Safety Evaluation of Employing Temporal Interference Transcranial Alternating Current Stimulation in Human Studies

Abstract

Temporal interference transcranial alternating current stimulation (TI-tACS) is a new technique of noninvasive brain stimulation. Previous studies have shown the effectiveness of TI-tACS in stimulating brain areas in a selective manner. However, its safety in modulating human brain neurons is still untested. In this study, 38 healthy adults were recruited to undergo a series of neurological and neuropsychological measurements regarding safety concerns before and after active (2 mA, 20/70 Hz, 30 min) or sham (0 mA, 0 Hz, 30 min) TI-tACS. The neurological and neuropsychological measurements included electroencephalography (EEG), serum neuron-specific enolase (NSE), the Montreal Cognitive Assessment (MoCA), the Purdue Pegboard Test (PPT), an abbreviated version of the California Computerized Assessment Package (A-CalCAP), a revised version of the Visual Analog Mood Scale (VAMS-R), a self-assessment scale (SAS), and a questionnaire about adverse effects (AEs). We found no significant difference between the measurements of the active and sham TI-tACS groups. Meanwhile, no serious or intolerable adverse effects were reported or observed in the active stimulation group of 19 participants. These results support that TI-tACS is safe and tolerable in terms of neurological and neuropsychological functions and adverse effects for use in human brain stimulation studies under typical transcranial electric stimulation (TES) conditions (2 mA, 20/70 Hz, 30 min).

Safety Recommendations for Temporal Interference Stimulation in the Brain

“…To date, there have few reports of TIS-associated AEs, all mild to moderate, and with no significant differences between sham and active conditions 11,79,93 . For carrier frequencies <2 kHz and current amplitudes <2 mA, TIS is comparable to tACS in terms of the magnitude and extent of fields and currents, and no physical or chemical damage has been observed for either technique.…”

“…In humans, a recent study by Piao et al sought to characterize the safety profile of TIS for brain stimulation in a single-blind parallel (sham-controlled) trial with n=38 healthy volunteers 79 . Participants received a total of 30 min of active/sham stimulation in 10 min blocks, with the active arm (n=19) receiving either 20 Hz amplitude-modulated TIS (2 mA, 2 kHz and 2.02 kHz; n=9) or 70 Hz amplitude-modulated TIS (2 mA, 2 kHz and 2.07 kHz; n=10).…”

“…Regarding AEs, several were reported though all were mild to moderate, and there were no significant differences between sham and active conditions. These included: mild itching, mild headache, mild warmth, mild tingling, fatigue, and vertigo 79 . Thus, the authors conclude that based on their findings, TIS is unlikely to induce neurological/neuropsychological state changes, or result in any adverse effects in humans for the range of stimulation parameters evaluated.…”

LTP-like noninvasive striatal brain stimulation enhances striatal activity and motor skill learning in humans

“…Currently, there is an open debate with alternative mechanistic hypotheses affirming the necessity of a rectification step prior to filtering to demodulate the electric field, thus allowing selective responses to the modulating envelope 60 . To date, only a small number of published studies have applied tTIS in humans [61][62][63][64] . Still, they have targeted primary motor and parieto-occipital cortices, which are already reachable with conventional NIBS techniques.…”

Non-invasive temporal interference electrical stimulation of the human hippocampus

“…Here, we aim to test the translation of these results by investigating the application of TI to the human hippocampus. Earlier human studies tested TI stimulation of cortical structures [15][16][17] , but the crucial non-invasive DBS capability has not been validated to date. We first focused on validating the locus of TI stimulation using computational modelling and cadaver measurements.…”