Aligning Event-Related Potentials with Transcranial Alternating Current Stimulation for Modulation-a Review.

This review aims to demonstrate the connections between event-related potentials (ERPs), event-related oscillations (EROs), and non-invasive brain stimulation (NIBS), with a specific focus on transcranial alternating current stimulation (tACS). We begin with a short examination and discussion of the relation between ERPs and EROs. Then, we investigate the diverse fields of NIBS, highlighting tACS as a potent tool for modulating neural oscillations and influencing cognitive performance. Emphasizing the impact of tACS on individual ERP components, this article offers insights into the potential of conventional tACS for targeted stimulation of single ERP components. Furthermore, we review recent articles that explore a novel approach of tACS: ERP-aligned tACS. This innovative technique exploits the temporal precision of ERP components, aligning tACS with specific neural events to optimize stimulation effects and target the desired neural response. In conclusion, this review combines current knowledge to explore how ERPs, EROs, and NIBS interact, particularly highlighting the modulatory possibilities offered by tACS. The incorporation of ERP-aligned tACS introduces new opportunities for future research, advancing our understanding of the complex connection between neural oscillations and cognitive processes.

Modulating the difficulty of a visual oddball-like task and P3m amplitude.

It is often necessary to modulate the difficulty of an experimental task without changing physical stimulus characteristics that are known to modulate event-related potentials. Here, we developed a new, oddball-like visual discrimination task with varying levels of difficulty despite using almost identical visual stimuli. Gabor patches of one orientation served as frequent standard stimuli with 75% probability. Gabor patches with a slightly different orientation served as infrequent target stimuli (25% probability). Analyzing the behavioral outcomes revealed a successful modulation of task difficulty, i.e. the hard condition revealed decreased d' values and longer reaction times for standard stimuli. In addition, we recorded MEG and computed event-related fields in response to the stimuli. In line with our expectation, the amplitude of the P3m was reduced in the hard condition. We localized the sources of the P3m with a focus on those that are modulated by changes in task difficulty. The sources of P3m modulation by difficulty were found primarily in the centro-parietal regions of both hemispheres. Additionally, we found significant differences in source activity between the easy and hard conditions in parts of the pre and post-central gyrus and inferior parietal lobe. Our findings are in line with previous research suggesting that the brain areas responsible for the conventional P3m generators also contribute to a modulation by task difficulty.

ERP-aligned delta transcranial alternating current stimulation modulates the P3 amplitude.

The underlying mechanisms of the event-related potential (ERP) generation are still under debate. One popular model considers the ERP as a superposition of phase-resets of ongoing endogenous oscillations of different frequencies. Brain oscillations have been shown to be modulated by transcranial alternating current stimulation (tACS). Thus, it seems feasible, that an ERP could be altered by modulating the contributing oscillations using tACS. One possible approach would be to target a frequency-matched stimulation signal to a specific ERP-component. One possible target for such an approach is the P3, which appears as delta/theta oscillations in the frequency-domain. Thus, an ERP-aligned stimulation in the delta/theta-range might be suitable to force synchronization in the stimulated frequency band and thus increase the amplitude of the P3 component. Building on an existing paradigm, in the present study 21 healthy participants received individualized ERP-aligned delta tACS and control stimulation while performing a visual task. The visual stimulation was matched to the continuous tACS in order to align the tACS peak with the P3 peak. Both the P3 amplitude and the evoked delta power were significantly increased after ERP-aligned tACS but not after control stimulation. The investigated behavioral parameter showed no stimulation dependent effect. Our results may provide new insights into the debate on the contribution of phase-reset mechanisms to the generation of ERPs and offer new opportunities for clinical trials.

Attempting to counteract vigilance decrement in older adults with brain stimulation.

Introduction: Against the background of demographic change and the need for enhancement techniques for an aging society, we set out to repeat a study that utilized 40-Hz transcranial alternating current stimulation (tACS) to counteract the slowdown of reaction times in a vigilance experiment but with participants aged 65 years and older. On an oscillatory level, vigilance decrement is linked to rising occipital alpha power, which has been shown to be downregulated using gamma-tACS. Method: We applied tACS on the visual cortex and compared reaction times, error rates, and alpha power of a group stimulated with 40 Hz to a sham and a 5-Hz-stimulated control group. All groups executed two 30-min-long blocks of a visual task and were stimulated according to group in the second block. We hypothesized that the expected increase in reaction times and alpha power would be reduced in the 40-Hz group compared to the control groups in the second block (INTERVENTION). Results: Statistical analysis with linear mixed models showed that reaction times increased significantly over time in the first block (BASELINE) with approximately 3 ms/min for the SHAM and 2 ms/min for the 5-Hz and 40-Hz groups, with no difference between the groups. The increase was less pronounced in the INTERVENTION block (1 ms/min for SHAM and 5-Hz groups, 3 ms/min for the 40-Hz group). Differences among groups in the INTERVENTION block were not significant if the 5-Hz or the 40-Hz group was used as the base group for the linear mixed model. Statistical analysis with a generalized linear mixed model showed that alpha power was significantly higher after the experiment (1.37 µV2) compared to before (1 µV2). No influence of stimulation (40 Hz, 5 Hz, or sham) could be detected. Discussion: Although the literature has shown that tACS offers potential for older adults, our results indicate that findings from general studies cannot simply be transferred to an old-aged group. We suggest adjusting stimulation parameters to the neurophysiological features expected in this group. Next to heterogeneity and cognitive fitness, the influence of motivation and medication should be considered.

A Comparison of Closed Loop vs. Fixed Frequency tACS on Modulating Brain Oscillations and Visual Detection.

Transcranial alternating current stimulation has emerged as an effective tool for the exploration of brain oscillations. By applying a weak alternating current between electrodes placed on the scalp matched to the endogenous frequency, tACS enables the specific modulation of targeted brain oscillations This results in alterations in cognitive functions or persistent physiological changes. Most studies that utilize tACS determine a fixed stimulation frequency prior to the stimulation that is kept constant throughout the experiment. Yet it is known that brain rhythms can encounter shifts in their endogenous frequency. This could potentially move the ongoing brain oscillations into a frequency region where it is no longer affected by the stimulation, thereby decreasing or negating the effect of tACS. Such an effect of a mismatch between stimulation frequency and endogenous frequency on the outcome of stimulation has been shown before for the parietal alpha-activity. In this study, we employed an intermittent closed loop stimulation protocol, where the stimulation is divided into short epochs, between which an EEG is recorded and rapidly analyzed to determine a new stimulation frequency for the next stimulation epoch. This stimulation protocol was tested in a three-group study against a classical fixed stimulation protocol and a sham-treatment. We targeted the parietal alpha rhythm and hypothesized that this setup will ensure a constant close match between the frequencies of tACS and alpha activity. This closer match should lead to an increased modulation of detection of visual luminance changes depending on the phase of the tACS and an increased rise in alpha peak power post stimulation when compared to a protocol with fixed pre-determined stimulation frequency. Contrary to our hypothesis, our results show that only a fixed stimulation protocol leads to a persistent increase in post-stimulation alpha power as compared to sham. Furthermore, in none of the stimulated groups significant modulation of detection performance occurred. While the lack of behavioral effects is inconclusive due to the short selection of different phase bins and trials, the physiological results suggest that a constant stimulation with a fixed frequency is actually beneficial, when the goal is to produce persistent synaptic changes.

Hemisphere-specific, differential effects of lateralized, occipital-parietal α- versus γ-tACS on endogenous but not exogenous visual-spatial attention.

Orienting spatial attention has been associated with interhemispheric asymmetry of power in the α- and γ-band. Specifically, increased α-power has been linked to the inhibition of unattended sensory streams (e.g. the unattended visual field), while increased γ-power is associated with active sensory processing. Here, we aimed to differentially modulate endogenous and exogenous visual-spatial attention using transcranial alternating current stimulation (tACS). In a single-blind, within-subject design, participants performed several blocks of a spatial cueing task comprised of endogenous and exogenous cues while receiving lateralized α- or γ-tACS or no stimulation over left or right occipital-parietal areas. We found a significant, differential effect of α- and γ-tACS on endogenous (top-down) spatial attention but not on exogenous (bottom-up) attention. The effect was specific to tACS applied to the left hemisphere and driven by a modulation of attentional disengagement and re-orientation as measured during invalid trials. Our results indicate a causal role of α-/γ-oscillations for top-down (endogenous) attention. They may further suggest a left hemispheric dominance in controlling interhemispheric α-/γ-power asymmetry. The absence of an effect on exogenous attention may be indicative of a differential role of α-/γ-oscillations during different attention types or spatially distinct attentional subsystems.

Corrigendum: Absence of Alpha-tACS Aftereffects in Darkness Reveals Importance of Taking Derivations of Stimulation Frequency and Individual Alpha Variability Into Account.

[This corrects the article DOI: 10.3389/fpsyg.2018.00984.].

Counteracting the Slowdown of Reaction Times in a Vigilance Experiment With 40-Hz Transcranial Alternating Current Stimulation.

Indicators for a decrement in vigilance are a slowdown in reaction times and an increase in alpha power in the electroencephalogram in posterior regions of the brain. Transcranial alternating current stimulation (tACS) is a neuropsychological technique that has been found to interact with intrinsic brain oscillations and is able to enhance cognitive and behavioral performance. Recent studies show that tACS in the gamma frequency range (30-80 Hz) is able to downregulate amplitudes in the alpha frequency range (8-12 Hz), in accordance to the effect referred to as cross-frequency coupling, where intrinsic alpha and gamma waves modulate each other. We applied 40 Hz gamma-tACS to the visual cortex during a vigilance experiment and investigated if stimulation improves reaction times and error rates with time-on-task. In our sham controlled experiment, participants completed two blocks of 30 minutes duration while performing the same visual two-choice task. The first block was used as BASELINE. A statistical analysis with a linear mixed model revealed a significantly lower increase of modeled reaction times over time in the INTERVENTION-block of the tACS-group as compared with their BASELINE-block whereas there was no significant change between the BASELINE- and INTERVENTION-block for the SHAM-group. Error rates did not differ between groups. This paper indicates that gamma-tACS can enhance performance in vigilance tasks as it significantly decreased the slowdown of reaction times in our study.

Absence of Alpha-tACS Aftereffects in Darkness Reveals Importance of Taking Derivations of Stimulation Frequency and Individual Alpha Variability Into Account.

Transcranial alternating current stimulation (tACS) has found widespread use as a basic tool in the exploration of the role of brain oscillations. Many studies have shown that frequency-specific tACS is able to not only alter cognitive processes during stimulation, but also cause specific physiological aftereffects visible in the electroencephalogram (EEG). The relationship between the emergence of these aftereffects and the necessary duration of stimulation is inconclusive. Our goal in this study was to narrow down the crucial length of tACS-blocks, by which aftereffects can be elicited. We stimulated participants with α-tACS in four blocks of 1-, 3-, 5-, and 10-min length, once in increasing and once in decreasing order. After each block, we measured the resting EEG for 10 min during a visual vigilance task. We could not find lasting enhancement of α-power following any stimulation block, when comparing the stimulated groups to the sham group. These findings offer no information regarding the crucial stimulation duration. In addition, this conflicts with previous findings, showing a power increase following 10 min of tACS in the alpha range. We performed additional explorative analyses, based on known confounds of (1) mismatches between stimulation frequency and individual alpha frequency and (2) abnormalities in baseline α-activity. The results of an ANCOVA suggested that both factor explain variance, but could not resolve how exactly both factors interfere with the stimulation effect. Employing a linear mixed model, we found a significant effect of stimulation following 10 min of α-tACS in the increasing sequence and a significant effect of the mismatch between stimulated frequency and individual alpha frequency. The implications of these findings for future research are discussed.

Ten Minutes of α-tACS and Ambient Illumination Independently Modulate EEG α-Power.

Transcranial alternating current stimulation (tACS) sees increased use in neurosciences as a tool for the exploration of brain oscillations. It has been shown that tACS stimulation in specific frequency bands can result in aftereffects of modulated oscillatory brain activity that persist after the stimulation has ended. The general relationship between persistency of the effect and duration of stimulation is sparsely investigated but previous research has shown that the occurrence of tACS aftereffects depends on the brain state before and during stimulation. Early alpha neurofeedback research suggests that particularly in the alpha band the responsiveness to a manipulation depends on the ambient illumination during measurement. Therefore, in the present study we assessed the brain's susceptibility to tACS at the individual alpha frequency during darkness compared to ambient illumination. We measured alpha power after 10 min of stimulation in 30 participants while they continuously performed a visual vigilance task. Our results show that immediately after stimulation, the alpha power in the illumination condition for both the stimulated and sham group has increased by only about 7%, compared to about 20% in both groups in the 'dark' condition. For the group that did not receive stimulation, the power in darkness remained stable after stimulation, whereas the power in light increased by an additional 10% during the next 30 min. For the group that did receive stimulation, alpha power during these 30 min increased by another 11% in light and 22% in darkness. Since alpha power already increased by about 10% without stimulation, the effect of illumination does not seem to have interacted with the effect of stimulation. Instead, both effects seem to have added up linearly. Although our findings do not show that illumination-induced differences in oscillatory activity influence the susceptibility toward tACS, they stress the importance of controlling for factors like ambient light that might add an independent increase or decrease to the power of brain oscillations during periods, where possible persistent effects of stimulation are explored.