"Broadband Alpha Transcranial Alternating Current Stimulation": Exploring a new biologically calibrated brain stimulation protocol.

Transcranial alternating current stimulation (tACS) can be used to study causal contributions of oscillatory brain mechanisms to cognition and behavior. For instance, individual alpha frequency (IAF) tACS was reported to enhance alpha power and impact visuospatial attention performance. Unfortunately, such results have been inconsistent and difficult to replicate. In tACS, stimulation generally involves one frequency, sometimes individually calibrated to a peak value observed in an M/EEG power spectrum. Yet, the 'peak' actually observed in such power spectra often contains a broader range of frequencies, raising the question whether a biologically calibrated tACS protocol containing this fuller range of alpha-band frequencies might be more effective. Here, we introduce 'Broadband-alpha-tACS', a complex individually calibrated electrical stimulation protocol. We band-pass filtered left posterior resting-state EEG data around the IAF (± 2 Hz), and converted that time series into an electrical waveform for tACS stimulation of that same left posterior parietal cortex location. In other words, we stimulated a brain region with a 'replay' of its own alpha-band frequency content, based on spontaneous activity. Within-subjects (N = 24), we compared to a sham tACS session the effects of broadband-alpha tACS, power-matched spectral inverse ('alpha-removed') control tACS, and individual alpha frequency (IAF) tACS, on EEG alpha power and performance in an endogenous attention task previously reported to be affected by alpha tACS. Broadband-alpha-tACS significantly modulated attention task performance (i.e., reduced the rightward visuospatial attention bias in trials without distractors, and reduced attention benefits). Alpha-removed tACS also reduced the rightward visuospatial attention bias. IAF-tACS did not significantly modulate attention task performance compared to sham tACS, but also did not statistically significantly differ from broadband-alpha-tACS. This new broadband-alpha-tACS approach seems promising, but should be further explored and validated in future studies.

Calibrating rhythmic stimulation parameters to individual electroencephalography markers: The consistency of individual alpha frequency in practical lab settings.

Rhythmic stimulation can be applied to modulate neuronal oscillations. Such 'entrainment' is optimized when stimulation frequency is individually calibrated based on magneto/encephalography markers. It remains unknown how consistent such individual markers are across days/sessions, within a session, or across cognitive states, hemispheres and estimation methods, especially in a realistic, practical, lab setting. We here estimated individual alpha frequency (IAF) repeatedly from short electroencephalography (EEG) measurements at rest or during an attention task (cognitive state), using single parieto-occipital electrodes in 24 participants on 4 days (between-sessions), with multiple measurements over an hour on 1 day (within-session). First, we introduce an algorithm to automatically reject power spectra without a sufficiently clear peak to ensure unbiased IAF estimations. Then we estimated IAF via the traditional 'maximum' method and a 'Gaussian fit' method. IAF was reliable within- and between-sessions for both cognitive states and hemispheres, though task-IAF estimates tended to be more variable. Overall, the 'Gaussian fit' method was more reliable than the 'maximum' method. Furthermore, we evaluated how far from an approximated 'true' task-related IAF the selected 'stimulation frequency' was, when calibrating this frequency based on a short rest-EEG, a short task-EEG, or simply selecting 10 Hz for all participants. For the 'maximum' method, rest-EEG calibration was best, followed by task-EEG, and then 10 Hz. For the 'Gaussian fit' method, rest-EEG and task-EEG-based calibration were similarly accurate, and better than 10 Hz. These results lead to concrete recommendations about valid, and automated, estimation of individual oscillation markers in experimental and clinical settings.

Does alpha phase modulate visual target detection? Three experiments with tACS-phase-based stimulus presentation.

In recent years, the influence of alpha (7-13 Hz) phase on visual processing has received a lot of attention. Magneto-/encephalography (M/EEG) studies showed that alpha phase indexes visual excitability and task performance. Studies with transcranial alternating current stimulation (tACS) aim to modulate oscillations and causally impact task performance. Here, we applied right occipital tACS (O2 location) to assess the functional role of alpha phase in a series of experiments. We presented visual stimuli at different pre-determined, experimentally controlled, phases of the entraining tACS signal, hypothesizing that this should result in an oscillatory pattern of visual performance in specifically left hemifield detection tasks. In experiment 1, we applied 10 Hz tACS and used separate psychophysical staircases for six equidistant tACS-phase conditions, obtaining contrast thresholds for detection of visual gratings in left or right hemifield. In experiments 2 and 3, tACS was at EEG-based individual peak alpha frequency. In experiment 2, we measured detection rates for gratings with (pseudo-)fixed contrast. In experiment 3, participants detected brief luminance changes in a custom-built LED device, at eight equidistant alpha phases. In none of the experiments did the primary outcome measure over phase conditions consistently reflect a one-cycle sinusoid. However, post hoc analyses of reaction times (RT) suggested that tACS alpha phase did modulate RT for specifically left hemifield targets in both experiments 1 and 2 (not measured in experiment 3). This observation requires future confirmation, but is in line with the idea that alpha phase causally gates visual inputs through cortical excitability modulation.

Spontaneous Fluctuations in Oscillatory Brain State Cause Differences in Transcranial Magnetic Stimulation Effects Within and Between Individuals.

Transcranial magnetic stimulation (TMS) can cause measurable effects on neural activity and behavioral performance in healthy volunteers. In addition, TMS is increasingly used in clinical practice for treating various neuropsychiatric disorders. Unfortunately, TMS-induced effects show large intra- and inter-subject variability, hindering its reliability, and efficacy. One possible source of this variability may be the spontaneous fluctuations of neuronal oscillations. We present recent studies using multimodal TMS including TMS-EMG (electromyography), TMS-tACS (transcranial alternating current stimulation), and concurrent TMS-EEG-fMRI (electroencephalography, functional magnetic resonance imaging), to evaluate how individual oscillatory brain state affects TMS signal propagation within targeted networks. We demonstrate how the spontaneous oscillatory state at the time of TMS influences both immediate and longer-lasting TMS effects. These findings indicate that at least part of the variability in TMS efficacy may be attributable to the current practice of ignoring (spontaneous) oscillatory fluctuations during TMS. Ignoring this state-dependent spread of activity may cause great individual variability which so far is poorly understood and has proven impossible to control. We therefore also compare two technical solutions to directly account for oscillatory state during TMS, namely, to use (a) tACS to externally control these oscillatory states and then apply TMS at the optimal (controlled) brain state, or (b) oscillatory state-triggered TMS (closed-loop TMS). The described multimodal TMS approaches are paramount for establishing more robust TMS effects, and to allow enhanced control over the individual outcome of TMS interventions aimed at modulating information flow in the brain to achieve desirable changes in cognition, mood, and behavior.

Can processing of face trustworthiness bypass early visual cortex? A transcranial magnetic stimulation masking study.

As a highly social species, we constantly evaluate human faces to decide whether we can trust someone. Previous studies suggest that face trustworthiness can be processed unconsciously, but the underlying neural pathways remain unclear. Specifically, the question remains whether processing of face trustworthiness relies on early visual cortex (EVC), required for conscious perception. If processing of trustworthiness can bypass EVC, then disrupting EVC should impair subjective (conscious) trustworthiness perception while leaving objective (forced-choice) trustworthiness judgment intact. We applied double-pulse transcranial magnetic stimulation (TMS) to right EVC, at different stimulus onset asynchronies (SOAs) from presentation of a face in either the left or right hemifield. Faces were slightly rotated clockwise or counterclockwise, and were either trustworthy or untrustworthy. On each trial, participants discriminated 1) trustworthiness, 2) stimulus rotation, and 3) reported subjective visibility of trustworthiness. At early SOAs and specifically in the left hemifield, performance on the rotation task was impaired by TMS. Crucially, though TMS also impaired subjective visibility of trustworthiness, no effects on trustworthiness discrimination were obtained. Thus, conscious perception of face trustworthiness (captured by subjective visibility ratings) relies on intact EVC, while objective forced-choice trustworthiness judgments may not. These results are consistent with the hypothesis that objective trustworthiness processing can bypass EVC. For basic visual features, extrastriate pathways are well-established; but face trustworthiness depends on a complex configuration of features. Its potential processing without EVC is therefore of particular interest, further highlighting its ecological relevance.