Miles Wischnewski

Oscillatory phase has been proposed to organize neural information processing, but whether endogenous phase can be leveraged to causally shape human cognition remains unclear. Here, we tested whether repetitive transcranial magnetic stimulation (rTMS) delivered at specific phases of endogenous beta oscillations over the left dorsolateral prefrontal cortex modulates working memory and response inhibition. Participants received EEG phase-controlled, closed-loop rTMS delivered at either the peak or trough of their endogenous beta rhythm, using each participant's dominant beta frequency (20-30 Hz). A conventional 20-Hz rTMS delivered independently of the beta phase served as an active control. Compared to this control and each other, peak-targeted rTMS improved response inhibition, whereas trough-targeted rTMS improved working memory. Both phase-specific behavioral effects were accompanied by corresponding increases in event-related potentials, which were not observed after conventional stimulation. Across participants, behavioral improvements correlated with stimulation-induced electrophysiological changes. Finally, phase-specific rTMS induced distinct DLPFC network expansions that complemented the behavioral effects: peak stimulation enhanced posterior centro-parietal connectivity for inhibitory control, while trough stimulation expanded anterior prefrontal networks for working memory. These findings provide first evidence that opposite phases of endogenous prefrontal beta oscillations coordinate distinct cognitive and neural processes. This establishes prefrontal beta phase as a causal dimension for shaping executive function and as a target for prefrontal rTMS to modulate cognition and non-invasively probe phase-dependent brain function.

Mentalization, the ability to interpret the mental states of others, is a central component of Theory of Mind (ToM). The medial prefrontal cortex (mPFC) has been consistently implicated in mentalization, but the neural oscillations that support this process are not fully understood. Theta oscillations are a candidate mechanism, because they have been linked to social-cognitive processing and may coordinate information processing through coupling with faster gamma activity. In the present sham-controlled, within-subjects study, we investigated whether mentalizing performance can be modulated using either conventional theta transcranial alternating current stimulation (tACS) or cross-frequency theta-gamma tACS over the mPFC. Thirty-four participants completed a mentalization task during theta, theta-gamma, and sham stimulation. Decision time and accuracy were assessed for affective and cognitive judgments. Theta stimulation slowed decision times compared with sham and theta-gamma stimulation, whereas theta-gamma stimulation did not differ from sham. Theta stimulation slowed both affective and cognitive judgments, with the effect being more pronounced for cognitive judgments. Accuracy was unaffected by stimulation. The observed slowing suggests that theta stimulation may have increased the weighting of competing social information, resulting in slower affective and cognitive judgments rather than improved performance. Together, these findings indicate that mPFC theta oscillations may influence the speed of mentalizing judgments.

Background: Theta-frequency transcranial alternating current stimulation (tACS) over prefrontal cortex has been proposed to modulate working memory (WM), yet behavioral effects are often inconsistent. One potential source of variability is the tACS phase during stimulus presentation. Objective: We tested whether behavioral performance during WM depends on the phase of prefrontal theta-tACS. Methods: Twenty participants completed two sessions of prefrontal 4 Hz tACS in a within-subject design, receiving active and sham stimulation in separate sessions. Participants performed a visuospatial change detection task (CDT) and a verbal N-back task. Stimulation effects on overall accuracy and reaction time were analyzed. Subsequently, phase-specific analyses related stimulation phase at task-relevant stimulus presentation to behavioral performance using circular regression models. Preferred phases across participants were tested using Rayleigh tests. Results: No significant overall effects of active compared with sham tACS on accuracy or reaction time were observed in either task. However, phase-specific analyses revealed stronger phase-dependent modulation of reaction time during active tACS compared with sham. In the CDT, this effect was present across difficulty levels, whereas in the N-back task it was observed only in the 3-back condition. No reliable phase-dependent effects were observed for accuracy. Preferred phases varied across participants and did not cluster around a common phase. Conclusions: Prefrontal theta-tACS can modulate WM performance in a phase-dependent manner even in the absence of average behavioral effects. The observation of phase-dependent reaction-time modulation across visuospatial and verbal WM tasks suggests that stimulation phase may be a relevant source of variability across cognitive domains.

Obsessive–compulsive disorder (OCD) is a condition with substantial disability and subclinical obsessive–compulsive behaviors affect up to 1 billion people globally. Transcranial electrical stimulation (tES) is emerging as a potential treatment for OCD, yet its effectiveness is uncertain due to the limited number of randomized controlled trials conducted so far. Here we applied 3 meta-analytic approaches to evaluate the pooled therapeutic effect size of included randomized controlled trials ( n _tDCS = 15, n _tACS = 1) (pair-wise meta-analysis), compare the efficacy of various tES interventions (network meta-analysis), and explore how treatment effect size correlates with induced electrical field in the target brain regions (meta-modeling). With these 3 distinct meta-analytic approaches, we first show a significant moderate effect of tES interventions (standardized mean difference 0.61; 95% confidence interval [0.37 to 0.85]; P < 0.001) as a whole on reducing OCD severity, with larger therapeutic effects of twice-daily intervention, and with other stimulation parameters also moderating efficacy. Next, we identify specific tES interventions with superior indicated and estimated effects, including entraining alpha frequency alternating stimulation of the medial prefrontal cortex, excitability-diminishing cathodal stimulation over the supplementary motor area and orbitofrontal cortex, and excitability-enhancing anodal stimulation of the lateral prefrontal cortex. Finally, we show based on computational approaches that longer stimulation targeting the medial prefrontal and frontopolar cortices has greater therapeutic effects and suggest an optimized intervention accordingly. We finally discuss other potentially effective tES interventions according to the latest neurobiological theory of OCD. The results contribute to establishing the clinical efficacy of tES for OCD treatment while suggesting future studies to further evaluate current and future approaches to enhance the efficacy of interventions.

Long‐term memory (LTM) has been associated with neural oscillation in the theta (3–8 Hz) range. Although previous studies have suggested that the dorsomedial prefrontal cortex (dmPFC) is a core region for LTM retrieval, causal evidence is sparse and mixed. Furthermore, the moderating effects of stimulus memorability have not yet been explored. In the present study, we used transcranial alternating current stimulation (tACS) to modulate theta oscillation in the dmPFC during the retrieval of visual images with varying levels of memorability. Specifically, we included n = 33 healthy volunteers who were exposed to 300 images of faces, scenes and items, which they had to memorize. Recognition accuracy was assessed 1 h later. During the retrieval phase, participants received either sham or verum (4 Hz, 2.5 mA) tACS and were asked whether they had seen the pictures before (150 new and 150 old). Contrary to our preregistered hypotheses, we found no significant effect of 4‐Hz tACS applied during retrieval on LTM recognition. Furthermore, although the memorability effect was observed, it did not interact with tACS, indicating that stimulation neither improved nor worsened performance on low‐ and high‐memorable images. Altogether, the present study does not support an active role of 4‐Hz oscillations in the dmPFC for the recognition of images with varying levels of memorability, under the specific task and stimulation parameters used here. However, this null effect may be specific to the task and particular parameters used in this study.