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
TITLES
1. INTRODUCTION OF PARKINSON’S DISEASE (PD)
2. SIMPLE MODELING3. COMPLETING THE MODEL4. MODELING THE TREATMENTS
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)
1-2.Parts of BG
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
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
Clinical Data Recording
Velocity laser recording of rest tremor
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 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 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 Membrane resistance Membrane capacitance longitudinal resistance
2-3.Mathematical model
Changing activity of blocks
Healthy Patient
Changes of strengths of connections
Block diagram of model
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
Relations of each blocks
)(40
1)(
)(40
1.)(:)(
2
14
sGPos
gsSTNo
sGPos
gsSTNosG
)(10
200)(
10
2001)(:)( 225 sSo
sgsSTNo
sgsOUTsG
Model response for illness case ( g=10 )
Model response for treated case ( g=1 )
Sample of clinical Data
Comparing power spectra of clinical Data and model response
Clinical Data Model Response
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
Step1
Step2
3-1.Synaptic transmission
Step3&4
3-1.Synaptic transmission
step5
3-1.Synaptic transmission
step6
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
Lower of uptake Up regulation Diffusion of neurotransmitters
3-4.Completing the model
Replacing with
Considering normal physiological Tremor:
)(tnagg g
50
50)(
s
sGlp
)())(1()()( snsGgbsOUTsOUTo lp
Comparing results with clinical data
g2rof record Model responsewith a=0.2
Comparing results with clinical data
S15rof record Model responsewith a=0.2&b=0.2
Changing activity of blocks
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
1-1. Medical treatment
1-2. Deep Brain Stimulation
Medical Treatment
Levodopa Drug
L-depernil Drug
DBS
Target of Stimulation GPi: The Globus Pallidus Internal
STN:The Subthalamic Nucleus
Vim: The Ventro-Intermediate nucleus Thlamus
4-2.Modeling drug effect
Pharmacodynamics
Pharmacokinetics
Pharmacodynamics
Input is Levodopa drug
Output is plasma level of drug
Model and clinical data
Relation of Pharmacodynamics
)1)(1()(
21 sTsT
kesG
Ts
2461.06073.0
05473.01418
2
1
TT
Tk
Pharmacokinetics
input is plasma level of drug
Output is g parameter of main model
Pharmacokinetics parts
A nonlinear system (Saturation element)
A first order system
Scaling part
Response signal of Parmacodynamics part
Response signal of Pharmacokinetics part
Simple model response to drug prescription
Complete model response to drug prescription
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
DBS characteristic for different subjects
Clinical data of subjects when DBS switch to on
Clinical data of subjects when DBS switch to off
Relation of DBS
ctezz
)( 01
c
c
c
t
tn
tn
n
e
eezz
1
)1(0
)()( 0 tzgtg
ctezz
)( 12
Relation of DBS
1
ctez
c
c
t
tt
e
egtg
1
)1()( 0
0ggg c
,
0g
cteg
11
Variation of Parameter of g in DBS
05.0ct076.0ct sec sec
Response of the simple model
05.0ct076.0ct sec sec
Response of the complete model
05.0ct076.0ct sec sec
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
4-4-1.Offering a new medical treatment
Including GABA effect
Model response with different g & k=1
g=10 g=1
Model response with g=10 & k=0.1
Model response with g=5 & k=0.1
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
Optimization problem
2461.0
121 T
xx
2121 ),( xbxaxxF
0)(89.401500 )/2715.18()/6466.1(1
22 xx eex
025.615242500 221 xxx
Answer of optimization
7977.2613.58 21 xx
hourTmg 6035.0613.58
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