basal ganglia
DESCRIPTION
BASAL GANGLIA. Amirkabir University of Technology. Supervisor: Dr Towhidkhah Designed by Yashar Sarbaz. Systems-Level Neural Modelling: What and Why?. We know a lot about the brain! Need to integrate data: molecular/ cellular/ systems levels. - PowerPoint PPT PresentationTRANSCRIPT
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BASAL GANGLIA
Supervisor: Dr TowhidkhahDesigned by Yashar Sarbaz
Amirkabir University of Technology
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Systems-Level Neural Modelling: What and Why?
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 SystemAssociative Cortex Middle Level (Motor Program):CerebellumMotor CortexBasal Ganglia Lowest Level (Movement):Spinal CordMuscular-Skeletal System
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Movement Block Diagram
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Brain
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Learning Strategies Supervised Learning (Cerebellum)
Reinforcement Learning (Basal Ganglia)
Unsupervised Learning (Cerebral Cortex)
Symbolic Learning (Hippocampal System)
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Learning Strategies
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Learning Strategies
thalamus
SN
IO
Cortex
BasalGanglia
Cerebellum
target
error+
-
outputinput
Cerebellum: Supervised Learning
reward
outputinput
Basal Ganglia: Reinforcement Learning
Cerebral Cortex : Unsupervised Learning
outputinput
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Basal Ganglia
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 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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It is one of the Old Area of Brain
BG with Thalamus act like a Little Brain
It is Like Funnel
Basal Ganglia
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BG Functions
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 control2.Reinforcement learning3.Sensorymotor associative learning4.Adaptive timing5.Temporal order learning6.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 Striatum: Putamen and Caudate
Globus Pallidus: External and Internal
Subthalamic Nucleus
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
PF: Prefrontal SMA: Supplementary
Motor Area M1: Primary Motor
Cortex PMv: Ventral pre-motor
Area C/P: Caudate Nucleus
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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
Disorders of the BG
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BG Diseases 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
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
Such diversity of function embodied in such an intricately organized structure, has inspired numerous models of basal ganglia function ranging from sensory-motor associative to the formation of motor plans
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Conceptual Models
BG as link between limbic system and motor output (eye movement)
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BG and learning to cortex to select a sequence
Conceptual Models
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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
Temporal Difference (TD) error:
A general idea of “goodness” is used to adjust how the system learns
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Reinforcement Learning Framework for learning state-action
mapping (policy) by exploration and reward feedback Critic
reward prediction Actor
action selection Learning
external reward r internal reward : difference from prediction
environment
reward r
action a
state s
agent
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Dopamine and Learning
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
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
)(t
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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
Reinforcement Learning and BG
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Reinforcement Learning and BG
Striatum striosome &
matrix dopamine-
dependent plasticity
Dopamine neurons
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 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 theShaking 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 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
Not clear Exactly Main Hypothesis:1. Free Radicals: Antioxidant
Molecules2. Genetic Factors3. Environmental Toxins: MPTP,
Retenone, 6Hydroxy Dopamin4. SNc Cells Age Faster than Normal
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Symptoms of PD
Movement Symptoms
Cognition Symptoms
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Cognition Symptoms Dementia Depression Anxiety and Panic Sleep Disorders Cognitive impairment Psychosis Behavioural disturbances Bradyphrenia: off Thinking
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Cognition Symptoms 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 movementAkinesia: lack or slowness of spontaneous
and associative movementsRigidity: increased tone on passive
manipulation of joints IrregularitiesTremor: rhythmic, involuntary, oscillatory
movements around 4-6 Hz Gait Disturbance: shuffling gait,
Freezing
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Problems in Diagnosis 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 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 At Least Two of these Four Features
(Cardinal Features):TremorRigidityAkinesiaGait disturbance 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
Inhibition of GPi Theory
BG Selective Theory
Oscillatory Theory
Complex Dynamic System Theory
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BG Changes in PD
Normal Person
ParkinsonianPerson
[Kandel, 2000]
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States of disease
After unfolding movement Symptoms
Before unfolding movement Symptoms
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Treatments for PD
Nonpharmacologic treatment
Pharmacologic treatment
Surgical treatment
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Nonpharmacologic treatment
EDUCATION (www.wemove.org) SUPPORT EXERCISE NUTRITION
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Pharmacologic treatment
NEUROPROTECTIVE THERAPY
SYMPTOMATIC THERAPY
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NEUROPROTECTIVE THERAPY 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
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 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)
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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