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Electrical Stimulation andRecording in the

Central NervousSystem

Cameron C. McIntyre, Ph.D.

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

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Neuromodualtion Market

$6.8 Bil lion - EstimatedGlobal Market by 2017

Markets and Markets, 2013Transparency Market Research, 2012

$2.7 Bil lion - 2011Global Market

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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

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DBS Technology

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DBS Surgery

Stereotactic Frame Image Guidance

Stealthstation, Medtronic Inc.Leksell model G, Elekta Corp.

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DBS Programming

Volkmann et al., Mov. Disord., 2002

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Patient-Specific DBS Models

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Basic Questions

What is the electric field generated inthe brain?

What neural elements are westimulating?

How can we customize the stimulationto the patient?

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Electric Field Simulations

Chaturvedi et al., Brain Stimul., 2010

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Experimental Measurement

Miocinovic et al., Exp. Neurol., 2009

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Various Neural Pathways

Chaturvedi et al., Brain Stimul., 2012

STN Pathway IC Pathway

GPi Pathway

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Neuron Models

Miocinovic et al., J. Neurophysiol., 2006

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Neural Stimulation Model

McNeal, IEEE Trans. Biomed. Eng., 1976

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Subthalamic Pathways

Chaturvedi et al., Brain Stimul., 2012

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Voltage Distribution

Chaturvedi et al., Brain Stimul., 2012

C2

-6 mA60 s120 Hz

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Directly Activated Axons

Chaturvedi et al., Brain Stimul., 2012

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Network Modulation

McIntyre and Hahn, Neurobiol. Dis., 2010

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Neuromodulation Dose

Controlled Release of Neurotransmitters

Dependent Upon:

Electrode Location Stimulus Pulse

Stimulus Frequency

Numerous Pathways SimultaneouslyActivated

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Patient-Specific DBS Models

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Volume of Tissue Activated

Butson et al.,Clin. Neurophysiol., 2006

Butson & McIntyre,Clin. Neurophysiol., 2005

Butson et al.,NeuroImage, 2007

Butson & McIntyre,J. Neural Eng., 2006

McIntyre et al.,

Clin. Neurophysiol., 2004

Butson & McIntyre,Brain Stimul., 2008

Maks et al.,JNNP, 2009

Chaturvedi et al.,Brain Stimul., 2010

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Probabilistic Stimulation Atlas

Butson et al., NeuroImage, 2011

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Therapeutic Target Regions

RigidityTarget

BradykinesiaTarget

Butson et al., NeuroImage, 2011

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Clinical Target Volume

Frankemolle et al., Brain, 2010

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Clinical Outcomes

Frankemolle et al., Brain, 2010

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Commercial Product

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Current-Steering

Butson and McIntyre, Brain Stimul., 2008

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Current Steering to Target

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Stimulus Waveforms

Foutz and McIntyre, J. Neural Eng., 2010

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Biophysical Efficiency

Foutz and McIntyre, J. Neural Eng., 2010

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Biophysical Efficiency

Foutz et al., PLoS ONE, 2012

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Experimental Testing

Foutz et al., PLoS ONE, 2012

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Stimulator Design

Dynamic

Adjustable

Converter

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Compliance Voltage

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Energy Consumption

Foutz et al., PLoS ONE, 2012

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Dynamic ComplianceFixed Dynamic

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DBS Paradigm

Tass et al., Ann. Neurol., 2012

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Electrodes

Medtronic 3389 Electrode Blackrock Utah Array

Large Contact Surface AreaHigh Charge CapacityLow ImpedanceLarge Stimulation Volume

Limited Specificity

vs.Small Contact Surface AreaLow Charge CapacityHigh ImpedanceSmall Stimulation Volume

Focal Specificity

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Current Density

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

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Current Density

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

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Charge Injection Capacity

Sahin and Tie, J. Neural Eng., 2007

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Electrode-Tissue Interface

Moss et al., Brain, 2004 Nielson et al., Eur J Neurosci, 2007

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Electrode Impedance

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

Tissue ComponentElectrode-ElectrolyteInterface

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Electrode Impedance

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

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Electrode Impedance

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

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Local Field Potential

Lempka and McIntyre, PLoS ONE, 2013

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DBS Control Signal

Eusebio et al., JNNP, 2011

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Local Field Potential

Lempka and McIntyre, PLoS ONE, 2013

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Cortical Microelectrode Recording

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

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Cortical Microelectrode Recording

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

l l d d

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Cortical Microelectrode Recording