MODELING THE PARKINSONIAN TREMOR AND ITS TREATMENT

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MODELING THE PARKINSONIAN TREMOR AND ITS TREATMENT
Amirkabir University of Technology

• Supervisor Dr Towhidkhah
• Designed by Yashar Sarbaz

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TITLES
PD

• INTRODUCTION OF PARKINSONS DISEASE (PD)
• SIMPLE MODELING
• COMPLETING THE MODEL
• MODELING THE TREATMENTS

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1.Intoduction of PD
PD

• 1-1. Origin of PD (Basal ganglia)
• 1-2. Parts of Basal ganglia (BG)
• 1-3. PD its symptoms

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1-1.Origion of PD (BG)
PD
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1-2.Parts of BG
PD
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1-3.PD its symptoms
PD

• Reason of PD
• Loss of nerve cells in substantia nigra pars
  compacta
• Low level of Dopamine in patients brain
• Changing activity of other blocks

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1-3.PD and its symptoms
PD

• Symptoms of PD
• Hypokinesia
• Akinesia lack of slowness of spontaneous and
  associative movement
• Rigidity increased tone on passive manipulation
  of joints
• Tremorrhythmic,involuntary,oscillatory
• movement around 4-6 Hz

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Clinical Data Recording
PD
Velocity laser recording of rest tremor
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2.Simple modeling
PD

• 2-1.Information about connections of Basal
  ganglia
• 2-2.Information about each block of Basal ganglia
• 2-3.Presenting mathematical model

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2-1.Connection of BG
PD

• The number of input and output of each block
• The type of each input to block (Inhibitory and
  excitatory effect )
• The strength changes of connections in patient
  and healthy cases
• A gain corresponding to Dopamine changes

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2-2.Each block of BG
PD

• There are not detailed information about
  function of each block
• The major criteria for separating the different
  parts of BG are their anatomical and structural
  appearance and the kind of neurotransmitters
• Each block contain large value of neurons

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Behavior of single neuron
PD

• Membrane resistance
• Membrane capacitance
• longitudinal resistance

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2-3.Mathematical model
PD
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Changing activity of blocks
PD
Healthy
Patient
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Changes of strengths of connections
PD
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Block diagram of model
PD
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Relations of each blocks
PD
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Relations of each blocks
PD
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Model response for illness case ( g10 )
PD
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Model response for treated case ( g1 )
PD
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Sample of clinical Data
PD
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Comparing power spectra of clinical Data and
model response
PD
Clinical Data
Model Response
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3.Completing the model
PD

• 3-1.Synaptic transmission
• 3-2.Noise sources in synaptic transmission of
  healthy persons
• 3-3.Noise sources in synaptic transmission of
  patients
• 3-4.Completing the model

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3-1.Synaptic transmission
PD
Step1
Step2
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3-1.Synaptic transmission
PD
Step34
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3-1.Synaptic transmission
PD
step5
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3-1.Synaptic transmission
PD
step6
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3-2.Noise sources in synaptic transmission of
healthy persons
PD

• Calsium amount in cell
• Voltage gated channels
• Diffusion of neurotransmitters
• Ligand gated channels

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3-3.Noise sources in synaptic transmission of
patients
PD

• Lower of uptake
• Up regulation
• Diffusion of neurotransmitters

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3-4.Completing the model
PD

• Replacing with
• Considering normal physiological Tremor

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Comparing results with clinical data
PD
Model response with a0.2
g2rof record
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Comparing results with clinical data
PD
Model response with a0.2b0.2
S15rof record
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Changing activity of blocks
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4.MODELING THE TREATMENTS
PD

• 4-1.Kinds of PD treatments
• 4-2.Modeling drug effect
• 4-3.Modeling DBS effect
• 4-4.Prediction based on the model

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4-1.Kinds of Treatments
PD

• 1-1. Medical treatment
• 1-2. Deep Brain Stimulation

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Medical Treatment
PD

• Levodopa Drug
• L-depernil Drug

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DBS
PD

• Target of Stimulation
• GPi The Globus Pallidus Internal
• STNThe Subthalamic Nucleus
• Vim The Ventro-Intermediate nucleus Thlamus

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4-2.Modeling drug effect
PD

• Pharmacodynamics
• Pharmacokinetics

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Pharmacodynamics
PD

• Input is Levodopa drug
• Output is plasma level of drug

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Model and clinical data
PD
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Relation of Pharmacodynamics
PD
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Pharmacokinetics
PD

• input is plasma level of drug
• Output is g parameter of main model

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Pharmacokinetics parts
PD

• A nonlinear system (Saturation element)
• A first order system
• Scaling part

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Response signal of Parmacodynamics part
PD
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Response signal of Pharmacokinetics part
PD
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Simple model response to drug prescription
PD
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Complete model response to drug prescription
PD
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4-3.Modeling DBS effect
PD

• Characteristics of the common DBS signal
• Frequency greater than 100
• Pulse width about 90
• Amplitude of stimulation voltage nearly 3 v

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DBS characteristic for different subjects
PD
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Clinical data of subjects when DBS switch to on
PD
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Clinical data of subjects when DBS switch to off
PD
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Relation of DBS
PD
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Relation of DBS
PD
,

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Variation of Parameter of g in DBS
PD
sec
sec
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Response of the simple model
PD
sec
sec
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Response of the complete model
PD
sec
sec
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4-4.Prediction based on the model
PD

• 4-4-1.Offering a new medical treatment
• 4-4-2.Optimization of the levodopa usage

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Problems of Levodopa usage
PD
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4-4-1.Offering a new medical treatment
PD
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Including GABA effect
PD
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Model response with different g k1
PD
g10
g1
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Model response with g10 k0.1
PD
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Model response with g5 k0.1
PD
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4-4-2.Optimization of the levodopa usage
PD
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Optimization problem
PD
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Answer of optimization
PD
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THE END