The effects of direct brain stimulation in humans depend on frequency, amplitude, and white-matter proximity.

Background: Researchers have used direct electrical brain stimulation to treat a range of neurological and psychiatric disorders. However, for brain stimulation to be maximally effective, clinicians and researchers should optimize stimulation parameters according to desired outcomes.
Objective: The goal of our large-scale study was to comprehensively evaluate the effects of stimulation at different parameters and locations on neuronal activity across the human brain.
Methods: To examine how different kinds of stimulation affect human brain activity, we compared the changes in neuronal activity that resulted from stimulation at a range of frequencies, amplitudes, and locations with direct human brain recordings. We recorded human brain activity directly with electrodes that were implanted in widespread regions across 106 neurosurgical epilepsy patients while systematically stimulating across a range of parameters and locations.
Results: Overall, stimulation most often had an inhibitory effect on neuronal activity, consistent with earlier work. When stimulation excited neuronal activity, it most often occurred from high-frequency stimulation. These effects were modulated by the location of the stimulating electrode, with stimulation sites near white matter more likely to cause excitation and sites near gray matter more likely to inhibit neuronal activity.
Conclusion: By characterizing how different stimulation parameters produced specific neuronal activity patterns on a large scale, our results provide an electrophysiological framework that clinicians and researchers may consider when designing stimulation protocols to cause precisely targeted changes in human brain activity.
Competing Interests: Declaration of competing interest M.K. and D.R. have started a company, Nia Therapeutics, Inc., intended to develop and commercialize brain stimulation therapies for memory restoration. Each of them holds >5% equity interest in Nia. R.E.G. serves as a consultant to Medtronic, which was a subcontractor on the RAM project. The terms of this arrangement have been reviewed and approved by Emory University in accordance with its conflict of interest policies. B.J. receives research funding from NeuroPace and Medtronic not relating to this research. G.W. has rights to receive future royalties from the licensing of brain stimulation technology. Mayo Clinic has a financial interest related to brain stimulation technology, and is co-owner of Cadence Neuroscience Inc, the development of which has been assisted by G.W. The remaining authors declare no competing interests.
(Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)