Amirkabir University of
Technology
BASAL GANGLIA
Supervisor: Dr Towhidkhah
Designed by Yashar Sarbaz
Systems-Level Neural
Modelling: What and Why?
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We know a lot about the brain!
Need to integrate data: molecular/ cellular/ systems
levels.
Complexity: Need to abstract away higher order
principles
Models are tools to develop explicit theories,
constrained by multiple levels (neural and
behavioural).
Key: Models (should) make novel testable predictions
on both neural & behavioural levels
Models are useful tools for guiding experiments
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Movement Levels
Highest Level (Need & Plan):
Limbic System
Associative Cortex
 Middle Level (Motor Program):
Cerebellum
Motor Cortex
Basal Ganglia
 Lowest Level (Movement):
Spinal Cord
Muscular-Skeletal System
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Movement Block Diagram
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Brain
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Learning Strategies
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Supervised Learning (Cerebellum)
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Reinforcement Learning (Basal Ganglia)
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Unsupervised Learning (Cerebral Cortex)
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Symbolic Learning (Hippocampal System)
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Learning Strategies
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Learning Strategies
Cerebral Cortex：Unsupervised Learning
output
input
Cortex
Basal Ganglia: Reinforcement Learning
reward
Basal thalamus
Ganglia
SN
output
input
Cerebellum
Cerebellum: Supervised Learning
target
IO
+
error
input
output
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Basal Ganglia
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Collection of Subcortical Nuclui
We Know a little about BG
It has main role in movement
Many movement disorders related to
this area
Involved in motor coordination, timing
and control
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Basal Ganglia
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Directly Receive No Direct Sensory
Inputs
Send Little Direct to Spinal Cord
Damage in BG has no loss of Specific
Motor Function
Damage in BG Cause mainly Deficit in
General Control and Initiation of
Movement
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Basal Ganglia
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It is one of the Old Area of Brain
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BG with Thalamus act like a Little Brain
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It is Like Funnel
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BG Functions
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1. Inhibition of muscle tone
2. Coordination of slow, sustained
movements
3. Suppression of useless patterns of
movements
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Duty of the BG
1.Motor control
2.Reinforcement learning
3.Sensorymotor associative learning
4.Adaptive timing
5.Temporal order learning
6.Initiation of voluntary movement
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BG is involved in a wide spectrum
of functions ranging from simple
sensory motor learning to planning,
it does not tell to us how this might
occur.
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BG Blocks
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Striatum: Putamen and Caudate
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Globus Pallidus: External and Internal
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Subthalamic Nucleus
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Subtantia Nigra: Pars Compacta and Pars
Reticulata
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Basal Ganglia Anatomy
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Basal Ganglia Anatomy
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Basal Ganglia Anatomy
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Basal Ganglia Anatomy
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Blocks of BG
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Converging Pathways
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PF: Prefrontal
SMA: Supplementary
Motor Area
M1: Primary Motor Cortex
PMv: Ventral pre-motor
Area
C/P: Caudate Nucleus
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Disorders of the BG
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Hyperkinesia: an excess or spontaneous involuntary
movements
Chorea abrupt movements of the limbs and facial muscles
Ballism violent, flailing movements
Athetosis slow writhing movements of the fingers and
hands and sometimes toes
Hypokinesia: a lack of or resistance to voluntary
movement
Akinesia lack of of slowness of spontaneous and
associative movements
Rigidity increased tone on passive manipulation of joints
Irregularities:
Tremor rhythmic, involuntary, oscillatory movements
around 4-6 Hz
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BG Diseases
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Parkinson: loss of Dopamine, with
hypokinesia (akinesia & rigidity) and
irregulaities
Huntington: death in striatum, with
hyperkinesia (chorea, ballism, athrtosis)
Hemiballism: lesion in STN with ballism
Tardive Dyskinesia: Using Antipsychotic
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BG Blocks in Diseases
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BG and Action Selection
BG selectively facilitates one command
while suppressing others
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Micro Circuitry of the BG
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Striosomes: input from limbic system
and output to dopaminergic neuron of
SNc (reinforcement signal)
Matriosomes: Input from cortical
(sensation and movement) and output
to SNr and GP
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Micro Circuitry of the BG
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Conceptual Models
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Such diversity of function embodied in
such an intricately organized structure,
has inspired numerous models of basal
ganglia function ranging from sensorymotor associative to the formation of
motor plans
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Conceptual Models
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BG as link
between limbic
system and
motor output
(eye movement)
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Conceptual Models
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BG and
learning to
cortex to
select a
sequence
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Reinforcement Learning
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Physiological Basis of
Reinforcement Learning
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Physiological Basis of
Reinforcement Learning
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Reinforcement Learning
A general idea of “goodness” is used
to adjust how the system learns
Temporal Difference (TD) error:
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Reinforcement Learning
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Framework for learning state-action mapping
(policy) by exploration and reward feedback
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Critic
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reward prediction
Actor
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reward r
action selection
Learning
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agent
action a
environment
state s
external reward r
internal reward d: difference from prediction
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Dopamine and Learning
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There is significant evidence that dopamine
acts as a reinforcement signal to neuron in
striatum and training them to recognize
patterns in their cerebral cortical input.
Dopamine modulates Go and No-Go
reinforcement learning in the basal ganglia
separately via D1 and D2 receptors
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Reinforcement Learning and
BG
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Data from neuronal recording and
lesion studies indicate that the basal
ganglia are involved in learning and
execution of goal-directed, sequential
behaviour
Dopamine neuron activity encoding the
reward prediction error d (t )
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Reinforcement Learning and
BG
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It is suggested that the Striosome
compartment works as the value
prediction mechanism while the
Matriosomes compartment works as
the action selection mechanism
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Reinforcement Learning and
BG
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Striatum
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Dopamine neurons
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striosome & matrix
dopaminedependent plasticity
reward-predictive
response
TD learning
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Reinforcement Learning and
BG
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Striatum Learning Mechanism
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Comparison of the Basal
Ganglia and the Cerebellum
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The basal ganglia receive input from the entire
cortex, whereas the cerebellum is innervated only by
parts of cortex directly related to sensorimotor
function
Cerebellar output is directed back to the premotor
and motor cortex, while the basal ganglia project to
these as well as the prefrontal association cortex;
The cerebellum receives somatosensory information
directly from the spinal cord and has major afferents
and efferents with many brain stem nuclei which are
directly connected with the spinal cord, while the
basal ganglia have very few connections with the
brainstem and no known direct connections with the
spinal cord
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One might also consider that the basal
ganglia are the deep nuclei of the
cortex, while the cerebellum itself
consists of a cerebellar cortex and deep
nuclei.
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History of Parkinson’s disease
Ancient Indian Text: Kampavata
 Galen 175 A.D.: Shaking Palsy
 James Parkinson 1817: “An Essay on the
Shaking Palsy” (6 patients)
 Charcot 1860: Parkinson’s Disease
 1960: Role of Dopamine
 1981: Levo Dopa
 1990s: DBS Treatments
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Parkinson’s Disease
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An Ancient Progressive Disease
Second Wide-Spread Brain Disease (After
Alzheimer)
Main Symptoms are Movement Disorders
Vast Range of Symptoms
Mean Age of onset is 60
Degeneration of Basal Ganglia
Not Epidemic
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Famous Parkinsonian People
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Etiology
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1.
2.
3.
4.
Not clear Exactly
Main Hypothesis:
Free Radicals: Antioxidant Molecules
Genetic Factors
Environmental Toxins: MPTP,
Retenone, 6Hydroxy Dopamin
SNc Cells Age Faster than Normal
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Symptoms of PD
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Movement Symptoms
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Cognition Symptoms
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Cognition Symptoms
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Dementia
Depression
Anxiety and Panic
Sleep Disorders
Cognitive impairment
Psychosis
Behavioural disturbances
Bradyphrenia: off Thinking
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Cognition Symptoms
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Different Movement and Cognition
History
Lewy Body
Another Degeneration of Brain Area
involve in Cognition (For Example in
Dementia: Dorsal tier neuron and
medial neuronal Groups)
Aging
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Movement Disorders
Hypokinesia: a lack of or resistance to
voluntary movement
Akinesia: lack or slowness of spontaneous and
associative movements
Rigidity: increased tone on passive manipulation
of joints
 Irregularities
Tremor: rhythmic, involuntary, oscillatory
movements around 4-6 Hz
 Gait Disturbance: shuffling gait, Freezing
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Problems in Diagnosis
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Autopsy Show 24% Error in PD
Diagnosis
There is no Laboratory Test for
Diagnosis
1. Patient History
2. Clinical tests
3. Using Levo dopa
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Problems in Diagnosis
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Starting Tremor, Slowness and Stiffness
approximately 12 month Before
Diagnosis
lesion of at least 50% of SNc Neuron
Approximately Degeneration Start 5
year before Symptoms (10 years in
some texts)
Prognosis is important
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Diagnosis of PD
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At Least Two of these Four Features
(Cardinal Features):
Tremor
Rigidity
Akinesia
Gait disturbance
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Presence of rest tremor, and a clear cut
response to treatment with levodopa
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Physiological Information
about PD
Origin of PD (Basal ganglia)
Parts of Basal ganglia (BG)
Comparing Normal and Patient
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Reason of PD
Loss of nerve cells in substantia nigra
pars compacta
Low level of Dopamine in patient’s brain
Changing activity of other blocks
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Theory of PD
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Inhibition of GPi Theory
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BG Selective Theory
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Oscillatory Theory
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Complex Dynamic System Theory
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BG Changes in PD
[Kandel, 2000]
Normal
Person
Parkinsonian
Person
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States of disease
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After unfolding movement Symptoms
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Before unfolding movement Symptoms
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Treatments for PD
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Nonpharmacologic treatment
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Pharmacologic treatment
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Surgical treatment
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Nonpharmacologic treatment
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EDUCATION (www.wemove.org)
SUPPORT
EXERCISE
NUTRITION
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Pharmacologic treatment
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NEUROPROTECTIVE THERAPY
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SYMPTOMATIC THERAPY
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NEUROPROTECTIVE THERAPY
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All of the available treatments are symptomatic and
do not appear to slow or reverse the natural course
of the disease.
Neuroprotective therapy of PD is still theoretical.
Neuroprotective drug could be used in patients with
early clinical signs of disease or potentially even prior
to the appearance of disease in those shown to be at
genetic risk.
Selegiline and rasagiline (both monoamine oxidase
inhibitors), dopamine agonists, and the complex I
mitochondrial fortifier coenzyme Q10 have been
evaluated in clinical trials and are receiving the most
attention as possible neuroprotective agents
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SYMPTOMATIC THERAPY
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Levodopa
MAO B inhibitors
Dopamine agonists
COMT inhibitors
Anticholinergic agents
Amantadine
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Drug Treatments of PD
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Surgical treatment
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DEEP BRAIN STIMULATION
THALAMOTOMY (With conventional thalamotomy, stereotactic surgical techniques are
employed to create a lesion in the ventral intermediate (VIM) nucleus of the thalamus under
electrophysiologic guidance. Gamma knife thalamotomy uses radiation delivered to the intracranial target,
but electrophysiologic guidance is not possible)
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PALLIDOTOMY
IMPLANTATIONS AND INFUSIONS:
1. Tissue transplantation
2. GDNF infusion
3. Duodenal levodopa infusion
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MainTreatment
Levodopa is the most effective drug in the treatment
of PD.
Most patients develop abnormal involuntary
movements (dyskinesias) and unpredictable
fluctuations in motor functioning within three years of
treatment.
Patients with onset before age 20 years are most
likely to be affected. As a result, therapy is initiated
with other drugs that will control the symptoms and
delay the need for levodopa.
They include anticholinergic drugs (eg,
trihexyphenidyl, amantadine) and dopamine agonists
(eg, pramipexole, ropinirole, and pergolide)
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