Effects Of tACS Research Articles

Enhancing visual working memory in schizophrenia: effects of frontoparietal theta tACS in low-performing patients

Schizophrenia is a complex neuro-psychiatric disorder including positive symptoms, negative symptoms, and cognitive deficits. A key cognitive dysfunction in schizophrenia is a deficit in visual working memory (VWM). VWM involves three distinct stages: encoding, maintenance, and retrieval. The deficit in any one stage would produce the same symptom (i.e., poor VWM), although their causes are not the same. In this study, we used a retro-cue VWM task that provides helpful cues at different stages: early in maintenance (early cue), late in maintenance (late cue), or during retrieval (retrieval cue). This modification would help “tag” or identify the cognitive stage(s) most responsible for impaired VWM performance in schizophrenia. Additionally, we took advantage of this tagging feature and applied 6 Hz transcranial alternating current stimulation (tACS) over the right dorsolateral prefrontal cortex (DLPFC) and right posterior parietal cortex (PPC)—which has previously been shown to enhance VWM in low-performing healthy individuals—to examine whether tACS would improve a specific stage or all stages of VWM processing in schizophrenia. We observed that cues significantly enhanced performance in low-performing patients, who benefited equally from early and late maintenance cues, but not from retrieval cues. These low-performers also responded well to theta tACS in their overall VWM performance as opposed to a specific VWM stage. No improvement effect was observed in high-performing patients for both retro cue and tACS. Together, our data suggest that 1) low-performing patients’ VWM deficits likely stem from poor memory consolidation rather than retrieval, 2) right frontoparietal theta tACS can improve low-performing patients’ VWM performance, and 3) such facilitatory tACS effect is not selective of a specific VWM stage and thus is likely driven by an improvement in overall visual attention.

The subjective experience of transcranial electrical stimulation: a within-subject comparison of tolerability and side effects between tDCS, tACS, and otDCS.

Low-intensity transcranial electrical stimulation (tES), including techniques like transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS), and oscillatory transcranial direct current stimulation (otDCS), has been widely explored for its neuromodulatory effects on motor, cognitive, and behavioral processes. Despite well-established safety, these techniques can induce varying degrees of discomfort and side effects, potentially impacting their application. This study presents a within-subject sham-controlled experiment directly comparing the subjective experience and side effects of tDCS, tACS, and otDCS. Participants reported their discomfort levels at multiple time points during 20-min stimulation sessions and completed a side-effects questionnaire before and after each session. Results indicated that the overall discomfort levels were low across all conditions, with ≥95% reporting the absence of discomfort or mild procedure-induced discomfort. Nevertheless, tDCS and otDCS were slightly less comfortable compared to sham, especially at the beginning of stimulation, with tACS-induced discomfort levels being overall comparable to sham. The most common side / adverse effects were mild skin sensations, including itching and tingling, particularly with tDCS and otDCS, while tACS occasionally caused phosphenes and blurred vision. These findings provide a systematic comparison of tES-induced discomfort and side effects between different tES techniques, highlighting the high safety of tES, but also the importance of considering within- and between-person variability and time-course effects in tES applications.

Distinct effects of slow and fast theta tACS in enhancing temporal memory

Abstract Temporal memory plays a crucial role in organizing real-life events into meaningful segments. Previous research suggests that the clustering of temporally related information builds on the neural correlates of associative memory, including theta oscillations. Transcranial alternating current stimulation (tACS) provides a means of modulating theta oscillations within associative memory networks, possibly including hippocampal modulation when targeting parietal cortex. Theta oscillations are not limited to a single frequency range, but instead, exhibit functional specialization, with slow theta (3 Hz) implicated in short-term episodic memory formation and fast theta (8 Hz) involved in spatial navigation. This study aimed to investigate the distinct effects of slow and fast theta stimulation on temporal memory. Participants encoded visual objects paired with frame color while receiving tACS stimulation at 8 Hz, 3 Hz, or sham targeting the left parietal cortex. The frame color would change for every eight objects, establishing a context boundary with each color change. Subsequently, participants performed a timeline task to assess temporal memory performance. Results showed that slow, but not fast, theta stimulation led to an enhancement in temporal accuracy (absolute temporal error) compared to sham tACS, in support of our main hypothesis. Under sham stimulation, participants consistently underestimated the temporal position of items presented further away from boundary, compared to those presented at boundary. This finding resembled temporal compression observed during event segmentation. Interestingly, fast, but not slow, theta stimulation reduced this temporal bias (rated position— actual position). This study represents the first tACS evidence for differential contributions of slow versus fast theta to temporal memory formation in humans. We speculate that parietal theta tACS may modulate the hippocampus and facilitate temporal memory formation.

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

BackgroundThe mechanistic effects of gamma transcranial alternating current stimulation (tACS) on hippocampal gamma oscillation activity in Alzheimer’s Disease (AD) remains unclear. This study aimed to clarify beneficial effects of gamma tACS on cognitive functioning in AD and to elucidate effects on hippocampal gamma oscillation activity.MethodsThis is a double-blind, randomized controlled single-center trial. Participants with mild AD were randomized to tACS group or sham group, and underwent 30 one-hour sessions of either 40 Hz tACS or sham stimulation over consecutive 15 days. Cognitive functioning, structural magnetic resonance imaging (MRI), and simultaneous electroencephalography–functional MRI (EEG-fMRI) were evaluated at baseline, the end of the intervention and at 3-month follow-up from the randomization.ResultsA total of 46 patients were enrolled (23 in the tACS group, 23 in the sham group). There were no group differences in the change of the primary outcome, 11-item cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-Cog) score after intervention (group*time, p = 0.449). For secondary outcomes, compared to the control group, the intervention group showed significant improvement in MMSE (group*time, p = 0.041) and MoCA scores (non-parametric test, p = 0.025), which were not sustained at 3-month follow-up. We found an enhancement of theta-gamma coupling in the hippocampus, which was positively correlated with improvements of MMSE score and delayed recall. Additionally, fMRI revealed increase of the local neural activity in the hippocampus.ConclusionEffects on the enhancement of theta-gamma coupling and neural activity within the hippocampus suggest mechanistic models for potential therapeutic mechanisms of tACS.Trial registrationClinicalTrials.gov, NCT 03920826; Registration Date: 2019-04-19.

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

BackgroundTheta-gamma transcranial alternating current stimulation (tACS) was recently found to enhance thumb acceleration in young, healthy participants, suggesting a potential role in facilitating motor skill acquisition. Given the relevance of motor skill acquisition in stroke rehabilitation, theta-gamma tACS may hold potential for treating stroke survivors. ObjectiveWe aimed to examine the effects of theta-gamma tACS on motor skill acquisition in young, healthy participants and stroke survivors. MethodsIn a pre-registered, double-blind, randomized, sham-controlled study, 78 young, healthy participants received either theta-gamma peak-coupled (TGP) tACS, theta-gamma trough-coupled (TGT) tACS or sham stimulation. 20 individuals with a chronic stroke received either TGP or sham. TACS was applied over motor cortical areas while participants performed an acceleration-dependent thumb movement task. Stroke survivors were characterized using standardized testing, with a subgroup receiving additional structural brain imaging. ResultsNeither TGP nor TGT tACS significantly modified general motor skill acquisition in the young, healthy cohort. In contrast, in the stroke cohort, TGP diminished motor skill acquisition compared to sham. Exploratory analyses revealed that, independent of general motor skill acquisition, healthy participants receiving TGP or TGT exhibited greater peak thumb acceleration than those receiving sham. ConclusionAlthough theta-gamma tACS increased thumb acceleration in young, healthy participants, consistent with previous reports, it did not enhance overall motor skill acquisition in a more complex motor task. Furthermore, it even had detrimental effects on motor skill acquisition in stroke survivors.

Investigating the Effects of Transcranial Alternating Current Stimulation on Cortical Oscillations and Network Dynamics.

Transcranial electrical brain stimulation techniques like transcranial direct current (tDCS) and transcranial alternating current (tACS) have emerged as potential tools for treating neurological diseases by modulating cortical excitability. These techniques deliver small electric currents to the brain non-invasively through electrodes on the scalp. tDCS uses constant direct current which weakly alters the membrane voltage of cortical neurons, while tACS utilizes alternating current to target and enhance cortical oscillations, though the underlying mechanisms are not fully understood more specifically. To elucidate how tACS perturbs endogenous network dynamics, we simulated spiking neuron network models. We identified distinct roles of the depolarizing and hyperpolarizing phases in driving network activity towards and away from the strong nonlinearity provided by pyramidal neurons. Exploring resonance effects, we found matching tACS frequency to the network's endogenous resonance frequency creates greater entrainment. Based on this, we developed an algorithm to determine the network's endogenous frequency, phase, and amplitude, then deliver optimized tACS to entrain network oscillations. Together, these computational results provide mechanistic insight into the effects of tACS on network dynamics and could inform future closed-loop tACS systems that dynamically tune stimulation parameters to ongoing brain activity.

Utilizing tACS to enhance memory confidence and EEG to predict individual differences in brain stimulation efficacy.

The information transfer necessary for successful memory retrieval is believed to be mediated by theta and gamma oscillations. These oscillations have been linked to memory processes in electrophysiological studies, which were correlational in nature. In the current study, we used transcranial alternating current stimulation (tACS) to externally modulate brain oscillations to examine its direct effects on memory performance. Participants received sham, theta (4 Hz), and gamma (50 Hz) tACS over frontoparietal regions while retrieving information in a source memory paradigm. Linear regression models were used to investigate the direct effects of oscillatory non-invasive brain stimulation (NIBS) on memory accuracy and confidence. Our results indicate that both theta and gamma tACS altered memory confidence. Specifically, theta tACS seemed to lower the threshold for confidence in retrieved information, while gamma tACS appeared to alter the memory confidence bias. Furthermore, the individual differences in tACS effects could be predicted from electroencephalogram (EEG) measures recorded prior to stimulation, suggesting that EEG could be a useful tool for predicting individual variability in the efficacy of NIBS.

Neural consequences of 5-Hz transcranial alternating current stimulation over right hemisphere: An eLORETA EEG study

IntroductionTranscranial alternating current stimulation (tACS) at 5-Hz to the right hemisphere can effectively alleviate anxiety symptoms. This study aimed to explore the neural mechanisms that drive the therapeutic benefits. MethodsWe collected electroencephalography (EEG) data from 24 participants with anxiety disorders before and after a tACS treatment session. tACS was applied over the right hemisphere, with 1.0 mA at F4, 1.0 mA at P4, and 2.0 mA at T8 (10–10 EEG convention). With eLORETA, we transformed the scalp signals into the current source density in the cortex. We then assessed the differences between post- and pre-treatment brain maps across multiple spectra (delta to low gamma) with non-parametric statistics. ResultsWe observed a trend of heightened power in alpha and reduced power in mid-to-high beta and low gamma, in accord with the EEG markers of anxiolytic effects reported in previous studies. Additionally, we observed a consistent trend of de-synchronization at the stimulating sites across spectra. ConclusiontACS 5-Hz over the right hemisphere demonstrated EEG markers of anxiety reduction. The after-effects of tACS on the brain are intricate and cannot be explained solely by the widely circulated entrainment theory. Rather, our results support the involvement of plasticity mechanisms in the offline effects of tACS.

Modulation of brain function and antidepressant effects by transcranial alternating current stimulation in patients with major depressive disorder: Evidence from ERP

Transcranial alternating current stimulation (tACS) is an emerging non-invasive neuromodulation treatment for major depressive disorder (MDD), but its mechanism remains unclear. Therefore, we evaluated the effects of tACS on event-related potentials (ERP) based on a randomized controlled study. All patients were divided into two groups to receive either 20 sessions 77.5Hz-tACS or 20 sessions of sham stimulation during 4 weeks. The Hamilton Depression Rating Scale for Depression −17 item (HAMD-17) and ERP during face-word Stroop task were recorded before and after the treatment (the fourth weekend). Our findings indicate a significant alleviation of depressive symptoms after tACS. For the behavioral performance, sham group showed a significant decrease in reaction time to the sad incongruent condition and an increase in accuracy to the happy condition. The active group showed an increase in accuracy to the incongruent condition. ERP analysis revealed that tACS significantly shortened the latency of P2 to incongruent condition, decreased the amplitude and prolonged the latency of N2 to negative condition. These ERP alterations suggest a potential rectification of negative bias and enhancement of cognitive functioning in patients with MDD, offering insights into the antidepressant mechanisms of tACS.

State-Dependent tACS Effects Reveal the Potential Causal Role of Prestimulus Alpha Traveling Waves in Visual Contrast Detection.

The intricate relationship between prestimulus alpha oscillations and visual contrast detection variability has been the focus of numerous studies. However, the causal impact of prestimulus alpha traveling waves on visual contrast detection remains largely unexplored. In our research, we sought to discern the causal link between prestimulus alpha traveling waves and visual contrast detection across different levels of mental fatigue. Using electroencephalography alongside a visual detection task with 30 healthy adults (13 females; 17 males), we identified a robust negative correlation between prestimulus alpha forward traveling waves (FTWs) and visual contrast threshold (VCT). Inspired by this correlation, we utilized 45/-45° phase-shifted transcranial alternating current stimulation (tACS) in a sham-controlled, double-blind, within-subject experiment with 33 healthy adults (23 females; 10 males) to directly modulate these alpha traveling waves. After the application of 45° phase-shifted tACS, we observed a substantial decrease in FTW and an increase in backward traveling waves, along with a concurrent increase in VCT, compared with the sham condition. These changes were particularly pronounced under a low fatigue state. The findings of state-dependent tACS effects reveal the potential causal role of prestimulus alpha traveling waves in visual contrast detection. Moreover, our study highlights the potential of 45/-45° phase-shifted tACS in cognitive modulation and therapeutic applications.

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

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. 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. 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. 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. 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.

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.

Effect of Transcranial Alternating Current Stimulation on Motor Performance

Transcranial alternating current stimulation (tACS) is a non-invasive method of brain stimulation that can modulate oscillatory brain activity in the cortical region. By applying alternating current through two electrodes attached to a subject’s head, it is possible to entrain the oscillation of the cortex directly under one electrode to a specific frequency. This study finds that applying tACS to the primary motor cortex and cerebellar hemisphere improves motor performance. The study also shows the effect of tACS on the supplementary motor cortex to modulate the maintenance and update of motor plans in a bimanual motor task. These recent findings show that individualized tACS interventions can be tailored by selecting the stimulation area and frequency depending on the subject’s performance level and exercise task. By further investigating the effects of tACS on motor performance, it is believed that tACS can be applied in rehabilitation.

No effects of the theta-frequency transcranial electrical stimulation for recall, attention control, and relation integration in working memory.

Recent studies have suggested that transcranial alternating current stimulation (tACS), and especially the theta-frequency tACS, can improve human performance on working memory tasks. However, evidence to date is mixed. Moreover, the two WM tasks applied most frequently, namely the n-back and change-detection tasks, might not constitute canonical measures of WM capacity. In a relatively large sample of young healthy participants (N = 62), we administered a more canonical WM task that required stimuli recall, as well as we applied two WM tasks tapping into other key WM functions: attention control (the antisaccade task) and relational integration (the graph mapping task). The participants performed these three tasks three times: during the left frontal 5.5-Hz and the left parietal 5.5-Hz tACS session as well as during the sham session, with a random order of sessions. Attentional vigilance and subjective experience were monitored. For each task administered, we observed significant gains in accuracy neither for the frontal tACS session nor for the parietal tACS session, as compared to the sham session. By contrast, the scores on each task positively inter-correlated across the three sessions. The results suggest that canonical measures of WM capacity are strongly stable in time and hardly affected by theta-frequency tACS. Either the tACS effects observed in the n-back and change detection tasks do not generalize onto other WM tasks, or the tACS method has limited effectiveness with regard to WM, and might require further methodological advancements.

Frequency-dependent membrane polarization across neocortical cell types and subcellular elements by transcranial alternating current stimulation.

Objective.Transcranial alternating current stimulation (tACS) is a non-invasive brain stimulation technique that directly interacts with ongoing brain oscillations in a frequency-dependent manner. However, it remains largely unclear how the cellular effects of tACS vary between cell types and subcellular elements.Approach.In this study, we use a set of morphologically realistic models of neocortical neurons to simulate the cellular response to uniform oscillating electric fields (EFs). We systematically characterize the membrane polarization in the soma, axons, and dendrites with varying field directions, intensities, and frequencies.Main results.Pyramidal cells are more sensitive to axial EF that is roughly parallel to the cortical column, while interneurons are sensitive to axial EF and transverse EF that is tangent to the cortical surface. Membrane polarization in each subcellular element increases linearly with EF intensity, and its slope, i.e. polarization length, highly depends on the stimulation frequency. At each frequency, pyramidal cells are more polarized than interneurons. Axons usually experience the highest polarization, followed by the dendrites and soma. Moreover, a visible frequency resonance presents in the apical dendrites of pyramidal cells, while the other subcellular elements primarily exhibit low-pass filtering properties. In contrast, each subcellular element of interneurons exhibits complex frequency-dependent polarization. Polarization phase in each subcellular element of cortical neurons lags that of field and exhibits high-pass filtering properties. These results demonstrate that the membrane polarization is not only frequency-dependent, but also cell type- and subcellular element-specific. Through relating effective length and ion mechanism with polarization, we emphasize the crucial role of cell morphology and biophysics in determining the frequency-dependent membrane polarization.Significance.Our findings highlight the diverse polarization patterns across cell types as well as subcellular elements, which provide some insights into the tACS cellular effects and should be considered when understanding the neural spiking activity by tACS.

Behavioral entrainment to rhythmic auditory stimulation can be modulated by tACS depending on the electrical stimulation field properties.

Synchronization between auditory stimuli and brain rhythms is beneficial for perception. In principle, auditory perception could be improved by facilitating neural entrainment to sounds via brain stimulation. However, high inter-individual variability of brain stimulation effects questions the usefulness of this approach. Here we aimed to modulate auditory perception by modulating neural entrainment to frequency modulated (FM) sounds using transcranial alternating current stimulation (tACS). In addition, we evaluated the advantage of using tACS montages spatially optimized for each individual's anatomy and functional data compared to a standard montage applied to all participants. Across two different sessions, 2 Hz tACS was applied targeting auditory brain regions. Concurrent with tACS, participants listened to FM stimuli with modulation rate matching the tACS frequency but with different phase lags relative to the tACS, and detected silent gaps embedded in the FM sound. We observed that tACS modulated the strength of behavioral entrainment to the FM sound in a phase-lag specific manner. Both the optimal tACS lag and the magnitude of the tACS effect were variable across participants and sessions. Inter-individual variability of tACS effects was best explained by the strength of the inward electric field, depending on the field focality and proximity to the target brain region. Although additional evidence is necessary, our results also provided suggestive insights that spatially optimizing the electrode montage could be a promising tool to reduce inter-individual variability of tACS effects. This work demonstrates that tACS effectively modulates entrainment to sounds depending on the optimality of the electric field. However, the lack of reliability on optimal tACS lags calls for caution when planning tACS experiments based on separate sessions.

Behavioral entrainment to rhythmic auditory stimulation can be modulated by tACS depending on the electrical stimulation field properties

Synchronization between auditory stimuli and brain rhythms is beneficial for perception. In principle, auditory perception could be improved by facilitating neural entrainment to sounds via brain stimulation. However, high inter-individual variability of brain stimulation effects questions the usefulness of this approach. Here we aimed to modulate auditory perception by modulating neural entrainment to frequency modulated (FM) sounds using transcranial alternating current stimulation (tACS). In addition, we evaluated the advantage of using tACS montages spatially optimized for each individual’s anatomy and functional data compared to a standard montage applied to all participants. Across two different sessions, 2 Hz tACS was applied targeting auditory brain regions. Concurrent with tACS, participants listened to FM stimuli with modulation rate matching the tACS frequency but with different phase lags relative to the tACS, and detected silent gaps embedded in the FM sound. We observed that tACS modulated the strength of behavioral entrainment to the FM sound in a phase-lag specific manner. Both the optimal tACS lag and the magnitude of the tACS effect were variable across participants and sessions. Inter-individual variability of tACS effects was best explained by the strength of the inward electric field, depending on the field focality and proximity to the target brain region. Although additional evidence is necessary, our results also provided suggestive insights that spatially optimizing the electrode montage could be a promising tool to reduce inter-individual variability of tACS effects. This work demonstrates that tACS effectively modulates entrainment to sounds depending on the optimality of the electric field. However, the lack of reliability on optimal tACS lags calls for caution when planning tACS experiments based on separate sessions.

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

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

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.

Comparison of online and offline applications of dual-site transcranial alternating current stimulation (tACS) over the pre-supplementary motor area (preSMA) and right inferior frontal gyrus (rIFG) for improving response inhibition

The efficacy of transcranial alternating current stimulation (tACS) is thought to be brain state-dependent, such that tACS during task performance would be hypothesised to offer greater potential for improving performance compared to tACS at rest. However, to date, no empirical study has tested this postulation. The current study compared the effects of dual-site beta tACS applied during a stop signal task (online) to the effects of the same tACS protocol applied prior to the task (offline) and a sham control stimulation in 53 young, healthy adults (32 female; 18–35 yrs). The right inferior frontal gyrus (rIFG) and centre (midline) of the pre-supplementary motor area (preSMA), which are thought to play critical roles in action cancellation, were simultaneously stimulated, sending phase-synchronised stimulation for 15 min with the aim of increasing functional connectivity. The offline group showed significant within-group improvement in response inhibition without showing overt task-related changes in functional connectivity measured with EEG connectivity analysis, suggesting offline tACS is efficacious in inducing behavioural changes potentially via a post-stimulation early plasticity mechanism. In contrast, neither the online nor sham group showed significant improvements in response inhibition. However, EEG connectivity analysis revealed significantly increased task-related functional connectivity following online stimulation and a medium effect size observed in correlation analyses suggested that an increase in functional connectivity in the beta band at rest was potentially associated with an improvement in response inhibition. Overall, the results indicate that both online and offline dual-site beta tACS can be beneficial in improving inhibitory control via distinct underlying mechanisms.