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

BackgroundElectrical 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/HypothesisTo 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. MethodsWe 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). ResultsIncreasing 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. ConclusionThese 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. HighlightsO_LIIntracranial single pulse electrical stimulation (SPES) response increases with increased pulse duration mostly near the stimulation site C_LIO_LISPES response varies nonlinearly with injected current with an effect of distance from the stimulation site. C_LIO_LISPES near the grey-white boundary and 90{degrees} to the nearest cortical axis induces larger local responses, but white matter stimulation produces larger distant responses. C_LIO_LIThe relationship between SPES location and responses depends on brain region stimulated C_LI