TACS effects on single-neuron and network activity

Symposium title: From tACS biophysics and neurophysiology to modulation of behavior Symposium description: Transcranial alternating current stimulation (tACS) is becoming increasingly popular to modulate cognition and behavior in healthy volunteers, as well as in neurological and psychiatric patients. To optimize results, it is crucial to understand 1) how tACS modulates neural processes; and 2) if and how these effects lead to changes in behavioral performance. TACS electric fields can alter neural spiking, but there are still many open questions how these effects lead to altered behavior. We will discuss computational modeling, animal and human data that show how modulation at microscale leads to macroscopic changes in phase-dependent neural output, synaptic plasticity, and long-range coherence. Furthermore, we will clarify the challenges and discuss recent tACS research that focused on the translation from physiology to cognition and clinical applications. Further, we discuss novel techniques, including phase-dependent stimulation and traveling-wave tACS, which have shown to be promising in optimizing modulatory tACS effects. Our results will have clear implications for cognitive and clinical research with tACS, as well as therapeutic application of tACS to combat brain disorders and improve mental health. The symposium is organized by an international team of early- and mid- career scientists studying tACS across different models and modalities. This symposium is targeted at cognitive and clinical researchers that are interested in broadening their understanding on the biophysical and neurophysiological principles of tACS. Abstract Transcranial alternating current stimulation (TACS) modulates brain activity using time-varying electric currents applied via the scalp. It is increasingly explored as a tool to normalize brain oscillations in patients with mental disorders. Here we aim to advance our understanding by investigating the effects of TACS across different levels and approaches. First, we develop computational models of morphologically realistic neurons with ongoing spiking activity and their response to alternating electric fields. We show that TACS doesn’t affect the spiking rate but entrains the spiking activity of predominantly large pyramidal neurons to the phase of the oscillating field even at low strengths (<1 V/m), readily achievable in humans. Second, we perform in-vivo recordings of single-unit activity in awake non-human primates while applying TACS. We record neural activity using a 128-channel amplifier at 30 kHz sampling rate with glass coated electrodes. Preliminary findings in one macaque (8 y.o., male) show that 83 out of 299 identified neurons demonstrate significant entrainment to TACS (Rayleigh test p ≤ 0.01) with linear dose-dependency. The entrainment increases from 0.03±0.02 phase-locking value (plv) for 0.2 mA stimulation to 0.24±0.14 plv for 0.8 mA. Finally, we investigate direct human brain activity during TACS in surgical epilepsy patients. Patients who met clinical guidelines and provided informed consent are implanted with intracranial electrodes according to medical needs. We record brain signals with 256-channel amplifier NeuraLynx Atlas. The patients perform the N-back working memory task to create a cognitive load or remain at rest while being subjected to TACS for 10 min at an intensity of 1 mA and frequency in theta or beta range. Preliminary analysis in three patients (one female, age 30-40 y.o.) using generalized linear mixed effect model indicate a significant improvement in memory performance during the stimulation at beta but not theta frequency (F=4.6, p=0.02). Research Category and Technology and Methods Translational Research: 8. Transcranial Alternating Current Stimulation (tACS) Keywords: Transcranial Alternating Current Stimulation, Electric Field Modeling, Neural Entrainment, Working Memory