Electrical Stimulation and Recording in the Central Nervous System

Cameron C. McIntyre, Ph.D.

Financial Conflict of Interest IntElect Medical, Inc. Boston Scientific Neuromodulation, Corp. Neuros Medical, Inc. Cardionomic, Inc. Autonomic Technologies, Inc. Surgical Information Sciences, Inc.

Neuromodualtion Market

$2.7 Billion - 2011 Global Market $6.8 Billion - Estimated Global Market by 2017
Transparency Market Research, 2012 Markets and Markets, 2013

Implanted Pulse Generators

~100,000 patients have been implanted with DBS systems ~50,000 currently alive => ~100,000 active IPGs stimulated at 100 Hz * 24 hours

864 Billion DBS Pulses per Day

DBS Technology

DBS Surgery
Stereotactic Frame Image Guidance

Leksell model G, Elekta Corp.

Stealthstation, Medtronic Inc.

DBS Programming

Volkmann et al., Mov. Disord., 2002

Patient-Specific DBS Models

Basic Questions
What is the electric field generated in the brain? What neural elements are we stimulating? How can we customize the stimulation to the patient?

Electric Field Simulations

Chaturvedi et al., Brain Stimul., 2010

Experimental Measurement

Miocinovic et al., Exp. Neurol., 2009

Various Neural Pathways

STN Pathway IC Pathway

GPi Pathway

Chaturvedi et al., Brain Stimul., 2012

Neuron Models

Miocinovic et al., J. Neurophysiol., 2006

Neural Stimulation Model

McNeal, IEEE Trans. Biomed. Eng., 1976

Subthalamic Pathways

Chaturvedi et al., Brain Stimul., 2012

Voltage Distribution

C2 -6 mA 60 s 120 Hz

Chaturvedi et al., Brain Stimul., 2012

Directly Activated Axons

Chaturvedi et al., Brain Stimul., 2012

Network Modulation

McIntyre and Hahn, Neurobiol. Dis., 2010

Neuromodulation Dose
Controlled Release of Neurotransmitters Dependent Upon: Electrode Location Stimulus Pulse Stimulus Frequency Numerous Pathways Simultaneously Activated

Patient-Specific DBS Models

Volume of Tissue Activated

McIntyre et al., Clin. Neurophysiol., 2004 Butson & McIntyre, Clin. Neurophysiol., 2005 Butson et al., Clin. Neurophysiol., 2006 Butson & McIntyre, J. Neural Eng., 2006 Butson et al., NeuroImage, 2007 Butson & McIntyre, Brain Stimul., 2008 Maks et al., JNNP, 2009 Chaturvedi et al., Brain Stimul., 2010

Probabilistic Stimulation Atlas

Butson et al., NeuroImage, 2011

Therapeutic Target Regions

Rigidity Target

Bradykinesia Target

Butson et al., NeuroImage, 2011

Clinical Target Volume

Frankemolle et al., Brain, 2010

Clinical Outcomes

Frankemolle et al., Brain, 2010

Commercial Product

Current-Steering

Butson and McIntyre, Brain Stimul., 2008

Current Steering to Target

Stimulus Waveforms

Foutz and McIntyre, J. Neural Eng., 2010

Biophysical Efficiency

Foutz and McIntyre, J. Neural Eng., 2010

Biophysical Efficiency

Foutz et al., PLoS ONE, 2012

Experimental Testing

Foutz et al., PLoS ONE, 2012

Stimulator Design

Adjustable Converter

Dynamic

Compliance Voltage

Energy Consumption

Foutz et al., PLoS ONE, 2012

Dynamic Compliance
Fixed Dynamic

DBS Paradigm

Tass et al., Ann. Neurol., 2012

Electrodes

Large Contact Surface Area High Charge Capacity Low Impedance Large Stimulation Volume Limited Specificity

vs.

Small Contact Surface Area Low Charge Capacity High Impedance Small Stimulation Volume Focal Specificity

Medtronic 3389 Electrode

Blackrock Utah Array

Current Density

Cantrell et al., J. Neural Eng., 2008

Current Density

McIntyre and Grill, Ann. Biomed. Eng., 2001

Charge Injection Capacity

Sahin and Tie, J. Neural Eng., 2007

Electrode-Tissue Interface

Moss et al., Brain, 2004

Nielson et al., Eur J Neurosci, 2007

Electrode Impedance

ElectrodeElectrolyte Interface

Tissue Component

Lempka et al., J. Neural Eng., 2009

Electrode Impedance

Williams et al., J. Neural Eng., 2007

Electrode Impedance

Lempka et al., J. Neural Eng., 2009

Local Field Potential

Lempka and McIntyre, PLoS ONE, 2013

DBS Control Signal

Eusebio et al., JNNP, 2011

Local Field Potential

Lempka and McIntyre, PLoS ONE, 2013

Cortical Microelectrode Recording

Lempka et al., J. Neural Eng., 2011

Cortical Microelectrode Recording

Lempka et al., J. Neural Eng., 2011

Cortical Microelectrode Recording

Lempka et al., J. Neural Eng., 2011