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. PD. TITLES. INTRODUCTION OF PARKINSON’S DISEASE (PD) SIMPLE MODELING COMPLETING THE MODEL MODELING THE TREATMENTS. PD. 1.Intoduction of PD.

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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


PD

TITLES

  • INTRODUCTION OF PARKINSON’S DISEASE (PD)

  • SIMPLE MODELING

  • COMPLETING THE MODEL

  • MODELING THE TREATMENTS


PD

1.Intoduction of PD

1-1. Origin of PD (Basal ganglia)

1-2. Parts of Basal ganglia (BG)

1-3. PD & it’s symptoms


PD

1-1.Origion of PD (BG)


PD

1-2.Parts of BG


PD

1-3.PD & it’s symptoms

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


PD

1-3.PD and it’s symptoms

Symptoms of PD:

  • Hypokinesia

    Akinesia: lack of slowness of spontaneous and associative movement

    Rigidity: increased tone on passive manipulation of joints

  • Tremor:rhythmic,involuntary,oscillatory

    movement around 4-6 Hz


PD

Clinical Data Recording

Velocity laser recording of rest tremor


PD

2.Simple modeling

2-1.Information about connections of Basal ganglia

2-2.Information about each block of Basal ganglia

2-3.Presenting mathematical model


PD

2-1.Connection of BG

  • 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


PD

2-2.Each block of BG

  • 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


PD

Behavior of single neuron

  • Membrane resistance

  • Membrane capacitance

  • longitudinal resistance


PD

2-3.Mathematical model


PD

Changing activity of blocks

Healthy

Patient


PD

Changes of strengths of connections


PD

Block diagram of model


PD

Relations of each blocks


PD

Relations of each blocks


PD

Model response for illness case ( g=10 )


PD

Model response for treated case ( g=1 )


PD

Sample of clinical Data


PD

Comparing power spectra of clinical Data and model response

Clinical Data

Model Response


PD

3.Completing the model

  • 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


PD

3-1.Synaptic transmission

Step1

Step2


PD

3-1.Synaptic transmission

Step3&4


PD

3-1.Synaptic transmission

step5


PD

3-1.Synaptic transmission

step6


PD

3-2.Noise sources in synaptic transmission of healthy persons

  • Calsium amount in cell

  • Voltage gated channels

  • Diffusion of neurotransmitters

  • Ligand gated channels


PD

3-3.Noise sources in synaptic transmission of patients

  • Lower of uptake

  • Up regulation

  • Diffusion of neurotransmitters


PD

3-4.Completing the model

  • Replacing with

  • Considering normal physiological Tremor:


PD

Comparing results with clinical data

Model response

with a=0.2

g2rof record


PD

Comparing results with clinical data

Model response

with a=0.2&b=0.2

S15rof record


Changing activity of blocks


PD

4.MODELING THE TREATMENTS

4-1.Kinds of PD treatments

4-2.Modeling drug effect

4-3.Modeling DBS effect

4-4.Prediction based on the model


PD

4-1.Kinds of Treatments

1-1. Medical treatment

1-2. Deep Brain Stimulation


PD

Medical Treatment

  • Levodopa Drug

  • L-depernil Drug


PD

DBS

Target of Stimulation

  • GPi: The Globus Pallidus Internal

  • STN:The Subthalamic Nucleus

  • Vim: The Ventro-Intermediate nucleus Thlamus


PD

4-2.Modeling drug effect

  • Pharmacodynamics

  • Pharmacokinetics


PD

Pharmacodynamics

  • Input is Levodopa drug

  • Output is plasma level of drug


PD

Model and clinical data


PD

Relation of Pharmacodynamics


PD

Pharmacokinetics

  • input is plasma level of drug

  • Output is g parameter of main model


PD

Pharmacokinetics parts

  • A nonlinear system (Saturation element)

  • A first order system

  • Scaling part


PD

Response signal of Parmacodynamics part


PD

Response signal of Pharmacokinetics part


PD

Simple model response to drug prescription


PD

Complete model response to drug prescription


PD

4-3.Modeling DBS effect

Characteristics of the common DBS signal:

  • Frequency greater than 100

  • Pulse width about 90

  • Amplitude of stimulation voltage nearly 3 v


PD

DBS characteristic for different subjects


PD

Clinical data of subjects when DBS switch to on


PD

Clinical data of subjects when DBS switch to off


PD

Relation of DBS


PD

Relation of DBS

,


PD

Variation of Parameter of g in DBS

sec

sec


PD

Response of the simple model

sec

sec


PD

Response of the complete model

sec

sec


PD

4-4.Prediction based on the model

4-4-1.Offering a new medical treatment

4-4-2.Optimization of the levodopa usage


PD

Problems of Levodopa usage


PD

4-4-1.Offering a new medical treatment


PD

Including GABA effect


PD

Model response with different g & k=1

g=10

g=1


PD

Model response with g=10 & k=0.1


PD

Model response with g=5 & k=0.1


PD

4-4-2.Optimization of the levodopa usage


PD

Optimization problem


PD

Answer of optimization


THE END


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