Targeting alpha-band oscillations in a cortical model with amplitude-modulated high-frequency transcranial electric stimulation

Abstract

Non-invasive brain stimulation to target specific network activity patterns, e.g. transcranial alternating current stimulation (tACS), has become an essential tool to understand the causal role of neuronal oscillations in cognition and behavior. However, conventional sinusoidal tACS limits the ability to record neuronal activity during stimulation and lacks spatial focality. One particularly promising new tACS stimulation paradigm uses amplitude-modulated (AM) high-frequency waveforms (AM-tACS) with a slow signal envelope that may overcome the limitations. Moreover. AM-tACS using high-frequency carrier signals is more tolerable than conventional tACS, e.g. in terms of skin irritation and occurrence of phosphenes, when applied at the same current intensities (e.g. 1-2 mA). Yet, the fundamental mechanism of neuronal target-engagement by AM-tACS waveforms has remained unknown. We used a computational model of cortex to investigate how AM-tACS modulates endogenous oscillations and compared the target engagement mechanism to the case of conventional (unmodulated) low-frequency tACS. Analysis of stimulation amplitude and frequency indicated that cortical oscillations were phase-locked to the envelope of the AM stimulation signal, which thus exhibits the same target engagement mechanism as conventional (unmodulated) low frequency tACS. However, in the computational model substantially higher current intensities were needed for AM-tACS than for low-frequency (unmodulated) tACS waveforms to achieve pronounced phase synchronization. Our analysis of the carrier frequency suggests that there might be a trade-off between the use of high-frequency carriers and the stimulation amplitude required for successful entrainment. Together, our computational simulations support the use of slow-envelope high frequency carrier AM waveforms as a tool for noninvasive modulation of brain oscillations. More empirical data will be needed to identify the optimal stimulation parameters and to evaluate tolerability and safety of both, AM- and conventional tACS.

Electrophysiology equipment for reliable study of kHz electrical stimulation

“…; Negahbani et al . ) unless (1) stimulation artifact removal depends on accurate field pick‐up (Helfrich et al . ; Dowsett and Herrmann ); (2) when recording hardware non‐linearities are of concern (Lesperance et al .…”

“…Amplifier and electrode attenuation may not be critical for conventional neurophysiological measures (e.g. action potential threshold or rate, low frequency oscillation power; Grossman et al 2017;Negahbani et al 2018) unless (1) stimulation artifact removal depends on accurate field pick-up (Helfrich et al 2014;Dowsett and Herrmann 2016); (2) when recording hardware non-linearities are of concern (Lesperance et al 2018; Kasten et al 2018); (3) when electrophysiological responses at kHz rate (e.g. kHz fluctuations in membrane potential) are of interest (Pelot et al 2017); and (4) when interactions between equipment and the body introduce complex distortions (Neuling et al 2017;Noury and Siegel, 2018;Gebodh et al 2019).…”

Transcranial Alternating Current Stimulation (tACS) Entrains Alpha Oscillations by Preferential Phase Synchronization of Fast-Spiking Cortical Neurons to Stimulation Waveform

“…This behavior resulted in a triangular-shaped synchrony region when quantifying the spike-tACS phase-locking as a function of stimulation frequency and amplitude. The triangular region was centered on endogenous alpha frequency and is known as an Arnold tongue, as previously reported in computational modeling studies of tACS effect (Ali et al, 2013;Herrmann et al, 2016b;Lefebvre et al, 2017;Li et al, 2017;Negahbani et al, 2018). Despite being statistically significant in only a small fraction of neurons, the Arnold tongue was evident in PPC.…”

“…We adopted and connected two previously developed computational models of a cortical (Negahbani et al, 2018) and thalamic network for complementary investigation of neuronal mechanisms of tACS effect during endogenous alpha oscillations. The cortical model was composed of fast spiking inhibitory neurons (FS) and regular spiking excitatory pyramidal neurons (PY).…”

“…Despite demonstration of long-lasting tACS effects in human studies, the full mapping of the stimulation parameters space and demonstration of resulting synchronization in the form of Arnold tongue structures remains unexplored. The major roadblock to explore this gap in human studies is associated with technical challenges in simultaneous tACS and EEG recording, despite some recent attempts to avoid or filter the large electrical artefact of tACS (Grossman et al, 2017;Negahbani et al, 2018;Witkowski et al, 2016).…”