Tobias Schwippel

BackgroundTranscranial alternating current stimulation (tACS) is a promising non-pharma-cological intervention for major depressive disorder (MDD), but its effects on endogenous alpha oscillatory dynamics and their relationship to clinical improvement remain unclear.MethodsIn this double-blind, sham-controlled randomized clinical trial, 20 adults with MDD received five consecutive days of prefrontal 10 Hz tACS or sham. Resting 128-channel EEG was acquired before stimulation on Day 1 (D1), Day 5 (D5), and two-week follow-up. Changes in alpha power spectral density were quantified at the stimulation frequency (10 Hz) and at each participant’s individual alpha frequency (IAF), using prefrontal regions of interest and whole-head topographical analyses. Depression severity was assessed using the Hamilton Depression Rating Scale (HDRS-17).ResultsBetween-group comparisons revealed no significant differences in prefrontal alpha power changes at either 10 Hz or IAF during the intervention week or at follow-up, although right prefrontal 10 Hz power showed a trend-level reduction with tACS. In contrast, within the tACS group, greater reductions in prefrontal IAF power were associated with greater HDRS-17 improvement from D1 to follow-up, and early IAF power suppression during the intervention week predicted later symptom improvement. Whole-head analyses identified a posterior cluster of reduced 10 Hz power at follow-up in the tACS group relative to sham, whereas clinically relevant correlations were specific to IAF power and distributed across frontal-central and parietal electrodes. Depression scores improved over time in both groups, with greater reductions in HDRS-17 scores observed in the tACS group.ConclusionsFindings suggest that five days of 10 Hz tACS engages depression-relevant alpha mechanisms, with symptom improvement linked specifically to modulation of alpha power at IAF. Results support personalization of tACS in future trials.

Background: Transcranial alternating current stimulation (tACS) is a promising non-pharmacological intervention for major depressive disorder (MDD), but its effects on endogenous alpha oscillatory dynamics and their relationship to clinical improvement remain unclear. Methods: In this double-blind, sham-controlled randomized clinical trial, 20 adults with MDD received five consecutive days of prefrontal 10 Hz tACS or sham. Resting 128-channel EEG was acquired before stimulation on Day 1 (D1), Day 5 (D5), and two-week follow-up. Changes in alpha power spectral density were quantified at the stimulation frequency (10 Hz) and at each participant’s individual alpha frequency (IAF), using prefrontal regions of interest and whole-head topographical analyses. Depression severity was assessed using the Hamilton Depression Rating Scale (HDRS-17). Results: Between-group comparisons revealed no significant differences in prefrontal alpha power changes at either 10 Hz or IAF during the intervention week or at follow-up, although right prefrontal 10 Hz power showed a trend-level reduction with tACS. In contrast, within the tACS group, greater reductions in prefrontal IAF power were associated with greater HDRS-17 improvement from D1 to follow-up, and early IAF power suppression during the intervention week predicted later symptom improvement. Whole-head analyses identified a posterior cluster of reduced 10 Hz power at follow-up in the tACS group relative to sham, whereas clinically relevant correlations were specific to IAF power and distributed across frontal-central and parietal electrodes. Depression scores improved over time in both groups, with greater reductions in HDRS-17 scores observed in the tACS group. Conclusions: Findings suggest that five days of 10 Hz tACS engages depression-relevant alpha mechanisms, with symptom improvement linked specifically to modulation of alpha power at IAF. Results support personalization of tACS in future trials.

Background: Major depressive disorder (MDD) is characterized by altered frontal alpha oscillations. Transcranial alternating current stimulation (tACS) can normalize aberrant oscillations in MDD, yet the daily dynamics of tACS target engagement of alpha oscillations in depression remain unclear. Methods: In a double-blind randomized controlled trial ( NCT03994081 ), 20 participants with MDD received verum or sham 10 Hz tACS (40 min/day, 5 days) targeted to left and right dorsolateral prefrontal cortex (F3/F4). High-density EEG was collected pre/post-stimulation each day to quantify within-session and cumulative changes in alpha power and functional connectivity (wPLI). Results: Verum stimulation produced late-emerging, session-specific alpha power decreases compared to sham, with robust day (D)4 post-pre reductions at both IAF and 10 Hz across frontal and parietal regions (t=-2.42 to -3.82, p<0.05; parietal t=-3.82, pFDR<0.05). Whole-brain topographical analysis confirmed a distinct condition x D4 effect at left prefrontal cortex (t=2.9, pFWE<0.05, cluster permutation). Connectivity changes emerged earlier and more transiently, with D2 bilateral frontal wPLI reductions (t=-2.53, p<0.05). Cumulative analyses (change from D1) showed significant wPLI decreases on D2 and D3 (t=-2.65 and t=-2.46; p<0.05). Exploratory clinical correlations showed that the D4 IAF power decrease was associated with increased reward sensitivity (spearman rho= -0.6, p<0.05, cluster-corrected). Conclusions: Alpha-tACS produced a temporally distinct neural response: an early, transient decrease in functional connectivity on D2, which may have driven a later suppression of left prefrontal alpha power on D4, correlated with clinical and behavioral improvements. These results delineate target engagement and validation mechanisms in a multi-day tACS trial, supporting optimized dosing in future tACS interventions.

Objective: This study explored whether modulating prefrontal alpha oscillations using transcranial alternating current stimulation (tACS) could alleviate depressive symptoms in individuals with systemic lupus erythematosus (SLE). Methods: Over the course of 5 days, three individuals underwent daily 40-min sessions of 2 mA bifrontal individual alpha frequency tACS (IAF-tACS) while watching a relaxing video. Resting-state 128-channel electroencephalography (EEG) was recorded on Day 1 and Day 5 before each tACS session. Self-reported assessments of depression, anxiety, insomnia, and fatigue were administered on Day 1, Day 5, and at the 2- and 4-week follow-ups. Results: Two out of three participants showed a reduction in left prefrontal alpha power after 5 days of IAF-tACS. Only those with this reduction reported short-term improvements in depression, insomnia, anxiety, and well-being. Conclusion: These preliminary results suggest that modulating prefrontal alpha oscillations through tACS may offer a potential approach for alleviating depressive symptoms in individuals with SLE.

Cognitive impairments in schizophrenia significantly impact daily functioning and quality of life, posing a major therapeutic challenge. While both cognitive training and transcranial direct current stimulation (tDCS) have shown promise in improving cognitive function, their combined effects remain underexplored. This double-blind, sham-controlled, randomized clinical trial investigated whether adaptive working memory training (aWMT) paired with anodal tDCS to the right dorsolateral prefrontal cortex (DLPFC) enhances cognitive outcomes in schizophrenia. Twenty-eight individuals with schizophrenia or schizoaffective disorder completed ten sessions of aWMT with concurrent 2 mA anodal or sham tDCS. Cognitive improvements were assessed using the Brief Assessment of Cognition in Schizophrenia (BACS) at baseline, three days after training, and at follow-ups one month, and three months later. Clinical measures evaluated psychopathology, depression, and quality of life. Anodal tDCS significantly improved working memory performance during training, with gains partially sustained at follow-ups. Short-term transfer effects with large effect sizes were observed in the BACS, although clinical symptoms and quality of life remained unaffected. While preliminary, these findings indicate that tDCS could support cognitive training outcomes in schizophrenia. Larger randomized controlled trials are needed to confirm transfer effects and determine the long-term benefits of this approach. If proven effective, integrating tDCS into cognitive remediation therapies could represent an innovative strategy to address cognitive deficits in schizophrenia.

Addictive behaviour is shaped by the dynamic interaction of implicit, bottom‐up and explicit, top‐down cognitive processes. In alcohol use disorder (AUD), implicit alcohol‐related associations have been shown to predict increased subsequent alcohol consumption and are linked to the risk of relapse. Explicit cognitive processes, exerting prefrontal top‐down control, are particularly significant during the critical period following the decision to abstain. This study aims to map implicit and explicit cognitive processes in recently abstinent individuals with AUD and to explore the effect of cathodal transcranial direct current stimulation (tDCS) on implicit associations by modulating top‐down control. In this preregistered, double‐blind, sham‐controlled clinical trial, 30 abstinent individuals with AUD participated in two experimental sessions. They received either 2 mA cathodal tDCS to the left dorsolateral prefrontal cortex (dlPFC) or sham tDCS in a crossover design. During tDCS, participants completed the alcohol approach implicit association test (IAT) and the drinking identity IAT, along with two control tasks. Additionally, we collected explicit ratings of the IAT stimuli and assessed craving before and after each experimental session. Preregistered ANOVAs revealed significant implicit alcohol–avoidance and non–drinking identity biases. Cathodal tDCS did not modulate IAT scores. Explicit ratings showed a preference for non‐alcoholic drinks and non‐drinking identity, correlating moderately with IAT scores. Exploratory analyses indicated that cathodal tDCS mitigated the increase in nicotine craving during the experimental session. This preregistered clinical trial provides robust evidence that single‐session cathodal tDCS to the left dorsolateral prefrontal cortex does not modulate implicit associations in AUD, with Bayesian analyses corroborating the absence of tDCS effects. Our results emphasize the impact of contextual factors on the interplay between explicit and implicit cognitive processes and underscore the importance of investigating multisession stimulation paradigms in future research.