Motor Systems

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COGNITIVE SCIENCE 107A Motor
Systems Basal Ganglia Jaime A. Pineda, Ph.D.
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Two major descending pathwaysPyramidal vs.
extrapyramidal
Motor cortex
Brain stem centers
Pyramidal system
Extrapyramidal system

• Pathway for voluntary movement
• Most fibers originate in motor cortex (BA 46)
• Most fibers cross to contralateral side at the
  medulla

• Pathways for postural control/certain reflex
  movement
• Originates in brainstem
• Fibers do not cross
• Cortex can influence this system via inputs to
  brain stem

Lower motor neurons (brain stem and spinal cord)
Striated muscles
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• In order to generate voluntary movement many
  components are necessary
• A representation of the actual position of the
  body segments (current program).. somatosensory
  systems
• 2) A representation of the desired position of
  the body segments in time (model
  program).....cortex
• 3) A spatial and temporal motor plan for
  achieving 2) starting from 1).cerebellum
• 4) Monitoring and maintaining the
  movement..basal ganglia

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Feedforward and feedback Processing are needed
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Optimal action requires a proper representation
of the external world A mistaken evaluation of
the weight of an object to be lifted generates a
different, more complex motor plan
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Voluntary Movement Conscious
Figure 13-11 Control of voluntary movements
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Cortical Motor System

• Primary motor cortex
• Execution of movement
• Somatotopically organized
• Massive descending projections to spinal cord
• Damage gt pronounced weakness in affected body
  parts
• Stimulation gt simple movt in small muscle
  groups

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• Somatotopy in M1

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Cortical Motor System
Area 8 frontal eye fields

• Pre-motor cortex
• Movement planning/sequencing
• Many projections to M1
• But also many projections directly into pyramidal
  tract
• Damage gt more complex motor coordination
  deficits
• Stimulation gt more complex movt
• Two distinct somatotopically organized subregions
• SMA (dorso-medial)
• May be more involved in internally generated
  movement
• (anti-mirror neurons)
• Lateral pre-motor
• May be more involved in externally guided
  movement
• (mirror neurons)

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These various motor areas execute different tasks
relative to motor learning Supplementary motor
area initiates learning Premotor area starts a
learnt motor program Primary motor cortex
coordinates the details of the movement
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Cortical Motor System

• Posterior parietal cortex (PPC)
• Sensory guidance of movement
• Many projections to pre-motor cortex
• But also many projections directly into pyramidal
  tract
• Damage can cause deficits in visually guided
  reaching (Balints syndrome) and/or apraxia
• Likely part of the dorsal visual stream

Areas 5, 7 visuo-motor integration
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Subcortical Motor SystemBasal Ganglia
Cortex
input
or neostriatum
output
(internal/external)
input
(STN)
(pars compacta, pars reticulata
output
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Subcortical Motor SystemBasal Ganglia
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BG is a basic release circuit that works through
disinhibition to translate perception and
cognition into action
VA BG input VL cerebellum input
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Motor Cortex-Basal Ganglia-Cerebellum Circuit
Cortex
M1, PM SMA
Striatum
Direct pathway
Indirect pathway
Somatosensory systems

GPe
Thalamus
STN
Cerebellum
excitatory
GPi/SNr
inhibitory
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Basal Ganglia Functions

• Motor planning, sequencing, learning, maintenance
• Rule-based and habit (reinforcement) learning
• Predictive control
• Working memory
• Attention
• Switches in behavioral set

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• Striatum caudate - putamen
• 80-95 medium spiny neurons
• GABAergic 0.1 - 1 Hz rate
• Receives vast majority of BG input
• cortical
• excitatory (glutamatergic)
• 2 types of medium spiny cells
• Those expressing D1 receptors
• Excited by DA
• contain dynorphin/Subst P
• send to GPi SNpr (direct)
• Those expressing D2 receptors
• Inhibited by DA
• contain enkephalin
• send to Gpe (indirect)
• Patchy
• ACh striosomes
• gets limbic input
• sends to SNpc

CORTEX

Striatum
_
D1
D2
Direct
Indirect
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Patches or striosomes (AChE-poor)
Matrix or matrisomes (AChE-richGABA)
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Sensorimotor association areas
Limbic areas
matrisomes
striasomes
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Thalamus

• GPi (Globus Pallidus internal)
• Major BG output for limb movement
• DIRECT pathway from striatum
• (striatopallidal pathway)
• Also receives STN input
• excitatory
• contacts many neurons
• 10-15ms faster than striatum
• GABA output to thalamus brain stem
• SNpr (Substantia Nigra pars reticulata)
• Major BG output for eye movement
• Also gets striatum STN input
• SNpr projects to SC to control eye movements

Direct
-

SC

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CORTEX
Thalamus
SC
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• GPe (Globus Pallidus external)
• Much like internal segment
• Gets striatum STN input
• Sends output to STN
• Striatum ? GPe ? STN ? GPi ? Thalamus
• INDIRECT striatopallidal pathway
• May act to oppose, limit, or focus the effect of
  striatal and STN projections to GPi and SNpr.

-
Striatum
Indirect

-
STN
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CORTEX
Thalamus
SC
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-

• SNpc (Substantia Nigra pars compacta)
• Most studied structure in the basal ganglia
• Large DAergic cells
• Receives inhibitory input from striasomes in
  striatum
• Sends DAergic output to same/adjacent striatal
  areas
• DA action (inhibitory/excitatory) depends on
  striatal receptors.
• D1 receptors excite
• D2 receptors inhibit

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CORTEX
Thalamus

-

-

Direct
-

-

Indirect

SC
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CORTEX
Thalamus

-

-
Hyperdirect
Direct
-

-

Indirect

SC
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Basal Ganglia Circuit

• Striatum receives input from cortical areas
• inputs are roughly topographical (multiple
  parallel circuits)
• GPi/SNr are the major output nuclei
• Output is inhibitory
• Gpi/SNr neurons have high baseline firing rates
  (baseline inhibition)
• Gpi/SNr input from the striatum is focal and
  inhibitory, whereas input from the STN is diffuse
  and excitatory
• Direct vs. indirect striatal pathways have
  opposing effects (inhib. vs. excit.)
• Output of thalamus is primary to motor areas

Cortex
M1, PM SMA
Striatum
Direct pathway
Indirect pathway
SNc
Hyperdirect pathway
GPe
Thalamus
STN
excitatory
GPi/SNr
inhibitory
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Malfunctioning of basal ganglia induces dramatic
abnormalities in voluntary movement. Basal
ganglia coordinates movement indirectly, by
receiving information from motor cortex and
re-sending back to the motor cortex processed
information through the thalamus.
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Basal Ganglia Circuit
Cortex
M1, PM SMA
Striatum
Direct pathway
Indirect pathway
SNc
Hyperdirect pathway
D2
D1 ()
(-)
GPe
Thalamus
Indirect
Direct
STN
(bias is to maintain thalamic channels opened and
info flowing to cortex)
excitatory
GPi/SNr
inhibitory
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Parkinsons Disease

• Etiology
• Adult onset, thought to be genetic without 100
  penetrance.
• One hypothesis is that it results from a genetic
  susceptibility to an environmental factor.
• Loss of DA input to striatum from SNpc
• Loss must involve over 90 of cells before
  symptoms appear.

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Parkinsons Disease Clinical Symptoms

• Motor
• Tremor
• Cogwheel rigidity
• Shuffling steps
• Akinesia
• Bradykinesia
• Dystonia

• Non-motor
• Cognitive slowing
• Difficulty with tasks requiring high level
  processing
• Depression

Akinesia Difficulty beginning or
maintaining a body motion Bradykinesia Slowness
of movement paucity or incompleteness of
movement Dystonia Sustained involuntary
muscle contractions and spasms
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Parkinsons Disease (Hypokinetic Movement)

• Decreased output of SNc dopaminergic projections
• Decrease excitation in direct pathway
• Increase inhibition in indirect pathway
• Net effect more inhibition of thalamus and
  therefore less excitatory input to motor cortex

Cortex
M1, PM SMA
Striatum
Direct pathway
Indirect pathway
SNc
GPe
Thalamus
STN
D2
D1 ()
(-)
excitatory
GPi/SNr
inhibitory
Indirect
Direct
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Parkinsons Disease Treatment

• L-DOPA (taken up by DA terminals in the
  striatum) converted to DA and then released.
• Not effective for long-term treatment
• Patients develop a tolerance to it
• Has many side effects (honeymoon period 3-5
  years)
• Transplantation of fetal tissue
• Pallidotomy (cells in the posteroventral GPi are
  surgically ablated either unilaterally or
  bilaterally
• Deep Brain Stimulation (DBS) a surgical
  treatment involving the implantation of a brain
  pacemaker, which sends electrical impulses to
  brain.

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DBS

• DBS leads are placed in the brain according to
  the type of symptoms to be addressed.
• For essential tremor and Parkinsonian tremors,
  the lead is placed in the thalamus.
• For symptoms associated with Parkinson's disease
  (rigidity, bradykinesia/akinesia and tremor), the
  lead may be placed in either the globus pallidus
  or subthalamic nucleus.

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Huntingtons Disease (Hyperkinetic Movement)
Cortex
M1, PM SMA

• Cell loss in the striatum that seems to affect
  the indirect pathway disproportionately
• Net effect less inhibition of the thalamus and
  therefore excessive excitation of motor cortex

Striatum
Direct pathway
Indirect pathway
SNc
GPe
Thalamus
STN
excitatory
GPi/SNr
inhibitory
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Subcortical Motor SystemBasal Ganglia

• Behavioral effects when damaged can include
• Resting tremor
• Akinesia (paucity of movt)
• Muscular rigidity
• Unstable posture
• Bradykinesia (slowness of voluntary movt)
• Tic-like involuntary movements
• Hemiballism (sudden involuntary large scale
  movt)
• Possibly obsessive compulsive disorder,
  Tourettes, stuttering
• Assorted cognitive deficits (e.g., aphasia)

Parkinsons disease
Huntingtons disease
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Because of its cellular inhibitory nature, the
core of the basal ganglia is a system with
multiple loops of inhibition in which cortical
activation has the effect of disinhibiting the
part of motor thalamus in the initiated movement
thalamus
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Subcortical Motor SystemBasal Ganglia

• So what is the basal ganglia circuit doing?
• The Brake hypothesis
• B.G. essentially acts like a brake to prevent
  unwanted movement.
• Excitation of STN via motor input leads to
  diffuse increase in inhibition.
• Excitation of the striatum in one motor circuit
  decreasing this inhibition focally thus
  releasing the brake for the selected movement.

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Real situation Clinically there are two types
of signs of malfunctioning of motor
control Negative signs loss of function of a
particular motor area Positive signs initiation
of stereotyped movements or exaggerate
strength This facts indicate that the motor
system not only uses a constructive approach to
movement, but it also uses an organized
inhibition that controls a menu of stereotyped,
learnt, motor sequences. Basal ganglia and
cerebellum are involved in this kind of
processing.
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Example running Although the initiation of the
action is typically voluntary, the complex motor
sequence underlying it is organized in an
automatic, stereotyped manner. The animal is
able only to control Initiation Stop Modulation
(increase, decrease, go right, go left and a
number of other variables) Without being able to
control the contraction or relaxation of a single
muscle This is the reason for the creation and
storage of automatic motor patterns
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The simplest motor pattern, the reciprocal
inhibition of couple of agonist and antagonist
muscles is organized at the spinal level
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CORTEX
Thalamus
SC
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CORTEX
Thalamus
SC
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CORTEX
Thalamus
SC
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CORTEX
Thalamus
SC
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CORTEX
Thalamus
SC
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CORTEX
Thalamus
SC
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CORTEX
Thalamus
SC
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CORTEX
Thalamus
SC
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CORTEX
Thalamus
SC
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CORTEX
Thalamus
SC
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Subcortical Motor SystemCerebellum
Three main systems
Damage causes
Decreased muscle tone (hypotonia), difficulty
coordinating multiple joint movt (ataxia),
tremor/ oscillation at the end of a movement.
Slowed movement initiation time, movements become
fractionated and performed sequentially rather
than as one smooth movt
1.
2.
3.
Impairs ability to use vestibular information to
control eye movements during head rotations or
limb movements during walking or
standing. Difficulty maintaining balance, fall
often
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The cerebellum receives and processes information
coming from muscles, joints and vestibulum,
creating a temporal template for the fine
adjustments of movement. In cerebellotomized
animals, cerebellum motor function may be
recovered by the rest of the motor system.
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