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

MODELING THE PARKINSONIAN TREMOR AND ITS TREATMENT

Amirkabir University of Technology

Supervisor : Dr Towhidkhah

Designed by Yashar Sarbaz


Titles

PD

TITLES

  • INTRODUCTION OF PARKINSON’S DISEASE (PD)

  • SIMPLE MODELING

  • COMPLETING THE MODEL

  • MODELING THE TREATMENTS


1 intoduction of pd

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


1 1 origion of pd bg

PD

1-1.Origion of PD (BG)


1 2 parts of bg

PD

1-2.Parts of BG


1 3 pd it s symptoms

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


1 3 pd and it s symptoms

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


Clinical data recording

PD

Clinical Data Recording

Velocity laser recording of rest tremor


2 simple modeling

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


2 1 connection of bg

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


2 2 each block of bg

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


Behavior of single neuron

PD

Behavior of single neuron

  • Membrane resistance

  • Membrane capacitance

  • longitudinal resistance


2 3 mathematical model

PD

2-3.Mathematical model


Changing activity of blocks

PD

Changing activity of blocks

Healthy

Patient


Changes of strengths of connections

PD

Changes of strengths of connections


Block diagram of model

PD

Block diagram of model


Relations of each blocks

PD

Relations of each blocks


Relations of each blocks1

PD

Relations of each blocks


Model response for illness case g 10

PD

Model response for illness case ( g=10 )


Model response for treated case g 1

PD

Model response for treated case ( g=1 )


Sample of clinical data

PD

Sample of clinical Data


Comparing power spectra of clinical data and model response

PD

Comparing power spectra of clinical Data and model response

Clinical Data

Model Response


3 completing the model

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


3 1 synaptic transmission

PD

3-1.Synaptic transmission

Step1

Step2


3 1 synaptic transmission1

PD

3-1.Synaptic transmission

Step3&4


3 1 synaptic transmission2

PD

3-1.Synaptic transmission

step5


3 1 synaptic transmission3

PD

3-1.Synaptic transmission

step6


3 2 noise sources in synaptic transmission of healthy persons

PD

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

  • Calsium amount in cell

  • Voltage gated channels

  • Diffusion of neurotransmitters

  • Ligand gated channels


3 3 noise sources in synaptic transmission of patients

PD

3-3.Noise sources in synaptic transmission of patients

  • Lower of uptake

  • Up regulation

  • Diffusion of neurotransmitters


3 4 completing the model

PD

3-4.Completing the model

  • Replacing with

  • Considering normal physiological Tremor:


Comparing results with clinical data

PD

Comparing results with clinical data

Model response

with a=0.2

g2rof record


Comparing results with clinical data1

PD

Comparing results with clinical data

Model response

with a=0.2&b=0.2

S15rof record


Changing activity of blocks1

Changing activity of blocks


4 modeling the treatments

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


4 1 kinds of treatments

PD

4-1.Kinds of Treatments

1-1. Medical treatment

1-2. Deep Brain Stimulation


Medical treatment

PD

Medical Treatment

  • Levodopa Drug

  • L-depernil Drug


Modeling the parkinsonian tremor and its treatment

PD

DBS

Target of Stimulation

  • GPi: The Globus Pallidus Internal

  • STN:The Subthalamic Nucleus

  • Vim: The Ventro-Intermediate nucleus Thlamus


4 2 modeling drug effect

PD

4-2.Modeling drug effect

  • Pharmacodynamics

  • Pharmacokinetics


Pharmacodynamics

PD

Pharmacodynamics

  • Input is Levodopa drug

  • Output is plasma level of drug


Model and clinical data

PD

Model and clinical data


Relation of pharmacodynamics

PD

Relation of Pharmacodynamics


Pharmacokinetics

PD

Pharmacokinetics

  • input is plasma level of drug

  • Output is g parameter of main model


Pharmacokinetics parts

PD

Pharmacokinetics parts

  • A nonlinear system (Saturation element)

  • A first order system

  • Scaling part


Response signal of parmacodynamics part

PD

Response signal of Parmacodynamics part


Response signal of pharmacokinetics part

PD

Response signal of Pharmacokinetics part


Simple model response to drug prescription

PD

Simple model response to drug prescription


Complete model response to drug prescription

PD

Complete model response to drug prescription


4 3 modeling dbs effect

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


Dbs characteristic for different subjects

PD

DBS characteristic for different subjects


Clinical data of subjects when dbs switch to on

PD

Clinical data of subjects when DBS switch to on


Clinical data of subjects when dbs switch to off

PD

Clinical data of subjects when DBS switch to off


Relation of dbs

PD

Relation of DBS


Relation of dbs1

PD

Relation of DBS

,


Variation of parameter of g in dbs

PD

Variation of Parameter of g in DBS

sec

sec


Response of the simple model

PD

Response of the simple model

sec

sec


Response of the complete model

PD

Response of the complete model

sec

sec


4 4 prediction based on the model

PD

4-4.Prediction based on the model

4-4-1.Offering a new medical treatment

4-4-2.Optimization of the levodopa usage


Problems of levodopa usage

PD

Problems of Levodopa usage


4 4 1 offering a new medical treatment

PD

4-4-1.Offering a new medical treatment


Including gaba effect

PD

Including GABA effect


Model response with different g k 1

PD

Model response with different g & k=1

g=10

g=1


Model response with g 10 k 0 1

PD

Model response with g=10 & k=0.1


Model response with g 5 k 0 1

PD

Model response with g=5 & k=0.1


4 4 2 optimization of the levodopa usage

PD

4-4-2.Optimization of the levodopa usage


Optimization problem

PD

Optimization problem


Answer of optimization

PD

Answer of optimization


Modeling the parkinsonian tremor and its treatment

THE END


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