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Transcranial alternating current stimulation (tACS) may modulate neuronal oscillations by applying sinusoidal alternating current, thereby alleviating associated symptoms in schizophrenia. Considering its possible utility in schizophrenia, we reviewed the literature for tACS protocols administered in schizophrenia and their findings. A scoping review was conducted following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guideline in databases and clinical trial registers. The search resulted in 59 publications. After excluding review articles unrelated to tACS, trials without published results or not involving patients with schizophrenia, 14 studies were included. Among the included studies/case reports only 5 were randomized controlled therapeutic trials. The studies investigated the utility of tACS for clinical and neurobiological outcomes. All studies reported good tolerability with only transient mild side effects. It was administered mostly during the working memory task (such as computerized n-back task, dual back task, and computerized digit symbol substitution task) for schizophrenia patients with cognitive deficits and during resting state while targeting positive symptoms. A possible reduction in hallucinations and delusions using alpha tACS, and improvement in negative and cognitive deficits with theta and gamma tACS were reported. Nevertheless, one of the randomized controlled trials targeting hallucinations was negative and rigorous large-sample studies are lacking for other domains. The current evidence for tACS in schizophrenia is preliminary though promising. In future, more sham controlled randomized trials assessing the effect of tACS on various domains are needed to substantiate these early findings. [ABSTRACT FROM AUTHOR]

Objective: Here, we report a retrospective, single‐center experience with a novel deep brain stimulation (DBS) device capable of chronic local field potential (LFP) recording in drug‐resistant epilepsy (DRE) and explore potential electrophysiological biomarkers that may aid DBS programming and outcome tracking. Methods: Five patients with DRE underwent thalamic DBS, targeting either the bilateral anterior (n = 3) or centromedian (n = 2) nuclei. Postoperative electrode lead localizations were visualized in Lead‐DBS software. Local field potentials recorded over 12–18 months were tracked, and changes in power were associated with patient events, medication changes, and stimulation. We utilized a combination of lead localization, in‐clinic broadband LFP recordings, real‐time LFP response to stimulation, and chronic recordings to guide DBS programming. Results: Four patients (80%) experienced a >50% reduction in seizure frequency, whereas one patient had no significant reduction. Peaks in the alpha and/or beta frequency range were observed in the thalamic LFPs of each patient. Stimulation suppressed these LFP peaks in a dose‐dependent manner. Chronic timeline data identified changes in LFP amplitude associated with stimulation, seizure occurrences, and medication changes. We also noticed a circadian pattern of LFP amplitudes in all patients. Button‐presses during seizure events via a mobile application served as a digital seizure diary and were associated with elevations in LFP power. Significance: We describe an initial cohort of patients with DRE utilizing a novel sensing DBS device to characterize potential LFP biomarkers of epilepsy that may be associated with seizure control after DBS in DRE. We also present a new workflow utilizing the Percept device that may optimize DBS programming using real‐time and chronic LFP recording. [ABSTRACT FROM AUTHOR]

Virtual reality (VR) applications are pervasive of everyday life, as in working, medical, and entertainment scenarios. There is yet no solution to cybersickness (CS), a disabling vestibular syndrome with nausea, dizziness, and general discomfort that most of VR users undergo, which results from an integration mismatch among visual, proprioceptive, and vestibular information. In a double-blind, controlled trial, we propose an innovative treatment for CS, consisting of online oscillatory imperceptible neuromodulation with transcranial alternating current stimulation (tACS) at 10 Hz, biophysically modelled to reach the vestibular cortex bilaterally. tACS significantly reduced CS nausea in 37 healthy subjects during a VR rollercoaster experience. The effect was frequency-dependent and placebo-insensitive. Subjective benefits were paralleled by galvanic skin response modulation in 25 subjects, addressing neurovegetative activity. Besides confirming the role of transcranially delivered oscillations in physiologically tuning the vestibular system function (and dysfunction), results open a new way to facilitate the use of VR in different scenarios and possibly to help treating also other vestibular dysfunctions. [ABSTRACT FROM AUTHOR]

BackgroundNoninvasive transcranial electrical stimulation (tES) research has been plagued with inconsistent effects. Recent work has suggested neuroanatomical and neurophysiological variability may alter tES efficacy. However, direct evidence is limited.ObjectiveWe have previously replicated effects of transcranial alternating current stimulation (tACS) on improving multitasking ability in young adults. Here, we attempt to assess whether these stimulation parameters have comparable effects in older adults (aged 60-80 years), which is a population known to have greater variability in neuroanatomy and neurophysiology. It is hypothesized that this variability in neuroanatomy and neurophysiology will be predictive of tACS efficacy.MethodsWe conducted a pre-registered study where tACS was applied above the prefrontal cortex (between electrodes F3-F4) while participants were engaged in multitasking. Participants were randomized to receive either 6-Hz (theta) tACS for 26.67 min daily for three days (80 min total; Long Exposure Theta group), 6-Hz tACS for 5.33 min daily (16-min total; Short Exposure Theta group), or 1-Hz tACS for 26.67 min (80 min total; Control group). To account for neuroanatomy, magnetic resonance imaging data was used to form individualized models of the tACS-induced electric field (EF) within the brain. To account for neurophysiology, electroencephalography data was used to identify individual peak theta frequency.ResultsResults indicated that only in the Long Theta group, performance change was correlated with modeled EF and peak theta frequency. Together, modeled EF and peak theta frequency accounted for 54%-65% of the variance in tACS-related performance improvements, which sustained for a month.ConclusionThese results demonstrate the importance of individual differences in neuroanatomy and neurophysiology in tACS research and help account for inconsistent effects across studies.

The article discusses the strong correlation between clinical improvement and low-frequency oscillations in pediatric dystonia, particularly in the context of deep brain stimulation (DBS) of the globus pallidus internus (GPi). The study highlights the potential of low-frequency oscillations (LFOs) as physiomarkers for predicting outcomes and guiding treatment in dystonia patients. By analyzing longitudinal LFO recordings and clinical symptoms in a pediatric patient with generalized dystonia, the researchers found a significant correlation between LFO power and dystonia severity, emphasizing the importance of this physiomarker for personalized DBS therapy. [Extracted from the article]

BackgroundChronic pain is common, disruptive, and often treatment-resistant. Hence, researchers and clinicians seek alternative therapies for chronic pain. Transcranial alternating current stimulation (tACS) is an emerging neuromodulation technique that non-invasively modulates neural oscillations in the human brain. tACS induces pain relief by allowing the neural network to restore adequate synchronization. We reviewed studies on the effectiveness of tACS in controlling chronic pain.MethodsThe PubMed, SCOPUS, Embase, and Cochrane Library databases were systematically searched for relevant studies published until December 6, 2023. The key search phrase for identifying potentially relevant articles was [(Transcranial Alternating Current Stimulation OR tACS) AND pain]. The following inclusion criteria were applied for article selection: (1) studies involving patients with chronic pain; (2) tACS was applied for controlling pain; and (3) follow-up evaluations were performed to assess the degree of pain reduction after the application of tACS.ResultsWe identified 2,330 potentially relevant articles. After reading the titles and abstracts and assessing eligibility based on the full-text articles, we included four articles in our review. Among the included studies, tACS was used for fibromyalgia in one study, low back pain (LBP) in two studies, and migraine in one study. In the study on fibromyalgia, it did not show a better pain-reducing effect of tACS compared with sham stimulation. Two studies on LBP showed conflicting results. In migraine, tACS showed a positive pain-reducing effect 24–48 h after its application.ConclusionThere is insufficient research to draw a conclusive judgment on the effectiveness of tACS in controlling chronic pain. More studies across various chronic pain-related diseases are required for a definitive conclusion.

Developmental dyslexia is characterized by the pathologically diminished ability to acquire reading and spelling skills. Accurate processing of acoustic information at the phonemic scale is crucial for successful sound-to-letter-mapping which, in turn, is elemental in reading and spelling. Altered activation patterns in the auditory cortex are thought to provide the neurophysiological basis for the inaccurate phonemic perception. Recently, transcranial electrical stimulation has been shown to be an effective method to ameliorate cortical activation patterns in the auditory cortex. In a sample of children and adolescents with dyslexia, we investigated the effect of multi-session transcranial alternating current stimulation delivered concurrently with a phonological training and in combination with a behavioral literacy skills training. Over a 5-week period the participants received 10 training sessions while gamma-tACS was administered over bilateral auditory cortex. We found that gamma-tACS shifted the peak frequency of auditory gamma oscillations reflecting a more fine-grained processing of time-critical acoustic information. This amelioration was accompanied by increased phonemic processing skills. Moreover, individuals who received gamma-tACS showed significant improvements in their spelling skills four months after the intervention. Our results demonstrate that multi-session gamma-tACS enhances the effects of a behavioral intervention and induces long-term improvement on literacy skills in dyslexia.

IntroductionTranscranial alternating current stimulation (tACS) can regulate brain functions by modulating endogenous brain rhythms. Theta-band neural oscillations are associated with memory function. In particular, theta neural oscillatory power evoked in the parietal cortex is closely related to memory retrieval processes. In this study, the immediate effects of high-definition theta transcranial alternating current stimulation (HDθ-tACS) on the human left parietal cortex were investigated using short-latency afferent inhibition (SAI) and electroencephalography (EEG).MethodsTen subjects participated in this study. We used 6-Hz HD tACS to stimulate the left parietal cortex for 15 min. SAI was calculated, and non-linear dynamic analysis of the EEG was performed to analyze neuronal function after HD θ-tACS.ResultsThe results showed a significant decrease in SAI (p < 0.05), while the left frontoparietal network was reinforced, leading to brain lateralization after HD θ-tACS. During performance of a memory task, F3 signals showed a significant upward trend in approximate entropy following treatment (p < 0.05). There was also a significant decrease in cross-approximate entropy in the C3–C4 and P3–P4 connections following the intervention (p < 0.05) in a resting eyes-open condition and in the memory task condition.DiscussionIn conclusion, HD θ-tACS could alter cholinergic transmission and cortical excitability between the parietal and motor cortices, as well as reinforcing the frontoparietal network and the left-lateralization phenomenon, which may facilitate memory formation, encoding, and consolidation.

Rhythmic entrainment echoes—rhythmic brain responses that outlast rhythmic stimulation—can demonstrate endogenous neural oscillations entrained by the stimulus rhythm. Here, we tested for such echoes in auditory perception. Participants detected a pure tone target, presented at a variable delay after another pure tone that was rhythmically modulated in amplitude. In four experiments involving 154 human (female and male) participants, we tested (1) which stimulus rate produces the strongest entrainment echo and, inspired by the tonotopical organization of the auditory system and findings in nonhuman primates, (2) whether these are organized according to sound frequency. We found the strongest entrainment echoes after 6 and 8 Hz stimulation, respectively. The best moments for target detection (in phase or antiphase with the preceding rhythm) depended on whether sound frequencies of entraining and target stimuli matched, which is in line with a tonotopical organization. However, for the same experimental condition, best moments were not always consistent across experiments. We provide a speculative explanation for these differences that relies on the notion that neural entrainment and repetition-related adaptation might exercise competing opposite influences on perception. Together, we find rhythmic echoes in auditory perception that seem more complex than those predicted from initial theories of neural entrainment. [ABSTRACT FROM AUTHOR]

Non-pharmacological treatment is essential for patients with major depressive disorder (MDD) that is medication resistant or who are unable to take medications. Transcranial alternating current stimulation (tACS) is a non-invasive brain stimulation method that manipulates neural oscillations. In recent years, tACS has attracted substantial attention for its potential as an MDD treatment. This review summarizes the latest advances in tACS treatment for MDD and outlines future directions for promoting its clinical application. We first introduce the neurophysiological mechanism of tACS and its novel developments. In particular, two well-validated tACS techniques have high application potential: high-definition tACS targeting local brain oscillations and bifocal tACS modulating interarea functional connectivity. Accordingly, we summarize the underlying mechanisms of tACS modulation for MDD. We sort out the local oscillation abnormalities within the reward network and the interarea oscillatory synchronizations among multiple MDD-related networks in MDD patients, which provide potential modulation targets of tACS interventions. Furthermore, we review the latest clinical studies on tACS treatment for MDD, which were based on different modulation mechanisms and reported alleviations in MDD symptoms. Finally, we discuss the main challenges of current tACS treatments for MDD and outline future directions to improve intervention target selection, tACS implementation, and clinical validations. [ABSTRACT FROM AUTHOR]

Background: Gamma (γ) brain oscillations are dysregulated in Alzheimer's disease (AD) and can be modulated using transcranial alternating stimulation (tACS). In the present paper, we describe the rationale and design of a study assessing safety, feasibility, clinical and biological efficacy, and predictors of outcome of a home-based intervention consisting of γ-tACS over the precuneus. Methods: In a first phase, 60 AD patients will be randomized into two arms: ARM1, 8-week precuneus γ-tACS (frequency: 40 Hz, intensity: 2 mA, duration: 5 60-min sessions/week); and ARM2, 8-week sham tACS (same parameters as the real γ-tACS, with the current being discontinued 5 s after the beginning of the stimulation). In a second phase, all participants will receive 8-week γ-tACS (same parameters as the real γ-tACS in the first phase). The study outcomes will be collected at several timepoints throughout the study duration and include information on safety and feasibility, neuropsychological assessment, blood sampling, electroencephalography, transcranial magnetic stimulation neurotransmitter measures, and magnetic resonance imaging or amyloid positron emission tomography. Results: We expect that this intervention is safe and feasible and results in the improvement of cognition, entrainment of gamma oscillations, increased functional connectivity, reduction of pathological burden, and increased cholinergic transmission. Conclusions: If our expected results are achieved, home-based interventions using γ-tACS, either alone or in combination with other therapies, may become a reality for treating AD. Trial registration: PNRR-POC-2022–12376021. [ABSTRACT FROM AUTHOR]

Summary: In natural environments, plants are exposed to rapidly changing light. Maintaining photosynthetic efficiency while avoiding photodamage requires equally rapid regulation of photoprotective mechanisms. We asked what the operation frequency range of regulation is in which plants can efficiently respond to varying light.Chlorophyll fluorescence, P700, plastocyanin, and ferredoxin responses of wild‐types Arabidopsis thaliana were measured in oscillating light of various frequencies. We also investigated the npq1 mutant lacking violaxanthin de‐epoxidase, the npq4 mutant lacking PsbS protein, and the mutants crr2‐2, and pgrl1ab impaired in different pathways of the cyclic electron transport.The fastest was the PsbS‐regulation responding to oscillation periods longer than 10 s. Processes involving violaxanthin de‐epoxidase dampened changes in chlorophyll fluorescence in oscillation periods of 2 min or longer. Knocking out the PGR5/PGRL1 pathway strongly reduced variations of all monitored parameters, probably due to congestion in the electron transport. Incapacitating the NDH‐like pathway only slightly changed the photosynthetic dynamics.Our observations are consistent with the hypothesis that nonphotochemical quenching in slow light oscillations involves violaxanthin de‐epoxidase to produce, presumably, a largely stationary level of zeaxanthin. We interpret the observed dynamics of photosystem I components as being formed in slow light oscillations partially by thylakoid remodeling that modulates the redox rates. [ABSTRACT FROM AUTHOR]

• Transcranial oscillatory currents may stimulate the vestibular cortex in the range of its physiological activity (1 or 2 Hz) • Induced behavioral effects (motion sickness and postural sways) are not due to a peripheral spread of the current towards vestibular receptors. • Motion sickness represents a previously neglected possible side effect of slow-frequency tACS. The vestibular cortex is a multisensory associative region that, in neuroimaging investigations, is activated by slow-frequency (1–2 Hz) galvanic stimulation of peripheral receptors. We aimed to directly activate the vestibular cortex with biophysically modeled transcranial oscillatory current stimulation (tACS) in the same frequency range. Thirty healthy subjects and one rare patient with chronic bilateral vestibular deafferentation underwent, in a randomized, double-blind, controlled trial, to tACS at slow (1 or 2 Hz) or higher (10 Hz) frequency and sham stimulations, over the Parieto-Insular Vestibular Cortex (PIVC), while standing on a stabilometric platform. Subjective symptoms of motion sickness were scored by Simulator Sickness Questionnaire and subjects' postural sways were monitored on the platform. tACS at 1 and 2 Hz induced symptoms of motion sickness, oscillopsia and postural instability, that were supported by posturographic sway recordings. Both 10 Hz-tACS and sham stimulation on the vestibular cortex did not affect vestibular function. As these effects persisted in a rare patient with bilateral peripheral vestibular areflexia documented by the absence of the Vestibular-Ocular Reflex, the possibility of a current spread toward peripheral afferents is unlikely. Conversely, the 10 Hz-tACS significantly reduced his chronic vestibular symptoms in this patient. Weak electrical oscillations in a frequency range corresponding to the physiological cortical activity of the vestibular system may generate motion sickness and postural sways, both in healthy subjects and in the case of bilateral vestibular deafferentation. This should be taken into account as a new side effect of tACS in future studies addressing cognitive functions. Higher frequencies of stimulation applied to the vestibular cortex may represent a new interventional option to reduce motion sickness in different scenarios. [ABSTRACT FROM AUTHOR]

Abstract: There are presently no studies investigating the effects of transcranial alternating current stimulation (tACS) on complex precision sports such as golf. For the golf putt, previous electrophysiological studies indicate a connection between putt performance and EEG alpha activity. Here, we investigate whether alpha-tACS over the motor cortex improves golf putting. To this end, 15 advanced golfers each received either alpha-tACS or sham stimulation in three blocks of 50 putts before, during, and after stimulation. We measured both movement execution (repeatability) and movement result (distance control) as dependent variables. We did not find an enhancing effect of alpha-tACS on golf putting performance. [ABSTRACT FROM AUTHOR]

Transcranial alternating current stimulation (tACS) offers a unique method to temporarily manipulate the activity of the stimulated brain region in a frequency-dependent manner. However, it is not clear if repetitive modulation of ongoing oscillatory activity with tACS over multiple days can induce changes in grey matter resting-state functional connectivity and white matter structural integrity. The current study addresses this question by applying multiple-session theta band stimulation on the left dorsolateral prefrontal cortex (L-DLPFC) during arithmetic training. Fifty healthy participants (25 males and 25 females) were randomly assigned to the experimental and sham groups, half of the participants received individually adjusted theta band tACS, and half received sham stimulation. Resting-state functional magnetic resonance (rs-fMRI) and diffusion-weighted imaging (DWI) data were collected before and after 3 days of tACS-supported procedural learning training. Resting-state network analysis showed a significant increase in connectivity for the frontoparietal network (FPN) with the precuneus cortex. Seed-based analysis with a seed defined at the primary stimulation site showed an increase in connectivity with the precuneus cortex, posterior cingulate cortex (PCC), and lateral occipital cortex. There were no effects on the structural integrity of white matter tracts as measured by fractional anisotropy, and on behavioral measures. In conclusion, the study suggests that multi-session task-associated tACS can produce significant changes in resting-state functional connectivity; however, changes in functional connectivity do not necessarily translate to changes in white matter structure or behavioral performance. [ABSTRACT FROM AUTHOR]

Amnestic mild cognitive impairment (aMCI) is a predementia stage of Alzheimer's disease associated with dysfunctional episodic memory and limited treatment options. We aimed to characterize feasibility, clinical, and biomarker effects of noninvasive neurostimulation for aMCI. 13 individuals with aMCI received eight 60-minute sessions of 40-Hz (gamma) transcranial alternating current stimulation (tACS) targeting regions related to episodic memory processing. Feasibility, episodic memory, and plasma Alzheimer's disease biomarkers were assessed. Neuroplastic changes were characterized by resting-state functional connectivity (RSFC) and neuronal excitatory/inhibitory balance. Gamma tACS was feasible and aMCI participants demonstrated improvement in multiple metrics of episodic memory, but no changes in biomarkers. Improvements in episodic memory were most pronounced in participants who had the highest modeled tACS-induced electric fields and exhibited the greatest changes in RSFC. Increased RSFC was also associated with greater hippocampal excitability and higher baseline white matter integrity. This study highlights initial feasibility and the potential of gamma tACS to rescue episodic memory in an aMCI population by modulating connectivity and excitability within an episodic memory network. [ABSTRACT FROM AUTHOR]

Obsessive-compulsive disorder (OCD) is a debilitating mental health condition that is largely resistant to conventional treatments, such as pharmacotherapy and behavioural interventions. Individualized noninvasive brain stimulation techniques such as transcranial alternating current stimulation (tACS) might be capable of successfully treating OCD through modulation of dysfunctional neural circuitry. A randomized, double-blind, sham-controlled, pilot clinical trial involving 25 OCD patients was conducted to investigate the efficacy of tACS in improving OCD severity. Treatments targeting the medial prefrontal cortex (mPFC) were self-administered at home for 6 weeks with a 3-month follow-up. Within the active group, each treatment was delivered at an individualized peak alpha frequency for 30 minutes, while the sham group received 2 blocks of 2-minute treatments at 25 Hz. The clinical severity of OCD and potential symptom improvements were quantified using serial measurements of the Yale-Brown Obsessive-Compulsive Scale (YBOCS), and a linear mixed model analysis was performed to estimate the time-condition effect. There was a significant time-condition interaction in the YBOCS from baseline to 6 weeks (p < 0.0001), indicating that active alpha-tACS was significantly superior to sham in improving OCD severity. A trend-level effect remained at the 3-month follow-up, suggestive of a sustained level of improvement. Additionally, depressive symptoms also showed a significant improvement from baseline to follow-up. Our findings suggest that a six-week, home-based treatment course of individualized alpha-tACS targeting the mPFC is capable of improving OCD symptoms. Further large-scale clinical trials are required to definitively establish tACS as a therapy for OCD. [ABSTRACT FROM AUTHOR]

This study focused on the use of Non-Invasive Transcranial Alternating Current Stimulation (NITACS) to induce and map phosphenes (spark-like percepts in the visual field) in healthy individuals. The study found optimal stimulation parameters to induce reliable phosphenes without skin irritation or pain. The results suggest NITACS can be used as a tool to investigate the relationship between facial stimulation location and phosphene localization within the field of vision (FOV) and raise questions about the origin of phosphenes generated through NITACS. The outcomes of this study could serve as a source of inspiration for creating non-invasive visual aids in the future. [ABSTRACT FROM AUTHOR]

Background: Cross-frequency phase-amplitude coupling (PAC) of cortical oscillations is observed within and across cortical regions during higher-order cognitive processes. Particularly, the PAC of alpha and gamma waves in the occipital cortex is closely associated with visual perception. In theory, gamma oscillation is a neuronal representation of visual stimuli, which drives the duty cycle of visual perception together with alpha oscillation. Therefore, it is believed that the timing of entrainment in alpha-gamma PAC may play a critical role in the performance of visual perception. We hypothesized that transcranial alternating current stimulation (tACS) with gamma waves entrained at the troughs of alpha waves would enhance the dynamic visual acuity (DVA). Method: We attempted to modulate the performance of DVA by using tACS. The waveforms of the tACS were tailored to target PAC over the occipital cortex. The waveforms contained gamma (80 Hz) waves oscillating at either the peaks or troughs of alpha (10 Hz) waves. Participants performed computerized DVA task before, immediately after, and 10 min after each stimulation sessions. EEG and EOG were recorded during the DVA task to assess inter-trial phase coherence (ITPC), the alpha-gamma PAC at occipital site and the eye movements. Results: tACS with gamma waves entrained at alpha troughs effectively enhanced DVA, while the tACS with gamma waves entrained at alpha peaks did not affect DVA performance. Importantly, analyses of EEG and EOG showed that the enhancement of DVA performance originated solely from the neuromodulatory effects, and was not related to the modulation of saccadic eye movements. Consequently, DVA, one of the higher-order cognitive abilities, was successfully modulated using tACS with a tailored waveform. Conclusions: Our experimental results demonstrated that DVA performances were enhanced when tACS with gamma bursts entrained on alpha wave troughs were applied over the occipital cortex. Our findings suggest that using tACS with tailored waveforms, modulation of complex neuronal features could effectively enhance higher-order cognitive abilities such as DVA, which has never been modulated with conventional noninvasive brain stimulation methods. [ABSTRACT FROM AUTHOR]

Objective: To investigate the relationship between cortico-motor excitability and cognitive reserve (CR) in cognitively unimpaired older adults (CU) and in older adults with mild cognitive impairment or mild dementia due to Alzheimer's disease (AD). Methods: Data were collected and analyzed from 15 CU and 24 amyloid-positive AD participants aged 50-90 years. A cognitive reserve questionnaire score (CRQ) assessed education, occupation, leisure activities, physical activities, and social engagement. Cortical excitability was quantified as the average amplitude of motor evoked potentials (MEP amplitude) elicited with single-pulse transcranial magnetic stimulation delivered to primary motor cortex. A linear model compared MEP amplitudes between groups. A linear model tested for an effect of CRQ on MEP amplitude across all participants. Finally, separate linear models tested for an effect of CRQ on MEP amplitude within each group. Exploratory analyses tested for effect modification of demographics, cognitive scores, atrophy measures, and CSF measures within each group using nested regression analysis. Results: There was no between-group difference in MEP amplitude after accounting for covariates. The primary model showed a significant interaction term of group-CRQ (R2 adj = 0.18, p = 0.013), but no main effect of CRQ. Within the CU group, higher CRQ was significantly associated with lower MEP amplitude (R2 adj = 0.45, p = 0.004). There was no association in the AD group. Conclusion: Lower cortico-motor excitability is related to greater CRQ in CU, but not in AD. Lower MEP amplitudes may reflect greater neural efficiency in cognitively unimpaired older adults. The lack of association seen in AD participants may reflect disruption of the protective effects of CR. Future work is needed to better understand the neurophysiologic mechanisms leading to the protective effects of CR in older adults with and without neurodegenerative disorders. [ABSTRACT FROM AUTHOR]

Background: Sleep disturbances are highly prevalent in patients with age-related neurodegenerative diseases, which severely affect cognition and even lead to accumulated β-amyloid. Encouraging results from recent studies on transcranial direct current stimulation (tDCS) showed moderate positive effects on sleep quality in preclinical Alzheimer's disease (AD). Compared to tDCS, transcranial alternating current stimulation (tACS) enables the entrainment of neuronal activity with optimized focality through injecting electric current with a specific frequency and has significant enhancement effects on slow wave activities. Methods and design: This is a randomized, double-blind, sham-controlled clinical trial comparing 40 Hz tACS with tDCS in mild neurocognitive disorders due to AD with sleep disturbances. Magnetic resonance imaging (MRI) data is used to construct personalized realistic head model. Treatment outcomes, including sleep quality, cognitive performance and saliva Aβ levels will be conducted at baseline, 4th week, 8th week, 12th week and 24th week. Conclusions: It is expected that the repeated gamma-band tACS will show significant improvements in sleep quality and cognitive functions compared to tDCS and sham tDCS. The findings will provide high-level evidence and guide further advanced studies in the field of neurodegenerative diseases and sleep medicine. Trial registration: ClinicalTrials.gov Identifier: NCT05544201. [ABSTRACT FROM AUTHOR]

This article provides an overview of compensation strategies for gait impairments in Parkinson's disease (PD). It emphasizes the importance of non-pharmacological interventions in managing gait impairments and discusses the different categories of compensation strategies and their efficacy. The article also explores the perceptions and use of these strategies among individuals with PD and healthcare professionals. It concludes by highlighting the need for personalized gait rehabilitation in PD. The document includes disclosures and references to other relevant studies on the topic. [Extracted from the article]

Previous research has shown that some forms of non-invasive brain stimulation can increase fatigue resistance. The purpose of this study is to determine the influence of transcranial alternating current stimulation (tACS) on the time to task failure (TTF) of a precision grip task. The study utilized a randomized, double-blind, SHAM-controlled, within-subjects design. Twenty-six young adults completed two experimental sessions (tACS and SHAM) with a 7-day washout period between sessions. Each session involved a fatiguing isometric contraction of the right hand with a precision grip with either a tACS or SHAM stimulation applied to the primary motor cortex (M1) simultaneously. For the fatiguing contraction, the participants matched an isometric target force of 20% of the maximum voluntary contraction (MVC) force until task failure. Pre- and post-MVCs were performed to quantify the force decline due to fatigue. Accordingly, the dependent variables were the TTF and MVC force decline as well as the average EMG activity, force error, and standard deviation (SD) of force during the fatiguing contractions. The results indicate that there were no significant differences in any of the dependent variables between the tACS and SHAM conditions (p value range: 0.256–0.820). These findings suggest that tACS does not increase the TTF during fatiguing contractions in young adults. [ABSTRACT FROM AUTHOR]

Background: In this study, we aimed to assess the factors that predict a dysfunctional conditioned pain modulation (CPM) in chronic knee OA. Methods: This is a cross-sectional analysis of patients with chronic knee OA from a prospective cohort study in Brazil (n = 85). We performed linear and logistic multivariate regression models using the purposeful selection approach to test the relationship between the CPM in both knees (average) as a dependent variable and demographics, clinical, and neurophysiological as independent variables. Results: A significant negative association between WOMAC pain scores and CPM (β: −0.13) was found. This association was modified by the subjects' race, being stronger in the non-white subjects. In our logistic regression models, pain intensity indexed with the WOMAC pain scale remained a significant association with dichotomized CPM. Furthermore, a significant CPM association with balance, indexed with the Berg Balance score, was evidenced (β: 0.04). Neurophysiological variables showed a significant negative relationship with CPM, such as the relative power of delta oscillations in the frontal area (β: −3.11) and central area (β: −3.23). There was no significant relationship between CPM and the following domains: cognitive, emotion, sleep, opioid receptor polymorphisms, and intrinsic variables of OA disease. There was no association of CPM with TMS-indexed inhibitory markers. Conclusions: These results may indicate that less function of the pain descending inhibitory system in patients with OA is correlated with higher activity-related pain (WOMAC), less balance, and cortical plasticity especially with increased low-frequency (delta) brain oscillations. These associations seem modified by race. [ABSTRACT FROM AUTHOR]

Transcranial alternating current stimulation (TACS) is commonly used to synchronize a cortical area and its outputs to the stimulus waveform, but gathering evidence for this based on brain recordings in humans is challenging. The corticospinal tract transmits beta oscillations (∼21 Hz) from the motor cortex to tonically contracted limb muscles linearly. Therefore, muscle activity may be used to measure the level of beta entrainment in the corticospinal tract due to TACS over the motor cortex. Here, we assessed whether TACS is able to modulate the neural inputs to muscles, which would provide indirect evidence for TACS‐driven neural entrainment. In the first part of the study, we ran simulations of motor neuron (MN) pools receiving inputs from corticospinal neurons with different levels of beta entrainment. Results suggest that MNs are highly sensitive to changes in corticospinal beta activity. Then, we ran experiments on healthy human subjects (N = 10) in which TACS (at 1 mA) was delivered over the motor cortex at 21 Hz (beta stimulation), or at 7 Hz or 40 Hz (control conditions) while the abductor digiti minimi or the tibialis anterior muscle were tonically contracted. Muscle activity was measured using high‐density electromyography, which allowed us to decompose the activity of pools of motor units innervating the muscles. By analysing motor unit pool activity, we observed that none of the TACS conditions could consistently alter the spectral contents of the common neural inputs received by the muscles. These results suggest that 1 mA TACS over the motor cortex given at beta frequencies does not entrain corticospinal activity. Key points: Transcranial alternating current stimulation (TACS) is commonly used to entrain the communication between brain regions.It is challenging to find direct evidence supporting TACS‐driven neural entrainment due to the technical difficulties in recording brain activity during stimulation.Computational simulations of motor neuron pools receiving common inputs in the beta (∼21 Hz) band indicate that motor neurons are highly sensitive to corticospinal beta entrainment.Motor unit activity from human muscles does not support TACS‐driven corticospinal entrainment. [ABSTRACT FROM AUTHOR]

Cerebellar transcranial alternating current stimulation (tACS) is an emerging non-invasive technique that induces electric fields to modulate cerebellar function. Although the effect of cortical tACS seems to be state-dependent, the impact of concurrent motor activation and the duration of stimulation on the effects of cerebellar tACS has not yet been examined. In our study, 20 healthy subjects received neuronavigated 50 Hz cerebellar tACS for 40 s or 20 min, each during performance using a motor sequence learning task (MSL) and at rest. We measured the motor evoked potential (MEP) before and at two time points after tACS application to assess corticospinal excitability. Additionally, we investigated the online effect of tACS on MSL. Individual electric field simulations were computed to evaluate the distribution of electric fields, showing a focal electric field in the right cerebellar hemisphere with the highest intensities in lobe VIIb, VIII and IX. Corticospinal excitability was only increased after tACS was applied for 40 s or 20 min at rest, and motor activation during tACS (MSL) cancelled this effect. In addition, performance was better (shorter reaction times) for the learned sequences after 20 min of tACS, indicating more pronounced learning under 20 min of tACS compared to tACS applied only in the first 40 s. [ABSTRACT FROM AUTHOR]

To the best of our knowledge, neurophysiological markers indicating changes induced by non-invasive brain stimulation (NIBS) on cognitive performance, especially one of the most investigated under these procedures, working memory (WM), are little known. Here, we will briefly introduce frontal midline theta (FM-theta) oscillation (4-8 Hz) as a possible indicator for NIBS effects on WM processing. Electrophysiological recordings of FM-theta oscillation seem to originate in the medial frontal cortex and the anterior cingulate cortex, but they may be driven more subcortically. FM-theta has been acknowledged to occur during memory and emotion processing, and it has been related to WM and sustained attention. It mainly occurs in the frontal region during a delay period, in which specific information previously shown is no longer perceived and must be manipulated to allow a later (delayed) response and observed in posterior regions during information maintenance. Most NIBS studies investigating effects on cognitive performance have used n-back tasks that mix manipulation and maintenance processes. Thus, if considering FM-theta as a potential neurophysiological indicator for NIBS effects on different WM components, adequate cognitive tasks should be considered to better address the complexity of WM processing. Future research should also evaluate the potential use of FM-theta as an index of the therapeutic effects of NIBS intervention on neuropsychiatric disorders, especially those involving the ventral medial prefrontal cortex and cognitive dysfunctions. [ABSTRACT FROM AUTHOR]

Neuromodulation techniques for modulating brain activity can affect performance in a variety of behaviors. Techniques including transcranial alternating current stimulation and random noise stimulation can modulate neural oscillations. However, the intervention effect of neuromodulation approaches on motor learning is poor, partly because the electroencephalography (EEG) power spectra associated with the motor learning process has not yet been fully elucidated. Therefore, we investigated the characteristics of EEG power spectra in the process of motor learning in 15 right-handed healthy participants (5 females; mean age = 22.8 ± 3.0 years). The motor task was a ball-rotation task in which participants rotated two balls in the palm of their left hand. Participants performed a pre-test, the motor learning tasks, and a post-test. In the motor learning tasks, twenty 60 s trials were performed in the clockwise (CW) direction. Before and after the motor learning tasks, CW and counterclockwise (CCW; control condition) tasks were performed for 60 s each as pre- and post-tests. Therefore, CW direction was set as a motor learning task, while CCW was a test-only control task. EEG was recorded during the tests and tasks, and the power spectra in the alpha, beta, and gamma oscillations were calculated and compared between pre- and post-tests. The results showed that in the CW post-test, the power of the gamma band in the left parietal areas and the right frontal area was significantly higher than in the pre-test. In the CCW, there was no significant difference in each band at each area between the pre- and post-tests. Our findings reveal the characteristics of the EEG spectra related to the motor learning process. These results may help to establish more effective neuromodulation approaches to modifying neural oscillations in motor learning, including in rehabilitation fields. [ABSTRACT FROM AUTHOR]

Stroke is a central nervous system disease that causes structural lesions and functional impairments of the brain, resulting in varying types, and degrees of dysfunction. The bimodal balance-recovery model (interhemispheric competition model and vicariation model) has been proposed as the mechanism of functional recovery after a stroke. We analyzed how combinations of motor observation treatment approaches, transcranial electrical (TES) or magnetic (TMS) stimulation and peripheral electrical (PES) or magnetic (PMS) stimulation techniques can be taken as accessorial physical therapy methods on symptom reduction of stroke patients. We suggest that top-down and bottom-up stimulation techniques combined with action observation treatment synergistically might develop into valuable physical therapy strategies in neurorehabilitation after stroke. We explored how TES or TMS intervention over the contralesional hemisphere or the lesioned hemisphere combined with PES or PMS of the paretic limbs during motor observation followed by action execution have super-additive effects to potentiate the effect of conventional treatment in stroke patients. The proposed paradigm could be an innovative and adjunctive approach to potentiate the effect of conventional rehabilitation treatment, especially for those patients with severe motor deficits. [ABSTRACT FROM AUTHOR]

Introduction: One of the most important cognitive functions in our everyday life is the working memory (WM). In several neuropsychiatric diseases such as ADHD or schizophrenia WM deficits can be observed, making it an attractive target for non-invasive brain stimulation methods like transcranial electrical stimulation (tES). However, the literature shows rather heterogeneous results of tES effects on WM performance. fMRI meta-analyses have identified a WM network including frontoparietal brain areas such as the dorsolateral prefrontal cortex (DLPFC) and the posterior parietal cortex (PPC). Neurophysiological studies revealed oscillatory activity in the theta band frequency range to be of crucial functional relevance for WM processes. Based on this, transcranial alternating current stimulation (tACS) in the theta frequency range targeting DLPFC and PPC in a spatially optimized way might further improve effects of tES on WM performance. Methods: Sixteen healthy subjects were stimulated with varying stimulation settings on four different days in a counterbalanced within-subject design. These setups included the application of (1) tACS with a frequency of 5 Hz (theta frequency range) over the left DLPFC and (2) the right superior parietal cortex, (3) transcranial direct current stimulation (tDCS) of the DLPFC and (4) a sham stimulation condition during the online performance of a visual delayed-match-to-sample task with varying working memory load. We introduce a procedure to calculate an optimal tES model revealing optimized high-density setups for the present study for 3 cathodes and 1 anode and stimulation currents of 1.5 mA. Results: A significant interaction effect of stimulation type and load condition on working memory capacity was found. This was reflected by a significant improvement of WM performance in the high load condition during tACS over the left DLPFC compared with sham stimulation, which was not the case for our parietal tACS or tDCS setup. Discussion: Working memory performance can be improved with optimized high-definition tACS with a frequency of 5 Hz over the left DLPFC. The conception of different mechanisms underlying transcranial electrical stimulation with alternating and direct currents is supported by these results. Patients suffering from working memory impairments due to neuropsychiatric diseases might potentially benefit from this brain stimulation approach. [ABSTRACT FROM AUTHOR]

(1) Background: The Go/NoGo task and color-word Stroop task were used to investigate the effect of applying different frequency bands of neural oscillations to the lDLPFC on inhibitory control modulation. (2) Methods: Participants were randomly categorized into four groups and received HD-tACS at 6, 10, and 20 Hz or sham stimulation at 1.5 mA for 20 min. All participants performed a color-word Stroop task and Go/NoGo task before and immediately after the stimulation; closed-eye resting-state EEG signals were acquired for 3 min before and after the tasks. (3) Results: There were no significant differences in the Go/NoGo behavioral indices task across the four groups. In the color-word Stroop task, the Stroop effect of response time was significantly reduced by 6 and 10 Hz stimulations compared to sham stimulation, and the Stroop effect of accuracy was significantly reduced by 10 Hz stimulation. There were no significant differences in the frequency range-specific (delta, theta, alpha, beta, or gamma) resting EEG power before and after stimulation. (4) Conclusions: HD-tACS at 6 and 10 Hz effectively improved participants' performance on the color-word Stroop task, demonstrating the importance of the lDLPFC in interference inhibition and supporting a causal relationship between theta and alpha oscillations in interference inhibition. [ABSTRACT FROM AUTHOR]

Background Technology-based interventions, such as electrical brain stimulation may be effective in the cognitive and personality processes of substance abusers, including nicotine dependents. Objective We conducted this study to investigate the effectiveness of transcranial alternating current stimulation (tACS) using alpha frequency on inhibitory control and impulsivity in nicotine-dependent individuals. Methods We used a pre-test/post-test/follow-up quasi-experimental design with control and sham groups. We selected 30 eligible nicotine addicts from Mashhad using the available sampling method and randomly divided the subjects into three groups. We applied the intervention in eight sessions for 20 minutes in the dorsolateral prefrontal cortex for the first group, fake interventions for the second group, and no intervention for the third group. The Fagerström questionnaire, Barrett impulsivity questionnaire, and go-no-go task were used to collect data. After eight sessions, people’s inhibitory control and impulsivity were evaluated and analyzed using multivariate analysis of covariance (MANCOVA). Also, after two months, we evaluated inhibitory control data with repeated-measures analysis of variance. Results The effectiveness of alpha-tACS intervention on short- and long-term inhibitory control was significantly different in the experimental group compared to other groups (P=0.001). There was no significant difference between these three groups in impulsivity (P=0.700). Conclusion Alpha-tACS intervention effectively increases inhibitory control in nicotine-dependent individuals but does not explicitly affect their impulsivity. [ABSTRACT FROM AUTHOR]

Midfrontal theta activity is crucial for attentional and cognitive control. However, its causal role in facilitating visual search, particularly from the perspective of distractor inhibition, is yet to be discovered. We applied theta band transcranial alternate current stimulation (tACS) over fronto-central regions when participants searched for targets among heterogeneous distractors with foreknowledge of distractor features. The results demonstrated improved visual search performance in the theta stimulation group compared to the active sham group. Moreover, we observed the facilitation effect of the distractor cue only in participants who exhibited larger inhibition benefits, which further confirms the role of theta stimulation in precise attentional control. Taken together, our results provide compelling causal evidence for the involvement of midfrontal theta activity in memory-guided visual search. [ABSTRACT FROM AUTHOR]

Flexible changes in behavior can involve changes in the processing of external information (i.e., shifts in attention between different stimuli) or internal information (i.e., shifts in task rules stored in memory). However, it is unclear if different types of flexible change rely on separate, domain-specific neural processes or on a domain-general system, which enables flexible actions independent of the type of change needed. In the current study, participants performed a task switching procedure while we measured neural oscillations via EEG. Importantly, we independently manipulated the need to switch attention between 2 types of stimuli, as well as the need to switch between two sets of stimuli–response rules stored in memory. Both attentional and rule switches significantly increased error rates and RTs. On a neural level, both types of changes were associated with a widespread decrease in alpha power, predominantly over the parietal cortex. Attentional switches and rule switches showed a subadditive interaction effect on both participants' performance as well as on their alpha power reactivity. This indicates that implementing both changes at the same time was more efficient than implementing each individual change separately. Independent of the presence or absence of either attentional or rule switches, higher frontal theta power and lower parietal/posterior alpha power predicted faster responses on correct trials. Our study suggests that flexible behavior relies on domain-general frontal and parietal oscillatory dynamics, which enable efficient implementation of goal-directed actions independent of which aspects of the task change. [ABSTRACT FROM AUTHOR]

Objective: This article aims to use computer model tools to discuss transcranial direct current stimulation (tDCS) for clinical treatment problems, applying ROAST（realistic volumetric ⁃ approach to simulate transcranial electric stimulation）to the analysis of the influence of electrode position errors in the tDCS clinical treatment, and quantitatively analyze effects from the position offsets. Methods：This study takes F3 and F4 as an example to treat depression, simulates and calculates the electric field dose excited in the intracranial target area, compares the influence of the electrode position errors on the intracranial treatment target electric field dose, and gives the electric field dose variation curve under application of 2 mA and 4 mA current. Results：The simulation shows among 32 kinds of physical position errors, the pad electrode and the disk electrode cause the electric field dose to vary from⁃10.3% to 72.4%, -12.9% to 11.3%, both decreasing and increasing；this result is due to the non⁃uniformity of the cerebral cortex. When the electric field dose is reduced, the electric field in intracranial target area will be low than the effective electric field dose, so it is possible that the clinical treatment effect of tDCS may not be good. The simulation also shows that when 4.0 mA is applied, the intracranial target area will produce an effective electric field dose. In addition, the variation of the electric field dose generated by 32 kinds of error positions in the intracranial target area is basically the same as that when 2 mA is applied. The degree of electric field dose change is consistent with the magnitude of the applied current It’s roughly okay. The degree of electric field dose change is roughly irrelevant to the magnitude of the applied current. Conclusion：ROAST can be used to find the individual dose optimization of tDCS for clinical doctors. [ABSTRACT FROM AUTHOR]

Temporal interference stimulation (TIS) aims at targeting deep brain areas during transcranial electrical alternating current stimulation (tACS) by generating interference fields at depth. Although its modulatory effects have been demonstrated in animal and human models and stimulation studies, direct experimental evidence is lacking for its utility in humans (in vivo). Herein, we directly test and compare three different structures: firstly, we perform peripheral nerve and muscle stimulation quantifying muscle twitches as readout, secondly, we stimulate peri-orbitally with phosphene perception as a surrogate marker, and thirdly, we attempt to modulate the mean power of alpha oscillations in the occipital area as measured with electroencephalography (EEG). We found strong evidence for stimulation efficacy on the modulated frequency in the PNS, but we found no evidence for its utility in the CNS. Possible reasons for failing to activate CNS targets could be comparatively higher activation thresholds here or inhibitory stimulation components to the carrier frequency interfering with the effects of the modulated signal. [ABSTRACT FROM AUTHOR]

Essential tremor (ET) is a disabling condition resulting from a dysfunction of cerebello-thalamo-cortical circuitry. Deep brain stimulation (DBS) or lesion of the ventral-intermediate thalamic nucleus (VIM) is an effective treatment for severe ET. Transcranial cerebellar brain stimulation has recently emerged as a non-invasive potential therapeutic option. Here, we aim to investigate the effects of high-frequency non-invasive cerebellar transcranial alternating current stimulation (tACS) in severe ET patients already operated for VIM-DBS. Eleven ET patients with VIM-DBS, and 10 ET patients without VIM-DBS and matched for tremor severity, were included in this double-blind proof-of-concept controlled study. All patients received unilateral cerebellar sham-tACS and active-tACS for 10 min. Tremor severity was blindly assessed at baseline, without VIM-DBS, during sham-tACS, during and at 0, 20, 40 min after active-tACS, using kinetic recordings during holding posture and action ('nose-to-target') task and videorecorded Fahn-Tolosa-Marin (FTM) clinical scales. In the VIM-DBS group, active-tACS significantly improved both postural and action tremor amplitude and clinical (FTM scales) severity, relative to baseline, whereas sham-tACS did not, with a predominant effect for the ipsilateral arm. Tremor amplitude and clinical severity were also not significantly different between ON VIM-DBS and active-tACS conditions. In the non-VIM-DBS group, we also observed significant improvements in ipsilateral action tremor amplitude, and clinical severity after cerebellar active-tACS, with a trend for improved postural tremor amplitude. In non-VIM-DBS group, sham- active-tACS also decreased clinical scores. These data support the safety and potential efficacy of high-frequency cerebellar-tACS to reduce ET amplitude and severity. [ABSTRACT FROM AUTHOR]

Motor imagery (MI), as a cognitive motor process, involves the coordinated activation of frontal and parietal cortices and has been widely studied as an effective way to improve motor functions. However, there are large inter-individual differences in MI performance, with many subjects unable to elicit sufficiently reliable MI brain patterns. It has been shown that dual-site transcranial alternating current stimulation (tACS) applied on two brain sites can modulate functional connectivity between the targeted regions. Here, we investigated whether electrically stimulating frontal and parietal regions using dual-site tACS at mu frequency will modulate motor imagery performance. Thirty-six healthy participants were recruited and randomly divided into in-phase (0° lag), anti-phase (180° lag) and sham stimulation group. All groups performed the simple (grasping movement) and complex (writing movement) motor imagery tasks before and after tACS. Simultaneously collected EEG data showed that the event-related desynchronization (ERD) of mu rhythm and classification accuracy during complex task were significantly improved after anti-phase stimulation. In addition, anti-phase stimulation resulted in decreased event-related functional connectivity between regions within frontoparietal network in the complex task. In contrast, no beneficial after-effects of anti-phase stimulation were found in the simple task. These findings suggest that dual-site tACS effects on MI dependent on the phase lag of the stimulation and the complexity of the task. Anti-phase stimulation applied to the frontoparietal regions is a promising way to foster demanding MI task.

Abstract Background A frequent post stroke disorder in lateralized attention is visuospatial neglect (VSN). As VSN has a strong negative impact on recovery in general and independence during daily life, optimal treatment is deemed urgent. Next to traditional stroke treatment, non-invasive brain stimulation offers the potential to facilitate stroke recovery as a complementary approach. In the present study, visual scanning training (VST; the current conventional treatment) will be combined with transcranial alternating current stimulation (tACS) to evaluate the additive effects of repeated sessions of tACS in combination with six-weeks VST rehabilitation. Methods In this double-blind randomized placebo-controlled intervention study (RCT), we will compare the effects of active tACS plus VST to sham (placebo) tACS plus VST, both encompassing 18 VST training sessions, 40 minutes each, during 6 weeks. Chronic stroke patients with VSN (> 6 months post-stroke onset) are considered eligible for study participation. In total 22 patients are needed for the study. The primary outcome is change in performance on a cancellation task. Secondary outcomes are changes in performance on a visual detection task, two line bisection tasks, and three measures to assess changes in activities of daily living. Assessment is at baseline, directly after the first and ninth training session, after the last training session (post training), and 1 week and 3 months after termination of the training (follow-up). Discussion If effective, a tACS-VST rehabilitation program could be implemented as a treatment option for VSN. Trial registration ClinicalTrials.gov ; registration number: NCT05466487; registration date: July 18, 2022 retrospectively registered; https://clinicaltrials.gov/ct2/show/NCT05466487

Background: Over 55 million people worldwide are currently diagnosed with Alzheimer's disease (AD) and live with debilitating episodic memory deficits. Current pharmacological treatments have limited efficacy. Recently, transcranial alternating current stimulation (tACS) has shown memory improvement in AD by normalizing high-frequency neuronal activity. Here we investigate the feasibility, safety, and preliminary effects on episodic memory of an innovative protocol where tACS is administered within the homes of older adults with AD with the help of a study companion (HB-tACS). Methods: Eight participants diagnosed with AD underwent multiple consecutive sessions of high-definition HB-tACS (40 Hz, 20-min) targeting the left angular gyrus (AG), a key node of the memory network. The Acute Phase comprised 14-weeks of HB-tACS with at least five sessions per week. Three participants underwent resting state electroencephalography (EEG) before and after the 14-week Acute Phase. Subsequently, participants completed a 2-3-month Hiatus Phase not receiving HB-tACS. Finally, in the Taper phase, participants received 2-3 sessions per week over 3-months. Primary outcomes were safety, as determined by the reporting of side effects and adverse events, and feasibility, as determined by adherence and compliance with the study protocol. Primary clinical outcomes were memory and global cognition, measured with the Memory Index Score (MIS) and Montreal Cognitive Assessment (MoCA), respectively. Secondary outcome was EEG theta/gamma ratio. Results reported as mean ± SD. Results: All participants completed the study, with an average of 97 HB-tACS sessions completed by each participant; reporting mild side effects during 25% of sessions, moderate during 5%, and severe during 1%. Acute Phase adherence was 98 ± 6.8% and Taper phase was 125 ± 22.3% (rates over 100% indicates participants completed more than the minimum of 2/week). After the Acute Phase, all participants showed memory improvement, MIS of 7.25 ± 3.77, sustained during Hiatus 7.00 ± 4.90 and Taper 4.63 ± 2.39 Phases compared to baseline. For the three participants that underwent EEG, a decreased theta/gamma ratio in AG was observed. Conversely, participants did not show improvement in the MoCA, 1.13 ± 3.80 after the Acute Phase, and there was a modest decrease during the Hiatus -0.64 ± 3.28 and Taper -2.56 ± 5.03 Phases. Conclusion: This pilot study shows that the home-based, remotely-supervised, study companion administered, multi-channel tACS protocol for older adults with AD was feasible and safe. Further, targeting the left AG, memory in this sample was improved. These are preliminary results that warrant larger more definite trials to further elucidate tolerability and efficacy of the HB-tACS intervention. NCT04783350. Clinical trial registration: https://clinicaltrials.gov/ct2/show/NCT04783350? term=NCT04783350&draw=2&rank=1, identifier NCT04783350. [ABSTRACT FROM AUTHOR]

Attention focus affects performance in postural control while standing, and it is divided into internal focus (IF) and external focus (EF). Each individual has a predominant attention focus, and research has revealed that the dominance of attention focus may be an acquired trait. However, the impact of non-invasive brain stimulation on attention-focus dominance remains unexplored in the current literature. Here, we examined the effect of high-definition transcranial alternating current stimulation (HD-tACS) on θ waves in the anterior cingulate cortex (ACC) on standing postural control tasks in an EF condition for IF- and EF-dominant groups. The effect of θ HD-tACS on the ACC differed between IF- and EF-dominant groups, and θ HD-tACS in the IF-dominant group decreased the performance of standing postural control under the EF condition. The forced activation of the ACC with θ HD-tACS may have conversely reduced the activity of brain regions normally activated by the IF-dominant group. Additionally, the activation of ACC prioritized visual information processing and suppressed the superficial sensory processing that is normally potentially prioritized by the IF-dominant group. These results highlight the importance of changing the type of rehabilitation and sports training tasks to account for the individual's dominance of attention focus. [ABSTRACT FROM AUTHOR]

Information integration in the brain requires functional connectivity between local neural networks. Here, we investigated the interregional coupling mechanism from the viewpoint of oscillations using optical recording methods. Low-frequency electrical stimulation of rat neocortical slices in a caffeine-containing medium induced oscillatory activity between the primary visual cortex (Oc1) and medial secondary visual cortex (Oc2M), in which the oscillation generator was located in the Oc2M and was triggered by a feedforward signal. During to-and-fro oscillatory activity, neural excitation was marked in layer II/III. When the upper layer was disrupted between Oc1 and Oc2M, feedforward signals could propagate through the deep layer and switch on the oscillator in the Oc2M. When the lower layer was disrupted between Oc1 and Oc2M, feedforward signals could propagate through the upper layer and switch on the oscillator in the Oc2M. In the backward direction, neither the upper layer cut nor the lower layer cut disrupted the propagation of the oscillations. In all cases, the horizontal and vertical pathways were used as needed. Fluctuations in the oscillatory waveforms of the local field potential at the upper and lower layers in the Oc2M were reversed, suggesting that the oscillation originated between the two layers. Thus, the neocortex may work as a safety device for interregional communications in an alternative way to drive voltage oscillators in the neocortex. • Caffeine-assisted oscillations are composed of initial propagation and backward propagation between the Oc2M to Oc1. • Neural oscillator is equipped in the Oc2M. • Roles of upper- and lower-layer pathways as well as vertical pathways are conveying signals safely as needed. • Vertical columns might form neural oscillator, and upper layer may work as a booster for signal delivery. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is Available in the Text. Alpha-transcranial alternating current stimulation of the unilateral sensorimotor region attenuated cortical processing of pain within bilateral sensorimotor regions as well as sensorimotor functional connectivity. Transcranial alternating current stimulation (tACS) is believed to modulate brain oscillations in a frequency-specific manner. Given the correlation between sensorimotor α-oscillations and pain perception, tACS that targets sensorimotor α-oscillations has the potential to reduce pain. Therefore, this study sought to determine the aftereffects of α-tACS over unilateral primary sensorimotor cortex (SM1) on the perceptual and neural responses to noxious painful stimulation of the contralateral hand. Using a double-blinded and sham-controlled design, 60 healthy participants were recruited to receive either α-tACS or sham stimulation of unilateral SM1 through an electrode montage in a 4 × 1 ring configuration. Neural responses to laser nociceptive stimuli were assessed using functional magnetic resonance imaging immediately before and after α-tACS intervention. Perceptual reports were recorded simultaneously. Compared with sham stimulation, α-tACS attenuated bilateral SM1 responses to painful stimuli delivered to the contralateral hand. Although α-tACS did not exert direct effect on subjective pain perception, it can indirectly decrease ratings of pain perception by reducing brain activity within the targeted SM1. Moreover, α-tACS decreased the functional connectivity between the targeted SM1 and a network of regions that are crucially involved in pain processing, including the middle cingulate cortex, contralateral somatosensory cortex, and dorsolateral prefrontal cortex. These results demonstrated that after α-tACS applied over the unilateral SM1 does attenuate subsequent neural processing of pain within bilateral sensorimotor regions as well as sensorimotor functional connectivity. The findings provide evidence that sensorimotor α-oscillations directly affect pain processing and support the application of sensorimotor α-tACS for inducing pain analgesia. [ABSTRACT FROM AUTHOR]

Confirmation of the exact voluntary movements of patients with disorder of consciousness following severe traumatic brain injury (TBI) is difficult because of the associated communication disturbances. In this pilot study, we investigated whether regional brain glucose metabolism assessed by 18F‐fluorodeoxyglucose positron emission tomography (FDG‐PET) at rest could predict voluntary movement in severe TBI patients, particularly those with sufficient upper limb capacity to use communication devices. We visually and verbally instructed patients to clasp or open their hands. After video capture, three independent rehabilitation therapists determined whether the patients' movements were voluntary or involuntary. The results were compared with the standardized uptake value in the primary motor cortex, referring to the Penfield's homunculus, by resting state by FDG‐PET imaged 1 year prior. Results showed that glucose uptake in the left (p = 0.0015) and right (p = 0.0121) proximal limb of the primary motor cortex, based on Penfield's homunculus on cerebral cartography, may reflect contralateral voluntary movement. Receiver operating characteristic curve analysis showed that a mean cutoff standardized uptake value of 5.47 ± 0.08 provided the best sensitivity and specificity for differentiating between voluntary and involuntary movements in each area. FDG‐PET may be a useful and robust biomarker for predicting long‐term recovery of motor function in severe TBI patients with disorders of consciousness. [ABSTRACT FROM AUTHOR]

• Sevoflurane diffusely augmented intraoperative high-frequency oscillation (HFO) effective connectivity, yet most in the epileptogenic zone. • Intraoperative HFO effective connectivity best classified the epileptogenic sites at sevoflurane 2 MAC. • HFO effective connectivity can be visualized on major white matter pathways, as a function of sevoflurane concentration. To determine how sevoflurane anesthesia modulates intraoperative epilepsy biomarkers on electrocorticography, including high-frequency oscillation (HFO) effective connectivity (EC), and to investigate their relation to epileptogenicity and anatomical white matter. We studied eight pediatric drug-resistant focal epilepsy patients who achieved seizure control after invasive monitoring and resective surgery. We visualized spatial distributions of the electrocorticography biomarkers at an oxygen baseline, three time-points while sevoflurane was increasing, and at a plateau of 2 minimum alveolar concentration (MAC) sevoflurane. HFO EC was combined with diffusion-weighted imaging, in dynamic tractography. Intraoperative HFO EC diffusely increased as a function of sevoflurane concentration, although most in epileptogenic sites (defined as those included in the resection); their ability to classify epileptogenicity was optimized at sevoflurane 2 MAC. HFO EC could be visualized on major white matter tracts, as a function of sevoflurane level. The results strengthened the hypothesis that sevoflurane-activated HFO biomarkers may help intraoperatively localize the epileptogenic zone. Our results help characterize how HFOs at non-epileptogenic and epileptogenic networks respond to sevoflurane. It may be warranted to establish a normative HFO atlas incorporating the modifying effects of sevoflurane and major white matter pathways, as critical reference in epilepsy presurgical evaluation. [ABSTRACT FROM AUTHOR]

Objective: We investigated changes in cortico--subcortical spatiotemporal dynamics to explore the treatment mechanisms of transcranial alternating current stimulation (tACS) in patients with Parkinson's disease (PD). Methods: Resting-state functional magnetic resonance imaging (rs-fMRI) data were collected from 20 patients with PD and 20 normal controls (NC). Each patient with PD received successive multidisciplinary intensive rehabilitation treatment and tACS treatment over a one-year interval. Individual functional brain network mapping and co-activation pattern (CAP) analysis were performed to characterize cortico--subcortical dynamics. Results: The same tACS electrode placement stimulated different proportions of functional brain networks across the participants. CAP analysis revealed that the visual network, attentional network, and default mode network co-activated with the thalamus, accumbens, and amygdala, respectively. The pattern characterized by the de-activation of the visual network and the activation of the thalamus showed a significantly low amplitude in the patients with PD than in NCs, and this amplitude increased after tACS treatment. Furthermore, the co-occurrence of cortico--subcortical CAPs was significantly higher in patients with PD than in NCs and decreased after tACS treatment. Conclusions: This study investigated cortico--subcortical spatiotemporal dynamics in patients with PD and further revealed the tACS treatment mechanism. These findings contribute to understanding cortico-- subcortical dynamics and exploring noninvasive neuromodulation targets of cortico--ubcortical circuits in brain diseases, such as PD, Alzheimer's disease, and depression. [ABSTRACT FROM AUTHOR]

Transcranial alternating current stimulation (tACS) has attracted interest as a technique for causal investigations into how rhythmic fluctuations in brain neural activity influence cognition and for promoting cognitive rehabilitation. We conducted a systematic review and meta-analysis of the effects of tACS on cognitive function across 102 published studies, which included 2893 individuals in healthy, aging, and neuropsychiatric populations. A total of 304 effects were extracted from these 102 studies. We found modest to moderate improvements in cognitive function with tACS treatment that were evident in several cognitive domains, including working memory, long-term memory, attention, executive control, and fluid intelligence. Improvements in cognitive function were generally stronger after completion of tACS ("offline" effects) than during tACS treatment ("online" effects). Improvements in cognitive function were greater in studies that used current flow models to optimize or confirm neuromodulation targets by stimulating electric fields generated in the brain by tACS protocols. In studies targeting multiple brain regions concurrently, cognitive function changed bidirectionally (improved or decreased) according to the relative phase, or alignment, of the alternating current in the two brain regions (in phase versus antiphase). We also noted improvements in cognitive function separately in older adults and in individuals with neuropsychiatric illnesses. Overall, our findings contribute to the debate surrounding the effectiveness of tACS for cognitive rehabilitation, quantitatively demonstrate its potential, and indicate further directions for optimal tACS clinical study design. Editor's summary: Transcranial alternating current stimulation (tACS) is a technique for modulating electrical activity in the human brain. In a meta-analysis of 102 published studies that included 2893 individuals in healthy, aging, and neuropsychiatric populations treated with tACS, Grover et al. report improvements in various types of cognitive function, including working memory, long-term memory, attention, executive control, and fluid intelligence. This meta-analysis suggests that tACS has potential for improving cognition, but further studies are needed to confirm this finding. —Orla Smith [ABSTRACT FROM AUTHOR]

Binaural beats are an auditory phenomenon that occurs when two tones of different frequencies, which are presented separately to each ear, elicit the sensation of a third tone oscillating at the difference frequency of the two tones. Binaural beats can be perceived in the frequency range of about 1–30 Hz, a range that coincides with the main human EEG frequency bands. The brainwave entrainment hypothesis, which assumes that external stimulation at a certain frequency leads to the brain's electrocortical activity oscillating at the same frequency, provides the basis for research on the effects of binaural beat stimulation on cognitive and affective states. Studies, particularly in more applied fields, usually refer to neuroscientific research demonstrating that binaural beats elicit systematic changes in EEG parameters. At first glance, however, the available literature on brainwave entrainment effects due to binaural beat stimulation appears to be inconclusive at best. The aim of the present systematic review is, thus, to synthesize existing empirical research. A sample of fourteen published studies met our criteria for inclusion. The results corroborate the impression of an overall inconsistency of empirical outcomes, with five studies reporting results in line with the brainwave entrainment hypothesis, eight studies reporting contradictory, and one mixed results. What is to be noticed is that the fourteen studies included in this review were very heterogeneous regarding the implementation of the binaural beats, the experimental designs, and the EEG parameters and analyses. The methodological heterogeneity in this field of study ultimately limits the comparability of research outcomes. The results of the present systematic review emphasize the need for standardization in study approaches so as to allow for reliable insight into brainwave entrainment effects in the future. [ABSTRACT FROM AUTHOR]

Video game players' faster speed of information processing has been shown to coincide with altered posterior alpha power modulation, that is, brain oscillatory activity around 10 Hz. Thus, it was proposed that improved cognitive processing in video game players may be related to differential alpha activity. However, a causal relationship thereof has not yet been established. We addressed this by conducting a non‐invasive brain stimulation study to demonstrate that modulating alpha power using transcranial alternating current stimulation (tACS) may impact on speed of information processing. Furthermore, we aimed to show that this effect correlated with altered attentional control, for example, visuospatial attention and/or top‐down control processing, given that this has been suggested to contribute to video gaming effects. Therefore, we recruited 19 non‐video game players to undergo one of five brain stimulation conditions while performing a visual short‐term memory task at five different days, respectively. Thus, we applied tACS either at 10 Hz (alpha frequency) or at 16.18 Hz (control frequency) either over their left or right posterior parietal cortex (PPC) or a sham stimulation. Individuals' speed of information processing, visuospatial attention and top‐down control processing were operationalised using a computational modelling approach based on the theory of visual attention. We found that alpha‐tACS applied over individuals' left PPC altered their visuospatial attention orientation but not their speed of information processing. Thus, we were not able to establish a causal relationship between speed of information processing and altered visuospatial attention processing through alpha power modulation using non‐invasive brain stimulation. [ABSTRACT FROM AUTHOR]

Background: Cerebellar ataxia (CA) is a movement disorder that can affect balance and gait, limb movement, oculomotor control, and cognition. Multiple system atrophy-cerebellar type (MSA-C) and spinocerebellar ataxia type 3 (SCA3) are the most common forms of CA, for which no effective treatment is currently available. Transcranial alternating current stimulation (tACS) is a noninvasive method of brain stimulation supposed to alter cortical excitability and brain electrical activity, modulating functional connectivity within the brain. The cerebellar tACS can modulate the cerebellar outflow and cerebellum-linked behavior and it is a proven safe technique for humans. Therefore, the aim of this study is to 1) examine whether cerebellar tACS improves ataxia severity and various non-motor symptoms in a homogeneous cohort of CA patients consisting of MSA-C and SCA3, 2) explore the time course of these effects, and 3) assess the safety and tolerance of cerebellar tACS in all participants. Methods/design: This is a 2-week, triple-blind, randomised, sham-controlled study. 164 patients (MSA-C: 84, SCA3: 80) will be recruited and randomly assigned to either active cerebellar tACS or sham cerebellar tACS, in a 1:1 ratio. Patients, investigators, and outcome assessors are unaware of treatment allocation. Cerebellar tACS (40 min, 2 mA, ramp-up and down periods of 10s each) will be delivered over 10 sessions, distributed in two groups of five consecutive days with a two-day break in between. Outcomes are assessed after the tenth stimulation (T1), and after 1 month (T2) and 3 months (T3). The primary outcome measure is the difference between the active and sham groups in the proportion of patients with an improvement of 1.5 points in the Scale for the Assessment and Rating of Ataxia (SARA) score after 2 weeks of treatment. In addition, effects on a variety of non-motor symptoms, quality of life, and autonomic nerve dysfunctions are assessed via relative scales. Gait imbalance, dysarthria, and finger dexterity are objectively valued via relative tools. Finally, functional magnetic resonance imaging is performed to explore the possible mechanism of treatment effects. Discussion: The results of this study will inform whether repeated sessions of active cerebellar tACS benefit CA patients and whether this form of non-invasive stimulation might be a novel therapeutic approach to consider in a neurorehabilitation setting. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT05557786; https://www.clinicaltrials.gov/ct2/show/NCT05557786. [ABSTRACT FROM AUTHOR]