Sham tACS Research Articles

Differential Effects of 10 and 20 Hz Brain Stimulation in Chronic Stroke: A tACS-fMRI Study.

Transcranial alternating current stimulation (tACS) is an emerging non-invasive neuromodulation technique, which could be potentially applied to enhance stroke rehabilitation. In this study, we aimed to characterize the frequency-specific effects of tACS in chronic stroke. Therefore, concurrent tACS and functional magnetic resonance imaging (fMRI) were conducted in 13 chronic stroke individuals. Resting-state and task-based fMRI were collected for each subject under different frequencies (10 Hz, 20 Hz, Sham). Task-based fMRI showed that increased activation was found in the ipsilesional precentral area during paretic hand movements after 10 Hz tACS, while increased activation was found in the contralesional precentral area during non-paretic hand movements after both 10 and 20 Hz tACS. Resting-state seed-based functional connectivity (FC) analysis showed that 10 Hz tACS mainly modulated FC within motor-related regions, while 20 Hz tACS also modulated regions beyond the motor-related areas. Graph theory analysis further demonstrated the functional interaction modulated by tACS in the whole-brain level. Taken together, our results showed that tACS might exhibit frequency-specific modulation in chronic stroke. 20 Hz tACS facilitates the functional interaction between the sensorimotor regions and brain regions involved in executive control, while 10 Hz and sham tACS has limited effect on motor-related brain activity. Our results reveal the neural response process under external current stimulation, providing new insight into the neuromodulation mechanism of tACS in a lesioned brain.

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.

Investigating Different Levels of Bimanual Interaction With a Novel Motor Learning Task: A Behavioural and Transcranial Alternating Current Stimulation Study.

Many tasks require the skilled interaction of both hands, such as eating with knife and fork or keyboard typing. However, our understanding of the behavioural and neurophysiological mechanisms underpinning bimanual motor learning is still sparse. Here, we aimed to address this by first characterising learning-related changes of different levels of bimanual interaction and second investigating how beta tACS modulates these learning-related changes. To explore early bimanual motor learning, we designed a novel bimanual motor learning task. In the task, a force grip device held in each hand (controlling x- and y-axis separately) was used to move a cursor along a path of streets at different angles (0°, 22.5°, 45°, 67.5°, and 90°). Each street corresponded to specific force ratios between hands, which resulted in different levels of hand interaction, i.e., unimanual (Uni, i.e., 0°, 90°), bimanual with equal force (Bieq, 45°), and bimanual with unequal force (Biuneq 22.5°, 67.5°). In experiment 1, 40 healthy participants performed the task for 45 min with a minimum of 100 trials. We found that the novel task induced improvements in movement time and error, with no trade-off between movement time and error, and with distinct patterns for the three levels of bimanual interaction. In experiment 2, we performed a between-subjects, double-blind study in 54 healthy participants to explore the effect of phase synchrony between both sensorimotor cortices using tACS at the individual’s beta peak frequency. The individual’s beta peak frequency was quantified using electroencephalography. 20 min of 2 mA peak-to-peak amplitude tACS was applied during task performance (40 min). Participants either received in-phase (0° phase shift), out-of-phase (90° phase shift), or sham (3 s of stimulation) tACS. We replicated the behavioural results of experiment 1, however, beta tACS did not modulate motor learning. Overall, the novel bimanual motor task allows to characterise bimanual motor learning with different levels of bimanual interaction. This should pave the way for future neuroimaging studies to further investigate the underlying mechanism of bimanual motor learning.

After-Effects of Intermittent Theta-Burst Stimulation Are Differentially and Phase-Dependently Suppressed by α- and β-Frequency Transcranial Alternating Current Stimulation.

Intermittent theta-burst stimulation (iTBS) using transcranial magnetic stimulation (TMS) is known to produce excitatory after-effects over the primary motor cortex (M1). Recently, transcranial alternating current stimulation (tACS) at 10 Hz (α) and 20 Hz (β) have been shown to modulate M1 excitability in a phase-dependent manner. Therefore, we hypothesized that tACS would modulate the after-effects of iTBS depending on the stimulation frequency and phase. To test our hypothesis, we examined the effects of α- and β-tACS on iTBS using motor evoked potentials (MEPs). Eighteen and thirteen healthy participants were recruited for α and β tACS conditions, respectively. tACS electrodes were attached over the left M1 and Pz. iTBS over left M1 was performed concurrently with tACS. The first pulse of the triple-pulse burst of iTBS was controlled to match the peak (90°) or trough (270°) phase of the tACS. A sham tACS condition was used as a control in which iTBS was administered without tACS. Thus, each participant was tested in three conditions: the peak and trough of the tACS phases and sham tACS. As a result, MEPs were enhanced after iTBS without tACS (sham condition), as observed in previous studies. α-tACS suppressed iTBS effects at the peak phase but not at the trough phase, while β-tACS suppressed the effects at both phases. Thus, although both types of tACS inhibited the facilitatory effects of iTBS, only α-tACS did so in a phase-dependent manner. Phase-dependent inhibition by α-tACS is analogous to our previous finding in which α-tACS inhibited MEPs online at the peak condition. Conversely, β-tACS reduced the effects of iTBS irrespective of its phase. The coupling of brain oscillations and tACS rhythms is considered important in the generation of spike-timing-dependent plasticity. Additionally, the coupling of θ and γ oscillations is assumed to be important for iTBS induction through long-term potentiation (LTP). Therefore, excessive coupling between β oscillations induced by tACS and γ or θ oscillations induced by iTBS might disturb the coupling of θ and γ oscillations during iTBS. To conclude, the action of iTBS is differentially modulated by neuronal oscillations depending on whether α- or β-tACS is applied.

Behavioral and electrocortical effects of transcranial alternating current stimulation during advice-guided decision-making

In decision-making with uncertain outcomes people may rely on external cues, such as expert advice, even if this information has no predictive value. While the fronto-parietal event-related potential (ERP) components feedback-related negativity (FRN) and P3 are associated with both reward/punishment feedback processing, the relationship between ERP modulation and expert advice during decision making remains unclear. In this double-blind sham-controlled within-subject study transcranial alternating current stimulation (tACS) at an intensity of 1 mA was applied to the frontal cortex in twenty-four healthy volunteers. The aim was to decrease reliance on expert advice by targeting FRN, P3a and P3b components. Following administration of frontal delta (2.5 Hz), theta (5 Hz) and sham tACS, ERPs and advice-guided decision making were evaluated. Results showed a tentative behavioral effect of delta tACS in the response bias. In contrast, theta tACS significantly lowered P3b and P3a amplitudes, but no effects of tACS were observed for the FRN. Effects on electrophysiology and advice following behavior were uncorrelated. Our findings suggest that theta tACS may modulate electrocortical signals and delta tACS advice following, yet the relationship between both remains unresolved.

Driving motor cortex oscillations modulates bradykinesia in Parkinson's disease.

In patients with Parkinson's disease, beta (β) and gamma (γ) oscillations are altered in the basal ganglia, and this abnormality contributes to the pathophysiology of bradykinesia. However, it is unclear whether β and γ rhythms at the primary motor cortex (M1) level influence bradykinesia. Transcranial alternating current stimulation (tACS) can modulate cortical rhythms by entraining endogenous oscillations. We tested whether β- and γ-tACS on M1 modulate bradykinesia in patients with Parkinson's disease by analysing the kinematic features of repetitive finger tapping, including movement amplitude, velocity and sequence effect, recorded during β-, γ- and sham tACS. We also verified whether possible tACS-induced bradykinesia changes depended on modifications in specific M1 circuits, as assessed by short-interval intracortical inhibition and short-latency afferent inhibition. Patients were studied OFF and ON dopaminergic therapy. Results were compared to those obtained in a group of healthy subjects. In patients, movement velocity significantly worsened during β-tACS and movement amplitude improved during γ-tACS, while the sequence effect did not change. In addition, short-latency afferent inhibition decreased (reduced inhibition) during β-tACS and short-interval intracortical inhibition decreased during both γ- and β-tACS in Parkinson's disease. The effects of tACS were comparable between OFF and ON sessions. In patients OFF therapy, the degree of short-interval intracortical inhibition modulation during β- and γ-tACS correlated with movement velocity and amplitude changes. Moreover, there was a positive correlation between the effect of γ-tACS on movement amplitude and motor symptoms severity. Our results show that cortical β and γ oscillations are relevant in the pathophysiology of bradykinesia in Parkinson's disease and that changes in inhibitory GABA-A-ergic interneuronal activity may reflect compensatory M1 mechanisms to counteract bradykinesia. In conclusion, abnormal oscillations at the M1 level of the basal ganglia-thalamo-cortical network play a relevant role in the pathophysiology of bradykinesia in Parkinson's disease.

A specific phase of transcranial alternating current stimulation at the \u03b2 frequency boosts repetitive paired-pulse TMS-induced plasticity

Transcranial alternating current stimulation (tACS) at 20 Hz (β) has been shown to modulate motor evoked potentials (MEPs) when paired with transcranial magnetic stimulation (TMS) in a phase-dependent manner. Repetitive paired-pulse TMS (rPPS) with I-wave periodicity (1.5 ms) induced short-lived facilitation of MEPs. We hypothesized that tACS would modulate the facilitatory effects of rPPS in a frequency- and phase-dependent manner. To test our hypothesis, we investigated the effects of combined tACS and rPPS. We applied rPPS in combination with peak or trough phase tACS at 10 Hz (α) or β, or sham tACS (rPPS alone). The facilitatory effects of rPPS in the sham condition were temporary and variable among participants. In the β tACS peak condition, significant increases in single-pulse MEPs persisted for over 30 min after the stimulation, and this effect was stable across participants. In contrast, β tACS in the trough condition did not modulate MEPs. Further, α tACS parameters did not affect single-pulse MEPs after the intervention. These results suggest that a rPPS-induced increase in trans-synaptic efficacy could be strengthened depending on the β tACS phase, and that this technique could produce long-lasting plasticity with respect to cortical excitability.

Enhancing visual motion discrimination by desynchronizing bifocal oscillatory activity

Visual motion discrimination involves reciprocal interactions in the alpha band between the primary visual cortex (V1) and mediotemporal areas (V5/MT). We investigated whether modulating alpha phase synchronization using individualized multisite transcranial alternating current stimulation (tACS) over V5 and V1 regions would improve motion discrimination. We tested 3 groups of healthy subjects with the following conditions: (1) individualized In-Phase V1alpha-V5alpha tACS (0° lag), (2) individualized Anti-Phase V1alpha-V5alpha tACS (180° lag) and (3) sham tACS. Motion discrimination and EEG activity were recorded before, during and after tACS. Performance significantly improved in the Anti-Phase group compared to the In-Phase group 10 and 30 min after stimulation. This result was explained by decreases in bottom-up alpha-V1 gamma-V5 phase-amplitude coupling. One possible explanation of these results is that Anti-Phase V1alpha-V5alpha tACS might impose an optimal phase lag between stimulation sites due to the inherent speed of wave propagation, hereby supporting optimized neuronal communication.

Modulating Brain Rhythms of Pain Using Transcranial Alternating Current Stimulation (tACS) - A Sham-Controlled Study in Healthy Human Participants

Chronic pain is a major health care problem. A better mechanistic understanding and new treatment approaches are urgently needed. In the brain, pain has been associated with neural oscillations at alpha and gamma frequencies, which can be targeted using transcranial alternating current stimulation (tACS). Thus, we investigated the potential of tACS to modulate pain and pain-related autonomic activity in an experimental model of chronic pain in 29 healthy participants. In 6 recording sessions, participants completed a tonic heat pain paradigm and simultaneously received tACS over prefrontal or somatosensory cortices at alpha or gamma frequencies or sham tACS. Concurrently, pain ratings and autonomic responses were collected. Using the present setup, tACS did not modulate pain or autonomic responses. Bayesian statistics confirmed a lack of tACS effects in most conditions. The only exception was alpha tACS over somatosensory cortex where evidence was inconclusive. Taken together, we did not find significant tACS effects on tonic experimental pain in healthy humans. Based on our present and previous findings, further studies might apply refined stimulation protocols targeting somatosensory alpha oscillations. Trial registrationThe study protocol was pre-registered at ClinicalTrials.gov (NCT03805854). PerspectiveModulating brain oscillations is a promising approach for the treatment of pain. We therefore applied transcranial alternating current stimulation (tACS) to modulate experimental pain in healthy participants. However, tACS did not modulate pain, autonomic responses, or EEG oscillations. These findings help to shape future tACS studies for the treatment of pain.

Exposure to gamma tACS in Alzheimer’s disease: A randomized, double-blind, sham-controlled, crossover, pilot study

ObjectiveTo assess whether exposure to non-invasive brain stimulation with transcranial alternating current stimulation at γ frequency (γ-tACS) applied over Pz (an area overlying the medial parietal cortex and the precuneus) can improve memory and modulate cholinergic transmission in mild cognitive impairment due to Alzheimer’s disease (MCI-AD). MethodsIn this randomized, double-blind, sham controlled, crossover pilot study, participants were assigned to a single 60 min treatment with exposure to γ-tACS over Pz or sham tACS. Each subject underwent a clinical evaluation including assessment of episodic memory pre- and post-γ-tACS or sham stimulation. Indirect measures of cholinergic transmission evaluated using transcranial magnetic stimulation (TMS) pre- and post-γ-tACS or sham tACS were evaluated. ResultsTwenty MCI-AD participants completed the study. No tACS-related side effects were observed, and the intervention was well tolerated in all participants. We observed a significant improvement at the Rey auditory verbal learning (RAVL) test total recall (5.7 [95% CI, 4.0 to 7.4], p < 0.001) and long delayed recall scores (1.3 [95% CI, 0.4 to 2.1], p = 0.007) after γ-tACS but not after sham tACS. Face-name associations scores improved during γ−tACS (4.3 [95% CI, 2.8 to 5.8], p < 0.001) but not after sham tACS. Short latency afferent inhibition, an indirect measure of cholinergic transmission evaluated with TMS, increased only after γ-tACS (0.31 [95% CI, 0.24 to 0.38], p < 0.001) but not after sham tACS. Conclusionsexposure to γ-tACS over Pz showed a significant improvement of memory performances, along with restoration of intracortical connectivity measures of cholinergic neurotransmission, compared to sham tACS.

The effect of somatosensory alpha transcranial alternating current stimulation on pain empathy is trait empathy and gender dependent.

BackgroundPain empathy enables a person to experience and understand other's pain state by observing others in pain condition. Such prosocial ability is deficient in many psychopathological disorders. Somatosensory alpha suppression is considered as neural correlates of pain empathy and is hypothesized as a target for enhancement of pain empathy. Researches demonstrated that alpha suppression could be enhanced by transcranial alternating current stimulation (tACS) at alpha frequency non‐invasively.AimsWe applied alpha tACS over the primary somatosensory cortex of healthy subjects to investigate whether alpha tACS is able to enhance the pain empathy performance.ResultsThe results showed that there was no difference of pain empathy performance between alpha tACS and sham tACS either when tACS was applied during the task or before task. While in the alpha tACS group, the pain empathy performance was positively correlated with empathic concern of male subjects, the sub‐component of personal trait empathy.ConclusionsAlpha tACS cannot alter the empathy performance overall, but the modulation effect of alpha tACS on pain empathy is dependent on the gender and trait empathy of subjects.

Gamma-induction in frontotemporal dementia (GIFTeD) randomized placebo-controlled trial: Rationale, noninvasive brain stimulation protocol, and study design.

IntroductionFrontotemporal dementia (FTD) is a neurodegenerative disorder for which there is no effective pharmacological treatment. Recently, interneuron activity responsible for fast oscillatory brain activity has been found to be impaired in a mouse model of FTD with consequent cognitive and behavioral alterations. In this study, we aim to investigate the safety, tolerability, and efficacy of a novel promising therapeutic intervention for FTD based on 40 Hz transcranial alternating current stimulation (tACS), a form of non‐invasive brain stimulation thought to engage neural activity in a frequency‐specific manner and thus suited to restore altered brain oscillatory patterns.MethodsThis is a multi‐site, randomized, double‐blind, placebo‐controlled trial on 50 patients with a diagnosis of behavioral variant FTD (bvFTD). Participants will be randomized to undergo either 30 days of 1‐hour daily tACS or Sham (placebo) tACS. The outcomes will be assessed at baseline, right after the intervention and at a 3‐ to 6‐months follow‐up. The primary outcome measures are represented by the safety and feasibility of tACS administration, which will be assessed considering the nature, frequency, and severity of adverse events as well as attrition rate, respectively. To assess secondary outcomes, participants will undergo extensive neuropsychological and behavioral assessments and fluorodeoxyglucose (FDG)–positron emission tomography (PET) scans to evaluate changes in brain metabolism, functional and structural magnetic resonance imaging (MRI), resting and evoked electroencephalography, as well as blood biomarkers to measure changes in neurodegenerative and neuroinflammatory markers.ResultsThe trial started in October 2020 and will end in October 2023. Study protocols have been approved by the local institutional review board (IRB) at each data‐collection site.DiscussionThis study will evaluate the safety and tolerability of 40 Hz tACS in bvFTD patients and its efficacy on gamma oscillatory activity, cognitive function, and brain glucose hypometabolism.

Gamma-transcranial alternating current stimulation and theta-burst stimulation: inter-subject variability and the role of BDNF

ObjectiveThe main limitation of neuromodulation techniques is inter-subject variability. Combining theta-burst stimulation (TBS) with gamma-transcranial alternating current stimulation (γ-tACS) allows to shape cortical plasticity. However, it is unknown whether γ-tACS modifies TBS-induced response variability. In this study, we measured the inter-subject variability of TBS-γ tACS and controlled the effect of the Brain-Derived Neurotrophic Factor (BDNF) Val66Met polymorphism. MethodsIntermittent TBS (iTBS)-sham tACS, iTBS-γ tACS, continuous TBS (cTBS)-sham tACS, and cTBS-γ tACS were applied in randomised sessions. Inter-subject variability was measured using grand average and clustering methods. TBS-γ tACS effects on motor evoked potentials (MEP) were compared between Val/Val and Met carriers. ResultsWe found that γ-tACS boosted iTBS-induced MEP facilitation and cancelled cTBS-induced MEP depression. Grand average analysis showed that γ-tACS prominently increased the percentage of iTBS responders and cTBS non-responders. The clustering method demonstrated that TBS-γ tACS response varied between subjects, a phenomenon unrelated to the BDNF genotype. ConclusionsEnhancing γ oscillations through tACS boosts iTBS-induced LTP-like plasticity and suppresses cTBS-induced LTD-like plasticity of the primary motor cortex in a reliable manner. The BDNF Val66Met polymorphism does not influence these effects. SignificanceSince γ-tACS significantly increases the number of iTBS responders, it may be used in clinical settings.

Transcranial Alternating Current Stimulation of the Primary Motor Cortex after Skill Acquisition Improves Motor Memory Retention in Humans: A Double-Blinded Sham-Controlled Study.

Consolidation leading to retention of motor memory following motor practice involves activity-dependent plastic processes in the corticospinal system. To investigate whether beta-band transcranial alternating current stimulation (tACS) applied immediately following skill acquisition can enhance ongoing consolidation processes and thereby motor skill retention 20 adults participated in a randomized, double-blinded, sham-controlled study. Participants received tACS at peak beta-band corticomuscular coherence (CMC) frequency or sham tACS for 10 min following practice of a visuomotor ankle dorsiflexion task. Performance was measured as the average percentage time on target. Electroencephalograhy (EMG) was measured at Cz and EMG from the right tibialis anterior muscle. CMC and intramuscular coherence (IMC) were estimated during 2-min tonic dorsiflexion. Motor skill retention was tested 1 and 7 days after motor practice. From the end of motor practice to the retention tests, motor performance improved more in the tACS group compared with the sham tACS group after 1 (P = 0.05) and 7 days (P < 0.001). At both retention tests, beta-band IMC increased in the tACS group compared with post-tACS. Beta-band CMC increased in the tACS group at retention day 1 compared with post-tACS. Changes in CMC but not IMC were correlated with performance 1 and 7 days following practice. This study shows that tACS applied at beta-band CMC frequency improves consolidation following visuomotor practice and increases beta-band CMC and IMC. We propose that oscillatory beta activity in the corticospinal system may facilitate consolidation of the motor skill.

The Effect of Alpha tACS on the Temporal Resolution of Visual Perception.

We experience the world around us as a smooth and continuous flow. However, there is growing evidence that the stream of sensory inputs is not elaborated in an analog way but is instead organized in discrete or quasi-discrete temporal processing windows. These discrete windows are suggested to depend on rhythmic neural activity in the alpha (and theta) frequency bands, which in turn reflect changes in neural activity within, and coupling between, cortical areas. In the present study, we investigated a possible causal link between oscillatory brain activity in the alpha range (8–12 Hz) and the temporal resolution of visual perception, which determines whether sequential stimuli are perceived as distinct entities or combined into a single representation. To this aim, we employed a two-flash fusion task while participants received focal transcranial alternating current stimulation (tACS) in extra-striate visual regions including V5/MT of the right hemisphere. Our findings show that 10-Hz tACS, as opposed to a placebo (sham tACS), reduces the temporal resolution of perception, inducing participants to integrate the two stimuli into a unique percept more often. This pattern was observed only in the contralateral visual hemifield, providing further support for a specific effect of alpha tACS. The present findings corroborate the idea of a causal link between temporal windows of integration/segregation and oscillatory alpha activity in V5/MT and extra-striate visual regions. They also stimulate future research on possible ways to shape the temporal resolution of human vision in an individualized manner.

Eye tracking of smoking-related stimuli in tobacco use disorder: A proof-of-concept study combining attention bias modification with alpha-transcranial alternating current stimulation

BackgroundTobacco use disorder (TUD) is characterized by the presence of an attentional bias (AB) towards smoking-related stimuli. We investigated whether combining an AB modification paradigm (ABM) with transcranial alternating current stimulation (tACS) applied over the dorsolateral prefrontal cortex (DLPFC) reduces the AB towards smoking-related stimuli, as well as craving level and impulsive choices. MethodsIn a sham-controlled, crossover preliminary study, 19 subjects with TUD received two stimulation arms: 1) active tACS (10 Hz, 2 mA, 30 min) combined with ABM and 2) sham tACS combined with ABM, in a randomized order, separated by one week. AB towards smoking cues during passive observation of smoking and neutral cues was assessed with an eye-tracking device and reactions times at a visual-probe task. Craving level was measured with the Questionnaire of Smoking Urges. Impulsive choices were assessed with the delay discounting task. ResultsActive tACS combined with ABM reduced the amount of time spent looking at smoking-related pictures (p = 0.03), prevented the increase of self-reported desire to smoke (p = 0.026), and reduced the proportion of impulsive choices (p = 0.049), compared to sham tACS combined with ABM. No significant effects were reported on other craving dimensions and on AB based on reaction times. ConclusionsThese preliminary findings suggest that combining tACS with ABM may help smokers who wish to quit by reducing the desire to smoke, attention to smoking-cues, and impulsive decision-making.

T54. EFFECTS OF GAMMA TRANSCRANIAL ALTERNATING CURRENT STIMULATION TO THE LEFT DORSOLATERAL PREFRONTAL CORTEX ON WORKING MEMORY IN SCHIZOPHRENIA PATIENTS

BackgroundWorking memory (WM) impairment is characteristic for schizophrenia patients, lowering their occupational status and quality of life. Recent research suggests that non-invasive brain stimulation could have the potential to treat such cognitive deficits. One novel and promising approach is the transcranial alternating current stimulation (tACS) that could entrain the endogenous gamma oscillations in the dorsolateral prefrontal cortex (DLPFC), previously shown to be abnormal in schizophrenia patients and associated with WM deficits. Indeed, first studies demonstrated WM improvement in healthy participants following tACS at the gamma frequency (γ-tACS) to the DLPFC in healthy participants. However, till date, there is only one pilot study with ten schizophrenia patients, where cognitive enhancement was not evident. Here, we aimed to investigate the efficacy and feasibility of γ-tACS on simultaneous WM performance in schizophrenia patients with a bigger study sample and in regard of cognitive loadMethodsA total of fifteen patients with schizophrenia (N = 15, 8 female) participated in the current study. They underwent a pre-stimulation baseline, an active γ-tACS and a sham single-session in a double-blind, cross-over design. Stimulation was administered over the left DLPFC (F3, anode) and the contralateral region (F4, cathode) at a current of -1mA to 1mA (peek-to-peek) at 40 Hz for 20 min (48000 cycles). We assessed WM during stimulation using a verbal n-back task with three cognitive loads (1- to 3-back). Reaction times and discriminability index d prime served as primary study outcomes. Using several RM-ANOVAs, we compared working memory performance during γ-tACS and sham across all cognitive loads.ResultsData analysis showed no significant main effect of γ-tACS compared to sham on both d prime values (p = .269) and reaction times (p = .166). However, we observed a significant stimulation x load interaction effect on reaction times (p = .043), suggesting that with increasing cognitive load participants responded slightly slower during active than during sham γ-tACS.DiscussionThe current work is one of the first to investigate the effects of γ-tACS to the DLPFC on simultaneous WM performance in schizophrenia patients. In line with previous research, we did not find any significant changes in cognition due to stimulation. Surprisingly, we observed a slight decrease in WM speed with higher cognitive load during active compared to sham tACS. Results are discussed in line of study protocol and tACS feasibility and emphasize the need for future research on the specific study design parameters.

Protocol on transcranial alternating current stimulation for the treatment of major depressive disorder: a randomized controlled trial.

Background:Transcranial alternating current stimulation (tACS) offers a new approach for adult patients with major depressive disorder (MDD). The study is to evaluate the efficacy and safety of tACS treating MDD.Methods:This is an 8-week, double-blind, randomized, placebo-controlled study. Ninety-two drug-naive patients with MDD aged 18 to 65 years will receive 20 daily 40-min, 77.5-Hz, 15-mA sessions of active or sham tACS targeting the forehead and both mastoid areas on weekdays for 4 consecutive weeks (week 4), following a 4-week observation period (week 8). The primary outcome is the remission rate defined as the 17-item Hamilton depression rating scale (HDRS-17) score ≤7 at week 8. Secondary outcomes are the rates of response at weeks 4 and 8 and rate of remission at week 4 based on HDRS-17, the proportion of participants having improvement in the clinical global impression-improvement, the change in HDRS-17 score (range, 0–52, with higher scores indicating more depression) over the study, and variations of brain imaging and neurocognition from baseline to week 4. Safety will be assessed by vital signs at weeks 4 and 8, and adverse events will be collected during the entire study.Discussion:The tACS applied in this trial may have treatment effects on MDD with minimal side effects.Trial registration:Chinese Clinical Trial Registry, ChiCTR1800016479; http://www.chictr.org.cn/showproj.aspx?proj=22048.

Effect of Transcranial Alternating Current Stimulation for the Treatment of Chronic Insomnia: A Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Clinical Trial

Background: Not all adults with chronic insomnia respond to the recommended therapeutic options of cognitive behavioral therapy and approved hypnotic drugs. Transcranial alternating current stimulation (tACS) may offer a novel potential treatment modality for insomnia. Objectives: This study aimed to examine the efficacy and safety of tACS for treating adult patients with chronic insomnia. Methods: Sixty-two participants with chronic primary insomnia received 20 daily 40-min, 77.5-Hz, 15-mA sessions of active or sham tACS targeting the forehead and both mastoid areas in the laboratory on weekdays for 4 consecutive weeks, followed by a 4-week follow-up period. The primary outcome was response rate measured by the Pittsburgh Sleep Quality Index (PSQI) at week 8. Secondary outcomes were remission rate, insomnia severity, sleep onset latency (SOL), total sleep time (TST), sleep efficiency, sleep quality, daily disturbances, and adverse events at the end of the 4-week intervention and at the 4-week follow-up. Results: Of 62 randomized patients, 60 completed the trial. During the 4-week intervention, 1 subject per group withdrew due to loss of interest and time restriction, respectively. Based on PSQI, at 4-week follow-up, the active group had a higher response rate compared to the sham group (53.4% [16/30] vs. 16.7% [5/30], p = 0.009), but remission rates were not different between groups. At the end of the 4-week intervention, the active group had higher response and remission rates than the sham group (p < 0.001 and p = 0.026, respectively). During the trial, compared with the sham group, the active group showed a statistically significant decrease in PSQI total score, a shortened SOL, an increased TST, improved sleep efficiency, and improved sleep quality (p < 0.05 or p < 0.001). Post hoc analysis revealed that, in comparison with the sham group, the active group had improved symptoms, except for daily disturbances, at the end of the 4-week intervention, and significant improvements in all symptoms at the 4-week follow-up. No adverse events or serious adverse responses occurred during the study. Conclusion: The findings show that the tACS applied in the present study has potential as an effective and safe intervention for chronic insomnia within 8 weeks.

Left parietal tACS at alpha frequency induces a shift of visuospatial attention.

BackgroundVoluntary shifts of visuospatial attention are associated with a lateralization of parieto-occipital alpha power (7-13Hz), i.e. higher power in the hemisphere ipsilateral and lower power contralateral to the locus of attention. Recent noninvasive neuromodulation studies demonstrated that alpha power can be experimentally increased using transcranial alternating current stimulation (tACS).Objective/HypothesisWe hypothesized that tACS at alpha frequency over the left parietal cortex induces shifts of attention to the left hemifield. However, spatial attention shifts not only occur voluntarily (endogenous/ top-down), but also stimulus-driven (exogenous/ bottom-up). To study the task-specificity of the potential effects of tACS on attentional processes, we administered three conceptually different spatial attention tasks.Methods36 healthy volunteers were recruited from an academic environment. In two separate sessions, we applied either high-density tACS at 10Hz, or sham tACS, for 35–40 minutes to their left parietal cortex. We systematically compared performance on endogenous attention, exogenous attention, and stimulus detection tasks.ResultsIn the endogenous attention task, a greater leftward bias in reaction times was induced during left parietal 10Hz tACS as compared to sham. There were no stimulation effects in either the exogenous attention or the stimulus detection task.ConclusionThe study demonstrates that high-density tACS at 10Hz can be used to modulate visuospatial attention performance. The tACS effect is task-specific, indicating that not all forms of attention are equally susceptible to the stimulation.