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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