Study of Stimulus Waveform Effect on Nerve Excitability and SENN - - PowerPoint PPT Presentation

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Study of Stimulus Waveform Effect on Nerve Excitability and SENN - - PowerPoint PPT Presentation

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Biomedicine and Molecular Biosciences COST Action BM1309 EMF-MED COST EMF-MED European network for innovative uses of EMFs in biomedical applications Study of Stimulus Waveform Effect on Nerve Excitability and SENN model verification in

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Biomedicine and Molecular Biosciences

COST Action BM1309 EMF-MED

COST EMF-MED European network for innovative uses of EMFs in biomedical applications

Study of Stimulus Waveform Effect on Nerve Excitability and SENN model verification in Lumbricus Terrestris as a Convenient Animal Model

  • Prof. Antonio Šarolić, PhD

Zlatko Živković, PhD FESB Split

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Biomedicine and Molecular Biosciences

COST Action BM1309 EMF-MED 2

Contents

  • 1. Introduction
  • 2. SENN model
  • 3. Animal model
  • 4. Measurement setup
  • 4. Measurement/simulation results
  • 5. Conclusion
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Biomedicine and Molecular Biosciences

COST Action BM1309 EMF-MED 3

Contents

  • 1. Introduction
  • 2. SENN model
  • 3. Animal model
  • 4. Measurement setup
  • 4. Measurement/simulation results
  • 5. Conclusion
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Introduction

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  • single axon studies
  • effects of stimulus parameters
  • computational stimulation model
  • controllable measurements
  • transition ELF -> higher frequencies (IF range)
  • complex pulses (single or repetitive)
  • optimized biomedical effects (healing, pain relief,…)
  • EMF safety (human exposure)
  • waveform effects (temporal and frequency parameters)
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Terminology

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  • Threshold level Vth [mV] - the transmembrane voltage level that should be exceeded

to excite the action potential.

  • Stimulus threshold level ITH [mA] - the minimum stimulus current magnitude (peak

value) just sufficient to excite the nerve and initiate AP propagation.

  • Monopolar stimulation - the type of electrical stimulation with the active electrode

positioned near the nerve that wants to be stimulated.

  • Bipolar stimulation - the type of stimulation where both the active and return

electrode are placed in the close proximity to an axon

  • Monophasic stimulus - the stimulus with unidirectional current
  • Biphasic stimulus - the stimulus with bidirectional current
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Biomedicine and Molecular Biosciences

COST Action BM1309 EMF-MED 6

Contents

  • 1. Introduction
  • 2. SENN model
  • 3. Animal model
  • 4. Measurement setup
  • 4. Measurement/simulation results
  • 5. Conclusion
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McNeal’s and SENN model of myelinated axon

rm cm Vr INTRACELLULAR MEDIUM EXTRACELLULAR MEDIUM rm cm Vr rm cm Vr Ri Ri Ri Ri

Vi,n-1 Vi,n Vi,n+1 Ve,n-1 Ve,n Ve,n+1

 

n m m i,n i i,n-1 i,n i,n+1

d 2 d V I C I G V V V t       

2 i

π 4

i i

d G L    

i

100 L D  0.7 d D 

 

n i n-1 n n+1 e,n-1 e,n e,n+1 i,n m

d 1 2 2 d V G V V V V V V I t C             

Vn=Vi,n-Ve,n

Second spatial difference of unknown transmembrane potential Second spatial difference of extracellural liqid potential (activation function): Δ2Ve,n=> Δ2Ve,n/Δx2=ΔEe,n/Δx

 

i,n Na K P L

π I d w J J J J       

Na Na n Na K K n K P P n P L L n L

( ) ( ) ( ) ( ) J G V V J G V V J G V V J G V V            

SENN model

Activation function

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Parameter Value Fiber diameter (D) 20 µm Axon diameter at node (d) 0.7∙D Nodal gap (w) 2.5 µm Axoplasmic resistivity (ρi) 100 Ωm External medium resistivity (ρe) 300 Ωm Membrane capacitance (cm) 2 µF/cm2 Membrane conductivity (gm) 30.4 mS/cm2 Internodal distance (Li) 100∙D

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SENN model parameters

0,1 0,2 0,3 0,4 0,5 0,6 1 10 100 1000 σe [S/m] f [kHz]

yA=5 mm L=20∙yA=10 cm NR=51 nodes

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Equivalent time constant - τ

c

ln 2    

approximate chronaxie (τc) – equivalent time constant (τ) relation

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τ=110 µs

rb rb

Q I  

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Biomedicine and Molecular Biosciences

COST Action BM1309 EMF-MED 10

Contents

  • 1. Introduction
  • 2. SENN model
  • 3. Animal model
  • 4. Measurement setup
  • 4. Measurement/simulation results
  • 5. Conclusion
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Lumbricus terrestris (Earthworm)

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Earthworm

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Why Earthworm (lat. Lumbricus Terrestris)

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Biomedicine and Molecular Biosciences

COST Action BM1309 EMF-MED 13

Contents

  • 1. Introduction
  • 2. SENN model
  • 3. Animal model
  • 4. Measurement setup
  • 4. Measurement/simulation results
  • 5. Conclusion
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SLIDE 14

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Measurement setup

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Measurement setup (photo)

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Biomedicine and Molecular Biosciences

COST Action BM1309 EMF-MED 16

Contents

  • 1. Introduction
  • 2. SENN model
  • 3. Animal model
  • 4. Measurement setup
  • 4. Measurement/simulation results
  • 5. Conclusion
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Single/repetitive monophasic square pulses

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20 40 60 80 100 120 0,2 0,4 0,6 0,8 1 Transmembrane voltage change [mV] t [ms] 1.1*I_TH I_TH 0.9*I_TH 0.5*I_TH

20 40 60 80 100 120 0.2 0.4 0.6 0.8 1 Transmembrane voltage change [mV] t [ms] 1.1*I_TH I_TH 0.8*I_TH 0.5*I_TH

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20 40 60 80 100 120 2 4 6 Transmembrane voltage change [mV] t [ms] 1.2 * I_TH I_TH 0.8 * I_TH

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20 40 60 80 100 120 1 2 3 4 Transmembrane voltage change [mV] t [ms] Case 2 1.2 * I_TH I_TH 0.8 * I_TH

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20 40 60 80 100 120 140 1 2 3 4 Transmembrane voltage change [mV] t [ms] Case 3 1.2 * I_TH I_TH 0.8 * I_TH

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20 40 60 80 100 120 0,2 0,4 0,6 0,8 1 Transmembrane voltage change [mV] t [ms] 1.2 * I_TH I_TH 0.8 * I_TH

Single pulse Repetitive pulses

tD=10 µs≈0.1τ ITH=24.75 mA tD=200 µs≈2τ ITH=4.15 mA tD=200 µs≈2τ tP=200 µs≈2τ ITH=3.21mA tD=200 µs≈2τ tP=10µs≈0.1τ ITH=2.21 mA tD=10 µs≈0.1τ tP=200 µs≈2τ ITH=15 mA tD=10 µs≈0.1τ tP=10 µs≈0.1τ ITH=4.5 mA

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Single/repetitive monophasic square pulses (2)

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 

single TH SR repetitive TH

dB 20log I I  

2 4 6 8 10 12 14 10 100 1000

ΔSR [dB] tD [μs]

tP=10 μs tP=30 μs tP=50 μs tP=100 μs tP=300 μs

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20 40 60 80 100 120 0,5 1 1,5 2 2,5 Transmembrane voltage change [mV] t [ms]

tD=100 µs

I_TH=4.31 mA 0.8*I_TH

Single/repetitive biphasic square pulses

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Single pulse Repetitive pulses

tD=100 µs≈τ

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30 60 90 120 0,2 0,4 0,6 0,8 Transmembrane voltage change [mV] t [ms]

D=100 µs

I_TH=4.68 mA 0.8*I_TH

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20 40 60 80 100 120 0,2 0,4 0,6 0,8 1 Transmembrane voltage change [mV] t [ms]

D=10 µs

I_TH=51.5 mA 0.8*I_TH

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30 60 90 120 0,2 0,4 0,6 0,8 1 Transmembrane voltage change [mV] t [ms]

µs

I_TH=27 mA 0.8*I_TH

tD=10 µs≈0.1τ tD=100 µs≈τ tD=10 µs≈0.1τ

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Single/repetitive biphasic square pulses (2)

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10 20 30 40 50 60 10 100 1000 ITH [mA] tD [µs] Single monophasic pulse Single biphasic pulse 10 monophasic pulses 10 biphasic pulses

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Single cycle/continuous sinusoid

Single cycle Continuous

ITH=6.2 mA

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20 40 60 80 100 120 0,5 1 1,5 2 Transmembrane voltage change [mV] t [ms] tD=100 µs 1.2*I_TH I_TH 0.8*I_TH

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20 40 60 80 100 120 0,2 0,4 0,6 0,8 Transmembrane voltage change [mV] t [ms] tD=10 µs 1.2*I_TH I_TH 0.8*I_TH

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20 40 60 80 100 120 140 1 2 3 4 Transmembrane voltage change [mV] t [ms] tD=100 µs 1.2*I_TH I_TH 0.8*I_TH

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20 40 60 80 100 120 140 160 0,2 0,4 0,6 0,8 1 Transmembrane voltage change [mV] t [ms] tD=10 µs 1.2*I_TH I_TH 0.8*I_TH

ITH=75 mA ITH=5.6 mA ITH=36.5mA

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Single cycle/continuous sinusoid (2)

10 20 30 40 50 60 70 80 10 100 1000 ITH [mA] tD [µs] Single monophasic pulse Single sinusoidal cycle 10 monophasic pulses 10 sinusoidal cycles

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Equivalence between repetitive monophasic square pulses and continuous sinusoid - tD=tP

0.2 0.4 0.6 0.8 1 1 10 100 ∆S/P fc [kHz]

1 2 3 4 5 6 7 8 9 10 11 0.01 0.1 1 10 100 ∆S/P f [kHz] 1 cycle 5 cycles 10 cycles 20 cycles 50 cycles 100 cycles

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D

1 2 f t  

c D

sine(rms) TH S/P pulse(peak) TH 1/2 f t

I I

 

1 10 100 1 10 100 ITH [mA] fc [kHz] Single monophasic pulse with tD=1/2fc (peak value) Continuous sinusoid with frequency fc (RMS value)

c D

sine(rms) TH S/P pulse(peak) TH 1/2 f t

I I

 

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Measurement results – SD curves

2 4 6 8 10 12 1 2 3 4 5 ITH [mA] tD [ms] Worm 1 Worm 2 Worm 3 Worm 4 Worm 5

Chronaxie - τc [ms] Time constant - τ [ms] Earthworm 1 1 1.44 Earthworm 2 1 1.44 Earthworm 3 1.05 1.51 Earthworm 4 0.5 0.72 Earthworm 5 0.55 0.8 SENN 0.078 0.11

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Measurement results – monophasic square pulse

1 10 100 0.001 0.01 0.1 1 10 ITH/Irb ϒD=tD/τ Worm 1 SENN 1 10 100 0.001 0.01 0.1 1 10 ITH/Irb ϒD=tD/τ Worm 2 SENN 1 10 100 0.01 0.1 1 10 ITH/Irb ϒD=tD/τ Worm 3 SENN 1 10 100 0.01 0.1 1 10 ITH/Irb ϒD=tD/τ Worm 4 SENN 1 10 100 0.01 0.1 1 ITH/Irb ϒD=tD/τ Worm 5 SENN

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Measurement results – continuous sinusoid

0,1 1 10 0,1 1 10 ITH [mA] f [kHz] Worm 1 Worm 2 Worm 3 Worm 4 Worm 5

1 10 100 0.01 0.1 1 10 ITH/Irb ϒD=tD/τ Worm 1 SENN 1 10 100 0.01 0.1 1 10 ITH/Irb ϒD=tD/τ Worm 2 SENN 1 10 100 0.01 0.1 1 10 ITH/Irb ϒD=tD/τ Worm 3 SENN 1 10 100 0.01 0.1 1 10 ITH/Irb ϒD=tD/τ Worm 4 SENN 1 10 100 0.01 0.1 1 10 ITH/Irb ϒD=tD/τ Worm 5 SENN

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Comparison of the single monophasic square pulse and continuous sinusoid with equal tD (fc=1/2tD)

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1 2 3 4 0,01 0,1 1 10 ∆S/P ϒD=tD/τ Worm 1 Worm 2 Worm 3 Worm 4 Worm 5 SENN

Comparison of the repetitive biphasic square pulses and continuous sinusoid with equal tD (fc=1/2tD)

1 2 3 4 5 6 7 8 0,01 0,1 1 10 ITH [mA] f [kHz] Sinusoid Biphasic square wave 0,2 0,4 0,6 0,8 1 1,2 0,01 0,1 1 10 ∆S/P ϒD=tD/τ Measurements SENN results

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Comparison of the repetitive monophasic square pulses and continuous sinusoid with equal tD and tP (fc=1/2tD)

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Comparison of the repetitive monophasic square pulses with arbitrary phase/pause durations and continuous sinusoid with (fc=1/2tD)

0,1 1 0,01 0,1 1 10 ITH [mA] ϒ=tD/τ [ms] tD=tP Single pulse Repetitive pulses (tP=tD)

1 2 3 4 5 6 7 8 9 10 11 12 13 14 0,01 0,1 1 10 ∆S/P ϒD=tD/τ tD=tP Measurement results SENN results

0,2 0,4 0,6 0,8 1 1,2 0,001 0,01 0,1 1 10 ∆P/S(ϒD,ϒP) ϒP=tP/τ tD=3τ Measurement results SENN results 0,2 0,4 0,6 0,8 1 0,001 0,01 0,1 1 10 ∆P/S(ϒD,ϒP) ϒP=tP/τ

tD=τ

Measurement results SENN results 0,1 0,2 0,3 0,4 0,5 0,6 0,7 0,001 0,01 0,1 1 10 ∆P/S(ϒD,ϒP) ϒP=tP/τ tD=0.1τ Measurement results SENN results

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Conclusion

The study produced a set of results that nicely agree both with the theory and with SENN model, proving that this setup could be conveniently used for following studies.

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THANK YOU FOR YOUR ATTENTION!

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