Dose-Dependent Effects of Transcranial Alternating Current Stimulation on Spike Timing in Awake Nonhuman Primates

Abstract

Weak extracellular electric fields can influence spike timing in neural networks. Approaches to impose such fields on the brain in a noninvasive manner have high potential for novel treatments of neurological and psychiatric disorders. One of these methods, transcranial alternating current stimulation (TACS), is hypothesized to affect spike timing and cause neural entrainment. However, the conditions under which these effects occur in-vivo are unknown. Here, we show that TACS modulates spike timing in awake nonhuman primates (NHPs) in a dose-dependent fashion. Recording single-unit activity from pre-and post-central gyrus regions in NHPs during TACS, we found that a larger population of neurons became entrained to the stimulation waveform for higher stimulation intensities. Performing a cluster analysis of changes in interspike intervals, we identified two main types of neural responses to TACS -increased burstiness and phase entrainment. Our results demonstrate the ability of TACS to affect spike-timing in the awake primate brain and identify fundamental neural mechanisms. Concurrent electric field recordings demonstrate that spike-timing changes occur with stimulation intensities readily achievable in humans. These results suggest that novel TACS protocols tailored to ongoing brain activity may be a potent tool to normalize spike-timing in maladaptive brain networks and neurological disease.

Selective enhancement of low-gamma activity by tACS improves phonemic processing and reading accuracy in dyslexia

“…The current results show that phonological processing improved via a focal and specific enhancement of 30-Hz oscillatory activity in left auditory cortex. This finding confirm others showing that tACS can indeed influence neuronal activity in a frequency-and location-specific manner [43,44]. Phonological performance improvement hence likely reflects changes in neuronal entrainment towards the frequency of the tACS stimulation [43,45].…”

“…If stabilized by repeated stimulation, this large-scale effect might also confer the 30 Hz tACS procedure the interesting advantage of (re)circumscribing phonemic processing to the left hemisphere, an important functional property for improving reading speed in the longer run. Future protocols might also exploit dose-dependent neural entrainment by tACS to tailor stimulation intensity to individual neural deficit in gamma activity [44].…”

Model-driven neuromodulation of the right posterior region promotes encoding of long-term memories

“…3A). Oscillating electric fields at 0.3 V m À1 or higher can induce immediate electrophysiological effects, e.g., modulate spike timing activity of single neurons [39,41]. None of our participants reported experiencing phosphenes during stimulation, but they did report a mild to moderate degree of transient skin sensations, which did not differ across the stimulation conditions (nonparametric ANOVA p ¼ 0.99, more details in Methods).…”

“…Furthermore, the model-driven tACS results showed that the electrical stimulation of the right but not the left posterior brain region during encoding improved subsequent recognition by particularly enhancing the familiarity process. Mechanistically, we suppose that the alternating current facilitated the synchronization in the parietal neuronal population [39,41] and dependent neural communications [16,59]. The increased degree of neural synchrony likely improved feature binding during encoding and made the stimulus more familiar at the next encounter.…”

“…Recent invasive electrophysiological studies of tACS mechanisms in animals highlight the importance of the brain state and adequate dose calculation for a successful intervention [37e42]. Whereas low intensity stimulation (<0.1 V m À1 ) [40] or stimulation under anesthesia induce no immediate electrophysiological effects [37,38], higher intensity stimulation (>0.3 V m À1 ) in awake primates has been shown to reliably modulate ongoing spike timing of single neurons in a frequency-specific manner [39,41]. Therefore, we employed computational modeling to ensure localized stimulation with a sufficient electric field in the parietal brain area of interest (>0.4 V m À1 ), and we compared target stimulation with placebo and active control conditions.…”