Exploring the correlation and causation between alpha oscillations and one-second time perception through EEG and tACS.

Alpha oscillations have been implicated in time perception, yet a consensus on their precise role remains elusive. This study directly investigates this relationship by examining the impact of alpha oscillations on time perception. Resting-state EEG recordings were used to extract peak alpha frequency (PAF) and peak alpha power (PAP) characteristics. Participants then performed a time generalization task under transcranial alternating current stimulation (tACS) at frequencies of PAF-2, PAF, and PAF+2, as well as a sham condition. Results revealed a significant correlation between PAP and accuracy, and between PAF and precision of one-second time perception in the sham condition. This suggests that alpha oscillations may influence one-second time perception by modulating their frequency and power. Interestingly, these correlations weakened with real tACS stimulations, particularly at higher frequencies. A second analysis aimed to establish a causal relationship between alpha peak modulation by tACS and time perception using repeated measures ANOVAs, but no significant effect was observed. Results were interpreted according to the state-dependent networks and internal clock model.

The effects of prefrontal tDCS and hf-tRNS on the processing of positive and negative emotions evoked by video clips in first- and third-person.

The causal role of the cerebral hemispheres in positive and negative emotion processing remains uncertain. The Right Hemisphere Hypothesis proposes right hemispheric superiority for all emotions, while the Valence Hypothesis suggests the left/right hemisphere's primary involvement in positive/negative emotions, respectively. To address this, emotional video clips were presented during dorsolateral prefrontal cortex (DLPFC) electrical stimulation, incorporating a comparison of tDCS and high frequency tRNS stimulation techniques and manipulating perspective-taking (first-person vs third-person Point of View, POV). Four stimulation conditions were applied while participants were asked to rate emotional video valence: anodal/cathodal tDCS to the left/right DLPFC, reverse configuration (anodal/cathodal on the right/left DLPFC), bilateral hf-tRNS, and sham (control condition). Results revealed significant interactions between stimulation setup, emotional valence, and POV, implicating the DLPFC in emotions and perspective-taking. The right hemisphere played a crucial role in both positive and negative valence, supporting the Right Hemisphere Hypothesis. However, the complex interactions between the brain hemispheres and valence also supported the Valence Hypothesis. Both stimulation techniques (tDCS and tRNS) significantly modulated results. These findings support both hypotheses regarding hemispheric involvement in emotions, underscore the utility of video stimuli, and emphasize the importance of perspective-taking in this field, which is often overlooked.

Tailoring transcranial alternating current stimulation based on endogenous event-related P3 to modulate premature responses: a feasibility study.

Background: Transcranial alternating current stimulation (tACS) is a brain stimulation method for modulating ongoing endogenous oscillatory activity at specified frequency during sensory and cognitive processes. Given the overlap between event-related potentials (ERPs) and event-related oscillations (EROs), ERPs can be studied as putative biomarkers of the effects of tACS in the brain during cognitive/sensory task performance. Objective: This preliminary study aimed to test the feasibility of individually tailored tACS based on individual P3 (latency and frequency) elicited during a cued premature response task. Thus, tACS frequency was individually tailored to match target-P3 ERO for each participant. Likewise, the target onset in the task was adjusted to match the tACS phase and target-P3 latency. Methods: Twelve healthy volunteers underwent tACS in two separate sessions while performing a premature response task. Target-P3 latency and ERO were calculated in a baseline block during the first session to allow a posterior synchronization between the tACS and the endogenous oscillatory activity. The cue and target-P3 amplitudes, delta/theta ERO, and power spectral density (PSD) were evaluated pre and post-tACS blocks. Results: Target-P3 amplitude significantly increased after activetACS, when compared to sham. Evoked-delta during cue-P3 was decreased after tACS. No effects were found for delta ERO during target-P3 nor for the PSD and behavioral outcomes. Conclusion: The present findings highlight the possible effect of phase synchronization between individualized tACS parameters and endogenous oscillatory activity, which may result in an enhancement of the underlying process (i.e., an increase of target-P3). However, an unsuccessful synchronization between tACS and EEG activity might also result in a decrease in the evoked-delta activity during cue-P3. Further studies are needed to optimize the parameters of endogenous activity and tACS synchronization. The implications of the current results for future studies, including clinical studies, are further discussed since transcranial alternating current stimulation can be individually tailored based on endogenous event-related P3 to modulate responses.

Computer-aided cognitive training combined with tDCS can improve post-stroke cognitive impairment and cerebral vasomotor function: a randomized controlled trial.

BACKGROUND: Post-stroke cognitive impairment (PSCI) is the focus and difficulty of poststroke rehabilitation intervention with an incidence of up to 61%, which may be related to the deterioration of cerebrovascular function. Computer-aided cognitive training (CACT) can improve cognitive function through scientific training targeting activated brain regions, becoming a popular training method in recent years. Transcranial direct current stimulation (tDCS), a non-invasive brain stimulation technique, can regulate the cerebral vascular nerve function, and has an effect on the rehabilitation of cognitive dysfunction after stroke. This study examined the effectiveness of both CACT and tDCS on cognitive and cerebrovascular function after stroke, and explored whether CACT combined with tDCS was more effective. METHODS: A total of 72 patients with PSCI were randomly divided into the conventional cognitive training (CCT) group (n = 18), tDCS group (n = 18), CACT group (n = 18), and CACT combined with tDCS group (n = 18). Patients in each group received corresponding 20-minute treatment 15 times a week for 3 consecutive weeks. Montreal Cognitive Assessment (MoCA) and the Instrumental Activities of Daily Living Scale (IADL) were used to assess patients' cognitive function and the activities of daily living ability. Transcranial Doppler ultrasound (TCD) was used to assess cerebrovascular function, including cerebral blood flow velocity (CBFV), pulse index (PI), and breath holding index (BHI). These outcome measures were measured before and after treatment. RESULTS: Compared with those at baseline, both the MoCA and IADL scores significantly increased after treatment (P < 0.01) in each group. There was no significantly difference in efficacy among CCT, CACT and tDCS groups. The CACT combined with tDCS group showed greater improvement in MoCA scores compared with the other three groups (P < 0.05), especially in the terms of visuospatial and executive. BHI significantly improved only in CACT combined with tDCS group after treatment (p ≤ 0.05) but not in the other groups. Besides, no significant difference in CBFV or PI was found before and after the treatments in all groups. CONCLUSION: Both CACT and tDCS could be used as an alternative to CCT therapy to improve cognitive function and activities of daily living ability after stroke. CACT combined with tDCS may be more effective improving cognitive function and activities of daily living ability in PSCI patients, especially visuospatial and executive abilities, which may be related to improved cerebral vasomotor function reflected by the BHI. TRIAL REGISTRATION NUMBER: The study was registered in the Chinese Registry of Clinical Trials (ChiCTR2100054063). Registration date: 12/08/2021.

Effect of transcranial direct current stimulation combined with transcutaneous auricular vagus nerve stimulation on poststroke cognitive impairment: a study protocol for a randomised controlled trial.

INTRODUCTION: Poststroke cognitive impairment is a common complication in stroke survivors, seriously affecting their quality of life. Therefore, it is crucial to improve cognitive function of patients who had a stroke. Transcranial direct current stimulation (tDCS) and transcutaneous auricular vagus nerve stimulation (taVNS) are non-invasive, safe treatments with great potential to improve cognitive function in poststroke patients. However, further improvements are needed in the effectiveness of a single non-invasive brain stimulation technique for cognitive rehabilitation. This study protocol aims to investigate the effect and neural mechanism of the combination of tDCS and taVNS on cognitive function in patients who had a stroke. METHODS AND ANALYSIS: In this single-centre, prospective, parallel, randomised controlled trial, a total of 66 patients with poststroke cognitive impairment will be recruited and randomly assigned (1:1:1) to the tDCS group, the taVNS group and the combination of tDCS and taVNS group. Each group will receive 30 min of treatment daily, five times weekly for 3 weeks. Primary clinical outcome is the Montreal Cognitive Assessment. Secondary clinical outcomes include the Mini-Mental State Examination, Stroop Colour Word Test, Trail Marking Test, Symbol Digit Modalities Test and Modified Barthel Index. All clinical outcomes, functional MRI and diffusion tensor imaging will be measured at preintervention and postintervention. ETHICS AND DISSEMINATION: The trial has been approved by the Ethics Committee of the First Affiliated Hospital of Yangtze University (approval no: KY202390). The results will be submitted for publication in peer-reviewed journals or at scientific conferences. TRIAL REGISTRATION NUMBER: ChiCTR2300076632.

Transcranial direct current stimulation is more effective than pregabalin in controlling nociceptive and anxiety-like behaviors in a rat fibromyalgia-like model.

OBJECTIVES: Despite the fact that fibromyalgia, a widespread disease of the musculoskeletal system, has no specific treatment, patients have shown improvement after pharmacological intervention. Pregabalin has demonstrated efficacy; however, its adverse effects may reduce treatment adherence. In this context, neuromodulatory techniques such as transcranial direct current stimulation (tDCS) may be employed as a complementary pain-relieving method. Consequently, the purpose of this study was to evaluate the effect of pregabalin and tDCS treatments on the behavioral and biomarker parameters of rats submitted to a fibromyalgia-like model. METHODS: Forty adult male Wistar rats were divided into two groups: control and reserpine. Five days after the end of the administration of reserpine (1 mg/kg/3 days) to induce a fibromyalgia-like model, rats were randomly assigned to receive either vehicle or pregabalin (30 mg/kg) along with sham or active- tDCS treatments. The evaluated behavioral parameters included mechanical allodynia by von Frey test and anxiety-like behaviors by elevated plus-maze test (time spent in opened and closed arms, number of entries in opened and closed arms, protected head-dipping, unprotected head-dipping [NPHD], grooming, rearing, fecal boluses). The biomarker analysis (brain-derived neurotrophic factor [BDNF] and tumor necrosis factor-α [TNF-α]) was performed in brainstem and cerebral cortex and in serum. RESULTS: tDCS reversed the reduction in the mechanical nociceptive threshold and the decrease in the serum BDNF levels induced by the model of fibromyalgia; however, there was no effect of pregabalin in the mechanical threshold. There were no effects of pregabalin or tDCS found in TNF-α levels. The pain model induced an increase in grooming time and a decrease in NPHD and rearing; while tDCS reversed the increase in grooming, pregabalin reversed the decrease in NPHD. CONCLUSIONS: tDCS was more effective than pregabalin in controlling nociception and anxiety-like behavior in a rat model-like fibromyalgia. Considering the translational aspect, our findings suggest that tDCS could be a potential non-pharmacological treatment for fibromyalgia.

The Application of tDCS to Treat Pain and Psychocognitive Symptoms in Cancer Patients: A Scoping Review.

Background: The use of transcranial direct current stimulation (tDCS) to modulate pain, psychological aspects, and cognitive functions has increased in recent years. The present scoping review aims to investigate the use of tDCS in cancer patients and its significant impact on psychocognitive and pain related symptoms. Methods: From the earliest available date to June 2023, a comprehensive search was conducted in three electronic scientific databases-PubMed, Scopus, and Embase-and other supplementary sources. Ten relevant studies were identified and included, comprising single case studies, randomized controlled trials, pilot studies, and one retrospective study. PRISMA guidelines for scoping reviews were followed. Results: These studies investigated the use of tDCS to improve pain and psychocognitive aspects in patients with various types of cancer, including breast, oral, bladder, lung, pancreatic, head and neck cancer, hepatocellular carcinoma, and meningioma. Overall, the results suggest that tDCS has shown efficacy in relieving pain, reducing anxiety and depression, and improving cognitive function in cancer patients. Conclusion: Due to the limited number and high heterogeneity of the existing literature in this field, more investigation and the establishment of standardized protocols would be required to obtain more conclusive evidence.

Improving SSVEP-BCI Performance Through Repetitive Anodal tDCS-Based Neuromodulation: Insights From Fractal EEG and Brain Functional Connectivity.

This study embarks on a comprehensive investigation of the effectiveness of repetitive transcranial direct current stimulation (tDCS)-based neuromodulation in augmenting steady-state visual evoked potential (SSVEP) brain-computer interfaces (BCIs), alongside exploring pertinent electroencephalography (EEG) biomarkers for assessing brain states and evaluating tDCS efficacy. EEG data were garnered across three distinct task modes (eyes open, eyes closed, and SSVEP stimulation) and two neuromodulation patterns (sham-tDCS and anodal-tDCS). Brain arousal and brain functional connectivity were measured by extracting features of fractal EEG and information flow gain, respectively. Anodal-tDCS led to diminished offsets and enhanced information flow gains, indicating improvements in both brain arousal and brain information transmission capacity. Additionally, anodal-tDCS markedly enhanced SSVEP-BCIs performance as evidenced by increased amplitudes and accuracies, whereas sham-tDCS exhibited lesser efficacy. This study proffers invaluable insights into the application of neuromodulation methods for bolstering BCI performance, and concurrently authenticates two potent electrophysiological markers for multifaceted characterization of brain states.

HD-tDCS mitigates the executive vigilance decrement only under high cognitive demands.

Maintaining vigilance is essential for many everyday tasks, but over time, our ability to sustain it inevitably decreases, potentially entailing severe consequences. High-definition transcranial direct current stimulation (HD-tDCS) has proven to be useful for studying and improving vigilance. This study explores if/how cognitive load affects the mitigatory effects of HD-tDCS on the vigilance decrement. Participants (N = 120) completed a modified ANTI-Vea task (single or dual load) while receiving either sham or anodal HD-tDCS over the right posterior parietal cortex (rPPC). This data was compared with data from prior studies (N = 120), where participants completed the standard ANTI-Vea task (triple load task), combined with the same HD-tDCS protocol. Against our hypotheses, both the single and dual load conditions showed a significant executive vigilance (EV) decrement, which was not affected by the application of rPPC HD-tDCS. On the contrary, the most cognitively demanding task (triple task) showed the greatest EV decrement; importantly, it was also with the triple task that a significant mitigatory effect of the HD-tDCS intervention was observed. The present study contributes to a more nuanced understanding of the specific effects of HD-tDCS on the vigilance decrement considering cognitive demands. This can ultimately contribute to reconciling heterogeneous effects observed in past research and fine-tuning its future clinical application.

Transcranial alternating current stimulation improves quality of life in Parkinson's disease: study protocol for a randomized, double-blind, controlled trial.

BACKGROUND: The neural cells in the brains of patients with Parkinson's disease (PWP) display aberrant synchronized oscillatory activity within the beta frequency range. Additionally, enhanced gamma oscillations may serve as a compensatory mechanism for motor inhibition mediated by beta activity and also reinstate plasticity in the primary motor cortex affected by Parkinson's disease. Transcranial alternating current stimulation (tACS) can synchronize endogenous oscillations with exogenous rhythms, thereby modulating cortical activity. The objective of this study is to investigate whether the addition of tACS to multidisciplinary intensive rehabilitation treatment (MIRT) can improve symptoms of PWP so as to enhance the quality of life in individuals with Parkinson's disease based on the central-peripheral-central theory. METHODS: The present study was a randomized, double-blind trial that enrolled 60 individuals with Parkinson's disease aged between 45 and 70 years, who had Hoehn-Yahr scale scores ranging from 1 to 3. Participants were randomly assigned in a 1:1 ratio to either the tACS + MIRT group or the sham-tACS + MIRT group. The trial consisted of a two-week double-blind treatment period followed by a 24-week follow-up period, resulting in a total duration of twenty-six weeks. The primary outcome measured the change in PDQ-39 scores from baseline (T0) to 4 weeks (T2), 12 weeks (T3), and 24 weeks (T4) after completion of the intervention. The secondary outcome assessed changes in MDS-UPDRS III scores at T0, the end of intervention (T1), T2, T3, and T4. Additional clinical assessments and mechanistic studies were conducted as tertiary outcomes. DISCUSSION: The objective of this study is to demonstrate that tACS can enhance overall functionality and improve quality of life in PWP, based on the framework of MIRT. Additionally, it seeks to establish a potential correlation between these therapeutic effects and neuroplasticity alterations in relevant brain regions. The efficacy of tACS will be assessed during the follow-up period in order to optimize neuroplasticity and enhance its potential impact on rehabilitation efficiency for PWP. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2300071969. Registered on 30 May 2023.

Using Home-based, Remotely Supervised, Transcranial Direct Current Stimulation for Phantom Limb Pain.

Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that uses low-amplitude direct currents to alter cortical excitability. Previous trials have established the safety and tolerability of tDCS, and its potential to mitigate symptoms. However, the effects are cumulative, making it more difficult to have adherence to the treatment since frequent visits to the clinic or outpatient center are required. Moreover, the time needed for transportation to the center and the related expenses limit the accessibility of the treatment for many participants. Following guidelines for remotely supervised transcranial direct current stimulation (RS-tDCS) implementation, we propose a protocol designed for remotely supervised and home-based participation that uses specific devices and materials modified for patient use, with real-time monitoring by researchers through an encrypted video conferencing platform. We have developed detailed instructional materials and structured training procedures to allow for self- or proxy-administration while supervised remotely in real time. This protocol has a specific design to have a series of checkpoints during training and execution of the visit. This protocol is currently in use in a large pragmatic study of RS-tDCS for phantom limb pain (PLP). In this article, we will discuss the operational challenges of conducting a home-based RS-tDCS session and show methods to enhance its efficacy with supervised sessions.

Excitatory cerebellar transcranial direct current stimulation boosts the leverage of prior knowledge for predicting actions.

The cerebellum causally supports social processing by generating internal models of social events based on statistical learning of behavioral regularities. However, whether the cerebellum is only involved in forming or also in using internal models for the prediction of forthcoming actions is still unclear. We used cerebellar transcranial Direct Current Stimulation (ctDCS) to modulate the performance of healthy adults in using previously learned expectations in an action prediction task. In a first learning phase of this task, participants were exposed to different levels of associations between specific actions and contextual elements, to induce the formation of either strongly or moderately informative expectations. In a following testing phase, which assessed the use of these expectations for predicting ambiguous (i.e. temporally occluded) actions, we delivered ctDCS. Results showed that anodic, compared to sham, ctDCS boosted the prediction of actions embedded in moderately, but not strongly, informative contexts. Since ctDCS was delivered during the testing phase, that is after expectations were established, our findings suggest that the cerebellum is causally involved in using internal models (and not just in generating them). This encourages the exploration of the clinical effects of ctDCS to compensate poor use of predictive internal models for social perception.

No Frequency-Specific Effect of Transcranial Random Noise Stimulation on Resting EEG.

BACKGROUND: Transcranial random noise stimulation (tRNS) is a form of noninvasive transcranial electrical stimulation that applies alternating current in various randomized frequencies to the cortex, thereby improving cognitive functioning in multiple domains. However, the precise mechanism of tRNS, as well as its impact on human electroencephalography (EEG), remains unclear. This is partly because most studies have used tRNS in conjunction with a cognitive task, making it difficult to tease apart whether the observed changes in EEG are a result of tRNS, the cognitive task, or their interaction. METHODS: Forty-nine healthy individuals participated in this study and were randomly assigned to active tRNS (n = 24) and sham (n = 25) groups. tRNS was delivered for 20 minutes over Fp1/Fp2 and Oz. Resting-state EEG data were collected before and after either tRNS or sham stimulation. RESULTS: Cluster-based permutation tests using FieldTrip revealed no frequency-specific effect of tRNS on resting-state EEG data across four frequency bands (theta, alpha, beta, gamma). CONCLUSIONS: These observations suggest that tRNS itself does not target or alter specific EEG frequencies. Rather, tRNS most likely interacts with the cognitive task/activity at hand to produce an observable difference in post-tRNS EEG. Positive tRNS-EEG findings from previous studies are also likely to have resulted from the interactive and cognitive activity-dependent nature of tRNS.

Transcranial random noise stimulation (tRNS) improves hot and cold executive functions in children with attention deficit-hyperactivity disorder (ADHD).

Children with attention deficit-hyperactivity disorder (ADHD) have impaired hot and cold executive functions, which is thought to be related to impaired ventromedial and dorsolateral prefrontal cortex (vmPFC and dlPFC) functions. The present study aimed to assess the impact concurrent stimulation of dlPFC and vmPFC through transcranial random noise stimulation (tRNS), a non-invasive brain stimulation tool which enhances cortical excitability via application of alternating sinusoidal currents with random frequencies and amplitudes over the respective target regions on hot and cold executive functions. Eighteen children with ADHD received real and sham tRNS over the left dlPFC and the right vmPFC in two sessions with one week interval. The participants performed Circle Tracing, Go/No-Go, Wisconsin Card Sorting, and Balloon Analogue Risk Tasks during stimulation in each session. The results showed improved ongoing inhibition, prepotent inhibition, working memory, and decision making, but not set-shifting performance, during real, as compared to sham stimulation. This indicates that simultaneous stimulation of the dlPFC and the vmPFC improves hot and cold executive functions in children with ADHD.

Increases in functional connectivity between the default mode network and sensorimotor network correlate with symptomatic improvement after transcranial direct current stimulation for obsessive-compulsive disorder.

BACKGROUND: Non-invasive neuromodulation is a promising intervention for obsessive-compulsive disorder (OCD), although its neurobiological mechanisms of action are still poorly understood. Recent evidence suggests that abnormalities in the connectivity of the default mode network (DMN) and the supplementary motor area (SMA) with other brain regions and networks are involved in OCD pathophysiology. We examined if transcranial direct current stimulation (tDCS) alters these connectivity patterns and if they correlate with symptom improvement in treatment-resistant OCD. METHODS: In 23 patients from a larger clinical trial (comparing active tDCS to sham) who underwent pre- and post-treatment MRI scans, we assessed resting-state functional MRI (rs-fMRI) data. The treatment involved 30-minute daily tDCS sessions for four weeks (weekdays only), with the cathode over the SMA and the anode over the left deltoid. We conducted whole-brain connectivity analysis comparing active tDCS-treated to sham-treated patients. RESULTS: We found that active tDCS, but not sham, led to connectivity increasing between the DMN and the bilateral pre/postcentral gyri (p = 0.004, FDR corrected) and temporal-auditory areas plus the SMA (p = 0.028, FDR corrected). Also, symptom improvement was directly associated with connectivity increasing between the left lateral sensorimotor network and the left precuneus (r = 0.589, p = 0.034). LIMITATIONS: Limited sample size (23 participants with resting-state neuroimaging), inability to analyze specific OCD symptom dimensions (e.g., harm, sexual/religious, symmetry/checking, cleaning/contamination). CONCLUSIONS: These data offer novel information concerning functional connectivity changes associated with non-invasive neuromodulation interventions in OCD and can guide new brain stimulation interventions in the framework of personalized interventions.

Causal functional maps of brain rhythms in working memory.

Human working memory is a key cognitive process that engages multiple functional anatomical nodes across the brain. Despite a plethora of correlative neuroimaging evidence regarding the working memory architecture, our understanding of critical hubs causally controlling overall performance is incomplete. Causal interpretation requires cognitive testing following safe, temporal, and controllable neuromodulation of specific functional anatomical nodes. Such experiments became available in healthy humans with the advance of transcranial alternating current stimulation (tACS). Here, we synthesize findings of 28 placebo-controlled studies (in total, 1,057 participants) that applied frequency-specific noninvasive stimulation of neural oscillations and examined working memory performance in neurotypical adults. We use a computational meta-modeling method to simulate each intervention in realistic virtual brains and test reported behavioral outcomes against the stimulation-induced electric fields in different brain nodes. Our results show that stimulating anterior frontal and medial temporal theta oscillations and occipitoparietal gamma rhythms leads to significant dose-dependent improvement in working memory task performance. Conversely, prefrontal gamma modulation is detrimental to performance. Moreover, we found distinct spatial expression of theta subbands, where working memory changes followed orbitofrontal high-theta modulation and medial temporal low-theta modulation. Finally, all these results are driven by changes in working memory accuracy rather than processing time measures. These findings provide a fresh view of the working memory mechanisms, complementary to neuroimaging research, and propose hypothesis-driven targets for the clinical treatment of working memory deficits.

Cognitive Effect of Transcranial Direct Current Stimulation on Left Dorsolateral Prefrontal Cortex in Mild Alzheimer's Disease: A Randomized, Double-Blind, Cross-Over Small-Scale Exploratory Study.

Background: Transcranial direct current stimulation (tDCS) is considered a potential therapeutic instrument for Alzheimer's disease (AD) because it affects long-term synaptic plasticity through the processes of long-term potentiation and long-term depression, thereby improving cognitive ability. Nevertheless, the efficacy of tDCS in treating AD is still debated. Dorsal lateral prefrontal cortex is the main role in executive functions. Objective: We investigate the cognitive effects of tDCS on AD patients. Methods: Thirty mild AD patients aged 66-86 years (mean = 75.6) were included in a double-blind, randomized, sham-controlled crossover study. They were randomly assigned to receive 10 consecutive daily sessions of active tDCS (2 mA for 30 min) or a sham intervention and switched conditions 3 months later. The anodal and cathodal electrodes were placed on the left dorsal lateral prefrontal cortex and the right supraorbital area, respectively. Subjects underwent various neuropsychological assessments before and after the interventions. Results: The results showed that tDCS significantly improved Cognitive Abilities Screening Instrument scores, especially on the items of "concentration and calculation", "orientation", "language ability", and "categorical verbal fluency". Mini-Mental State Examination and Wisconsin Card Sorting Test scores in all domains of "concept formation", "abstract thinking", "cognitive flexibility", and "accuracy" also improved significantly after tDCS. For the sham condition, no difference was found between the baseline scores and the after-intervention scores on any of the neuropsychological tests. Conclusion: >: Using tDCS improves the cognition of AD patients. Further large size clinical trials are necessary to validate the data.

Repetitive Transcranial Alternating Current Stimulation to Improve Working Memory: An EEG-fNIRS Study.

Transcranial electrical stimulation has demonstrated the potential to enhance cognitive functions such as working memory, learning capacity, and attentional allocation. Recently, it was shown that periodic stimulation within a specific duration could augment the human brain's neuroplasticity. This study investigates the effects of repetitive transcranial alternating current stimulation (tACS; 1 mA, 5 Hz, 2 min duration) on cognitive function, functional connectivity, and topographic changes using both electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS). Fifteen healthy subjects were recruited to measure brain activity in the pre-, during-, and post-stimulation sessions under tACS and sham stimulation conditions. Fourteen trials of working memory tasks and eight repetitions of tACS/sham stimulation with a 1-minute intersession interval were applied to the frontal cortex of the participants. The working memory score, EEG band-wise powers, EEG topography, concentration changes of oxygenated hemoglobin, and functional connectivity (FC) were individually analyzed to quantify the behavioral and neurophysiological effects of tACS. Our results indicate that tACS increases: i) behavioral scores (i.e., 15.08, ) and EEG band-wise powers (i.e., theta and beta bands) compared to the sham stimulation condition, ii) FC of both EEG-fNIRS signals, especially in the large-scale brain network communication and interhemispheric connections, and iii) the hemodynamic response in comparison to the pre-stimulation session and the sham condition. Conclusively, the repetitive theta-band tACS stimulation improves the working memory capacity regarding behavioral and neuroplasticity perspectives. Additionally, the proposed fNIRS biomarkers (mean, slope), EEG band-wise powers, and FC can be used as neuro-feedback indices for closed-loop brain stimulation.

intensity- and frequency-specific effects of transcranial alternating current stimulation are explained by network dynamics.

Objective. Transcranial alternating current stimulation (tACS) can be used to non-invasively entrain neural activity and thereby cause changes in local neural oscillatory power. Despite its increased use in cognitive and clinical neuroscience, the fundamental mechanisms of tACS are still not fully understood.Approach. We developed a computational neuronal network model of two-compartment pyramidal neurons (PY) and inhibitory interneurons, which mimic the local cortical circuits. We modeled tACS with electric field strengths that are achievable in human applications. We then simulated intrinsic network activity and measured neural entrainment to investigate how tACS modulates ongoing endogenous oscillations.Main results. The intensity-specific effects of tACS are non-linear. At low intensities (<0.3 mV mm-1), tACS desynchronizes neural firing relative to the endogenous oscillations. At higher intensities (>0.3 mV mm-1), neurons are entrained to the exogenous electric field. We then further explore the stimulation parameter space and find that the entrainment of ongoing cortical oscillations also depends on stimulation frequency by following an Arnold tongue. Moreover, neuronal networks can amplify the tACS-induced entrainment via synaptic coupling and network effects. Our model shows that PY are directly entrained by the exogenous electric field and drive the inhibitory neurons.Significance. The results presented in this study provide a mechanistic framework for understanding the intensity- and frequency-specific effects of oscillating electric fields on neuronal networks. This is crucial for rational parameter selection for tACS in cognitive studies and clinical applications.

The phase of tACS-entrained pre-SMA beta oscillations modulates motor inhibition.

Inhibitory control has been linked to beta oscillations in the fronto-basal ganglia network. Here we aim to investigate the functional role of the phase of this oscillatory beta rhythm for successful motor inhibition. We applied 20 Hz transcranial alternating current stimulation (tACS) to the pre-supplementary motor area (pre-SMA) while presenting stop signals at 4 (Experiment 1) and 8 (Experiment 2) equidistant phases of the tACS entrained beta oscillations. Participants showed better inhibitory performance when stop signals were presented at the trough of the beta oscillation whereas their inhibitory control performance decreased with stop signals being presented at the oscillatory beta peak. These results are consistent with the communication through coherence theory, in which postsynaptic effects are thought to be greater when an input arrives at an optimal phase within the oscillatory cycle of the target neuronal population. The current study provides mechanistic insights into the neural communication principles underlying successful motor inhibition and may have implications for phase-specific interventions aimed at treating inhibitory control disorders such as PD or OCD.