The effects of electrical stimulation of ventromedial prefrontal cortex on skin sympathetic nerve activity.

Skin sympathetic nerve activity (SSNA) is primarily involved in thermoregulation and emotional expression; however, the brain regions involved in the generation of SSNA are not completely understood. In recent years, our laboratory has shown that blood-oxygen-level-dependent signal intensity in the ventromedial prefrontal cortex (vmPFC) and dorsolateral prefrontal cortex (dlPFC) are positively correlated with bursts of SSNA during emotional arousal and increases in signal intensity in the vmPFC occurring with increases in spontaneous bursts of SSNA even in the resting state. We have recently shown that unilateral transcranial alternating current stimulation (tACS) of the dlPFC causes modulation of SSNA but given that the current was delivered between electrodes over the dlPFC and the nasion, it is possible that the effects were due to current acting on the vmPFC. To test this, we delivered tACS to target the right vmPFC or dlPFC and nasion and recorded SSNA in 11 healthy participants by inserting a tungsten microelectrode into the right common peroneal nerve. The similarity in SSNA modulation between ipsilateral vmPFC and dlPFC suggests that the ipsilateral vmPFC, rather than the dlPFC, may be causing the modulation of SSNA during ipsilateral dlPFC stimulation.

Dissociable rhythmic mechanisms enhance memory for conscious and nonconscious perceptual contents.

Understanding the neural mechanisms of conscious and unconscious experience is a major goal of fundamental and translational neuroscience. Here, we target the early visual cortex with a protocol of noninvasive, high-resolution alternating current stimulation while participants performed a delayed target-probe discrimination task and reveal dissociable mechanisms of mnemonic processing for conscious and unconscious perceptual contents. Entraining ß-rhythms in bilateral visual areas preferentially enhanced short-term memory for seen information, whereas α-entrainment in the same region preferentially enhanced short-term memory for unseen information. The short-term memory improvements were frequency-specific and long-lasting. The results add a mechanistic foundation to existing theories of consciousness, call for revisions to these theories, and contribute to the development of nonpharmacological therapeutics for improving visual cortical processing.

Out-of-phase transcranial alternating current stimulation modulates the neurodynamics of inhibitory control.

Transcranial alternating current stimulation (tACS) is an efficient neuromodulation technique that enhances cognitive function in a non-invasive manner. Using functional magnetic resonance imaging, we investigated whether tACS with different phase lags (0° and 180°) between the dorsal anterior cingulate and left dorsolateral prefrontal cortices modulated inhibitory control performance during the Stroop task. We found out-of-phase tACS mediated improvements in task performance, which was neurodynamically reflected as putamen, dorsolateral prefrontal, and primary motor cortical activation as well as prefrontal-based top-down functional connectivity. Our observations uncover the neurophysiological bases of tACS-phase-dependent neuromodulation and provide a feasible non-invasive approach to effectively modulate inhibitory control.

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.

Non-invasive electrical brain stimulation modulates human conscious perception of mental representation.

Mental representation is a key concept in cognitive science; nevertheless, its neural foundations remain elusive. We employed non-invasive electrical brain stimulation and functional magnetic resonance imaging to address this. During this process, participants perceived flickering red and green visual stimuli, discerning them either as distinct, non-fused colours or as a mentally generated, fused colour (orange). The application of transcranial alternating current stimulation to the medial prefrontal region (a key node of the default-mode network) suppressed haemodynamic activation in higher-order subthalamic and central executive networks associated with the perception of fused colours. This implies that higher-order thalamocortical and default-mode networks are crucial in humans' conscious perception of mental representation.

Differential online and offline effects of theta-tACS on memory encoding and retrieval.

Theta oscillations support memory formation, but their exact contribution to the communication between prefrontal cortex (PFC) and the hippocampus is unknown. We tested the functional relevance of theta oscillations as a communication link between both areas for memory formation using transcranial alternating current stimulation (tACS). Healthy, young participants learned two lists of Dutch-German word pairs and retrieved them immediately and with a 30-min delay. In the encoding group (N = 30), tACS was applied during the encoding of list 1. List 2 was used to test stimulation aftereffects. In the retrieval group (N = 23), we stimulated during the delayed recall. In both groups, we applied tACS bilaterally at prefrontal and tempo-parietal sites, using either individualized theta frequency or 15 Hz (as control), according to a within-subject design. Stimulation with theta-tACS did not alter overall learning performance. An exploratory analysis revealed that immediate recall improved when word-pairs were learned after theta-tACS (list 2). Applying theta-tACS during retrieval had detrimental effects on memory. No changes in the power of the respective frequency bands were observed. Our results do not support the notion that impacting the communication between PFC and the hippocampus during a task by bilateral tACS improves memory. However, we do find evidence that direct stimulation had a trend for negatively interfering effects during immediate and delayed recall. Hints for beneficial effects on memory only occurred with aftereffects of the stimulation. Future studies need to further examine the effects during and after stimulation on memory formation.

Cognitive and Neuropathophysiological Outcomes of Gamma-tACS in Dementia: A Systematic Review.

Despite the numerous pharmacological interventions targeting dementia, no disease-modifying therapy is available, and the prognosis remains unfavorable. A promising perspective involves tackling high-frequency gamma-band (> 30 Hz) oscillations involved in hippocampal-mediated memory processes, which are impaired from the early stages of typical Alzheimer's Disease (AD). Particularly, the positive effects of gamma-band entrainment on mouse models of AD have prompted researchers to translate such findings into humans using transcranial alternating current stimulation (tACS), a methodology that allows the entrainment of endogenous cortical oscillations in a frequency-specific manner. This systematic review examines the state-of-the-art on the use of gamma-tACS in Mild Cognitive Impairment (MCI) and dementia patients to shed light on its feasibility, therapeutic impact, and clinical effectiveness. A systematic search from two databases yielded 499 records resulting in 10 included studies and a total of 273 patients. The results were arranged in single-session and multi-session protocols. Most of the studies demonstrated cognitive improvement following gamma-tACS, and some studies showed promising effects of gamma-tACS on neuropathological markers, suggesting the feasibility of gamma-tACS in these patients anyhow far from the strong evidence available for mouse models. Nonetheless, the small number of studies and their wide variability in terms of aims, parameters, and measures, make it difficult to draw firm conclusions. We discuss results and methodological limitations of the studies, proposing possible solutions and future avenues to improve research on the effects of gamma-tACS on dementia.

Comparing Cerebellar tDCS and Cerebellar tACS in Neurodegenerative Ataxias Using Wearable Sensors: A Randomized, Double-Blind, Sham-Controlled, Triple-Crossover Trial.

Cerebellar transcranial direct current stimulation (tDCS) represents a promising therapeutic approach for both motor and cognitive symptoms in neurodegenerative ataxias. Recently, transcranial alternating current stimulation (tACS) was also demonstrated to modulate cerebellar excitability by neuronal entrainment. To compare the effectiveness of cerebellar tDCS vs. cerebellar tACS in patients with neurodegenerative ataxia, we performed a double-blind, randomized, sham controlled, triple cross-over trial with cerebellar tDCS, cerebellar tACS or sham stimulation in twenty-six participants with neurodegenerative ataxia. Before entering the study, each participant underwent motor assessment with wearable sensors considering gait cadence (steps/minute), turn velocity (degrees/second) and turn duration (seconds), and a clinical evaluation with the scale for the Assessment and Rating of Ataxia (SARA) and the International Cooperative Ataxia Rating Scale (ICARS). After each intervention, participants underwent the same clinical assessment along with cerebellar inhibition (CBI) measurement, a marker of cerebellar activity. The gait cadence, turn velocity, SARA, and ICARS significantly improved after both tDCS and tACS, compared to sham stimulation (all p<0.010). Comparable effects were observed for CBI (p<0.001). Overall, tDCS significantly outperformed tACS on clinical scales and CBI (p<0.01). A significant correlation between changes of wearable sensors parameters from baseline and changes of clinical scales and CBI scores was detected. Cerebellar tDCS and cerebellar tACS are effective in ameliorating symptoms of neurodegenerative ataxias, with the former being more beneficial than the latter. Wearable sensors may serve as rater-unbiased outcome measures in future clinical trials. ClinicalTrial.gov Identifier: NCT05621200.

Impact of theta transcranial alternating current stimulation on language production in adult classic galactosemia patients.

Patients with classic galactosemia (CG), an inborn error of galactose metabolism, suffer from impairments in cognition, including language processing. Potential causes are atypical brain oscillations. Recent electroencephalogram (EEG) showed differences in the P300 event-related-potential (ERP) and alterations in the alpha/theta-range during speech planning. This study investigated whether transcranial alternating current stimulation (tACS) at theta-frequency compared to sham can cause a normalization of the ERP post stimulation and improves language performance. Eleven CG patients and fourteen healthy controls participated in two tACS-sessions (theta 6.5 Hz/sham). They were engaged in an active language task, describing animated scenes at three moments, that is, pre/during/post stimulation. Pre and post stimulation, behavior (naming accuracy, voice-onset-times; VOT) and mean-amplitudes of ERP were compared, by means of a P300 time-window analysis and cluster-based-permutation testing during speech planning. The results showed that theta stimulation, not sham, significantly reduced naming error-percentage in patients, not in controls. Theta did not systematically speed up naming beyond a general learning effect, which was larger for the patients. The EEG analysis revealed a significant pre-post stimulation effect (P300/late positivity), in patients and during theta stimulation only. In conclusion, theta-tACS improved accuracy in language performance in CG patients compared to controls and altered the P300 and late positive ERP-amplitude, suggesting a lasting effect on neural oscillation and behavior.

Transcranial temporal interference stimulation (tTIS) influences event-related alpha activity during mental rotation.

Non-invasive brain stimulation techniques offer therapeutic potential for neurological and psychiatric disorders. However, current methods are often limited in their stimulation depth. The novel transcranial temporal interference stimulation (tTIS) aims to overcome this limitation by non-invasively targeting deeper brain regions. In this study, we aimed to evaluate the efficacy of tTIS in modulating alpha activity during a mental rotation task. The effects of tTIS were compared with transcranial alternating current stimulation (tACS) and a sham control. Participants were randomly assigned to a tTIS, tACS, or sham group. They performed alternating blocks of resting and mental rotation tasks before, during, and after stimulation. During the stimulation blocks, participants received 20 min of stimulation adjusted to their individual alpha frequency (IAF). We assessed shifts in resting state alpha power, event-related desynchronization (ERD) of alpha activity during mental rotation, as well as resulting improvements in behavioral performance. Our results indicate tTIS and tACS to be effective in modulating cortical alpha activity during mental rotation, leading to an increase in ERD from pre- to poststimulation as well as compared to sham stimulation. However, this increase in ERD was not correlated with enhanced mental rotation performance, and resting state alpha power remained unchanged. Our findings underscore the complex nature of tTIS and tACS efficacy, indicating that stimulation effects are more observable during active cognitive tasks, while their impacts are less pronounced on resting neuronal systems.

Aligning Event-Related Potentials with Transcranial Alternating Current Stimulation for Modulation-a Review.

This review aims to demonstrate the connections between event-related potentials (ERPs), event-related oscillations (EROs), and non-invasive brain stimulation (NIBS), with a specific focus on transcranial alternating current stimulation (tACS). We begin with a short examination and discussion of the relation between ERPs and EROs. Then, we investigate the diverse fields of NIBS, highlighting tACS as a potent tool for modulating neural oscillations and influencing cognitive performance. Emphasizing the impact of tACS on individual ERP components, this article offers insights into the potential of conventional tACS for targeted stimulation of single ERP components. Furthermore, we review recent articles that explore a novel approach of tACS: ERP-aligned tACS. This innovative technique exploits the temporal precision of ERP components, aligning tACS with specific neural events to optimize stimulation effects and target the desired neural response. In conclusion, this review combines current knowledge to explore how ERPs, EROs, and NIBS interact, particularly highlighting the modulatory possibilities offered by tACS. The incorporation of ERP-aligned tACS introduces new opportunities for future research, advancing our understanding of the complex connection between neural oscillations and cognitive processes.

The left inferior frontal gyrus is causally linked to vocal feedback control: evidence from high-definition transcranial alternating current stimulation.

Current models of speech motor control propose a role for the left inferior frontal gyrus (IFG) in feedforward control of speech production. There is evidence, however, that has implicated the functional relevance of the left IFG for the neuromotor processing of vocal feedback errors. The present event-related potential (ERP) study examined whether the left IFG is causally linked to auditory feedback control of vocal production with high-definition transcranial alternating current stimulation (HD-tACS). After receiving active or sham HD-tACS over the left IFG at 6 or 70 Hz, 20 healthy adults vocalized the vowel sounds while hearing their voice unexpectedly pitch-shifted by ±200 cents. The results showed that 6 or 70 Hz HD-tACS over the left IFG led to larger magnitudes and longer latencies of vocal compensations for pitch perturbations paralleled by larger ERP P2 responses than sham HD-tACS. Moreover, there was a lack of frequency specificity that showed no significant differences between 6 and 70 Hz HD-tACS. These findings provide first causal evidence linking the left IFG to vocal pitch regulation, suggesting that the left IFG is an important part of the feedback control network that mediates vocal compensations for auditory feedback errors.

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

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

Transcranial alternating current stimulation can modulate the blink reflex excitability. Effects of a 10- and 20-Hz tACS session on the blink reflex recovery cycle in healthy subjects.

BACKGROUND: The blink reflex excitability, assessed through paired electrical stimuli responses, has been modulated using traditional non-invasive neurostimulation techniques. Recently, transcranial Alternating Current Stimulation (tACS) emerged as a tool to modulate brain oscillations implicated in various motor, perceptual, and cognitive functions. This study aims to investigate the influence of 20-Hz and 10-Hz tACS sessions on the primary motor cortex and their impact on blink reflex excitability. MATERIALS AND METHODS: Fifteen healthy volunteers underwent 10-min tACS sessions (intensity 1 mA) with active/reference electrodes placed over C4/Pz, delivering 20-Hz, 10-Hz, and sham stimulation. The blink reflex recovery cycle (BRrc) was assessed using the R2 amplitude ratio at various interstimulus intervals (ISIs) before (T0), immediately after (T1), and 30 min post-tACS (T2). RESULTS: Both 10-Hz and 20-Hz tACS sessions significantly increased R2 ratio at T1 (10-Hz: p = 0.02; 20-Hz: p < 0.001) and T2 (10-Hz: p = 0.01; 20-Hz: p < 0.001) compared to baseline (T0). Notably, 20-Hz tACS induced a significantly greater increase in blink reflex excitability compared to sham at both T1 (p = 0.04) and T2 (p < 0.001). CONCLUSION: This study demonstrates the modulatory effect of tACS on trigemino-facial reflex circuits, with a lasting impact on BRrc. Beta-band frequency tACS exhibited a more pronounced effect than alpha-band frequency, highlighting the influential role of beta-band oscillations in the motor cortex on blink reflex excitability modulation.

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

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

Selective modulation of interhemispheric connectivity by transcranial alternating current stimulation influences binaural integration.

Brain connectivity plays a major role in the encoding, transfer, and integration of sensory information. Interregional synchronization of neural oscillations in the γ-frequency band has been suggested as a key mechanism underlying perceptual integration. In a recent study, we found evidence for this hypothesis showing that the modulation of interhemispheric oscillatory synchrony by means of bihemispheric high-density transcranial alternating current stimulation (HD-TACS) affects binaural integration of dichotic acoustic features. Here, we aimed to establish a direct link between oscillatory synchrony, effective brain connectivity, and binaural integration. We experimentally manipulated oscillatory synchrony (using bihemispheric γ-TACS with different interhemispheric phase lags) and assessed the effect on effective brain connectivity and binaural integration (as measured with functional MRI and a dichotic listening task, respectively). We found that TACS reduced intrahemispheric connectivity within the auditory cortices and antiphase (interhemispheric phase lag 180°) TACS modulated connectivity between the two auditory cortices. Importantly, the changes in intra- and interhemispheric connectivity induced by TACS were correlated with changes in perceptual integration. Our results indicate that γ-band synchronization between the two auditory cortices plays a functional role in binaural integration, supporting the proposed role of interregional oscillatory synchrony in perceptual integration.

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.

Neuromodulation of inhibitory control using phase-lagged transcranial alternating current stimulation.

BACKGROUND: Transcranial alternating current stimulation (tACS) is a prominent non-invasive brain stimulation method for modulating neural oscillations and enhancing human cognitive function. This study aimed to investigate the effects of individualized theta tACS delivered in-phase and out-of-phase between the dorsal anterior cingulate cortex (dACC) and left dorsolateral prefrontal cortex (lDLPFC) during inhibitory control performance. METHODS: The participants engaged in a Stroop task with phase-lagged theta tACS over individually optimized high-density electrode montages targeting the dACC and lDLPFC. We analyzed task performance, event-related potentials, and prestimulus electroencephalographic theta and alpha power. RESULTS: We observed significantly reduced reaction times following out-of-phase tACS, accompanied by reduced frontocentral N1 and N2 amplitudes, enhanced parieto-occipital P1 amplitudes, and pronounced frontocentral late sustained potentials. Out-of-phase stimulation also resulted in significantly higher prestimulus frontocentral theta and alpha activity. CONCLUSIONS: These findings suggest that out-of-phase theta tACS potently modulates top-down inhibitory control, supporting the feasibility of phase-lagged tACS to enhance inhibitory control performance.

Neuroprotection of Transcranial Cortical and Peripheral Somatosensory Electrical Stimulation by Modulating a Common Neuronal Death Pathway in Mice with Ischemic Stroke.

Therapeutic electrical stimulation, such as transcranial cortical stimulation and peripheral somatosensory stimulation, is used to improve motor function in patients with stroke. We hypothesized that these stimulations exert neuroprotective effects during the subacute phase of ischemic stroke by regulating novel common signaling pathways. Male C57BL/6J mouse models of ischemic stroke were treated with high-definition (HD)-transcranial alternating current stimulation (tACS; 20 Hz, 89.1 A/mm2), HD-transcranial direct current stimulation (tDCS; intensity, 55 A/mm2; charge density, 66,000 C/m2), or electroacupuncture (EA, 2 Hz, 1 mA) in the early stages of stroke. The therapeutic effects were assessed using behavioral motor function tests. The underlying mechanisms were determined using transcriptomic and other biomedical analyses. All therapeutic electrical tools alleviated the motor dysfunction caused by ischemic stroke insults. We focused on electrically stimulating common genes involved in apoptosis and cell death using transcriptome analysis and chose 11 of the most potent targets (Trem2, S100a9, Lgals3, Tlr4, Myd88, NF-kB, STAT1, IL-6, IL-1ß, TNF-α, and Iba1). Subsequent investigations revealed that electrical stimulation modulated inflammatory cytokines, including IL-1ß and TNF-α, by regulating STAT1 and NF-kB activation, especially in amoeboid microglia; moreover, electrical stimulation enhanced neuronal survival by activating neurotrophic factors, including BDNF and FGF9. Therapeutic electrical stimulation applied to the transcranial cortical- or periphery-nerve level to promote functional recovery may improve neuroprotection by modulating a common neuronal death pathway and upregulating neurotrophic factors. Therefore, combining transcranial cortical and peripheral somatosensory stimulation may exert a synergistic neuroprotective effect, further enhancing the beneficial effects on motor deficits in patients with ischemic stroke.

Standard intensities of transcranial alternating current stimulation over the motor cortex do not entrain corticospinal inputs to motor neurons.

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.