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

Abstract

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.

Enhancing neuronal plasticity through intracranial theta burst stimulation in the human sensorimotor cortex

“…In the comparison condition (i8Hz), single stimulation pulses were administered at intervals of 125ms for a period of five seconds (40 pulses/train) and repeated every fifteen seconds (10-s intratrain interval). Similar stimulation frequencies ranging from 3-8 Hz were used in recent DBS studies [15,36,37]. In our study, the number of total pulses was similar across treatment modalities (iTBS, 30*20=600 pulses; i8Hz, 40*15=600 pulses).…”

“…2b and 2c), suggesting that iTBS enhanced connectivity of already pre-existent rhythms. Prior studies showed that the frequency of stimulation is an important factor in driving specific clinical outcomes in Parkinson's patients [10,36,56,57], in epilepsy patients [15,51], in modulating focal excitability in macaque brains [48], and in prolonging the duration of the effects (acute vs. plasticity) [52,58,59]. The focal spread of our treatment effects is supported by invasive studies that showed the majority of modulated regions being anatomically and functionally closer to the stimulation site [21,34].…”

“…In DBS, the therapeutic effect is thought to be related to acutely enhancing or inhibiting activity in specific brain regions and until recently, less emphasis was placed on the potential contributing role of neural plasticity induced by electrical stimulation. Despite the important role of neural plasticity as part of the therapeutic effects in DBS [12][13][14], there is still much to learn about the most efficient plasticity inducing stimulation parameters using this approach [15].…”

Neuromodulation: The Search Is On for the Most Effective Parameters

“…Until the report by Mohan et al, 6 there has not been a systematic study of the various parameters that can affect the neuronal response to closed-loop neuromodulation. The authors evaluated the effects of stimulation in a group of 109 patients with refractory epilepsy evaluated with depth and subdural cortical electrodes who were participating in a multicenter stimulation study aimed at determining which parameters could enhance episodic and spatial memory.…”

Excitation of the Pre-frontal and Primary Visual Cortex in Response to Transcorneal Electrical Stimulation in Retinal Degeneration Mice

“…Specifically, the effect of altering retinal electrical stimulation frequency on cortical activity of RP mice has not been reported. It is known that electrical stimulation paradigms modify neural activity in various ways, either by increasing or decreasing cortical excitability depending on the parameters of stimulation ( Winawer and Parvizi, 2016 ; Mohan et al, 2019 ). This unique feature to alter cortical activity is being explored for many experimental and therapeutic applications.…”