EXTRAPYRAMIDAL SYSTEM
(Basal ganglia and cerebellum)
Session 5 - Lecture 1
Dr. Mohammed Radhi
• Previously we described the anatomy and function of the four
levels of the motor system hierarchy: the spinal cord, the
brainstem, the motor cortex, and the association cortex.
• Two other brain structures can be considered as “side loops” in
the motor hierarchy. They influence the processing of motor
control and modulate the output of the descending pathways
without directly causing motor output.
• Both of these structures—the basal ganglia and the cerebellum—
are now known to have other functions in addition to modulating
motor control
• The output of the cerebellum is excitatory, while the basal ganglia
are inhibitory. The balance between these two systems allows for
smooth, coordinated movement, and a disturbance in either
system will show up as movement disorders.
Basal Ganglia
• the caudate and putamen are collectively referred to as the striatum or
neostriatum, receive most of the input from cerebral cortex.
• The putamen and the globus pallidus are collectively called the lenticular
nucleus, or lentiform nucleus.
• The globus pallidus is divided into two segments: the internal (or medial)
segment and the external (or lateral) segment.
• The metabolism of the basal ganglia is unique in a number of ways. These
structures have high oxygen consumption. The copper content of the
substantia nigra and the nearby locus ceruleus is particularly high.
Function of BG
• Voluntary movement
▪ Shared in control the learned complex pattern motor activity: Basal gangli in
association with the motor and sensory cortex and cerebellum responsible for
planning, programming and timing(initiation, maintenance and stoppage) of
the learned complex pattern of motor activity
▪ Control of movement volume and velocity
▪ Control the instinctive cognition of the sequences of motor response:
Cognition means the thinking processes of the brain for the sensory input to it
and the information already stored in memory.
• Postural control
• Automatic associated movement (walking)
• Control of muscle tone Inhibitory
• Reticulospinal
• Vestibulospinal
Connection of basal ganglia
• The caudate and putamen receive most of the input from cerebral
cortex; in this sense they are the doorway into the basal ganglia.
• Globus pallidus interna (GPi) and substantia nigra pars reticulata (SNr)
are the outflow of almost all inhibitory signals from the basal ganglia
back to thalamus. The two output nuclei of the basal ganglia, GPi and
SNr, tonically inhibit their target nuclei in the thalamus.
• The inhibitory outflow signals from globus pallidus interna (GPi) and
substantia nigra pars reticulata (SNr) to the thalamus are modulated by
two parallel pathways that project from the striatum
These two pathways are:
[1] Direct pathway has positive feedback, decreases inhibition on the
thalamus, i.e, an increased stimulation from the cortex will decreases the
inhibition on the thalamus, and consequently an increase stimulation of the
cortex, and vice versa. It is consisting of the loop – Cortex + ➔ striatum - ➔
GPi - ➔ thalamus +➔ cortex . تدز انهبتوري للثالمس ف شنوgpiعادة ال
اسويلها انهبشن حتى الثالمس يشتغل
[2] Indirect pathway has negative feedback, increases inhibition on the
thalamus, i.e, an increased stimulation from the cortex will increases the
inhibition on the thalamus, and consequently a decrease stimulation of the
cortex, and vice versa. It is consisting of the loop - Cortex + ➔striatum - ➔ GPe
- ➔ STN + ➔ GPi ➔ thalamus +➔ cortex.
• Direct pathway: Disinhibits motor thalamus, and thus activates thalamo-cortical
neurons. Consequently, activates motor cortex and facilitates movement.
• Indirect pathway: Inhibits motor thalamus, and thus inhibits thalamo-cortical
neurons. Consequently, inhibits motor cortex and inhibits movement
• The two striatal output pathways are affected differently by the dopaminergic
projection from the substantia nigra pars compacta (SNc) because they have
different dopamine receptors (D1 and D2).
Cortex
Direct pathway
Striatum Excitation (glutamate)
Inhibition (GABA)
VA/VL
* GPe
STN
* GPi/SNr * tonically active
~100 Hz
Modified from Wichmann and Delong,
Curr Opin Neurobiol. 6:751-758,
1996.
Cortex
Direct pathway:
pathway
facilitates
movement
Striatum
Excitation (glutamate)
Inhibition (GABA)
VA/VL
* GPe
Disinhibition
STN
* GPi/SNr * tonically active
~100 Hz
Modified from Wichmann and Delong,
Brain stem/ Curr Opin Neurobiol. 6:751-758,
Spinal cord 1996.
Cortex
Striatum
Indirect pathway
pathway:
inhibits
movement
VA/VL
* GPe
Excitation (glutamate)
Disinhibition Inhibition (GABA)
STN
* GPi/SNr * tonically active
~100 Hz
Modified from Wichmann and Delong,
Brain stem/ Curr Opin Neurobiol. 6:751-758,
Spinal cord 1996.
Cortex
Direct pathway:
facilitates
Striatum movement
D2 D1 Indirect pathway:
inhibits
movement
SNc
VA/VL
* GPe
Excitation (glutamate)
Inhibition (GABA)
STN
* GPi/SNr * tonically active
~100 Hz
Modified from Wichmann and Delong,
Brain stem/ Curr Opin Neurobiol. 6:751-758,
Spinal cord 1996.
• Overactivity in the indirect pathway is a major factor in Parkinsonian signs, while
underactivity in the indirect pathway is a major factor in hyperkinetic disorders
such as hemiballism (violent involuntary throwing movements of the limb after a
lesion in the contralateral subthalamic nucleus), Huntington disease (which is an
autosomal dominant hyperkinetic disorder characterized by chorea, dementia
and behavioral disturbance).
Motor behavior is determined by the balance
between direct/indirect striatal outputs
Hypokinetic disorders
• insufficient direct pathway output
• excess indirect pathway output
Hyperkinetic disorders
• excess direct pathway output
• insufficient indirect pathway output
The cerebellum
• The little brain, also termed the motor autopilot, helps regulate movements and
posture, influences muscle tone, eye movements and balance.
• The cerebellum is especially vital to the control of very rapid muscular activities
such as running, typing, playing the piano, and talking. Loss of this area of the
brain can cause almost total incoordination of these activities even though its loss
causes no paralysis of any muscle.
Cerebellar cortex:
The cerebellar cortex contains only 5 types of neurons; Purkinje,
granule, basket, stellete, and Golgi cells. The axons of the Purkinje
cells are inhibitory (the neurotransmitter is gamma amino butyric
acid, GABA) and are the only output from the cerebellar cortex pass
to the deep nuclei.
3 functional divisions
• Vestibulocerebellum
• Flocculus + nodulus
• Spinocerebellum
• Vermis and adjacent
intermediate zone
• Cerebrocerebellum
• Lateral zone
21
Cerebellar cortex: functional divisions
• Vestibulocerebellum
• Inputs:
From vestibular nuclei in brainstem
• Function:
- Regulate movements underlying posture and
equilibrium
-Coordination of eye and head movements
• Damage:
-Impairs ability to stand upright, maintain posture and
balance
-Cerebellar nystagmus
22
Cerebellar cortex: functional divisions
• Spinocerebellum
• Inputs:
Directly from spinal cord
• Function:
• Lateral portion
Movement of distal muscle (ex. gross movements
during walking)
• Central portion (vermis)
Movement of proximal muscles
• Damage:
- Overshoot and intension tremor
- Impaired gait
23
Cerebellar cortex: functional divisions
• Cerebrocerebellum
• Inputs:
Many areas of cerebral cortex (relayed through pons)
• Function:
- Planning and timing of sequential movements
- Speech
• Damage:
Ataxia: incoordination of complex, purposeful movements of hands,
fingers, feet and speech apparatus
• Failure of smooth progression of movement
Lesions to any division of cerebellum result in impairments
on ipsilateral side of the body
24
• The cerebellum receives information from:
1. Spinal cord through the dorsal spinocerebellar tracts and the ventral spinocerebellar tract which
apprises.
2. Eyes and ears through tectocerebellar tract from colliculi.
3. Cerebral cortex through corticopontocerebellar tract..
4. Olivary nucleus through olivocerebellar..
5. Cuneate nucleus through cuneocerebellar tract which transmitte the same information as dorsal
spinocerebellar tract but from neck and upper limbs.
6. Vestibular nucleus through vestibulocerebellar tract.
• The ingoing pathways to the cerebellum arranged into two main input fibers that pass to the
cerebellar cortex and these are climbing fibers (originated from inferior olive of the medulla) and
mossy fibers (originated from many centers in the brain stem and spinal cord). Both are excitatory
which send collaterals to the deep nuclei and pass to the cortex.
• Deep cerebellar nuclei which are dentate, globose, emboliform,
and fastigiel nuclei. Deep nuclei receive excitatory inputs from the
mossy and climbing fibers and inhibitory inputs from Purkinje cells.
The output of the deep cerebellar nuclei to the brain stem and
thalamus is always excitatory.
• cerebellar peduncles
[Link] (efferent)
[Link] (afferent)
[Link] (mixed)
Cerebellum: projections
4 deep cerebellar nuclei
receive input from cerebellar
cortex and send projections
to thalamus
1. Fastigial
2. 2 Interposed
3. Dentate
Information travels via
cerebellar peduncles
1. Superior (efferent)
2. Middle (afferent)
3. Inferior (mixed)
27
Sunderland Fig 19.1
Cerebellum:
inputs
Receive many inputs
from periphery, spinal
cord and brain regions
28
Sunderland Fig 19.3
Cerebellum:
outputs
Why would lesions to the cerebellar
cortex affect movement on ipsilateral
side of the body?
29
Sunderland Fig 19.6