Transcranial alternating current stimulation does not modulate corticospinal activity in humans

Transcranial alternating current stimulation (TACS) is commonly used to synchronise the output of a cortical area to other parts of the nervous system, but evidence for this based on brain recordings in humans is challenging. The brain transmits beta oscillations (~21Hz) to tonically contracted limb muscles linearly and through the fastest corticospinal pathways. Therefore, muscle activity may be used as a proxy measure for the level of beta entrainment in the corticospinal tract due to TACS over motor cortex. Here, we assessed if TACS is able to modulate the neural inputs to muscles, which would provide an indirect evidence for TACS-driven neural entrainment. In the first part of this study, we ran a series of simulations of motor neuron (MN) pools receiving inputs from corticospinal neurons with different levels of beta entrainment. Results indicated that MNs should be highly sensitive to changes in corticospinal beta activity. Then, we ran experiments on healthy human subjects (N=10) in which TACS (at 1mA) was delivered over the motor cortex at 21Hz (beta stimulation), or at 7Hz or 40Hz (control conditions) while the abductor digiti minimi (ADM) or the tibialis anterior muscle (TA) were tonically contracted. Muscle activity was measured using high-density electromyography, which allowed us to decompose the spiking activity of pools of motor units innervating the studied muscles. By analysing motor unit pool activity, we observed that none of the tested TACS conditions could consistently alter the spectral characteristics of the common neural inputs received by the muscles. These results suggest that 1mA-TACS over motor cortex given at frequencies in the beta band does not affect corticospinal beta entrainment.

Effects of transcranial alternating current stimulation over right-DLPFC on vigilance tasks depend on the arousal level

Current theoretical accounts on the oscillatory nature of sustained attention predict that entrainment via transcranial alternating current stimulation (tACS) at alpha and theta frequencies on specific areas of the prefrontal cortex could prevent the drops in vigilance across time-on-task. Nonetheless, most previous studies have neglected both the fact that vigilance comprises two dissociable components (i.e., arousal and executive vigilance) and the potential role of differences in arousal levels. We examined the effects of theta- and alpha-tACS over the right dorsolateral prefrontal cortex in both components of vigilance and in participants who differed in arousal level according to their chronotype and time of testing. Intermediate-types performed the vigilance tasks when their arousal level was optimal, whereas evening-types performed the vigilance tasks when their arousal levels were non-optimal. Both theta- and alpha-tACS improved arousal vigilance in the psychomotor vigilance task (PVT), whereas alpha-tACS, but not theta-tACS, improved executive vigilance in the sustained attention to response task (SART), and counteracted the typical vigilance decrement usually observed in this task. Importantly, these stimulation effects were only found when arousal was low (i.e., with evening-types performing the tasks at their non-optimal time of day). The results support the multicomponent view of vigilance, the relevance of heeding individual differences in arousal, and the role of alpha oscillations as a long-range cortical scale synchronization mechanism that compensates the decrements in performance as a function of time-on-task by exerting and maintaining cognitive control attributed to activation of the right dorsolateral prefrontal cortex.

Transcranial stimulation of alpha oscillations up-regulates the default mode network

The default mode network (DMN) is the most-prominent intrinsic connectivity network, serving as a key architecture of the brain’s functional organization. Conversely, dysregulated DMN is characteristic of major neuropsychiatric disorders. However, the field still lacks mechanistic insights into the regulation of the DMN and effective interventions for DMN dysregulation. The current study approached this problem by manipulating neural synchrony, particularly alpha (8 to 12 Hz) oscillations, a dominant intrinsic oscillatory activity that has been increasingly associated with the DMN in both function and physiology. Using high-definition alpha-frequency transcranial alternating current stimulation (α-tACS) to stimulate the cortical source of alpha oscillations, in combination with simultaneous electroencephalography and functional MRI (EEG-fMRI), we demonstrated that α-tACS (versus Sham control) not only augmented EEG alpha oscillations but also strengthened fMRI and (source-level) alpha connectivity within the core of the DMN. Importantly, increase in alpha oscillations mediated the DMN connectivity enhancement. These findings thus identify a mechanistic link between alpha oscillations and DMN functioning. That transcranial alpha modulation can up-regulate the DMN further highlights an effective noninvasive intervention to normalize DMN functioning in various disorders.

Impact of 40 Hz Transcranial Alternating Current Stimulation on Cerebral Tau Burden in Patients with Alzheimer’s Disease: A Case Series

Background: Alzheimer’s disease (AD) is characterized by diffuse amyloid-β (Aβ) and phosphorylated Tau (p-Tau) aggregates as well as neuroinflammation. Exogenously-induced 40 Hz gamma oscillations have been showing to reduce Aβ and p-Tau deposition presumably via microglia activation in AD mouse models. Objective: We aimed to translate preclinical data on gamma-induction in AD patients by means of transcranial alternating current stimulation (tACS). Methods: Four participants with mild-to-moderate AD received 1 h of daily 40 Hz (gamma) tACS for 4 weeks (Monday to Friday) targeting the bitemporal lobes (20 h treatment duration). Participant underwent Aβ, p-Tau, and microglia PET imaging with [11C]-PiB, [18F]-FTP, and [11C]-PBR28 respectively, before and after the intervention along with electrophysiological assessment. Results: No adverse events were reported, and an increase in gamma spectral power on EEG was observed after the treatment. [18F]-FTP PET revealed a significant decrease over 2% of p-Tau burden in 3/4 patients following the tACS treatment, primarily involving the temporal lobe regions targeted by tACS and especially mesial regions (e.g., entorhinal cortex). The amount of intracerebral Aβ as measured by [11C]-PiB was not significantly influenced by tACS, whereas 1/4 reported a significant decrease of microglia activation as measured by [11C]-PBR28. Conclusion: tACS seems to represent a safe and feasible option for gamma induction in AD patients, with preliminary evidence of a possible effect on protein clearance partially mimicking what is observed in animal models. Longer interventions and placebo control conditions are needed to fully evaluate the potential for tACS to slow disease progression.

Remotely Monitored Home-Based Neuromodulation With Transcranial Alternating Current Stimulation (tACS) for Mal de Débarquement Syndrome

Objective: To determine whether remotely-monitored transcranial alternating current stimulation (tACS) may be a viable and safe treatment option for Mal de Débarquement Syndrome (MdDS).Background: Mal de Débarquement Syndrome is a neurotological disorder characterized by persistent oscillating vertigo that is triggered by entrainment to passive oscillatory motion such as occurs during water-based travel. Treatment options for MdDS are limited, variably effective, and can be undone by further travel.Design and Methods: This was a remotely-monitored open-label optional extension phase of a double-blind randomized onsite study of tACS for medically refractory MdDS. The primary goal was to determine safety, feasibility, and blinded participant feedback. The secondary goal was to determine efficacy. Thirteen participants (all women), aged 22–67 years, experiencing a duration of illness of 11–72 months, were a subset of 24 individuals who participated in an on-site study of tACS. They had either not responded to the on-site protocol or had relapsed after travel home. Treatment accessories and a tablet controlled tACS stimulator (Pulvinar XCSITE-100) were mailed to participants. Three teaching sessions were performed via webcam followed by on-going remote monitoring of treatment logs and participants' reports through a daily on-line diary and weekly questionnaires. Treatment continued until an effective protocol was administered for 4 weeks and then tapered over 4 weeks. Participants completed a blinded feedback survey and a debriefing interview at the completion of the entire study.Results: Treatment duration ranged from 4 to 31 weeks followed by a 4-week taper accounting for 578 verified sessions. Of the 13 total participants, seven agreed or agreed strongly in the blinded survey that tACS treatment was beneficial; 2) Twelve were comfortable utilizing tACS on their own; 3) Eleven preferred stimulation above their individual alpha frequency; 4) Side effects were generally mild and typical of tACS. In the debriefing interview completed 2–9 months after the last stimulation, five participants reported doing “great,” with no to minimal symptoms, four reported doing “good,” with moderate symptoms, and four reported no change compared to pre-study baseline.Conclusion: Remotely-monitored tACS may be a safe treatment option for MdDS with the potential for lasting outcomes, increased accessibility, and reduction in travel-related treatment reversal.

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.

tACS facilitates flickering driving by boosting steady-state visual evoked potentials

Objective. There has become of increasing interest in transcranial alternating current stimulation (tACS) since its inception nearly a decade ago. tACS in modulating brain state is an active area of research and has been demonstrated effective in various neuropsychological and clinical domains. In the visual domain, much effort has been dedicated to brain rhythms and rhythmic stimulation, i.e. tACS. However, less is known about the interplay between the rhythmic stimulation and visual stimulation. Approach. Here, we used steady-state visual evoked potential (SSVEP), induced by flickering driving as a widely used technique for frequency-tagging, to investigate the aftereffect of tACS in healthy human subjects. Seven blocks of 64-channel electroencephalogram were recorded before and after the administration of 20min 10Hz tACS, while subjects performed several blocks of SSVEP tasks. We characterized the physiological properties of tACS aftereffect by comparing and validating the temporal, spatial, spatiotemporal and signal-to-noise ratio (SNR) patterns between and within blocks in real tACS and sham tACS. Main results. Our result revealed that tACS boosted the 10Hz SSVEP significantly. Besides, the aftereffect on SSVEP was mitigated with time and lasted up to 5 min. Significance. Our results demonstrate the feasibility of facilitating the flickering driving by external rhythmic stimulation and open a new possibility to alter the brain state in a direction by noninvasive transcranial brain stimulation.

Increasing human motor skill acquisition by driving theta-gamma coupling

Skill learning is a fundamental adaptive process, but the mechanisms remain poorly understood. Some learning paradigms, particularly in the memory domain, are closely associated with gamma activity that is amplitude-modulated by the phase of underlying theta activity, but whether such nested activity patterns also underpin skill learning is unknown. Here we addressed this question by using transcranial alternating current stimulation (tACS) over sensorimotor cortex to modulate theta-gamma activity during motor skill acquisition, as an exemplar of a non-hippocampal-dependent task. We demonstrated, and then replicated, a significant improvement in skill acquisition with theta-gamma tACS, which outlasted the stimulation by an hour. Our results suggest that theta-gamma activity may be a common mechanism for learning across the brain and provides a putative novel intervention for optimising functional improvements in response to training or therapy.