Action potential initiation, propagation, and cortical invasion in the hyperdirect pathway during subthalamic deep brain stimulation

Brain Stimulation
Ross W AndersonCameron C McIntyre

Abstract

High frequency (∼130 Hz) deep brain stimulation (DBS) of the subthalamic region is an established clinical therapy for the treatment of late stage Parkinson's disease (PD). Direct modulation of the hyperdirect pathway, defined as cortical layer V pyramidal neurons that send an axon collateral to the subthalamic nucleus (STN), has emerged as a possible component of the therapeutic mechanisms. However, numerous questions remain to be addressed on the basic biophysics of hyperdirect pathway stimulation. Quantify action potential (AP) initiation, propagation, and cortical invasion in hyperdirect neurons during subthalamic stimulation. We developed an anatomically and electrically detailed computational model of hyperdirect neuron stimulation with explicit representation of the stimulating electric field, axonal response, AP propagation, and synaptic transmission. We found robust AP propagation throughout the complex axonal arbor of the hyperdirect neuron. Even at therapeutic DBS frequencies, stimulation induced APs could reach all of the intracortical axon terminals with ∼100% fidelity. The functional result of this high frequency axonal driving of the thousands of synaptic connections made by each directly stimulated hyperdirect n...Continue Reading

Citations

May 15, 2020·Nature Communications·Sébastien ValverdeLaurent Venance
Sep 12, 2020·Movement Disorders : Official Journal of the Movement Disorder Society·Kurt E WeaverAndrew L Ko
May 18, 2020·Journal of Mathematical Biology·Dan Wilson
Aug 16, 2018·Brain Structure & Function·Dymka CoudéMartin Parent
Mar 11, 2020·Frontiers in Computational Neuroscience·Clayton S BinghamTheodore W Berger
Mar 10, 2020·Neuromodulation : Journal of the International Neuromodulation Society·Bryan Howell, Cameron C McIntyre
Sep 13, 2020·Brain Stimulation·Kelsey L Bower, Cameron C McIntyre
Nov 7, 2020·Cell Systems·Ehsan MirzakhaliliScott F Lempka
Mar 13, 2021·Journal of Neural Engineering·AmirAli Farokhniaee, Madeleine Lowery
Jun 7, 2021·Brain Structure & Function·Clayton S BinghamCameron C McIntyre

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