Theta-gamma-coupling as predictor of working memory performance in young and elderly healthy people.

The relationship between working memory (WM) and neuronal oscillations can be studied in detail using brain stimulation techniques, which provide a method for modulating these oscillations and thus influencing WM. The endogenous coupling between the amplitude of gamma oscillations and the phase of theta oscillations is crucial for cognitive control. Theta/gamma peak-coupled transcranial alternating current stimulation (TGCp-tACS) can modulate this coupling and thus influence WM performance. This study investigated the effects of TGCp-tACS on WM in older adults and compared their responses with those of younger participants from our previous work who underwent the same experimental design. Twenty-eight older subjects underwent both TGCp-tACS and sham stimulation sessions at least 72 h apart. Resting-state electroencephalography (EEG) was recorded before and after the interventions, and a WM task battery with five different WM tasks was performed during the interventions to assess various WM components. Outcomes measured included WM task performance (e.g., accuracy, reaction time (RT)) and changes in power spectral density (PSD) in different frequency bands. TGCp-tACS significantly decreased accuracy and RT on the 10- and 14-point Sternberg tasks and increased RT on the Digit Symbol Substitution Test in older adults. In contrast, younger participants showed a significant increase in accuracy only on the 14-item Sternberg task. Electrophysiological analysis revealed a decrease in delta and theta PSD and an increase in high gamma PSD in both younger and older participants after verum stimulation. In conclusion, theta-gamma coupling is essential for WM and modulation of this coupling affects WM performance. The effects of TGCp-tACS on WM vary with age due to natural brain changes. To better support older adults, the study suggests several strategies to improve cognitive function, including: Adjusting stimulation parameters, applying stimulation to two sites, conducting multiple sessions, and using brain imaging techniques for precise targeting.

Beta tACS of varying intensities differentially affect resting-state and movement-related M1-M1 connectivity.

Due to the interconnected nature of the brain, changes in one region are likely to affect other structurally and functionally connected regions. Emerging evidence indicates that single-site transcranial alternating current stimulation (tACS) can modulate functional connectivity between stimulated and interconnected unstimulated brain regions. However, our understanding of the network response to tACS is incomplete. Here, we investigated the effect of beta tACS of different intensities on phase-based connectivity between the left and right primary motor cortices in 21 healthy young adults (13 female; mean age 24.30 ± 4.84 years). Participants underwent four sessions of 20 min of 20 Hz tACS of varying intensities (sham, 0.5 mA, 1.0 mA, or 1.5 mA) applied to the left primary motor cortex at rest. We recorded resting-state and event-related electroencephalography (EEG) before and after tACS, analyzing changes in sensorimotor beta (13-30 Hz) imaginary coherence (ImCoh), an index of functional connectivity. Event-related EEG captured movement-related beta activity as participants performed self-paced button presses using their right index finger. For resting-state connectivity, we observed intensity-dependent changes in beta ImCoh: sham and 0.5 mA stimulation resulted in an increase in beta ImCoh, while 1.0 mA and 1.5 mA stimulation decreased beta ImCoh. For event-related connectivity, 1.5 mA stimulation decreased broadband ImCoh (4-90 Hz) during movement execution. None of the other stimulation intensities significantly modulated event-related ImCoh during movement preparation, execution, or termination. Interestingly, changes in ImCoh during movement preparation following 1.0 mA and 1.5 mA stimulation were significantly associated with participants' pre-tACS peak beta frequency, suggesting that the alignment of stimulation frequency and peak beta frequency affected the extent of neuromodulation. Collectively, these results suggest that beta tACS applied to a single site influences connectivity within the motor network in a manner that depends on the intensity and frequency of stimulation. These findings have significant implications for both research and clinical applications.

Attention improvement to transcranial alternating current stimulation at gamma frequency over the right frontoparietal network: a preliminary report.

Applying transcranial alternating current stimulation (tACS) at 40 Hz to the frontal and parietal regions, either unilaterally (left or right) or bilaterally, can improve cognitive dysfunctions. This study aimed to explore the influence of tACS at gamma frequency over right fronto-parietal (FP) region on attention. The analysis is based on retrospective data from a clinical intervention. We administered test of variables of attention (TOVA; visual mode) to 44 participants with various neuropsychiatric diagnoses before and after 12 sessions of tACS treatment. Alternating currents at 2.0 mA were delivered to the electrode positions F4 and P4, following the 10-20 EEG convention, for 20 mins in each session. We observed significant improvement across 3 indices of the TOVA, including reduction of variability in reaction time (p = 0.0002), increase in d-Prime (separability of targets and non-targets; p = 0.0157), and decrease in commission error rate (p = 0.0116). The mean RT and omission error rate largely remained unchanged. Artificial injection of tACS at 40 Hz over right FP network may improve attention function, especially in the domains of consistency in performance, target/non-target discrimination, and inhibitory control.

Intraoperative rapid immunohistochemistry of microsatellite instability using non-contact alternating current electric field mixing.

OBJECTIVES: Tumors caused by failure of the DNA-mismatch repair system generally show microsatellite instability (MSI). High-frequency MSI cancers have been shown to be susceptible to immuno-oncology therapies. The aim of this study was to evaluate the clinical reliability of a rapid immunohistochemistry (IHC) technique for intraoperatively assessing molecular status through detection of tumoral deficiencies in the expression of mismatch repair proteins (dMMR; MLH1, MSH2, MSH6, and PMS2). METHODS: The rapid IHC method uses non-contact alternating current (AC) mixing to achieve more rapid/stable staining within a minimum of 13 min during surgery. Sixteen formalin-fixed paraffin-embedded (FFPE) tumor samples from 3 dMMR patients with Lynch syndrome and 6 FFPE samples from 6 dMMR-cancer patients were collected to establish an IHC protocol for MMR proteins. Next, 26 surgical patients treated and whose MSI status was determined using PCR-based tests were retrospectively analyzed. The concordance of dMMR diagnoses for thoracic tumors between the conventional (frozen section (FS)- and FFPE-IHCs) and rapid AC-mixing IHC with FSs were compared. RESULTS: A rapid IHC protocol using primary antibodies against four MMR proteins (mixed 5-10 min) was established (entire process within 40 min). The concordance rate for MMR-IHC between the conventional and rapid IHC was 100%. dMMR diagnoses including an MSI-high pulmonary sarcoma patient entirely matched between FS- and FFPE-IHC. CONCLUSION: Rapid MMR-IHC could potentially serve as a clinical tool for intraoperative determination of tumor MSI/dMMR status. AC-mixing technology will contribute to improving pathological diagnostic capability through the development of an original and innovative rapid IHC.

Improving working memory by electrical stimulation and cross-frequency coupling.

Working memory (WM) is essential for the temporary storage and processing of information required for complex cognitive tasks and relies on neuronal theta and gamma oscillations. Given the limited capacity of WM, researchers have investigated various methods to improve it, including transcranial alternating current stimulation (tACS), which modulates brain activity at specific frequencies. One particularly promising approach is theta-gamma peak-coupled-tACS (TGCp-tACS), which simulates the natural interaction between theta and gamma oscillations that occurs during cognitive control in the brain. The aim of this study was to improve WM in healthy young adults with TGCp-tACS, focusing on both behavioral and neurophysiological outcomes. Thirty-one participants completed five WM tasks under both sham and verum stimulation conditions. Electroencephalography (EEG) recordings before and after stimulation showed that TGCp-tACS increased power spectral density (PSD) in the high-gamma region at the stimulation site, while PSD decreased in the theta and delta regions throughout the cortex. From a behavioral perspective, although no significant changes were observed in most tasks, there was a significant improvement in accuracy in the 14-item Sternberg task, indicating an improvement in phonological WM. In conclusion, TGCp-tACS has the potential to promote and improve the phonological component of WM. To fully realize the cognitive benefits, further research is needed to refine the stimulation parameters and account for individual differences, such as baseline cognitive status and hormonal factors.

High-Definition Trans-Spinal Current Stimulation Improves Balance and Somatosensory Control: A Randomised, Placebo-Controlled Trial.

OBJECTIVES: To investigate and compare the effects of three different high-definition (HD) non-invasive current stimulation (NICS) protocols on the spinal cord on support balance and somatosensory abilities in healthy young people. METHODS: Fifty-eight students were enrolled in this crossover study. All participants underwent application of (i) 1.5 mA anodal high-definition trans spinal direct current stimulation (HD-tsDCS), (ii) 1.5 mA cathodal HD-tsDCS, (iii) 1.5 mA high-definition trans spinal alternating current stimulation (HD-tsACS), and (iv) sham HD-tsDCS/ACS over the eighth thoracic vertebra in a randomised order. Balance (Y Balance test), deep sensitivity (Tuning Fork Test), and superficial sensitivity (Monofilament Test) of the lower limbs were tested immediately before and after each intervention. RESULTS: Balance ability improved significantly following anodal HD-tsDCS and HD-tsACS compared with that following sham HD-tsDCS/ACS. Similarly, deep sensitivity increased significantly with anodal HD-tsDCS and HD-tsACS compared to that with sham HD-tsDCS/ACS and cathodal HD-tsDCS. Furthermore, superficial sensitivity improved significantly following anodal HD-tsDCS compared with that after HD-tsACS and cathodal HD-tsDCS. CONCLUSIONS: Our data show that HD-tsNICS effectively modulates the balance and somatosensory control of the lower limbs. Several diseases are associated with illness-induced changes in the spinal network in parallel with sensorimotor disabilities. Non-invasive spinal modulation may be a favourable alternative to conventional brain applications in rehabilitation. Future studies should therefore investigate these promising approaches among cohorts of patients with disabilities.

Transcranial Alternating Current Stimulation: A Novel Neuromodulatory Treatment for Anxiety and Related Disorders.

Given the high prevalence and socioeconomic burden of anxiety disorders, there is an urgent need for effective, fast-acting, cost-efficient treatment alternatives to traditional psychotherapy. Transcranial alternating current stimulation (tACS), a noninvasive brain stimulation technique that modulates endogenous brain oscillations via the application of sinusoidal currents to the scalp, emerges as a promising neuromodulatory treatment. We reviewed oscillatory neuropsychopathology in anxiety, examined current evidence of tACS interventions for anxiety and related disorders, and proposed novel simulation targets and protocols. We emphasize the need for rigorously designed clinical trials to systematically investigate the neuropsychological effects of different tACS protocols on diverse populations with pathological anxiety.

Neuromodulation of the Cerebellum for Motor Applications: A Systematic Review.

BACKGROUND: Despite the connections and clear importance of the cerebellum in motor function, research utilizing cerebellar neuromodulation for treatment of movement disorders is still underdeveloped. Here we conduct a systematic review to investigate non-invasive neurostimulation of the cerebellum and its potential impact on motor systems and its function. Our aim is to give a general review of each neurostimulation study focusing on the cerebellum as a treatment target in the past five years at time of search, in order to update the field on current findings and inspire similar cerebellar neurostimulation research without unnecessary repetition. METHODS: Using the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, our search included articles over the past five years that evaluated neurostimulation of the cerebellum (e.g., transcranial magnetic stimulation, transcranial direct current stimulation, and transcranial alternating current stimulation, etc.). Inclusion criteria included: (1) neurostimulation (repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS)) of the cerebellum; (2) only original articles, and (3) outcomes focused on motor functions. Exclusion criteria included: (1) neurostimulation with the goal of targeting any brain structure other than the cerebellum and (2) reviews and conference abstracts. RESULTS: The search revealed 82 distinct articles relevant to the research question. Included are 17 articles concerning rTMS, 56 articles concerning tDCS, and 9 articles concerning tACS. The majority of the studies are controlled trials of varying types, with 79, with two case studies and one pilot study. CONCLUSIONS: Many studies showed significant effects on motor function and circuitry via non-invasive neurostimulation of the cerebellum. Common targets of cerebellar neurostimulation include visuomotor control, stroke rehabilitation for improvements in balance and coordination, and motor skill acquisition. The field is still exploring ideal parameters of neurostimulation for each disorder or function of interest. Future research areas should include the inclusion of individual anatomy, including functional connectivity, and improving stimulation selectivity.

Brain Stimulation in Alzheimer's Disease Trials.

Alzheimer's disease (AD) continues to lack definitive curative therapies, necessitating an urgent exploration of innovative approaches. This review provides a comprehensive analysis of recent clinical trials focusing on invasive and non-invasive brain stimulation techniques as potential interventions for AD. Deep brain stimulation (DBS), repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS), and transcranial alternating current stimulation (tACS) are evaluated for their therapeutic efficacy, safety, and applicability. DBS, though invasive, has shown promising results in mitigating cognitive decline, but concerns over surgical risks and long-term effects persist. On the other hand, non-invasive methods like rTMS, tDCS, and tACS have demonstrated potential in enhancing cognitive performance and delaying disease progression, with minimal side effects, but with varied consistency. The evidence hints towards an individualized, patient-centric approach to brain stimulation, considering factors such as disease stage, genetic traits, and stimulation parameters. The review also highlights emerging technologies and potential future directions, emphasizing the need for larger, multi-center trials to confirm preliminary findings and establish robust clinical guidelines. In conclusion, while brain stimulation techniques present a promising avenue in AD therapy, further research is imperative for more comprehensive understanding and successful clinical implementation. Through this review, we aim to catalyze the scientific discourse and stimulate further investigation into these novel interventions for AD.

Potentiation of Motor Adaptation Via Cerebellar tACS: Characterization of the Stimulation Frequency.

Motor adaptation is critical to update motor tasks in new or modified environmental conditions. While the cerebellum supports error-based adaptations, its neural implementation is partially known. By controlling the frequency of cerebellar transcranial alternating current stimulation (c-tACS), we can test the influence of neural oscillation from the cerebellum for motor adaptation. Two independent experiments were conducted. In Experiment 1, 16 participants received four c-tACS protocols (45 Hz, 50 Hz, 55 Hz, and sham) on four different days while they practiced a visuomotor adaptation task (30 degrees CCW) with variable intensity (within-subject design). In Experiment 2, 45 participants separated into three groups received the effect of 45 Hz, 55 Hz c-tACS, and sham, respectively (between-subject design), performing the same visuomotor task with a fixed intensity (0.9 mA). In Experiment 1, 45 Hz and 50 Hz of c-tACS accelerated motor adaptation when participants performed the task only for the first time, independent of the time interval between sessions or the stimulation intensity. The effect of active c-tACS was ratified in Experiment 2, where 45 Hz c-tACS benefits motor adaptation during the complete practice period. Reaction time, velocity, or duration of reaching are not affected by c-tACS. Cerebellar alternating current stimulation is an effective strategy to potentiate visuomotor adaptations. Frequency-dependent effects on the gamma band, especially for 45 Hz c-tACS, ratify the oscillatory profile of cerebellar processes behind the motor adaptation. This can be exploited in future interventions to enhance motor learning.

Is transcranial alternating current stimulation effective for improving working memory? A three-level meta-analysis.

Working memory, an essential component of cognitive function, can be improved through specific methods. This meta-analysis evaluates the effectiveness of transcranial alternating current stimulation (tACS), an emerging technique for enhancing working memory, and explores its efficacy, influencing factors, and underlying mechanisms. A PRISMA systematic search was conducted. Hedges's g was used to quantify effect sizes. We constructed a three-level meta-analytic model to account for all effect sizes and performed subgroup analyses to assess moderating factors. Recognizing the distinct neural underpinnings of various working memory processes, we separately assessed the effects on n-back tasks and traditional working memory tasks. A total of 39 studies with 405 effect sizes were included (170 from n-back tasks and 235 from other tasks). The overall analysis indicated a net benefit of g = 0.060 of tACS on working memory. Separate analyses showed that tACS had a small positive effect on n-back tasks (g = 0.102), but almost no effect on traditional working memory tasks (g = 0.045). Further analyses revealed mainly: A moderately positive effect of theta tACS (without anti-phase stimulation) on n-back tasks (g = 0.207); and a small effect of offline stimulation on working memory maintenance (g = 0.127). Overall, tACS has minimal impact on working memory improvement, but it shows potential under certain conditions. Specifically, both online and offline theta tACS can improve n-back task performance, while only offline stimulation enhances working memory maintenance. More research is needed to understand the mechanisms behind these effects to make tACS an effective method.

Differential effects of theta-gamma tACS on motor skill acquisition in young individuals and stroke survivors: A double-blind, randomized, sham-controlled study.

BACKGROUND: Theta-gamma transcranial alternating current stimulation (tACS) was recently found to enhance thumb acceleration in young, healthy participants, suggesting a potential role in facilitating motor skill acquisition. Given the relevance of motor skill acquisition in stroke rehabilitation, theta-gamma tACS may hold potential for treating stroke survivors. OBJECTIVE: We aimed to examine the effects of theta-gamma tACS on motor skill acquisition in young, healthy participants and stroke survivors. METHODS: In a pre-registered, double-blind, randomized, sham-controlled study, 78 young, healthy participants received either theta-gamma peak-coupled (TGP) tACS, theta-gamma trough-coupled (TGT) tACS or sham stimulation. 20 individuals with a chronic stroke received either TGP or sham. TACS was applied over motor cortical areas while participants performed an acceleration-dependent thumb movement task. Stroke survivors were characterized using standardized testing, with a subgroup receiving additional structural brain imaging. RESULTS: Neither TGP nor TGT tACS significantly modified general motor skill acquisition in the young, healthy cohort. In contrast, in the stroke cohort, TGP diminished motor skill acquisition compared to sham. Exploratory analyses revealed that, independent of general motor skill acquisition, healthy participants receiving TGP or TGT exhibited greater peak thumb acceleration than those receiving sham. CONCLUSION: Although theta-gamma tACS increased thumb acceleration in young, healthy participants, consistent with previous reports, it did not enhance overall motor skill acquisition in a more complex motor task. Furthermore, it even had detrimental effects on motor skill acquisition in stroke survivors.

Neuromodulation and mindfulness as therapeutic treatment in detoxified patients with alcohol use disorder.

BACKGROUND: Alcohol use disorder (AUD) poses a significant global health challenge. Traditional management strategies often face high relapse rates, leading to a need for innovative approaches. Mindfulness-based relapse prevention (MBRP) has emerged as a promising intervention to enhance cognitive control, reduce cue-related craving and improve interoceptive processing. Neuroimaging studies suggest that mindfulness training can modulate brain networks associated with these factors, potentially improving treatment outcomes for AUD. Neuroimaging studies suggest that mindfulness training can modulate brain networks linked to these brain functions, potentially improving treatment outcomes for AUD. However, it is unclear how MBRP links to neurophysiological measures such as frontal midline theta oscillations (FMΘ) and whether the beneficial effects of MBRP can be increased by enhancing FMΘ. Here, we will use two different forms of neuromodulation to target and enhance these oscillations, and evaluate their impact on the effectiveness of MBRP. METHODS: This study will employ a four-arm randomized controlled trial to evaluate the synergistic effects of MBRP augmented with transcutaneous vagus nerve stimulation (tVNS) or closed-loop amplitude-modulated transcranial alternating current stimulation (CLAM-tACS) on cognitive control, cue reactivity and interoceptive processing in AUD patients. Participants will undergo six weekly group MBRP sessions and daily individual mindfulness practices. Assessments will include an inhibition task, cue-induced craving task, and heartbeat discrimination task, alongside heart rate variability and 32-channel EEG recordings. Participants will be assessed pre and post treatment, with a three-month follow-up to evaluate long-term effects on abstinence and alcohol consumption. DISCUSSION: This study will not only elucidate the causal link between FMΘ and efficacy of MBRP, but contribute to a better understanding of how combined psychological and neuromodulation interventions can improve treatment outcomes for AUD, potentially leading to more effective therapeutic strategies. This study also seeks to explore individual differences in response to treatment, which could inform future approaches to AUD management. TRIAL REGISTRATION: This study received approval by the Charité-Universitätsmedizin Berlin Institutional Review Board (EA1/030/23, 10.11.2023). It was registered on ClinicalTrials.gov (NCT06308484).

The role of the somatosensory system in the feeling of emotions: a neurostimulation study.

Emotional experiences deeply impact our bodily states, such as when we feel 'anger', our fists close and our face burns. Recent studies have shown that emotions can be mapped onto specific body areas, suggesting a possible role of the primary somatosensory system (S1) in emotion processing. To date, however, the causal role of S1 in emotion generation remains unclear. To address this question, we applied transcranial alternating current stimulation (tACS) on the S1 at different frequencies (beta, theta, and sham) while participants saw emotional stimuli with different degrees of pleasantness and levels of arousal. Results showed that modulation of S1 influenced subjective emotional ratings as a function of the frequency applied. While theta and beta-tACS made participants rate the emotional images as more pleasant (higher valence), only theta-tACS lowered the subjective arousal ratings (more calming). Skin conductance responses recorded throughout the experiment confirmed a different arousal for pleasant versus unpleasant stimuli. Our study revealed that S1 has a causal role in the feeling of emotions, adding new insight into the embodied nature of emotions. Importantly, we provided causal evidence that beta and theta frequencies contribute differently to the modulation of two dimensions of emotions-arousal and valence-corroborating the view of a dissociation between these two dimensions of emotions.

Application of Transcranial Direct and Alternating Current Stimulation (tDCS and tACS) on Major Depressive Disorder.

The exploration of brain stimulation methods offers a promising avenue to overcome the shortcomings of traditional drug therapies and psychological treatments for major depressive disorder (MDD). Over the past years, there has been an increasing focus on transcranial electrical stimulation (tES), notably for its ease of use and potentially fewer side effects. This chapter delves into the use of transcranial direct current stimulation (tDCS) and transcranial alternating current stimulation (tACS), which are key components of tES, in managing depression. It begins by introducing tDCS and tACS, summarizing their action mechanisms. Following this introduction, the chapter provides an in-depth analysis of existing meta-analyses, systematic reviews, clinical studies, and case reports that have applied tES in MDD treatment. It also considers the role of tES in personalized medicine by looking at specific patient groups and evaluating research on possible biomarkers that could predict how patients with MDD respond to tES therapy.

Altered Neuronal Activity Patterns of the Prefrontal Cortex in Alzheimer's Disease After Transcranial Alternating Current Stimulation: A Resting-State fMRI Study.

Background: Transcranial alternating current stimulation (tACS) could improve cognition in patients with Alzheimer's disease (AD). However, the effects of tACS on brain activity remain unclear. Objective: The purpose is to investigate the change in regional neuronal activity after tACS in AD patients employing resting-state functional magnetic resonance imaging (rs-fMRI). Methods: A total of 46 patients with mild AD were enrolled. Each patient received 30 one-hour sessions of real or sham tACS for three weeks (clinical trial: NCT03920826). The fractional amplitude of low-frequency fluctuations (fALFF) and the regional homogeneity (ReHo) measured by rs-fMRI were calculated to evaluate the regional brain activity. Results: Compared to baseline, AD patients in the real group exhibited increased fALFF in the left middle frontal gyrus-orbital part and right inferior frontal gyrus-orbital part, as well as increased ReHo in the left precentral gyrus and right middle frontal gyrus at the end of intervention. At the 3-month follow-up, fALFF increased in the left superior parietal lobule and right inferior temporal gyrus, as well as ReHo, in the left middle frontal gyrus and right superior medial frontal gyrus. A higher fALFF in the right lingual gyrus and ReHo in the right parahippocampal gyrus were observed in the response group than in the nonresponse group. Conclusions: The findings demonstrated the beneficial effects of tACS on the neuronal activity of the prefrontal cortex and even more extensive regions and provided a neuroimaging biomarker of treatment response in AD patients.

Recent Advances in Perovskite-Based Flexible Electroluminescent Devices.

Perovskite-based flexible electroluminescent (EL) devices are emerging as promising candidates in the display field due to their exceptional optoelectronic properties and potential for cost-effective production. However, simultaneously achieving high EL performance, excellent flexibility and stretchability, robust mechanical strength, and diverse applications remains a significant challenge. In this review, we provide a comprehensive overview of the latest developments in perovskite-based flexible EL devices, covering both direct-current (DC) and alternating-current (AC) electroluminescent formats. Our discussion encompasses the materials, working principles, device architectures, failure mechanisms, optimization strategies, and practical applications. Through this review, we aim to deepen our understanding of the current challenges and future directions of perovskite-based flexible light-emitting technologies, hoping to facilitate their potential commercial applications.

TRanscranial AlterNating current stimulation FOR patients with mild Alzheimer's Disease (TRANSFORM-AD): a randomized controlled clinical trial.

BACKGROUND: The mechanistic effects of gamma transcranial alternating current stimulation (tACS) on hippocampal gamma oscillation activity in Alzheimer's Disease (AD) remains unclear. This study aimed to clarify beneficial effects of gamma tACS on cognitive functioning in AD and to elucidate effects on hippocampal gamma oscillation activity. METHODS: This is a double-blind, randomized controlled single-center trial. Participants with mild AD were randomized to tACS group or sham group, and underwent 30 one-hour sessions of either 40 Hz tACS or sham stimulation over consecutive 15 days. Cognitive functioning, structural magnetic resonance imaging (MRI), and simultaneous electroencephalography-functional MRI (EEG-fMRI) were evaluated at baseline, the end of the intervention and at 3-month follow-up from the randomization. RESULTS: A total of 46 patients were enrolled (23 in the tACS group, 23 in the sham group). There were no group differences in the change of the primary outcome, 11-item cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-Cog) score after intervention (group*time, p = 0.449). For secondary outcomes, compared to the control group, the intervention group showed significant improvement in MMSE (group*time, p = 0.041) and MoCA scores (non-parametric test, p = 0.025), which were not sustained at 3-month follow-up. We found an enhancement of theta-gamma coupling in the hippocampus, which was positively correlated with improvements of MMSE score and delayed recall. Additionally, fMRI revealed increase of the local neural activity in the hippocampus. CONCLUSION: Effects on the enhancement of theta-gamma coupling and neural activity within the hippocampus suggest mechanistic models for potential therapeutic mechanisms of tACS. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03920826; Registration Date: 2019-04-19.

An overview of the effects and mechanisms of transcranial stimulation frequency on motor learning.

Many studies over the recent decades have attempted the modulation of motor learning using brain stimulation. Alternating currents allow for researchers not only to electrically stimulate the brain, but to further investigate the effects of specific frequencies, in and beyond the context of their endogenous associations. Transcranial alternating current stimulation (tACS) has therefore been used during motor learning to modulate aspects of acquisition, consolidation and performance of a learned motor skill. Despite numerous reviews on the effects of tACS, and its role in motor learning, there are few studies which synthesize the numerous frequencies and their respective theoretical mechanisms as they relate to motor and perceptual processes. Here we provide a short overview of the main stimulation frequencies used in motor learning modulation (e.g., alpha, beta, and gamma), and discuss the effect and proposed mechanisms of these studies. We summarize with the current state of the field, the effectiveness and variability in motor learning modulation, and novel mechanistic proposals from other fields.

Controlled electrocatalysis of the dechlorination and detoxification of chlorinated ethylenes to avoid production of highly toxic intermediates.

In this study, electrochemical dechlorination and detoxification of a mixture of chlorinated ethylenes was investigated under various conditions using a double monoatomic synergistic metal catalytic cathode. Electrocatalytic degradation of mixed chlorinated with stepwise voltage and alternating current exhibited excellent dechlorination efficiency. The removal ratios of 1,2-dichloroethylene (1,2-DCE), trichloroethylene (TCE), and tetrachloroethylene (PCE) reached 78.79 %, 79.27 %, and 93.44 % in 10 min, and 98.14 %, 97.56 %, and 98.70 % in 30 min, respectively. The toxicity was evaluated using a quantitative structure-activity relationship model. The cumulative toxicity was reduced to 8.00 % of the initial cumulative toxicity in 30 min. An electrochemical dechlorination strategy for selective degradation and detoxification of mixtures of chlorinated pollutants is proposed. Controlled dechlorination and detoxification under low-voltage control avoided the accumulation of toxic intermediates. Cumulative toxicity was reduced by strategies of selective dechlorination, and segmented and alternating current decreased the energy consumption. The strategy provides a basis for alternating current electrocatalytic dechlorination associated with mixed chlorinated pollutants treatment.