Phase-shifted tACS can modulate cortical alpha waves in human subjects.

In the present study, we investigated traveling waves induced by transcranial alternating current stimulation in the alpha frequency band of healthy subjects. Electroencephalographic data were recorded in 12 healthy subjects before, during, and after phase-shifted stimulation with a device combining both electroencephalographic and stimulation capacities. In addition, we analyzed the results of numerical simulations and compared them to the results of identical analysis on real EEG data. The results of numerical simulations indicate that imposed transcranial alternating current stimulation induces a rotating electric field. The direction of waves induced by stimulation was observed more often during at least 30 s after the end of stimulation, demonstrating the presence of aftereffects of the stimulation. Results suggest that the proposed approach could be used to modulate the interaction between distant areas of the cortex. Non-invasive transcranial alternating current stimulation can be used to facilitate the propagation of circulating waves at a particular frequency and in a controlled direction. The results presented open new opportunities for developing innovative and personalized transcranial alternating current stimulation protocols to treat various neurological disorders. Supplementary Information: The online version contains supplementary material available at 10.1007/s11571-023-09997-1.

Boosting working memory in the elderly: driving prefrontal theta-gamma coupling via repeated neuromodulation.

The escalating global burden of age-related neurodegenerative diseases and associated healthcare costs necessitates innovative interventions to stabilize or enhance cognitive functions. Deficits in working memory (WM) are linked to alterations in prefrontal theta-gamma cross-frequency coupling. Low-intensity transcranial alternating current stimulation (tACS) has emerged as a non-invasive, low-cost approach capable of modulating ongoing oscillations in targeted brain areas through entrainment. This study investigates the impact of multi-session peak-coupled theta-gamma cross-frequency tACS administered to the dorsolateral prefrontal cortex (DLPFC) on WM performance in older adults. In a randomized, sham-controlled, triple-blinded design, 77 participants underwent 16 stimulation sessions over six weeks while performing n-back tasks. Signal detection measures revealed increased 2-back sensitivity and robust modulations of response bias, indicating improved WM and decision-making adaptations, respectively. No effects were observed in the 1-back condition, emphasizing dependencies on cognitive load. Repeated tACS reinforces behavioral changes, indicated by increasing effect sizes. This study supports prior research correlating prefrontal theta-gamma coupling with WM processes and provides unique insights into the neurocognitive benefits of repeated tACS intervention. The well-tolerated and highly effective multi-session tACS intervention among the elderly underscores its therapeutic potential in vulnerable populations.

Scalp acupuncture guidance for identifying the optimal site for transcranial electrical stimulation of the hand.

Transcranial electrical stimulation (tES) often targets the EEG-guided C3/C4 area that may not accurately represent M1 for hand muscles. This study aimed to determine if the neuroanatomy-based scalp acupuncture-guided site (AC) was a more effective spot than the C3 site for neuromodulation. Fifteen healthy subjects received one 20-minute session of high-definition transcranial alternating current stimulation (HD-tACS) intervention (20 Hz at 2 mA) at the AC or C3 sites randomly with a 1-week washout period. Subjects performed ball-squeezing exercises with the dominant hand during the HD-tACS intervention. The AC site was indiscernible from the finger flexor hotspot detected by TMS. At the baseline, the MEP amplitude from finger flexors was greater with less variability at the AC site than at the C3 site. HD-tACS intervention at the AC site significantly increased the MEP amplitude. However, no significant changes were observed after tACS was applied to the C3 site. Our results provide evidence that HD-tACS at the AC site produces better neuromodulation effects on the flexor digitorum superficialis (FDS) muscle compared to the C3 site. The AC localization approach can be used for future tES studies.

The effect of transcranial electrical stimulation on the relief of mental fatigue.

Objective: The presence of mental fatigue seriously affects daily life and working conditions. Non-invasive transcranial electrical stimulation has become an increasingly popular tool for relieving mental fatigue. We investigated whether transcranial direct current stimulation (tDCS) and transcranial alternating current stimulation (tACS) could be used to alleviate the state of mental fatigue in a population of healthy young adults and compared their effects. Methods: We recruited 10 participants for a blank control, repeated measures study. Each participant received 15 min of anodal tDCS, α-tACS, and blank stimulation. Participants were required to fill in the scale, perform the test task and collect ECG signals in the baseline, fatigue and post-stimulus states. We then assessed participants' subjective fatigue scale scores, test task accuracy and HRV characteristics of ECG signals separately. Results: We found that both anodal tDCS and α-tACS significantly (P < 0.05) reduced subjective fatigue and improved accuracy on the test task compared to the blank group, and the extent of change was greater with tACS. For the HRV features extracted from ECG signals. After tACS intervention, SDNN (t = -3.241, P = 0.002), LF (t = -3.511, P = 0.001), LFn (t = -3.122, P = 0.002), LFn/HFn (-2.928, P = 0.005), TP (t = -2.706, P = 0.008), VLF (t = -3.002, P = 0.004), SD2 (t = -3.594, P = 0.001) and VLI (t = -3.564, P = 0.001) showed a significant increasing trend, and HFn (t = 3.122, P = 0.002), SD1/SD2 (t = 3.158, P = 0.002) and CCM_1 (t = 3.106, P = 0.003) showed a significant decreasing trend. After tDCS intervention, only one feature, TINN, showed a significant upward trend (P < 0.05). The other features showed non-significant changes but roughly the same trend as the tACS group. Conclusion: Both tDCS and α-tACS can be effective in relieving mental fatigue, and α-tACS is more effective than tDCS. This study provides theoretical support for tDCS with α-tACS having a alleviating effect on mental fatigue and the use of ECG as a valid objective assessment tool.

Utilizing tACS to enhance memory confidence and EEG to predict individual differences in brain stimulation efficacy.

The information transfer necessary for successful memory retrieval is believed to be mediated by theta and gamma oscillations. These oscillations have been linked to memory processes in electrophysiological studies, which were correlational in nature. In the current study, we used transcranial alternating current stimulation (tACS) to externally modulate brain oscillations to examine its direct effects on memory performance. Participants received sham, theta (4 Hz), and gamma (50 Hz) tACS over frontoparietal regions while retrieving information in a source memory paradigm. Linear regression models were used to investigate the direct effects of oscillatory non-invasive brain stimulation (NIBS) on memory accuracy and confidence. Our results indicate that both theta and gamma tACS altered memory confidence. Specifically, theta tACS seemed to lower the threshold for confidence in retrieved information, while gamma tACS appeared to alter the memory confidence bias. Furthermore, the individual differences in tACS effects could be predicted from electroencephalogram (EEG) measures recorded prior to stimulation, suggesting that EEG could be a useful tool for predicting individual variability in the efficacy of NIBS.

Neural consequences of 5-Hz transcranial alternating current stimulation over right hemisphere: An eLORETA EEG study.

INTRODUCTION: Transcranial alternating current stimulation (tACS) at 5-Hz to the right hemisphere can effectively alleviate anxiety symptoms. This study aimed to explore the neural mechanisms that drive the therapeutic benefits. METHODS: We collected electroencephalography (EEG) data from 24 participants with anxiety disorders before and after a tACS treatment session. tACS was applied over the right hemisphere, with 1.0 mA at F4, 1.0 mA at P4, and 2.0 mA at T8 (10-10 EEG convention). With eLORETA, we transformed the scalp signals into the current source density in the cortex. We then assessed the differences between post- and pre-treatment brain maps across multiple spectra (delta to low gamma) with non-parametric statistics. RESULTS: We observed a trend of heightened power in alpha and reduced power in mid-to-high beta and low gamma, in accord with the EEG markers of anxiolytic effects reported in previous studies. Additionally, we observed a consistent trend of de-synchronization at the stimulating sites across spectra. CONCLUSION: tACS 5-Hz over the right hemisphere demonstrated EEG markers of anxiety reduction. The after-effects of tACS on the brain are intricate and cannot be explained solely by the widely circulated entrainment theory. Rather, our results support the involvement of plasticity mechanisms in the offline effects of tACS.

Perspectives on Optimized Transcranial Electrical Stimulation Based on Spatial Electric Field Modeling in Humans.

Background: Transcranial electrical stimulation (tES) generates an electric field (or current density) in the brain through surface electrodes attached to the scalp. Clinical significance has been demonstrated, although with moderate and heterogeneous results partly due to a lack of control of the delivered electric currents. In the last decade, computational electric field analysis has allowed the estimation and optimization of the electric field using accurate anatomical head models. This review examines recent tES computational studies, providing a comprehensive background on the technical aspects of adopting computational electric field analysis as a standardized procedure in medical applications. Methods: Specific search strategies were designed to retrieve papers from the Web of Science database. The papers were initially screened based on the soundness of the title and abstract and then on their full contents, resulting in a total of 57 studies. Results: Recent trends were identified in individual- and population-level analysis of the electric field, including head models from non-neurotypical individuals. Advanced optimization techniques that allow a high degree of control with the required focality and direction of the electric field were also summarized. There is also growing evidence of a correlation between the computationally estimated electric field and the observed responses in real experiments. Conclusions: Computational pipelines and optimization algorithms have reached a degree of maturity that provides a rationale to improve tES experimental design and a posteriori analysis of the responses for supporting clinical studies.

The Potential Reversible Transition between Stem Cells and Transient-Amplifying Cells: The Limbal Epithelial Stem Cell Perspective.

Stem cells (SCs) undergo asymmetric division, producing transit-amplifying cells (TACs) with increased proliferative potential that move into tissues and ultimately differentiate into a specialized cell type. Thus, TACs represent an intermediary state between stem cells and differentiated cells. In the cornea, a population of stem cells resides in the limbal region, named the limbal epithelial stem cells (LESCs). As LESCs proliferate, they generate TACs that move centripetally into the cornea and differentiate into corneal epithelial cells. Upon limbal injury, research suggests a population of progenitor-like cells that exists within the cornea can move centrifugally into the limbus, where they dedifferentiate into LESCs. Herein, we summarize recent advances made in understanding the mechanism that governs the differentiation of LESCs into TACs, and thereafter, into corneal epithelial cells. We also outline the evidence in support of the existence of progenitor-like cells in the cornea and whether TACs could represent a population of cells with progenitor-like capabilities within the cornea. Furthermore, to gain further insights into the dynamics of TACs in the cornea, we outline the most recent findings in other organ systems that support the hypothesis that TACs can dedifferentiate into SCs.

State-Dependent tACS Effects Reveal the Potential Causal Role of Prestimulus Alpha Traveling Waves in Visual Contrast Detection.

The intricate relationship between prestimulus alpha oscillations and visual contrast detection variability has been the focus of numerous studies. However, the causal impact of prestimulus alpha traveling waves on visual contrast detection remains largely unexplored. In our research, we sought to discern the causal link between prestimulus alpha traveling waves and visual contrast detection across different levels of mental fatigue. Using electroencephalography alongside a visual detection task with 30 healthy adults (13 females; 17 males), we identified a robust negative correlation between prestimulus alpha forward traveling waves (FTWs) and visual contrast threshold (VCT). Inspired by this correlation, we utilized 45/-45° phase-shifted transcranial alternating current stimulation (tACS) in a sham-controlled, double-blind, within-subject experiment with 33 healthy adults (23 females; 10 males) to directly modulate these alpha traveling waves. After the application of 45° phase-shifted tACS, we observed a substantial decrease in FTW and an increase in backward traveling waves, along with a concurrent increase in VCT, compared with the sham condition. These changes were particularly pronounced under a low fatigue state. The findings of state-dependent tACS effects reveal the potential causal role of prestimulus alpha traveling waves in visual contrast detection. Moreover, our study highlights the potential of 45/-45° phase-shifted tACS in cognitive modulation and therapeutic applications.

Tripod transcranial alternating current stimulation at 5-Hz to alleviate anxiety symptoms: A preliminary report.

INTRODUCTION: One of the most common applications of transcranial electrical stimulation (tES) at low current intensity is to induce a relaxed state or reduce anxiety. With technical advancement, different waveforms, montages, and parameters can be incorporated into the treatment regimen. We developed a novel protocol to treat individuals with anxiety disorders by transcranial alternating current stimulation (tACS). METHODS: A total of 27 individuals with anxiety disorders underwent tACS treatment for 12 sessions, with each session lasting 25 min. tACS at 5 Hz was applied to F4 (1.0 mA), P4 (1.0 mA), and T8 (2.0 mA) EEG lead positions (tripod), with sinewave oscillation between T8 and F4/P4. We evaluated the primary and secondary outcomes using the Beck Anxiety Inventory (BAI) and neuropsychological assessments. RESULTS: Of the 27 patients, 19 (70.4 %) experienced a reduction in symptom severity >50 %, with an average reduction of BAI 58.5 %. All reported side effects were mild, with itching or tingling being the most common complaint. No significant differences were noted in attention, linguistic working memory, visuospatial working memory, or long-term memory in neuropsychological assessments. CONCLUSION: The results suggest the potential of this novel tripod tACS design as a rapid anxiety alleviator and the importance of a clinical trial to verify its efficacy.

Transcranial Alternating Current Stimulation over Frontal Eye Fields Mimics Attentional Modulation of Visual Processing.

Attentional control over sensory processing has been linked to neural alpha oscillations and related inhibition of cerebral cortex. Despite the wide consensus on the functional relevance of alpha oscillations for attention, precise neural mechanisms of how alpha oscillations shape perception and how this top-down modulation is implemented in cortical networks remain unclear. Here, we tested the hypothesis that alpha oscillations in frontal eye fields (FEFs) are causally involved in the top-down regulation of visual processing in humans (male and female). We applied sham-controlled, intermittent transcranial alternating current stimulation (tACS) over bilateral FEF at either 10 Hz (alpha) or 40 Hz (gamma) to manipulate attentional preparation in a visual discrimination task. Under each stimulation condition, we measured psychometric functions for contrast perception and introduced a novel linear mixed modeling approach for statistical control of neurosensory side effects of the electric stimulation. tACS at alpha frequency reduced the slope of the psychometric function, resulting in improved subthreshold and impaired superthreshold contrast perception. Side effects on the psychometric functions were complex and showed large interindividual variability. Controlling for the impact of side effects on the psychometric parameters by using covariates in the linear mixed model analysis reduced this variability and strengthened the perceptual effect. We propose that alpha tACS over FEF mimicked a state of endogenous attention by strengthening a fronto-occipitoparietal network in the alpha band. We speculate that this network modulation enhanced phasic gating in occipitoparietal cortex leading to increased variability of single-trial psychometric thresholds, measurable as a reduction of psychometric slope.

Transcranial alternating current stimulation barely enhances working memory in healthy adults: A meta-analysis.

Working memory (WM) is a pivotal neural mechanism for cognitive function and ability. Transcranial alternating current stimulation (tACS) was used to improve WM by entraining key brain rhythms. We submitted to meta-analysis 143 effects of tACS on WM performance, found in 42 reports published between 2014 and 2023, encompassing a total of 1386 healthy adults stimulated. The overall effect size of 134 interventions intended to improve WM equaled Hedges' g = 0.076 [0.039, 0.113]. However, after correcting for a significant publication bias this effect size dropped to zero. By contrast, 9 interventions distorting the brain synchronization using antiphase tACS reliably decreased WM performance, with Hedges' g = -0.266, [-0.458, -0.074]. Individuating the targeted frequency band was the only reliable moderator. The disparity between our null outcome and moderately positive tACS effects estimated by previous meta-analyses resulted from our inclusion of the most recent studies mostly reporting negligible effects. Our results suggest that current tACS protocols barely enhance WM in healthy adults. More research is needed to develop effective methods for WM stimulation.

Tailoring transcranial alternating current stimulation based on endogenous event-related P3 to modulate premature responses: a feasibility study.

Background: Transcranial alternating current stimulation (tACS) is a brain stimulation method for modulating ongoing endogenous oscillatory activity at specified frequency during sensory and cognitive processes. Given the overlap between event-related potentials (ERPs) and event-related oscillations (EROs), ERPs can be studied as putative biomarkers of the effects of tACS in the brain during cognitive/sensory task performance. Objective: This preliminary study aimed to test the feasibility of individually tailored tACS based on individual P3 (latency and frequency) elicited during a cued premature response task. Thus, tACS frequency was individually tailored to match target-P3 ERO for each participant. Likewise, the target onset in the task was adjusted to match the tACS phase and target-P3 latency. Methods: Twelve healthy volunteers underwent tACS in two separate sessions while performing a premature response task. Target-P3 latency and ERO were calculated in a baseline block during the first session to allow a posterior synchronization between the tACS and the endogenous oscillatory activity. The cue and target-P3 amplitudes, delta/theta ERO, and power spectral density (PSD) were evaluated pre and post-tACS blocks. Results: Target-P3 amplitude significantly increased after activetACS, when compared to sham. Evoked-delta during cue-P3 was decreased after tACS. No effects were found for delta ERO during target-P3 nor for the PSD and behavioral outcomes. Conclusion: The present findings highlight the possible effect of phase synchronization between individualized tACS parameters and endogenous oscillatory activity, which may result in an enhancement of the underlying process (i.e., an increase of target-P3). However, an unsuccessful synchronization between tACS and EEG activity might also result in a decrease in the evoked-delta activity during cue-P3. Further studies are needed to optimize the parameters of endogenous activity and tACS synchronization. The implications of the current results for future studies, including clinical studies, are further discussed since transcranial alternating current stimulation can be individually tailored based on endogenous event-related P3 to modulate responses.

Exploring the Prospects of Transcranial Electrical Stimulation (tES) as a Therapeutic Intervention for Post-Stroke Motor Recovery: A Narrative Review.

INTRODUCTION: Stroke survivors often have motor impairments and related functional deficits. Transcranial Electrical Stimulation (tES) is a rapidly evolving field that offers a wide range of capabilities for modulating brain function, and it is safe and inexpensive. It has the potential for widespread use for post-stroke motor recovery. Transcranial Direct Current Stimulation (tDCS), Transcranial Alternating Current Stimulation (tACS), and Transcranial Random Noise Stimulation (tRNS) are three recognized tES techniques that have gained substantial attention in recent years but have different mechanisms of action. tDCS has been widely used in stroke motor rehabilitation, while applications of tACS and tRNS are very limited. The tDCS protocols could vary significantly, and outcomes are heterogeneous. PURPOSE: the current review attempted to explore the mechanisms underlying commonly employed tES techniques and evaluate their prospective advantages and challenges for their applications in motor recovery after stroke. CONCLUSION: tDCS could depolarize and hyperpolarize the potentials of cortical motor neurons, while tACS and tRNS could target specific brain rhythms and entrain neural networks. Despite the extensive use of tDCS, the complexity of neural networks calls for more sophisticated modifications like tACS and tRNS.

Advances in Non-Invasive Neuromodulation Techniques for Improving Cognitive Function: A Review.

Non-invasive neuromodulation techniques are widely utilized to study and improve cognitive function, with the aim of modulating different cognitive processes. For workers performing high-intensity mental and physical tasks, extreme fatigue may not only affect their working efficiency but may also lead to cognitive decline or cognitive impairment, which, in turn, poses a serious threat to their physical health. The use of non-invasive neuromodulation techniques has important research value for improving and enhancing cognitive function. In this paper, we review the research status, existing problems, and future prospects of transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS), transcranial magnetic stimulation (TMS), and transcutaneous acupoint stimulation (TAS), which are the most studied physical methods in non-invasive neuromodulation techniques to improve and enhance cognition. The findings presented in this paper will be of great reference value for the in-depth study of non-invasive neuromodulation techniques in the field of cognition.

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.

Impact of theta transcranial alternating current stimulation on language production in adult classic galactosemia patients.

Patients with classic galactosemia (CG), an inborn error of galactose metabolism, suffer from impairments in cognition, including language processing. Potential causes are atypical brain oscillations. Recent electroencephalogram (EEG) showed differences in the P300 event-related-potential (ERP) and alterations in the alpha/theta-range during speech planning. This study investigated whether transcranial alternating current stimulation (tACS) at theta-frequency compared to sham can cause a normalization of the ERP post stimulation and improves language performance. Eleven CG patients and fourteen healthy controls participated in two tACS-sessions (theta 6.5 Hz/sham). They were engaged in an active language task, describing animated scenes at three moments, that is, pre/during/post stimulation. Pre and post stimulation, behavior (naming accuracy, voice-onset-times; VOT) and mean-amplitudes of ERP were compared, by means of a P300 time-window analysis and cluster-based-permutation testing during speech planning. The results showed that theta stimulation, not sham, significantly reduced naming error-percentage in patients, not in controls. Theta did not systematically speed up naming beyond a general learning effect, which was larger for the patients. The EEG analysis revealed a significant pre-post stimulation effect (P300/late positivity), in patients and during theta stimulation only. In conclusion, theta-tACS improved accuracy in language performance in CG patients compared to controls and altered the P300 and late positive ERP-amplitude, suggesting a lasting effect on neural oscillation and behavior.

No effects of the theta-frequency transcranial electrical stimulation for recall, attention control, and relation integration in working memory.

Introduction: Recent studies have suggested that transcranial alternating current stimulation (tACS), and especially the theta-frequency tACS, can improve human performance on working memory tasks. However, evidence to date is mixed. Moreover, the two WM tasks applied most frequently, namely the n-back and change-detection tasks, might not constitute canonical measures of WM capacity. Method: In a relatively large sample of young healthy participants (N = 62), we administered a more canonical WM task that required stimuli recall, as well as we applied two WM tasks tapping into other key WM functions: attention control (the antisaccade task) and relational integration (the graph mapping task). The participants performed these three tasks three times: during the left frontal 5.5-Hz and the left parietal 5.5-Hz tACS session as well as during the sham session, with a random order of sessions. Attentional vigilance and subjective experience were monitored. Results: For each task administered, we observed significant gains in accuracy neither for the frontal tACS session nor for the parietal tACS session, as compared to the sham session. By contrast, the scores on each task positively inter-correlated across the three sessions. Discussion: The results suggest that canonical measures of WM capacity are strongly stable in time and hardly affected by theta-frequency tACS. Either the tACS effects observed in the n-back and change detection tasks do not generalize onto other WM tasks, or the tACS method has limited effectiveness with regard to WM, and might require further methodological advancements.

No Frequency-Specific Effect of Transcranial Random Noise Stimulation on Resting EEG.

BACKGROUND: Transcranial random noise stimulation (tRNS) is a form of noninvasive transcranial electrical stimulation that applies alternating current in various randomized frequencies to the cortex, thereby improving cognitive functioning in multiple domains. However, the precise mechanism of tRNS, as well as its impact on human electroencephalography (EEG), remains unclear. This is partly because most studies have used tRNS in conjunction with a cognitive task, making it difficult to tease apart whether the observed changes in EEG are a result of tRNS, the cognitive task, or their interaction. METHODS: Forty-nine healthy individuals participated in this study and were randomly assigned to active tRNS (n = 24) and sham (n = 25) groups. tRNS was delivered for 20 minutes over Fp1/Fp2 and Oz. Resting-state EEG data were collected before and after either tRNS or sham stimulation. RESULTS: Cluster-based permutation tests using FieldTrip revealed no frequency-specific effect of tRNS on resting-state EEG data across four frequency bands (theta, alpha, beta, gamma). CONCLUSIONS: These observations suggest that tRNS itself does not target or alter specific EEG frequencies. Rather, tRNS most likely interacts with the cognitive task/activity at hand to produce an observable difference in post-tRNS EEG. Positive tRNS-EEG findings from previous studies are also likely to have resulted from the interactive and cognitive activity-dependent nature of tRNS.

Using transcranial alternating current stimulation to enhance working memory skills in youths with 22q11.2 deletion syndrome: A randomized double-blind sham-controlled study.

Abnormal cognitive development, particularly working memory (WM) deficits, is among the first apparent manifestations of psychosis. Yet, cognitive impairment only shows limited response to current pharmacological treatment. Alternative interventions to target cognition are highly needed in individuals at high risk for psychosis, like carriers of 22q11.2 deletion syndrome (22q11.2DS). Here we applied theta-tuned transcranial alternating current stimulation (tACS) between frontal and temporal regions during a visual WM task in 34 deletion carriers. We conducted a double-blind sham-controlled study over three consecutive days. The stimulation parameters were derived from individual structural MRI scan and HD-EEG data acquired at baseline (Day 1) to model current intensity and individual preferential theta peak. Participants were randomized to either sham or tACS (Days 2 and 3) and then completed a visual WM task and a control task. Our findings reveal that tACS was safe and well-tolerated among participants. We found a significantly increased accuracy in the visual WM but not the control task following tACS. Moreover, this enhancement in WM accuracy was greater after tACS than during tACS, indicating stronger offline effects than online effects. Our study therefore supports the application of repeated sessions of brain stimulation in 22q11.2DS.