Extraversion Is Linked to Volume of the Orbitofrontal

Cortex and Amygdala

Henk Cremers1,2*., Marie-José van Tol2,3,4., Karin Roelofs1,2, Andre Aleman4, Frans G. Zitman3, Mark A.
van Buchem2,5, Dick J. Veltman6, Nic J. A. van der Wee2,3
1 Institute for Psychological Research, Clinical, Health and Neuropsychology Unit, Leiden University, Leiden, The Netherlands, 2 Leiden Institute for Brain and Cognition,
Leiden University, Leiden, The Netherlands, 3 Department of Psychiatry, Leiden University Medical Center, Leiden, The Netherlands, 4 BCN Neuroimaging Center,
University Medical Center Groningen, University of Groningen, Groningen, The Netherlands, 5 Department of Radiology, Leiden University Medical Center, Leiden, The
Netherlands, 6 Department of Psychiatry, VU University Medical Center, Amsterdam, The Netherlands

Abstract
Neuroticism and extraversion are personality factors associated with the vulnerability for developing depression and anxiety
disorders, and are possibly differentially related to brain structures implicated in the processing of emotional information
and the generation of mood states. To date, studies on brain morphology mainly focused on neuroticism, a dimension
primarily related to negative affect, yielding conflicting findings concerning the association with personality, partially due to
methodological issues and variable population samples under study. Recently, extraversion, a dimension primarily related to
positive affect, has been repeatedly inversely related to with symptoms of depression and anxiety disorders. In the present
study, high resolution structural T1-weighted MR images of 65 healthy adults were processed using an optimized Voxel
Based Morphometry (VBM) approach. Multiple regression analyses were performed to test for associations of neuroticism
and extraversion with prefrontal and subcortical volumes. Orbitofrontal and right amygdala volume were both positively
related to extraversion. Extraversion was differentially related to volume of the anterior cingulate cortex in males (positive)
and females (negative). Neuroticism scores did not significantly correlate with these brain regions. As extraversion is
regarded a protective factor for developing anxiety disorders and depression and has been related to the generation of
positive affect, the present results indicate that the reduced likelihood of developing affective disorders in individuals high
on extraversion is related to modulation of emotion processing through the orbitofrontal cortex and the amygdala.

Citation: Cremers H, van Tol M-J, Roelofs K, Aleman A, Zitman FG, et al. (2011) Extraversion Is Linked to Volume of the Orbitofrontal Cortex and Amygdala. PLoS
ONE 6(12): e28421. doi:10.1371/[Link].0028421
Editor: Angela Sirigu, French National Centre for Scientific Research, France
Received January 25, 2011; Accepted November 8, 2011; Published December 9, 2011
Copyright: ß 2011 Cremers et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: Henk Cremers and Karin Roelofs are supported by the Netherlands Organization of Scientific Research (NWO), VIDI grant #452-07-008. The
infrastructure for the NESDA study ([Link]) is funded through the Geestkracht program of the Netherlands Organisation for Health Research and
Development (Zon-Mw, grant number 10-000-1002) and is supported by participating universities and mental health care organizations (VU University Medical
Center, GGZ inGeest, Arkin, Leiden University Medical Center, GGZ Rivierduinen, University Medical Center Groningen, Lentis, GGZ Friesland, GGZ Drenthe,
Scientific Institute for Quality of Healthcare (IQ healthcare), Netherlands Institute for Health Services Research (NIVEL) and Netherlands Institute of Mental Health
and Addiction (Trimbos Institute). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing Interests: Author Andre Aleman is an Academic Editor at PLoS.
* E-mail: cremershr@[Link]
. These authors contributed equally to this work.

Introduction emotional information, and hence, in vulnerability to mood and

anxiety disorders. On a functional level, it has previously been
Neuroticism and extraversion are personality factors that have shown that neuroticism modulates neural activity in prefrontal and
been directly linked to emotional states: neuroticism has been subcortical brain regions related to affective processing [5,6].
associated with susceptibility to negative emotional states, whereas Neuroticism has been related to more amygdala activation in
extraversion has been linked to susceptibility to positive emotional response to distracting negative facial expressions during a
states [1]. Also, neuroticism correlates positively, whereas cognitive task [7], and to less anterior cingulate cortex (ACC)–
extraversion correlates negatively, with (subsyndromal) symptoms amygdala connectivity during processing of negative emotional
of depression and anxiety in the general population [2]. Other facial expressions [5]. Extraversion on the other hand, was found
personality traits, such as agreeableness, openness to experiences, to be positively associated with amygdala activation in response to
and conscientiousness, have been proposed to play a more indirect happy faces [8]. Together, these findings indicate that core brain
role in influencing affective states [1]. Consequently, neuroticism structures involved in emotion processing (e.g. the amygdala, the
and extraversion may respectively put one at risk for [3,4] or anterior cingulate gyrus, and the ventral part of the prefrontal
protect one against [3] development of affective disorders such as cortex including the orbitofrontal cortex (OFC)) may play a role in
depression, panic disorder and social anxiety disorder. the relation between personality, the processing of emotional
More insight into the relation between personality and brain information, and the production of mood states [9].
regions associated with emotion processing and regulation may Structural variation might underlie the relation between
help to illuminate how personality is involved in the processing of personality and activity in brain regions related to emotion

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 Extraversion Is Linked to Brain Volume

perception and appraisal. In an adolescent sample, a positive Amsterdam, and University Medical Center Groningen (UMCG),
association between extraversion and (medial) prefrontal volume equipped with SENSE-8 (LUMC and UMCG) and SENSE-6
[10] has been observed, which has also been demonstrated in (AMC) channel head coils, respectively. For each subject,
adults [11], although not consistently [12]. Therefore, the relation anatomical images were obtained using a sagittal 3D gradient-
between brain volume and affect-related personality traits remains echo T1-weighted sequence (TR = 9 ms, TE = 3.5 ms; matrix
unclear. Inconsistencies in reported findings may be due to 2566256; voxel size: 16161 mm; 170 slices).
methodological and technical issues, such as the use of different
segmentation and normalization strategies (e.g. analyses based on Data analysis
modulated vs unmodulated images [13], not accounting for total VBM following the Diffeomorphic Anatomical Registration
brain volume [14], or to sample characteristics and processes of Through Exponentiated Lie (DARTEL) algebra software [20]
brain maturation). For example, Jackson et al., 2009 [15], and implemented in Matlab 7.1.0 (The Matlab Inc, Natick, MA,
Wright et al., 2007 [16] studied the relation between neuroticism [Link] was used. The preprocessing and
and regional brain volume in an elderly population, whereas masking procedure is described in detail elsewhere [18]. Briefly,
Blankstein et al., 2009 [10] included an adolescent sample. As after segmentation, data were registered, normalized, and
aging is an important predictor of regional brain volume, and modulated using the DARTEL pipeline. Grey matter (GM)
because the process of aging (including brain maturation) has been images were normalized to Montreal Neurological Institute (MNI)
shown to interact with personality [15], it is possible that the space and smoothed at 8 mm full width at half maximum
conflicting finding may depend on the age range of the sample. It (FWHM). In the resulting images, each voxel represents an
is therefore necessary to further elucidate the complex relation absolute amount of brain volume, equivalent to the brain volume
between affect-related personality traits and regional brain volume per unit prior to normalization.
in an adult sample, controlling for these important factors (i.e. age, Next, we performed a multiple regression analysis with
total brain volume and modulation) but also testing for possible neuroticism and extraversion as independent variables and
interaction effect with sex, as Blankstein et al. 2009 [10] suggested voxel-wise GM density maps as the dependent factor. In addition,
that personality differentially affects regional brain volume in male sex6personality interaction terms were calculated by setting up a
and female adolescents. flexible factorial design. In each model, age, scan center, and GM
In the present study, we used an optimized VBM approach to total volumes were entered as nuisance variables. Based on the
investigate the relationship between neuroticism, extraversion, and literature on emotion processing in affective disorders [21], we set
regional brain volume in a large sample of healthy adults. We the following regions of interest (ROI): amygdala, orbitofrontal
focused on brain regions involved in the initial processing of cortex (OFC), anterior cingulate cortex (ACC). A family wise error
emotional information (amygdala) and on regions related to the (FWE) at p,.05 correction for the spatial extent of the ROIs (small
appraisal and decision making influence of emotional information, volume corrections) was applied. The ROIs were defined by the
ACC and orbitofrontal cortex [16]. As such, we aimed to identify Automated Anatomical Labeling (AAL) templates implemented in
neuro-anatomical substrates associated with affect-related person- the Wake Forest University School of Medicine (WFU) pickatlas
ality traits. [22]. For regions other than the ROIs, a voxel level threshold of
p,.05 whole brain FWE corrected was set a priori. For
Methods completeness, explorative analysis are performed at an uncorrect-
ed threshold of p,.001, with a spatial cluster extent of 25
Ethics Statement contiguous voxels. Demographic and clinical data were analyzed
The study was carried out in accordance with the Declaration of with SPSS 16.0 ([Link]
Helsinki. Also, the Ethical Review Boards of the Leiden University spss/) and significance was set at p,.05.
Medical Center (LUMC), Academic Medical Center (AMC),
University of Amsterdam, and University Medical Center
Results
Groningen (UMCG) approved this study. All participants
provided written informed consent after complete description of Sample characteristics and personality scores
the study. The age range of the 65 participants (42 females) was: 21–56,
Mean (M) = 40.5, standard deviation (sd) = 9.7; years of education:
Participants M = 14.3, sd = 2.9. Neuroticism (range = 13–36; M = 24.2,
Sixty-five healthy participants were selected from the NESDA sd = 4.9) correlated negatively to extraversion (range 27–56;
(Netherlands Study of Depression and Anxiety) neuroimaging M = 43.7, sd = 6.2) (r = 20.38, p = .002). Neuroticism correlated
study [17]. The MRI main sample is described in detail elsewhere negatively with total GM, whereas Extraversion correlated
[18]. Exclusion criteria for the current sample were: 1) a history of positively with total GM (Neuroticism: r = 0.29, p = .02; Extraver-
or current DSM IV axis I pathology, 2) taking any psychoactive sion: r = .29, p = .02). After partialling out variations in age and
drugs, 3) the presence or history of major internal or neurological sex, only the correlation between Extraversion and GM total
disorder, 4) dependency or recent abuse (past year) of alcohol and/ remained significant (Neuroticism: rpartial = 2.17, p = .18; Extra-
or drugs, 5) hypertension 6) general MR-contraindications. version: rpartial = .27, p = .03). Neither age nor years of education
were significantly correlated with either neuroticism or extraver-
Personality questionnaire sion (all p..13), and no effect of sex was observed (F,1.74, p..19)
To asses personality traits, all participants completed the NEO
Five Factor Inventory [19]. Personality and regional brain volume
Volumes of both the right medial OFC (BA 11) (encompassing
Image acquisition the rectal gyrus, the orbitofrontal region of Brodmann area 13 and
Imaging data were acquired using Philips 3T MR-systems (Best, the subgenual cingulate gyrus (BA 25)) and the right centro-medial
The Netherlands) located at the Leiden University Medical Center amygdala were positively related with extraversion at the set
(LUMC), Academic Medical Center (AMC), University of threshold (pFWE,.05 corrected for extent of ROI). At p,.001

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 Extraversion Is Linked to Brain Volume

uncorrected, the positive correlation of extraversion was also FWE corrected for the volume of the bilateral ACC as defined by
observed in the left OFC. Neuroticism did not show a significant the AAL templates). Post-hoc analysis showed that males displayed
relation with regional brain volume in any of the ROIs. Adding a significant positive association with extraversion (b = .40,
the other three personality variables (openness, agreeableness, and p = .008, 95% C.I.(B) = [0.005–0. 26], zero-order correlation:
conscientiousness) from the NEO FFI did not significantly change r = .43), with GM totals, neuroticism, age, and scan center added
the results (OFC: Z = 3.28; amygdala, Z = 3.50). Results are shown to the model, whereas the association was in the opposite direction
in figure 1 and table 1. No significant whole brain FWE p,.05 in female (b = 2.28, p = ,006, 95% C.I.(B) = [20.24–20. 004],
corrected effects outside these ROIs were found. For complete- zero-order correlation: r = .15). Sex by neuroticism interactions
ness, positive and negative correlations of neuroticism and were not observed in any other region of interest.
extraversion that were observed at p,.001, uncorrected with a
spatial cluster extent of 25 contiguous voxels are listed in table 1 Discussion
(non-ROI effects). However, these effects will not be further
discussed, as these were not part of our a priori set regions of In the present report, we used an optimized VBM approach to
interest. test for personality related variations in regional brain volume in
Extraversion6sex interaction analysis showed an effect in the an adult sample. While controlling for age, sex and total GM we
pregenual ACC (MNI coordinate: [x = 3, y = 48, z = 7] (p = .01 demonstrated positive correlations between extraversion and

Figure 1. Correlations of Extraversion and volume in the OFC and amygdala. A) Positive correlation of extraversion and volume of the right
orbital frontal gyrus scaled for total gray matter volume (r = .33; rpartial = .47 when neuroticism and age were partialled out) . B) Positive correlation of
extraversion and right amygdala volume scaled for total gray matter volume (r = .31, rpartial = .39 when neuroticism and age were partialled out). Mean
volume in ml of the significant voxels was extracted per subject and divided by total GM volume. In the correlation plots, mean volume of the
significant amygdala and ofc region is depicted in scaled volume in ml * 1023.
doi:10.1371/[Link].0028421.g001

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 Extraversion Is Linked to Brain Volume

Table 1. VBM effects.

positive correlations of extraversion

MNI-coordinate

R/L region BA k x y z Z-score r

OFC
R medial OFC, subgenual cingulate gyrus 11/25 329 13 16 14 3.77 .47
medial OFC, rectal gyrus 11 2 22 18 3.54 .45
L medial OFC, subcallosal gyrus 34 68 20 12 14 3.33 .42
amygdala
R amygdala, dorsal subdivision n.a. 31 21 10 21 3.34 .42
non-ROI effects
R superior parietal lobule 7 60 34 65 58 4.18
L cerebellar declive, posterior lobe n.a. 65 56 65 29 3.93
L posterior cingulate gyrus 31 63 27 41 27 3.60

negative correlations of extraversion

MNI-coordinate

R/L region BA k x y z Z-score

R precentral gyrus 4 144 41 20 47 3.75

34 16 46 3.65
L calcarine sulcus 30 16 69 13 3.55
L inferior frontal gyrus 45 59 49 20 14 3.46
L superior parietal lobule 7 65 21 54 61 3.45

positive correlations of neuroticism

MNI-coordinate

R/L region BA k x y z Z-score

L middle temporal gyrus 21 278 64 43 22 3.86

negative correlations of neuroticism

MNI-coordinate

R/L region BA k x y z Z-score

R supplemental motor area (SMA) 6 45 13 20 68 3.57

R/L: Right vs. Left hemisphere; BA: Brodmann area; k = clustersize at p,.001, uncorrected; r = correlation coefficient at peak voxel.
doi:10.1371/[Link].0028421.t001

regional brain volume in the medial OFC and centro-medial OFC [27]. Interestingly, a positive correlation of OFC thickness
amygdala. This result confirms the role of the OFC in personality, with extraversion and fear extinction has been previously
a region that was already associated with personality changes in described [30]. In another study, humor-driven activation,
the case report of Phineas Gage [23]. We also found a positive reflecting hedonic capacity, was found to be positively correlated
correlation between extraversion and total gray matter volume. with extraversion in the right medial OFC [9]. Moreover, in the
However, we did not find strong structural correlates of amygdala, activation during happy face viewing was found to be
neuroticism. positively related to extraversion [6]. Hence, the increased
The observation that extraversion correlated positively with volumes of medial OFC and amygdala may play a role in the
volume of both the medial OFC (extending into subgenual ACC increased sensitivity to positive, pleasant information and (social)
area 25) and the amygdala is of interest because of the role these reward, and thus, the propensity to experience the positive affect
regions play in affective processing [24,25]. The medial OFC has which characterizes extraversion [3]. The nature of this role,
often been associated with controlling reward and punishment however, awaits further elucidation, as relations between volume
related behavior, emotion regulation, approach related behaviour and function are not straightforward: increased volumes of GM in
[26] and decision making [27,28], and has projections to visceral brain areas may be reflective of a number of processes involving,
control structures, such as the ventral striatum, amygdala, among others, glial cells, inhibitory or excitatory neurons and
hypothalamus, periaqueductal grey, and hippocampus: regions interneurons. However, these processes cannot as yet be assessed
that are critical in modulating behavior and emotional expression in vivo in humans.
[26,27,29]. The amygdala has a well-documented role in emotion Beside the overall positive correlation between OFC and
processing and has bi-directional connections with the medial amygdala volume and extraversion, we also found a sex6extraver-

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 Extraversion Is Linked to Brain Volume

sion interaction in the ACC. Males showed a positive correlation Accordingly, in the present study, we expected neuroticism to
between ACC volume and extraversion, while this correlation was account for a substantial portion of the volumetric variation in
negative in females. A similar effect in the medial prefrontal gyrus regions associated with emotional perception and regulation.
was previously shown in adolescents [10]. These findings could However, no such relation was observed. Instead, extraversion was
suggest that, in men, the ACC is included in the same extraversion found to be the main predictor of regional brain volume in
mediated regulatory network as the amygdala and OFC, while this affective brain regions. This discrepancy in findings might be due
is not the case in females. This could imply that extraversion has a to methodological issues such as those outlined before, most
stronger protective effect in men than in women, in line with the importantly, this study used an optimized VBM method in a
well known observation that men are less susceptible to affective relatively large adult subject sample. Future research has to
disorders [31]. elucidate whether this lack of neuroticism - brain volume relations
It is also interesting to note that our findings were mainly right- is a stable finding.
lateralized. In a study by Hasting et al, 2004 [32] it was found that In the present study we examined structural correlates of
non-medicated depressed patients showed smaller right amygdala extraversion and neuroticism in a cross-sectional design. There-
volume than controls (an effect which was driven by the female fore, it is possible that the found correlates are not primary, but
participants). Since we found that low extraversion is linked to secondary to individual lifetime experiences. For instance, high
smaller right amygdala volume, our results can be considered in extraversion is known to be associated with different lifetime
line with this study. Moreover, a meta-analysis on lateralization experiences than low extraversion. Findings from the same
has found that the right amygdala is more involved in processing NESDA study indicate that extraversion and negative life events
masked stimuli, whereas the left amygdala is more involved in mediate the course of depressive symptoms [37], suggesting that
processing stimuli which contain language [33]. Relating this extraversion, also defined as the tendency to engage in reward-
finding to our data, it might suggest that extraversion is more enhancing behavior, could influence the likelihood of experiencing
strongly linked to the subconscious emotion-processing role of the
positive life events or how certain life events are perceived. In
amygdala. However, the lack of consensus regarding lateralization
addition, extraversion is argued to be a protective factor for
and amygdala function among functional MRI meta-analyses
dysthemia and social anxiety rather than other anxiety disorders
should be noted [34–36]. Moreover a positive correlation between
[38]. Interactions between extraversion, lifetime experiences (both
the left amygdala and extraversion was also observed at a more
positive and negative) and brain structures should be investigated
liberal threshold (p,.005 uncorrected), and no formal interaction
as this could shed light on the development of different psychiatric
of extraversion6lateralization was observed in a repeated
disorders.
measures anova. Therefore, no strong statements on lateralization
can be made. Furthermore the positive correlation between Given the augmenting evidence for a significant relation
extraversion and right amygdala volume was localized in the between extraversion and OFC and amygdala volumes, future
central-medial amygdala, which contains (most of) the efferent research should address structural and functional connectivity of
connections from the amygdala to the brainstem and hypothal- the OFC and the amygdala, and further investigate the role of the
amus [27]. These connections are particularly important for fight/ pregenual ACC in this circuitry. This might provide more insight
flight responses, and taken together, our findings might fit with the about the trajectory from health to psychopathology, and, in doing
idea that extraversion is linked to moderating unconscious so, identify neuroanatomical markers which relates to one’s risk of
emotion processing and primary stress responses. developing affective disorders.
The present result with respect to extraversion is in line with
findings of Blankstein and colleagues [10], who used a similar Author Contributions
methodology (i.e. an optimized VBM approach) in an adolescent Conceived and designed the experiments: AA FGZ MAvB DJV NJAvdW.
sample, and another study that showed a relation between Performed the experiments: M-JvT AA DJV NJAvdW. Analyzed the data:
extraversion and PFC volume in an adults sample [11]. However, HC M-JvT. Wrote the paper: HC M-JvT KR AA FGZ MAvB DJV
also neuroticism has been related to OFC volume [12]. NJAvdW.

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