COMPUTATIONAL MODELING OF DEEP BRAIN STIMULATION

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COMPUTATIONAL MODELING OF DEEP BRAIN STIMULATION

• Cameron C. McIntyre
• Department of Neurology
• Emory University School of Medicine

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Background

• DBS results in a dramatic clinical effect for
  treatment of movement disorders
• DBS shows promise for treatment of epilepsy and
  neuropsychiatric disorders
• Mechanisms of action are unknown

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Deep Brain Stimulation
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Basal Ganglia
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Fundamental Questions

• What is the effect of DBS on the neurons
  surrounding the electrode?
• Activation or Inhibition?
• How does DBS modulate the neuronal network
  activity?
• Override normal/abnormal patterns?
• GOAL Improve Efficacy and Reduce Side Effects

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Overview

• Use Computer Modeling to Address the Effects of
  DBS
• I. Finite Element Model of Electric Field
  Generated by the Stimulation
• II. Multi-Compartment Cable Models of Neurons
  Surrounding the Electrode
• III. Large Scale Neuronal Network Model of the
  Feedback Circuits

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DBS Field Model
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II. Neural Stimulation

• Build neuron geometry based on 3D reconstructions
  from filled cells
• Incorporate membrane dynamics from experimental
  studies
• Position neuron in field model and predict the
  effects of stimulation

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TC Neuron Model
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TC Neuron Model
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TC Neuron Model
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Field-Neuron Model
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High-Frequency Stimulation
150 Hz 0.1 ms Pulses
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High-Frequency Stimulation
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High-Frequency Stimulation
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DBS Mechanisms

• Mechanisms of DBS may be related to many factors
• Mechanism of DBS (frequency)
• K1Inhibition of Efferents
• K2Excitation of Efferents
• K3Excitation of Afferents
• K4Network Desynchronization
• K5Plasticity

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Acknowledgements

• Financial support provided by
• National Institutes of Health
• Whitaker Foundation
• Medtronic Inc.
• Collaborators
• Warren Grill CWRU
• Jerrold Vitek Emory
• Susumu Mori - JHU
• David Sherman - JHU
• Nitish Thakor - JHU