Local and distant cortical responses to single pulse intracranial stimulation in the human brain are differentially modulated by specific stimulation parameters

Angelique C Paulk; Rina Zelmann; Britni Crocker; Alik S Widge; Darin D Dougherty; Emad N Eskandar; Daniel S Weisholtz; R Mark Richardson; G Rees Cosgrove; Ziv M Williams; Sydney S Cash

doi:10.1016/j.brs.2022.02.017

Local and distant cortical responses to single pulse intracranial stimulation in the human brain are differentially modulated by specific stimulation parameters

Brain Stimul. 2022 Mar-Apr;15(2):491-508. doi: 10.1016/j.brs.2022.02.017. Epub 2022 Mar 2.

Authors

Affiliations

¹ Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA; Center for Neurotechnology and Neurorecovery, Department of Neurology, Massachusetts General Hospital, Boston, MA, USA. Electronic address: apaulk@mgh.harvard.edu.
² Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA; Center for Neurotechnology and Neurorecovery, Department of Neurology, Massachusetts General Hospital, Boston, MA, USA.
³ Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA; Harvard-MIT Health Sciences and Technology, Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
⁴ Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, 02129, USA.
⁵ Center for Neurotechnology and Neurorecovery, Department of Neurology, Massachusetts General Hospital, Boston, MA, USA; Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, 02129, USA.
⁶ Department of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA.
⁷ Department of Neurology, Brigham and Women's Hospital, Boston, MA, 02114, USA.
⁸ Center for Neurotechnology and Neurorecovery, Department of Neurology, Massachusetts General Hospital, Boston, MA, USA; Department of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA.
⁹ Department of Neurosurgery, Brigham and Women's Hospital, Boston, MA, 02114, USA.

Abstract

Background: Electrical neuromodulation via direct electrical stimulation (DES) is an increasingly common therapy for a wide variety of neuropsychiatric diseases. Unfortunately, therapeutic efficacy is inconsistent, likely due to our limited understanding of the relationship between the massive stimulation parameter space and brain tissue responses.

Objective: To better understand how different parameters induce varied neural responses, we systematically examined single pulse-induced cortico-cortico evoked potentials (CCEP) as a function of stimulation amplitude, duration, brain region, and whether grey or white matter was stimulated.

Methods: We measured voltage peak amplitudes and area under the curve (AUC) of intracranially recorded stimulation responses as a function of distance from the stimulation site, pulse width, current injected, location relative to grey and white matter, and brain region stimulated (N = 52, n = 719 stimulation sites).

Results: Increasing stimulation pulse width increased responses near the stimulation location. Increasing stimulation amplitude (current) increased both evoked amplitudes and AUC nonlinearly. Locally (<15 mm), stimulation at the boundary between grey and white matter induced larger responses. In contrast, for distant sites (>15 mm), white matter stimulation consistently produced larger responses than stimulation in or near grey matter. The stimulation location-response curves followed different trends for cingulate, lateral frontal, and lateral temporal cortical stimulation.

Conclusion: These results demonstrate that a stronger local response may require stimulation in the grey-white boundary while stimulation in the white matter could be needed for network activation. Thus, stimulation parameters tailored for a specific anatomical-functional outcome may be key to advancing neuromodulatory therapy.

Keywords: Cortex; Human; Intracranial; Nonlinear; Single pulse electrical stimulation; White matter.

Publication types

Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, Non-U.S. Gov't

MeSH terms

Brain
Cerebral Cortex* / physiology
Electric Stimulation / methods
Evoked Potentials / physiology
Humans
White Matter*

Abstract

Publication types

MeSH terms

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