MODELING THE PARKINSONIAN TREMOR AND ITS TREATMENT Supervisor : Dr Towhidkhah Designed by Yashar...

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MODELING THE PARKINSONIAN TREMOR AND ITS TREATMENT Supervisor : Dr Towhidkhah Designed by Yashar Sarbaz Amirkabir University of Technology

Transcript of MODELING THE PARKINSONIAN TREMOR AND ITS TREATMENT Supervisor : Dr Towhidkhah Designed by Yashar...

Page 1: MODELING THE PARKINSONIAN TREMOR AND ITS TREATMENT Supervisor : Dr Towhidkhah Designed by Yashar Sarbaz Amirkabir University of Technology.

MODELING THE PARKINSONIAN TREMOR

AND ITS TREATMENT Supervisor : Dr Towhidkhah

Designed by Yashar Sarbaz

Amirkabir University of Technology

Page 2: MODELING THE PARKINSONIAN TREMOR AND ITS TREATMENT Supervisor : Dr Towhidkhah Designed by Yashar Sarbaz Amirkabir University of Technology.

TITLES

1. INTRODUCTION OF PARKINSON’S DISEASE (PD)

2. SIMPLE MODELING3. COMPLETING THE MODEL4. MODELING THE TREATMENTS

Page 3: MODELING THE PARKINSONIAN TREMOR AND ITS TREATMENT Supervisor : Dr Towhidkhah Designed by Yashar Sarbaz Amirkabir University of Technology.

1.Intoduction of PD

1-1. Origin of PD (Basal ganglia)

1-2. Parts of Basal ganglia (BG)

1-3. PD & it’s symptoms

Page 4: MODELING THE PARKINSONIAN TREMOR AND ITS TREATMENT Supervisor : Dr Towhidkhah Designed by Yashar Sarbaz Amirkabir University of Technology.

1-1.Origion of PD (BG)

Page 5: MODELING THE PARKINSONIAN TREMOR AND ITS TREATMENT Supervisor : Dr Towhidkhah Designed by Yashar Sarbaz Amirkabir University of Technology.

1-2.Parts of BG

Page 6: MODELING THE PARKINSONIAN TREMOR AND ITS TREATMENT Supervisor : Dr Towhidkhah Designed by Yashar Sarbaz Amirkabir University of Technology.

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

Page 7: MODELING THE PARKINSONIAN TREMOR AND ITS TREATMENT Supervisor : Dr Towhidkhah Designed by Yashar Sarbaz Amirkabir University of Technology.

1-3.PD and it’s symptoms

Symptoms of PD: HypokinesiaAkinesia: lack of slowness of

spontaneous and associative movement Rigidity: increased tone on passive

manipulation of joints Tremor:rhythmic,involuntary,oscillatorymovement around 4-6 Hz

Page 8: MODELING THE PARKINSONIAN TREMOR AND ITS TREATMENT Supervisor : Dr Towhidkhah Designed by Yashar Sarbaz Amirkabir University of Technology.

Clinical Data Recording

Velocity laser recording of rest tremor

Page 9: MODELING THE PARKINSONIAN TREMOR AND ITS TREATMENT Supervisor : Dr Towhidkhah Designed by Yashar Sarbaz Amirkabir University of Technology.

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

Page 10: MODELING THE PARKINSONIAN TREMOR AND ITS TREATMENT Supervisor : Dr Towhidkhah Designed by Yashar Sarbaz Amirkabir University of Technology.

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

Page 11: MODELING THE PARKINSONIAN TREMOR AND ITS TREATMENT Supervisor : Dr Towhidkhah Designed by Yashar Sarbaz Amirkabir University of Technology.

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

Page 12: MODELING THE PARKINSONIAN TREMOR AND ITS TREATMENT Supervisor : Dr Towhidkhah Designed by Yashar Sarbaz Amirkabir University of Technology.

Behavior of single neuron Membrane resistance Membrane capacitance longitudinal resistance

Page 13: MODELING THE PARKINSONIAN TREMOR AND ITS TREATMENT Supervisor : Dr Towhidkhah Designed by Yashar Sarbaz Amirkabir University of Technology.

2-3.Mathematical model

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Changing activity of blocks

Healthy Patient

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Changes of strengths of connections

Page 16: MODELING THE PARKINSONIAN TREMOR AND ITS TREATMENT Supervisor : Dr Towhidkhah Designed by Yashar Sarbaz Amirkabir University of Technology.

Block diagram of model

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Relations of each blocks

)(240

10)()),(sgn()(:)(1 sSogs

sAtAtSNcosG

)()30(

10)(

)(30

1)(:)(

2

12

sSNcoss

sSo

sSNcos

sSosG

)(10

501)(

10

101)(:)( 113 sSTNo

sgsSo

sgsGPosG

Page 18: MODELING THE PARKINSONIAN TREMOR AND ITS TREATMENT Supervisor : Dr Towhidkhah Designed by Yashar Sarbaz Amirkabir University of Technology.

Relations of each blocks

)(40

1)(

)(40

1.)(:)(

2

14

sGPos

gsSTNo

sGPos

gsSTNosG

)(10

200)(

10

2001)(:)( 225 sSo

sgsSTNo

sgsOUTsG

Page 19: MODELING THE PARKINSONIAN TREMOR AND ITS TREATMENT Supervisor : Dr Towhidkhah Designed by Yashar Sarbaz Amirkabir University of Technology.

Model response for illness case ( g=10 )

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Model response for treated case ( g=1 )

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Sample of clinical Data

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Comparing power spectra of clinical Data and model response

Clinical Data Model Response

Page 23: MODELING THE PARKINSONIAN TREMOR AND ITS TREATMENT Supervisor : Dr Towhidkhah Designed by Yashar Sarbaz Amirkabir University of Technology.

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

Page 24: MODELING THE PARKINSONIAN TREMOR AND ITS TREATMENT Supervisor : Dr Towhidkhah Designed by Yashar Sarbaz Amirkabir University of Technology.

3-1.Synaptic transmission

Step1

Step2

Page 25: MODELING THE PARKINSONIAN TREMOR AND ITS TREATMENT Supervisor : Dr Towhidkhah Designed by Yashar Sarbaz Amirkabir University of Technology.

3-1.Synaptic transmission

Step3&4

Page 26: MODELING THE PARKINSONIAN TREMOR AND ITS TREATMENT Supervisor : Dr Towhidkhah Designed by Yashar Sarbaz Amirkabir University of Technology.

3-1.Synaptic transmission

step5

Page 27: MODELING THE PARKINSONIAN TREMOR AND ITS TREATMENT Supervisor : Dr Towhidkhah Designed by Yashar Sarbaz Amirkabir University of Technology.

3-1.Synaptic transmission

step6

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

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

Page 29: MODELING THE PARKINSONIAN TREMOR AND ITS TREATMENT Supervisor : Dr Towhidkhah Designed by Yashar Sarbaz Amirkabir University of Technology.

3-3.Noise sources in synaptic transmission of patients

Lower of uptake Up regulation Diffusion of neurotransmitters

Page 30: MODELING THE PARKINSONIAN TREMOR AND ITS TREATMENT Supervisor : Dr Towhidkhah Designed by Yashar Sarbaz Amirkabir University of Technology.

3-4.Completing the model

Replacing with

Considering normal physiological Tremor:

)(tnagg g

50

50)(

s

sGlp

)())(1()()( snsGgbsOUTsOUTo lp

Page 31: MODELING THE PARKINSONIAN TREMOR AND ITS TREATMENT Supervisor : Dr Towhidkhah Designed by Yashar Sarbaz Amirkabir University of Technology.

Comparing results with clinical data

g2rof record Model responsewith a=0.2

Page 32: MODELING THE PARKINSONIAN TREMOR AND ITS TREATMENT Supervisor : Dr Towhidkhah Designed by Yashar Sarbaz Amirkabir University of Technology.

Comparing results with clinical data

S15rof record Model responsewith a=0.2&b=0.2

Page 33: MODELING THE PARKINSONIAN TREMOR AND ITS TREATMENT Supervisor : Dr Towhidkhah Designed by Yashar Sarbaz Amirkabir University of Technology.

Changing activity of blocks

Page 34: MODELING THE PARKINSONIAN TREMOR AND ITS TREATMENT Supervisor : Dr Towhidkhah Designed by Yashar Sarbaz Amirkabir University of Technology.

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

Page 35: MODELING THE PARKINSONIAN TREMOR AND ITS TREATMENT Supervisor : Dr Towhidkhah Designed by Yashar Sarbaz Amirkabir University of Technology.

4-1.Kinds of Treatments

1-1. Medical treatment

1-2. Deep Brain Stimulation

Page 36: MODELING THE PARKINSONIAN TREMOR AND ITS TREATMENT Supervisor : Dr Towhidkhah Designed by Yashar Sarbaz Amirkabir University of Technology.

Medical Treatment

Levodopa Drug

L-depernil Drug

Page 37: MODELING THE PARKINSONIAN TREMOR AND ITS TREATMENT Supervisor : Dr Towhidkhah Designed by Yashar Sarbaz Amirkabir University of Technology.

DBS

Target of Stimulation GPi: The Globus Pallidus Internal

STN:The Subthalamic Nucleus

Vim: The Ventro-Intermediate nucleus Thlamus

Page 38: MODELING THE PARKINSONIAN TREMOR AND ITS TREATMENT Supervisor : Dr Towhidkhah Designed by Yashar Sarbaz Amirkabir University of Technology.

4-2.Modeling drug effect

Pharmacodynamics

Pharmacokinetics

Page 39: MODELING THE PARKINSONIAN TREMOR AND ITS TREATMENT Supervisor : Dr Towhidkhah Designed by Yashar Sarbaz Amirkabir University of Technology.

Pharmacodynamics

Input is Levodopa drug

Output is plasma level of drug

Page 40: MODELING THE PARKINSONIAN TREMOR AND ITS TREATMENT Supervisor : Dr Towhidkhah Designed by Yashar Sarbaz Amirkabir University of Technology.

Model and clinical data

Page 41: MODELING THE PARKINSONIAN TREMOR AND ITS TREATMENT Supervisor : Dr Towhidkhah Designed by Yashar Sarbaz Amirkabir University of Technology.

Relation of Pharmacodynamics

)1)(1()(

21 sTsT

kesG

Ts

2461.06073.0

05473.01418

2

1

TT

Tk

Page 42: MODELING THE PARKINSONIAN TREMOR AND ITS TREATMENT Supervisor : Dr Towhidkhah Designed by Yashar Sarbaz Amirkabir University of Technology.

Pharmacokinetics

input is plasma level of drug

Output is g parameter of main model

Page 43: MODELING THE PARKINSONIAN TREMOR AND ITS TREATMENT Supervisor : Dr Towhidkhah Designed by Yashar Sarbaz Amirkabir University of Technology.

Pharmacokinetics parts

A nonlinear system (Saturation element)

A first order system

Scaling part

Page 44: MODELING THE PARKINSONIAN TREMOR AND ITS TREATMENT Supervisor : Dr Towhidkhah Designed by Yashar Sarbaz Amirkabir University of Technology.

Response signal of Parmacodynamics part

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Response signal of Pharmacokinetics part

Page 46: MODELING THE PARKINSONIAN TREMOR AND ITS TREATMENT Supervisor : Dr Towhidkhah Designed by Yashar Sarbaz Amirkabir University of Technology.

Simple model response to drug prescription

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Complete model response to drug prescription

Page 48: MODELING THE PARKINSONIAN TREMOR AND ITS TREATMENT Supervisor : Dr Towhidkhah Designed by Yashar Sarbaz Amirkabir University of Technology.

4-3.Modeling DBS effect

Characteristics of the common DBS signal:

1. Frequency greater than 100 2. Pulse width about 90 3. Amplitude of stimulation voltage

nearly 3 v

sec

Page 49: MODELING THE PARKINSONIAN TREMOR AND ITS TREATMENT Supervisor : Dr Towhidkhah Designed by Yashar Sarbaz Amirkabir University of Technology.

DBS characteristic for different subjects

Page 50: MODELING THE PARKINSONIAN TREMOR AND ITS TREATMENT Supervisor : Dr Towhidkhah Designed by Yashar Sarbaz Amirkabir University of Technology.

Clinical data of subjects when DBS switch to on

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Clinical data of subjects when DBS switch to off

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Relation of DBS

ctezz

)( 01

c

c

c

t

tn

tn

n

e

eezz

1

)1(0

)()( 0 tzgtg

ctezz

)( 12

Page 53: MODELING THE PARKINSONIAN TREMOR AND ITS TREATMENT Supervisor : Dr Towhidkhah Designed by Yashar Sarbaz Amirkabir University of Technology.

Relation of DBS

1

ctez

c

c

t

tt

e

egtg

1

)1()( 0

0ggg c

,

0g

cteg

11

Page 54: MODELING THE PARKINSONIAN TREMOR AND ITS TREATMENT Supervisor : Dr Towhidkhah Designed by Yashar Sarbaz Amirkabir University of Technology.

Variation of Parameter of g in DBS

05.0ct076.0ct sec sec

Page 55: MODELING THE PARKINSONIAN TREMOR AND ITS TREATMENT Supervisor : Dr Towhidkhah Designed by Yashar Sarbaz Amirkabir University of Technology.

Response of the simple model

05.0ct076.0ct sec sec

Page 56: MODELING THE PARKINSONIAN TREMOR AND ITS TREATMENT Supervisor : Dr Towhidkhah Designed by Yashar Sarbaz Amirkabir University of Technology.

Response of the complete model

05.0ct076.0ct sec sec

Page 57: MODELING THE PARKINSONIAN TREMOR AND ITS TREATMENT Supervisor : Dr Towhidkhah Designed by Yashar Sarbaz Amirkabir University of Technology.

4-4.Prediction based on the model

4-4-1.Offering a new medical treatment

4-4-2.Optimization of the levodopa usage

Page 58: MODELING THE PARKINSONIAN TREMOR AND ITS TREATMENT Supervisor : Dr Towhidkhah Designed by Yashar Sarbaz Amirkabir University of Technology.

Problems of Levodopa usage

Page 59: MODELING THE PARKINSONIAN TREMOR AND ITS TREATMENT Supervisor : Dr Towhidkhah Designed by Yashar Sarbaz Amirkabir University of Technology.

4-4-1.Offering a new medical treatment

Page 60: MODELING THE PARKINSONIAN TREMOR AND ITS TREATMENT Supervisor : Dr Towhidkhah Designed by Yashar Sarbaz Amirkabir University of Technology.

Including GABA effect

Page 61: MODELING THE PARKINSONIAN TREMOR AND ITS TREATMENT Supervisor : Dr Towhidkhah Designed by Yashar Sarbaz Amirkabir University of Technology.

Model response with different g & k=1

g=10 g=1

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Model response with g=10 & k=0.1

Page 63: MODELING THE PARKINSONIAN TREMOR AND ITS TREATMENT Supervisor : Dr Towhidkhah Designed by Yashar Sarbaz Amirkabir University of Technology.

Model response with g=5 & k=0.1

Page 64: MODELING THE PARKINSONIAN TREMOR AND ITS TREATMENT Supervisor : Dr Towhidkhah Designed by Yashar Sarbaz Amirkabir University of Technology.

4-4-2.Optimization of the levodopa usage

T

cbTF ),(

)(89.40)( )2461.0(2715.18)2461.0(6466.1 tt eety

)(89.401500 )2461.0(2715.18)2461.0(6466.1 TT ee

250024

T

Page 65: MODELING THE PARKINSONIAN TREMOR AND ITS TREATMENT Supervisor : Dr Towhidkhah Designed by Yashar Sarbaz Amirkabir University of Technology.

Optimization problem

2461.0

121 T

xx

2121 ),( xbxaxxF

0)(89.401500 )/2715.18()/6466.1(1

22 xx eex

025.615242500 221 xxx

Page 66: MODELING THE PARKINSONIAN TREMOR AND ITS TREATMENT Supervisor : Dr Towhidkhah Designed by Yashar Sarbaz Amirkabir University of Technology.

Answer of optimization

7977.2613.58 21 xx

hourTmg 6035.0613.58

Page 67: MODELING THE PARKINSONIAN TREMOR AND ITS TREATMENT Supervisor : Dr Towhidkhah Designed by Yashar Sarbaz Amirkabir University of Technology.