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Model-based deconstruction of cortical evoked potentials generated by subthalamic nucleus deep brain stimulation.

Publication ,  Journal Article
Kumaravelu, K; Oza, CS; Behrend, CE; Grill, WM
Published in: Journal of neurophysiology
August 2018

Parkinson's disease is associated with altered neural activity in the motor cortex. Chronic high-frequency deep brain stimulation (DBS) of the subthalamic nucleus (STN) is effective in suppressing parkinsonian motor symptoms and modulates cortical activity. However, the anatomical pathways responsible for STN DBS-mediated cortical modulation remain unclear. Cortical evoked potentials (cEP) generated by STN DBS reflect the response of cortex to subcortical stimulation, and the goal of this study was to determine the neural origin of STN DBS-generated cEP using a two-step approach. First, we recorded cEP over ipsilateral primary motor cortex during different frequencies of STN DBS in awake healthy and unilateral 6-OHDA-lesioned parkinsonian rats. Second, we used a detailed, biophysically based model of the thalamocortical network to deconstruct the neural origin of the recorded cEP. The in vivo cEP included short (R1)-, intermediate (R2)-, and long-latency (R3) responses. Model-based cortical responses to simulated STN DBS matched remarkably well the in vivo responses. The short-latency response was generated by antidromic activation of layer 5 pyramidal neurons, whereas recurrent activation of layer 5 pyramidal neurons via excitatory axon collaterals reproduced the intermediate-latency response. The long-latency response was generated by polysynaptic activation of layer 2/3 pyramidal neurons via the cortico-thalamic-cortical pathway. Antidromic activation of the hyperdirect pathway and subsequent intracortical and cortico-thalamo-cortical synaptic interactions were sufficient to generate cortical potential evoked by STN DBS, and orthodromic activation through basal ganglia-thalamus-cortex pathways was not required. These results demonstrate the utility of cEP to determine the neural elements activated by STN DBS that might modulate cortical activity and contribute to the suppression of parkinsonian symptoms. NEW & NOTEWORTHY Subthalamic nucleus (STN) deep brain stimulation (DBS) is increasingly used to treat Parkinson's disease (PD). Cortical potentials evoked by STN DBS in patients with PD exhibit consistent short-latency (1-3 ms), intermediate-latency (5-15 ms), and long-latency (18-25 ms) responses. The short-latency response occurs as a result of antidromic activation of the hyperdirect pathway comprising corticosubthalamic axons. However, the neural origins of intermediate- and long-latency responses remain elusive, and the dominant view is that these are produced through the orthodromic pathway (basal ganglia-thalamus-cortex). By combining in vivo electrophysiology with computational modeling, we demonstrate that antidromic activation of the cortico-thalamic-cortical pathway is sufficient to generate the intermediate- and long-latency cortical responses to STN DBS.

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Published In

Journal of neurophysiology

DOI

EISSN

1522-1598

ISSN

0022-3077

Publication Date

August 2018

Volume

120

Issue

2

Start / End Page

662 / 680

Related Subject Headings

  • Thalamus
  • Subthalamic Nucleus
  • Rats, Long-Evans
  • Parkinsonian Disorders
  • Neurons
  • Neurology & Neurosurgery
  • Neural Pathways
  • Neural Networks, Computer
  • Motor Cortex
  • Models, Neurological
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Kumaravelu, K., Oza, C. S., Behrend, C. E., & Grill, W. M. (2018). Model-based deconstruction of cortical evoked potentials generated by subthalamic nucleus deep brain stimulation. Journal of Neurophysiology, 120(2), 662–680. https://doi.org/10.1152/jn.00862.2017
Kumaravelu, Karthik, Chintan S. Oza, Christina E. Behrend, and Warren M. Grill. “Model-based deconstruction of cortical evoked potentials generated by subthalamic nucleus deep brain stimulation.Journal of Neurophysiology 120, no. 2 (August 2018): 662–80. https://doi.org/10.1152/jn.00862.2017.
Kumaravelu K, Oza CS, Behrend CE, Grill WM. Model-based deconstruction of cortical evoked potentials generated by subthalamic nucleus deep brain stimulation. Journal of neurophysiology. 2018 Aug;120(2):662–80.
Kumaravelu, Karthik, et al. “Model-based deconstruction of cortical evoked potentials generated by subthalamic nucleus deep brain stimulation.Journal of Neurophysiology, vol. 120, no. 2, Aug. 2018, pp. 662–80. Epmc, doi:10.1152/jn.00862.2017.
Kumaravelu K, Oza CS, Behrend CE, Grill WM. Model-based deconstruction of cortical evoked potentials generated by subthalamic nucleus deep brain stimulation. Journal of neurophysiology. 2018 Aug;120(2):662–680.

Published In

Journal of neurophysiology

DOI

EISSN

1522-1598

ISSN

0022-3077

Publication Date

August 2018

Volume

120

Issue

2

Start / End Page

662 / 680

Related Subject Headings

  • Thalamus
  • Subthalamic Nucleus
  • Rats, Long-Evans
  • Parkinsonian Disorders
  • Neurons
  • Neurology & Neurosurgery
  • Neural Pathways
  • Neural Networks, Computer
  • Motor Cortex
  • Models, Neurological