Oscillatory transcranial direct current stimulation (otDCS) is a form of non-invasive electrical stimulation that has shown promise in modulating human cognition and behavior. This method merges constant polarization with an oscillation, resulting in a combination of features that characterize transcranial direct and alternating current stimulation (tDCS, tACS). While tDCS and tACS have been extensively characterized during the last two decades, otDCS remains comparatively underexplored. However, recent studies emphasize its potential efficacy in modulating, e.g., sleep-related slow oscillations, memory, and awake cognition. This review synthesizes the current understanding of otDCS mechanisms, its unique neurophysiological characteristics, and its behavioral and cognitive effects. We describe how the combination of a constant offset and oscillatory component yields an asymmetric electric field, potentially resulting in distinct subthreshold modulation and entrainment dynamics. Empirical findings suggest that otDCS can modulate cortical excitability, activity, and oscillatory power. Furthermore, we describe evidence on how otDCS may enhance memory consolidation during sleep, as well as modulate attention, executive function, and associative learning during wakefulness. Together, the available evidence indicates that otDCS represents a promising approach for frequency-specific and polarity-dependent modulation of cortical activity, warranting further mechanistic and translational research.

BACKGROUND:The use of preoperative neuronavigated transcranial magnetic stimulation (nTMS) is becoming increasingly common in patients undergoing eloquent brain tumor surgery. Yet the optimal stimulation paradigms for language mapping still lack specificity and need to be refined. In the frontoparietal network, a protocol of dual-site TMS, termed the condition-and-perturb approach (CAP), was shown to effectively sensitize the semantic network in healthy subjects. OBJECTIVE/HYPOTHESIS:This study aims to evaluate the added value of the CAP to preoperative language mapping in non-aphasic patients with language-eloquent brain tumors involving the anterior inferior frontal (aIFG) or angular (AG) gyrus. METHODS:Patients underwent peritumoral online nTMS involving the affected node (AG or aIFG) with or without prior offline neuronavigated repetitive TMS (nrTMS, 1 Hz, 15 min) of the ipsilateral healthy node (aIFG or AG). RESULTS:Eight patients underwent the full protocol. Offline nrTMS decreased error threshold of online language mapping in all patients in comparison to sham nrTMS in those patients. Four peritumoral language hotspots [2-5] could be isolated in each patient. Compared to direct cortical stimulation, nTMS language mapping with CAP achieved a sensitivity of 84.2%, a specificity of 98.3%, a PPV of 84.2% and an NPV of 98.3%. This means that nearly all CAP-nTMS hotspots induced language disturbances when stimulated intraoperatively with DCS. CONCLUSIONS:This pilot study suggests that the CAP could be a possible solution to the specificity concerns of preoperative TMS mapping, as prior frontoparietal network disruption might enhance the precision of language mapping around semantically eloquent brain tumors.

Non-pharmacological methods including training and low-intensity transcranial electrical stimulation (tES) have demonstrated potential in delaying cognitive decline with aging. This study aims to investigate the efficacy of combining repeated tES targeting the left dorsolateral prefrontal cortex with task training on cognitive function in the healthy elderly. In this triple-blind, randomized, sham-controlled study, fifty-five participants received ten 20-min sessions of concurrent task training and stimulation, including anodal transcranial direct current stimulation (tDCS + T), theta transcranial alternating current stimulation (tACS + T), or sham tES (sham + T). The training consisted of cognitive N-back tasks and dynamic balance exercises delivered across sessions. Attention Network Test (ANT) and the Stroop Color–Word Test (SCWT) were administered before and after the intervention, with a four-week follow-up. Group × Time effects were analyzed using linear or generalized linear mixed-effects models, adjusting for age, sex, and baseline cognitive status. Improved overall reaction time (RT) and executive network efficiency were observed in all groups after intervention in ANT. Participants in the sham + T group showed greater improvements with long-term efficacy across all cue-related conditions, and significantly faster RT than tDCS + T group under the double-cue condition at follow-up was observed (χ2 (2) = 6.60, p = 0.03, 95

Non-invasive brain stimulation (NIBS) includes a growing set of techniques aimed at modulating brain activity without surgery or implants. Transcranial magnetic (TMS) and electrical stimulation (tES) are among the most established methods. tES delivers low-intensity current via scalp electrodes, offering a cheaper and portable option, especially for home-based use. Clinical evidence suggests that the effects of tES are cumulative with consecutive applications needed to achieve meaningful changes. The therapeutic application of the clinic-based tES usually involves a minimum of two weeks of daily visits to the clinical institute, which poses a large burden and stress on patients. Home-based tES, e.g. under remote supervision (RS-tES), following adequate training by trained professionals paves the path to increasing the accessibility of the technology to patients. In 2025, the US FDA approved the first home-based tDCS system for the treatment of "moderate to severe major depressive disorder in the current episode, either as monotherapy or as an adjunctive treatment, in patients 18 years and older who are not considered treatment refractory to medication. In this work, the latest knowledge related to home-use of tES is introduced, including the methodology, most frequent clinical applications, advances and limitations.

In this open-label single-arm study, we tested the preliminary therapeutic effects of a four-week mindfullness-based intervention (MBI) tailored for fibromyalgia, including weekly online group meetings and daily mindfulness practices. Forty-six patients completed the intervention. The primary outcome was pain intensity scored on a numerical rating scale (NRS). Secondary outcomes included verbal fluency and self-reports of affective pain, quality of life, sleep quality, mood, emotion regulation, and psychological impairment. Transcranial magnetic stimulation was used to measure mindfulness-induced cortical excitability changes. Participants reported statistically reduced pain intensity post-training, with only 15.3% of the patients demonstrating clinically meaningful pain relief. A moderate improvement in quality of life, with only 45.6% clinical responders, were noted. Small-to-medium improvements in affective pain level, mindfulness level, and resilience as well as increase in long-interval intracortical inhibition-a measure of GABABergic inhibition-were observed. The study introduces a novel MBI tailored for fibromyalgia. Nonetheless, given the current study design and the lack of clinical significance of the findings despite statistical significance, the results are insufficient to draw firm conclusions regarding its potential therapeutic efficacy. Future sham-controlled randomized clinical trials are necessary to validate and expand upon these results.

Background Enhancing dual-task (DT) performance in older adults through cognitive improvement may help prevent neurodegenerative decline. Objective This study aimed to investigate the efficacy of combining repeated transcranial electrical stimulation (tES) targeting the left dorsolateral prefrontal cortex (L-DLPFC) with task training on DT ability in healthy older adults. Methods Fifty-eight participants were randomized to receive ten 20-min sessions of cognitive and motor task training concurrently applied with either anodal transcranial direct current stimulation (tDCS), 4 Hz transcranial alternating current stimulation (tACS), or sham tES. Results All groups demonstrated significant cognitive improvements under both single- and DT conditions immediately and four weeks after the intervention, with no between-group differences. Although motor dual-task costs decreased across all groups, this did not translate into measurable performance gains. Conclusion Overall, tES did not provide significant additive effects on DT performance when combined with multi-session training interventions.

Background:The dorsolateral prefrontal cortex (DLPFC) is a key contributor to memory categorization. Brain-Derived Neurotrophic Factor (BDNF) Val66Met polymorphism affects the efficacy of neuronal plasticity induction. We investigated whether DLPFC-transcranial direct current stimulation (tDCS) influences categorization performance, and whether BNDF genotype modulates this effect. Methods:Sixty-two healthy individuals were randomized to receive 10 min of either anodal right DLPFC-tDCS at 1 mA, or sham tDCS during the training phase of a prototype distortion task. Categorization performance was assessed during, shortly after, and the morning following the stimulation. Val66Met polymorphism status was determined through BNDF genotyping. Results:Val66Met carriers showed poorer categorization ability than Val/Val homozygotes (p < 0.0001). tDCS did not enhance categorization performance overall, or reduce genotype-associated differences with these specific stimulation parameters. However, tDCS extinguished the prototype effect of the categorization task observed in our sample. Conclusions:Our findings underscore the importance of BDNF polymorphism in category learning. 1 mA anodal right DLPFC over the right DLPFC does not improve performance or offset genotype differences under tested conditions. Significance:BDNF Val66Met polymorphism influences category learning, and low-intensity tDCS does not counteract this effect, emphasizing the need to refine stimulation protocols for genotype-specific cognitive enhancement.

Pain is a common debilitating symptom in cancer patients and its management remains a challenge. Among the non-pharmacological analgesic treatment options, low intensity transcranial electrical stimulation (tES) represents a new unique analgesic modality. However, the evidence of tES effectiveness for cancer pain is limited, while the mechanisms of pain relief due to tES are still poorly understood. We propose to test the efficacy of repetitive transcranial direct current stimulation (tDCS) and alternating current stimulation (tACS) in cancer pain patients, and attempt to understand their mechanisms using electroencephalography (EEG) and quantitative sensory testing (QST) measures. This article describes the protocol of a multicenter, sham-controlled, parallel-arm, triple-blinded randomized clinical trial assessing home-based tDCS and tACS in the treatment of cancer patients with persistent pain. 450 patients between 18 and 75 years old will be enrolled in this study. Treatment consists of 15 consecutive daily sessions of either anodal tDCS at 2 mA targeting the primary motor cortex or 10 Hz tACS targeting the dorsolateral prefrontal cortex. Following randomization (2:2:1 ratio), 180 patients will receive active tDCS, 180 patients active tACS, and 90 patients sham stimulation. The primary outcome is self-reported pain intensity on a numerical rating scale (NRS) assessed daily (15 days pre-treatment, 15 days during treatment and 15 days post-treatment). The secondary endpoints are medication intake, other cancer-associated symptoms and quality of life. We will also analyze psychophysical and neurophysiological correlates of ascending and descending pain processing using QST and EEG paradigms. Besides the NRS, which will be reported daily, assessments will be conducted at baseline (T0) and at three time points post-intervention (T1, T2, and T3). Positive findings of the study will indicate the therapeutic benefit of tES in patients with cancer-related pain. Group differences in mechanistic measures would yield potential biomarkers for tDCS- and tACS-induced analgesia, which could be used for personalizing and optimizing the intervention. In addition, changes in EEG or QST could provide insights into the mechanisms underlying the tES effects. The study was registered at the German Clinical Trials Register under the identification number DRKS00031070.

Objective This study assessed variability in cervical electrical (CEPNS) and magnetic (CMPNS) phrenic nerve stimulation alongside transcranial magnetic stimulation (diTMS) of the diaphragm, focusing on motor response latency and amplitude at individually calculated suprathreshold intensities. Methods Diaphragm motor responses were elicited via CEPNS and CMPNS (measuring compound muscle action potentials, CMAPs) and diTMS (measuring diaphragm motor evoked potentials, diMEPs). Latency and amplitude were recorded. Statistical analyses compared methods, evaluated variability using coefficients of variation (CV), and explored associations with height and central motor conduction time. Results Among 25 participants (mean age 25 ± 4 years), CMPNS evoked CMAPs in 21 subjects, CEPNS in 16, with 12 responding to both. No significant latency or amplitude differences emerged between CEPNS and CMPNS responders. TMS evoked diMEPs in 24 participants. Latency was more consistent than amplitude across all methods; CMPNS exhibited the lowest amplitude variability. Height moderately correlated positively with CMAP latency and negatively with central motor conduction time. Conclusions Individually adapted suprathreshold CEPNS and CMPNS assessed phrenic nerve conduction with varying success rates. Latency was a more reliable measure than amplitude. CMPNS and diTMS surpassed CEPNS in response reliability, positioning magnetic stimulations as preferable for assessing phrenic nerve conduction. CEPNS might not be suitable for examining motor response amplitudes when not applied at supramaximal intensity. Height-related anatomical factors influencing conduction merit further study. Significance Latency of diaphragm motor responses elicited at individually estimated stimulation intensities offers a more consistent biomarker over amplitude for assessing phrenic nerve function.

Cognitive decline in older adults has significant implications for autonomy and quality of life. This study evaluated the combined effects of cognitive training (CT) and transcranial direct current stimulation (tDCS) on cognitive performance in older adults. Two CT approaches-core training and strategy training-were paired with either active or sham anodal tDCS over the left DLPFC. Eighty-five participants were assigned to three groups: (1) CT with active tDCS, (2) CT with sham tDCS, and (3) a control group attending memory-related lectures. Participants underwent 16 intervention sessions and completed cognitive assessments at three points: pre-intervention, immediately after, and three months post-intervention. Results showed that the active tDCS group experienced immediate and sustained improvements across all cognitive tests, while the sham tDCS group showed gains only in specific memory tasks. The control group showed no significant changes. These findings suggest that combining CT with active tDCS is more effective in enhancing and sustaining cognitive performance in older adults compared to CT alone. The study highlights the importance of further research to explore the mechanisms underlying the effectiveness of combined CT and tDCS interventions and their potential in mitigating age-related cognitive decline.Trial registration: NCT04997226. 09/08/2021.

This guideline summarizes updated safety data (2017-2025) and provides expert recommendations on the use of low intensity transcranial electrical stimulation (tES) in humans. tES encompasses several techniques including transcranial direct current stimulation (tDCS), oscillatory transcranial direct current stimulation (otDCS), transcranial alternating current stimulation (tACS), transcranial random noise stimulation (tRNS), transcranial temporal interference stimulation (tTIS), and their combinations or variations. Across over 300,000 sessions involving healthy individuals, patients with neuropsychiatric conditions, and other clinical populations, no tES-related serious adverse events (AEs) have been reported. Moderate AEs are rare and limited to a small range of specific applications. Mild AEs are common and include transient symptoms such as localized sensations (e.g., tingling or burning), headaches, and fatigue. Similar mild AEs are also reported by individuals receiving placebo stimulation. The frequency, magnitude, and type of AEs are comparable across healthy, clinical, and vulnerable groups, including children, elderly, or pregnant women. Combined interventions (e.g., co-application with EEG, TMS, or neuroimaging) have not shown increased safety risks. Safety is well-established for both bipolar and multichannel tES when applied up to 4 mA and up to 60 min per day. Higher intensities and longer stimulation durations may also be safe. Nevertheless, the number of studies using intensities above 4 mA or stimulating longer than 60 min is low. Home-based use of treatments is growing rapidly, leveraging remote supervision to provide patients with greater access and enable repeated, sustained dosing paradigms. We recommend using screening and AE questionnaires in future controlled studies, in particular when planning to extend the stimulation parameters applied. We discuss recent regulatory and ethical issues.