pp. 549-586). MIT
Press.
Weintraub, S., Dikmen, S. S., Heaton, R. K., Tulsky, D. S., Zelazo, P. D., Bauer, P. J.,
Carlozzi, N. E., Slotkin, J., Blitz, D., Wallner-Allen, K., Fox, N. A., Beaumont, J. L.,
Mungas, D., Nowinski, C. J., Richler, J., Deocampo, J. A., Anderson, J. E., Manly, J. J.,
Borosh, B., ... Gershon, R. C. (2013). Cognition assessment using the NIH Toolbox.
Neurology, 80(11 Suppl 3), S54-S64.

Weintraub, S., Dikmen, S. S., Heaton, R. K., Tulsky, D. S., Zelazo, P. D., Slotkin, J.,
Carlozzi, N. E., Bauer, P. J., Wallner-Allen, K., Fox, N., Havlik, R., Beaumont, J. L.,
Mungas, D., Manly, J. J., Moy, C., Conway, K., Edwards, E., Nowinski, C. J., & Gershon,
R. (2014). The cognition battery of the NIH Toolbox for assessment of neurological and
behavioral function: Validation in an adult sample. Journal of the International
Neuropsychological Society, 20(6), 567-578.

Whitton, A. E., Treadway, M. T., & Pizzagalli, D. A. (2015). Reward processing

dysfunction in major depression, bipolar disorder and schizophrenia. Current Opinion in
Psychiatry, 28(1), 7-12.

Whitton, A. E., Kakani, P., Foti, D., Van't Veer, A., Haile, A., Crowley, D. J., Pizzagalli, D.
A., & Janes, A. C. (2016). Blunted neural responses to reward in remitted major
depression: A high-density event-related potential study. Biological Psychiatry:
Cognitive Neuroscience and Neuroimaging, 1(1), 87-95.

Wildgruber, D., Ackermann, H., Kreifelts, B., & Ethofer, T. (2006). Cerebral processing of
linguistic and emotional prosody: fMRI studies. Progress in Brain Research, 156,
249-268.

Willems, R. M., & Hagoort, P. (2007). Neural evidence for the interplay between
language, gesture, and action: A review. Brain and Language, 101(3), 278-289.
Wolpert, D. M., Ghahramani, Z., & Jordan, M. I. (1995). An internal model for
sensorimotor integration. Science, 269(5232), 1880-1882.

Yang, Y. J. D., Sukhodolsky, D. G., Lei, J., Dayan, E., Pelphrey, K. A., & Ventola, P.
(2017). Brain responses to biological motion predict treatment outcome in young adults
with autism receiving Virtual Reality Social Cognition Training: Preliminary findings.
Behaviour Research and Therapy, 93, 55-66.

Yang, Y. J. D., Allen, T., Abdullahi, S. M., Pelphrey, K. A., Volkmar, F. R., & Chapman, S.
B. (2017). Brain responses to biological motion predict treatment outcome in young
children with autism. Translational Psychiatry, 6(11), e948.

Yau, J. O. Y., & McNally, G. P. (2023). The Rescorla-Wagner model, prediction error,
and fear learning. Neurobiology of Learning and Memory, 204, 107799.

Yin, H. H., & Knowlton, B. J. (2006). The role of the basal ganglia in habit formation.
Nature Reviews Neuroscience, 7(6), 464-476.