Entrainment and Spike-Timing Dependent Plasticity – A Review of Proposed Mechanisms of Transcranial Alternating Current Stimulation

Abstract

Specific frequency bands of neural oscillations have been correlated with a range of cognitive and behavioral effects (e.g., memory and attention). The causal role of specific frequencies may be investigated using transcranial alternating current stimulation (tACS), a non-invasive brain stimulation method. TACS involves applying a sinusoidal current between two or more electrodes attached on the scalp, above neural regions that are implicated in cognitive processes of interest. The theorized mechanisms by which tACS affects neural oscillations have implications for the exact stimulation frequency used, as well as its anticipated effects. This review outlines two main mechanisms that are thought to underlie tACS effects – entrainment, and spike-timing dependent plasticity (STDP). Entrainment suggests that the stimulated frequency synchronizes the ongoing neural oscillations, and is thought to be most effective when the stimulated frequency is at or close to the endogenous frequency of the targeted neural network. STDP suggests that stimulation leads to synaptic changes based on the timing of neuronal firing in the target neural network. According to the principles of STDP, synaptic strength is thought to increase when pre-synaptic events occur prior to post-synaptic events (referred to as long-term potentiation, LTP). Conversely, when post-synaptic events occur prior to pre-synaptic events, synapses are thought to be weakened (referred to as long-term depression, LTD). In this review, we summarize the theoretical frameworks and critically review the tACS evidence for each hypothesis. We also discuss whether each mechanism alone can account for tACS effects or whether a combined account is necessary.

Long-term gamma transcranial alternating current stimulation improves the memory function of mice with Alzheimer’s disease

“…Long-term gamma tACS can better reduce Aβ deposition and activate microglia, restore normal gamma oscillations in the brain, and improve short-term memory function in AD mice ( Figure 9 ). On the other hand, tACS is considered to achieve the intervention of AD through modulation of spike timing dependent plasticity and enhancing synaptic plasticity ( Di Lorenzo et al, 2018 ; Vogeti et al, 2022 ). These biomarkers are considered to predict the clinical progression to dementia in patients with memory impairment of AD ( Di Lorenzo et al, 2020 ).…”

Medial prefrontal transcranial alternating current stimulation for apathy in Huntington’s disease

“…Alpha-tACS was administered at each participant’s peak individualized alpha frequency (IAF) based on evidence that tACS at IAF can increase alpha power more effectively than when administered at a generic frequency, such as 10Hz (Negahbani et al 2018, Vogeti, Boetzel, and Herrmann 2022). Each participant’s peak IAF was calculated in MATLAB using five minutes of resting eyes open EEG data collected at the start of the session in which they were scheduled to receive alpha-tACS (refer to supplementary materials for IAF detection procedure).…”

“…Transcranial alternating current stimulation (tACS) is a NIBS technique that can target pathophysiologically relevant oscillatory frequencies within specific regions of the cortex (Thut, Schyns, and Gross 2011, Tavakoli and Yun 2017, Onoda et al 2017. The immediate ('online') effects of tACS are considered to reflect exogenous entrainment of endogenous oscillatory activity and stochastic resonance (Fertonani and Miniussi 2017, Thut, Schyns, and Gross 2011, Huang, Lu, et al 2017, Liu et al 2018, while post-stimulation ('offline') effects are considered secondary to spike timing dependent plasticity (Herrmann et al 2013, Vossen, Gross, and Thut 2015, Vogeti, Boetzel, and Herrmann 2022. The post-stimulation effects on behaviour following a single 20-minute session of tACS may last as long as 70 minutes (Kasten, Dowsett, and Herrmann 2016), with daily sessions over a period of one to several weeks able to engender clinically meaningful outcomes (Elyamany et al 2021).…”

Alpha-tACS Alters Attentional Control but not Cognitive Functions as Video Games Do: A Psychophysical Investigation based on the Theory of Visual Attention

“…Hereby, we operationalized and modulated attentional control in two different ways: one approach was to apply alpha-tACS to participants' PPC to alter attentional control as operationalized by alpha activity; another one to model their visusopatial attentional processing and top-down control based on TVA (Dyrholm, Kyllingsbaek, Espeseth, & Bundesen, 2011;Kyllingsbaek, 2006). We used tACS in this context since it represents an established non-invasive brain stimulation method to alter brain oscillatory activity (Herrmann, Strüber, Helfrich, & Engel, 2016); and applied at alpha frequency to the PPC it seems to reliably modulate visuospatial attentional processing (Helfrich et al, 2014;Kemmerer et al, 2022;Vogeti, Boetzel, & Herrmann, 2022). This might apply in particular to right hemispheric stimulation given that firstly, unilateral damage especially to the right hemispheric PPC is often associated with severe impairment of visuospatial attention as already mentioned (Corbetta, Kincade, Lewis, Snyder, & Sapir, 2005;Corbetta, Patel, & Shulman, 2008;Corbetta & Shulman, 2011;Husain, 2008).…”