Ch2Ch1

Bioelectronics Laboratory - The Yoshida Lab

In-silico Model Framework of the Neural Interface A realistic model to understand the biophysics and inform interface design

Biophysics & Modeling - Electrode Coupling Function - Electrode Sensitivity Function - Active Nerve Fiber Model - Neural Interface Design Tools - In-silico Model Framework

Instrumentation, System Control, Signal Processing - Spike Detection and Tracking - Closed Loop Control of FES - Kalman Filter System Identification - Universal Invertible Amplifier - Rapid Impedance Measurement

Neural Interfaces - thin film LIFE - TIME - microTIME - Multi-Contact Cuff

Biointegration & Biocompatibility - in-vivo Testing - Histology - Shaping of Glial Scarring - Softening Electrode Structures

Disruptive Technologies - GraFET Bioelectric Interface - Configurable Artificial Neural Net Chip - PS1 Light Activated Muscle - Low Frequency Alternating Current Nerve Block

Basic Science- Characterization of Tissue Properties- Biophysics of Membranes and Channels- Sensory Motor Electrophysiology

Sensory-Motor Bioelectronic Therapies - Operant Conditioning and Sensory Replacement Therapy for Phantom Limb Pain - Functional Electrical Stimulation - Bioelectronic Medicines

Neural engineering to translate neuroscience to therapies, develop bioelectronic medicines and improve the quality of life of those with sensory-motor injuries & diseases

Research Areas and Projects

Low Frequency Alternating Current BlockExperimental in-vivo measurement of % block

well formed

stites

25μm TungstenNeedle

μTIME

Intacttraces

The microTIME Electrode ArrayA gateway to the Autonomic Nervous System

Contact: Ken Yoshida Office: SL220F Ph: +1 (317) 274-9714 Email: yoshidak@iupui.edu

The Team10.2019

A means to do the impossible: Access the information in small caliber nerve fibers

VR

VL

REF

Wagner

DP-311 Amp

RadnotiPressure

Transducer

Trac

hea

ECG

LFACb

BP

Digitimer

DS-3 Stimulator

VStim

Rigol DG-5072 Func Gen

SRS CS-580

Current Source

Experimental ParadigmTwo Pt-Ir bipolar hook electrode sets (800μm anode/cathode spacing, FHC, Bowdoin, ME) were positioned on the exposed left cervical vagus nerve. Standard rectangular pulse trains (1 ms PW, 25 Hz, 10 pulses, 1 Hz train rate) were applied to the vagus nerve to evoke bradycardia and hypotension. Adequate block amplitude was determined using a 1 Hz sinusoidal waveform and increasing the amplitude of the waveform until the effect of the vagal stimulation was blocked. To test the effect of LFACb, the vagal stimulus train and the LFACb waveform were presented in a regular continuous sequence as follows: (1) Pre: 20s baseline period of no stimulation(2) LFAC_only: 20s LFACb delivered to the caudal electrode(3) LFAC+VStim: 20s LFACb at the caudal electrode and vagal stimulation at the rostral electrode(4) VStim_only: Vagal stimulation at rostral electrode until BP falls below ~50mmHg(5) Post: No stimulation return to baseline

RR

Rat

e (H

z)

1

2

3

4

5

Time (s)0 10 20 30 40 50 60 70 80 90

Mea

n B

P (

mm

Hg)

0

20

40

60

80

100

120Pre LFAC only LFAC+VStim VStim Post

Time (s)

ECG vs LFAC and Vagal StimulationRat 56 Test Case

Filt

ered

EC

G (

mV

)

0 10 20 30 40 50 60 70 80 90-1

-0.5

0

0.5

Pre LFAC only LFAC+VStim VStim Post

21 22 36 37 51 52 60 61 91 92

Pre LFAC only LFAC+Stim Stim only Post

-0.6

-0.4

-0.2

0

0.2

0.4

Filt

ered

EC

G (

mV

)

Time (s)

In-silico Experiments of LFAC Block

Block

ConductingAction Potential

Blocking CuffIntracellularStimulation

Nerve Fascicle

Nerve Fiber

2μA

150

100

50

00 10 20 30 40 50

Position (mm)

Tim

e (m

s)

3μA

150

100

50

00 10 20 30 40 50

Position (mm)

Tim

e (m

s)

Action potential initiated

Conducting AP

Electrode Contacts

LFAC Block

AP Slowing

50

0

-50

-100

-150

Tra

nsm

embr

ane

Po

tent

ial (

mV

)

Subthreshold LFAC Block Threshold

30μA

150

100

50

00 10 20 30 40 50

Position (mm)

Tim

e (m

s)

100μA

150

100

50

00 10 20 30 40 50

Position (mm)

Tim

e (m

s)

LFAC BlockAP Slowing

Activation

AnodalBlock

Activation

LFAC Activation Threshold Anodal Block Threshold

Onset Activation

LFAC threshold predictions(1μm unmyelinated autonomic fiber, 1.3 mm fascicle, cuff electrode)

In-silico results using the Horn-Schild autonomic nerve model combined with the spatial-temporal potential distributions from a Comsol Multiphysics FEM model during application of a LFAC waveform through a bipolar cuff electrode to a nerve fascicle at different LFAC current amplitudes. The in-silico experiment predicts the slowing and block of seen in the in-vitro experiments. Inspection of the channel state variables suggests a closed state Na+ channel block as the mechanism for LFACb. Increasing the current amplitude, the model predicts activation and anodal block, which are both experimentally seen in-vivo