Impact of stimulation location relative to grey and white matter on single pulse electrical stimulation responses in the human brain

Abstract

Background: Electrical neuromodulation is an increasingly common therapy for a wide variety of neuropsychiatric diseases. Unfortunately, therapeutic efficacy is inconsistent, possibly a result of our limited understanding of the mechanisms and the massive stimulation parameter space. Objective/Hypothesis: To better understand the role different parameters play in inducing a response, we systematically examined single pulse-induced cortico-cortico evoked potentials (CCEP) as a function of stimulation amplitude, duration and location in the brain and relative to grey and white matter. Methods: We measured voltage peak amplitudes and area under the curve 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 response values near the stimulation location. Increasing stimulation amplitude (current) increased responses nonlinearly. Locally (<15 mm from the stimulation site), stimulation closer to the grey matter-white matter boundary induced larger responses. In contrast, for distant sites (>15 mm), white matter stimulation consistently produced larger responses than stimulation in or near grey matter. These relationships were different between cingulate, lateral prefrontal, and lateral temporal cortical stimulation. Conclusion: These results demonstrate the importance of location and stimulation parameters in inducing a specific output and indicate that a stronger local response may require stimulation in the grey-white boundary while stimulation in the white matter may be needed for network activation, suggesting that stimulation location can be tailored for a specific outcome, key to informed neuromodulatory therapy.

Evoking artificial speech perception through invasive brain stimulation for brain-computer interfaces: current challenges and future perspectives

“…Finally, stimulation of white matter tracts elicits a different behavior than stimulation of the surrounding gray matter. Studies show that white matter proximity to the stimulation point has a substantial impact on the behavioral and physiological responses of each patient ( Duffau, 2015 ; Paulk et al, 2021 , 2022 ). In fact, a recent study shows that stimulation at the boundary between gray and white matter elicited a larger response locally (<15 mm to stimulation site), whereas white matter stimulation evoked a larger response than gray matter stimulation at distant sites (>15 mm to stimulation site) ( Paulk et al, 2022 ).…”