Human Neural Activity Research Articles

Implanted cortical neuroprosthetics for speech and movement restoration.

Implanted cortical neuroprosthetics (ICNs) are medical devices developed to replace dysfunctional neural pathways by creating information exchange between the brain and a digital system which can facilitate interaction with the external world. Over the last decade, researchers have explored the application of ICNs for diverse conditions including blindness, aphasia, and paralysis. Both transcranial and endovascular approaches have been used to record neural activity in humans, and in a laboratory setting, high-performance decoding of the signals associated with speech intention has been demonstrated. Particular progress towards a device which can move into clinical practice has been made with ICNs focussed on the restoration of speech and movement. This article provides an overview of contemporary ICNs for speech and movement restoration, their mechanisms of action and the unique ethical challenges raised by the field.

Human Pluripotent Stem Cell-Derived Astrocyte Functionality Compares Favorably with Primary Rat Astrocytes.

Astrocytes are essential for the formation and maintenance of neural networks. However, a major technical challenge for investigating astrocyte function and disease-related pathophysiology has been the limited ability to obtain functional human astrocytes. Despite recent advances in human pluripotent stem cell (hPSC) techniques, primary rodent astrocytes remain the gold standard in coculture with human neurons. We demonstrate that a combination of leukemia inhibitory factor (LIF) and bone morphogenetic protein-4 (BMP4) directs hPSC-derived neural precursor cells to a highly pure population of astroglia in 28 d. Using single-cell RNA sequencing, we confirm the astroglial identity of these cells and highlight profound transcriptional adaptations in cocultured hPSC-derived astrocytes and neurons, consistent with their further maturation. In coculture with human neurons, multielectrode array recordings revealed robust network activity of human neurons in a coculture with hPSC-derived or rat astrocytes [3.63 ± 0.44 min-1 (hPSC-derived), 2.86 ± 0.64 min-1 (rat); p = 0.19]. In comparison, we found increased spike frequency within network bursts of human neurons cocultured with hPSC-derived astrocytes [56.31 ± 8.56 Hz (hPSC-derived), 24.77 ± 4.04 Hz (rat); p < 0.01], and whole-cell patch-clamp recordings revealed an increase of postsynaptic currents [2.76 ± 0.39 Hz (hPSC-derived), 1.07 ± 0.14 Hz (rat); p < 0.001], consistent with a corresponding increase in synapse density [14.90 ± 1.27/100 μm2 (hPSC-derived), 8.39 ± 0.63/100 μm2 (rat); p < 0.001]. Taken together, we show that hPSC-derived astrocytes compare favorably with rat astrocytes in supporting human neural network activity and maturation, providing a fully human platform for investigating astrocyte function and neuronal-glial interactions.

Patterns identification using blind source separation with application to neural activities associated with anticipated falls

Exploring the nature of neural activity in humans attracts much attention in human-machine interfaces. However, there is still a lack of understanding about the neural activities associated with human anticipated falls. This study examines how the brain responds to anticipated falls by identifying the patterns of neural activities associated with anticipated falls with Electroencephalograms (EEG). We developed a method for pattern identification of neural activities with second-order blind identification in the machine learning framework. The effects of artifact removal within EEG data are compared between the second-order blind identification (SOBI) algorithm and a related method. Experiments involving 135 anticipated falls and 135 walk controls show that the median sample entropy of the EEG signals in the anticipated falls is from 0.1151 to 0.2267 smaller (p-value <0.01) than those in the walk controls. In anticipated falls detection, the average accuracy with random forests is 85.2% for channel O2, which is nearly 10% higher than the channel temporal cerebral cortex (T3 and T4). The results can further guide us in developing new systems of human–machine interfaces, such as EEG data-augmented wearable airbags, to prevent anticipated falls.

TMS provokes target-dependent intracranial rhythms across human cortical and subcortical sites

BackgroundTranscranial magnetic stimulation (TMS) is believed to alter ongoing neural activity and cause circuit-level changes in brain function. While the electrophysiological effects of TMS have been extensively studied with scalp electroencephalography (EEG), this approach generally evaluates low-frequency neural activity at the cortical surface. However, TMS can be safely used in patients with intracranial electrodes (iEEG), allowing for direct assessment of deeper and more localized oscillatory responses across the frequency spectrum. Objective/HypothesisOur study used iEEG to understand the effects of TMS on human neural activity in the spectral domain. We asked (1) which brain regions respond to cortically-targeted TMS, and in what frequency bands, (2) whether deeper brain structures exhibit oscillatory responses, and (3) whether the neural responses to TMS reflect evoked versus induced oscillations. MethodsWe recruited 17 neurosurgical patients with indwelling electrodes and recorded neural activity while patients underwent repeated trials of single-pulse TMS at either the dorsolateral prefrontal cortex (DLPFC) or parietal cortex. iEEG signals were analyzed using spectral methods to understand the oscillatory responses to TMS. ResultsStimulation to DLPFC drove widespread low-frequency increases (3–8 Hz) in frontolimbic cortices and high-frequency decreases (30–110 Hz) in frontotemporal areas, including the hippocampus. Stimulation to parietal cortex specifically provoked low-frequency responses in the medial temporal lobe. While most low-frequency activity was consistent with phase-locked evoked responses, anterior frontal regions exhibited induced theta oscillations following DLPFC stimulation. ConclusionsBy combining TMS with intracranial EEG recordings, our results suggest that TMS is an effective means to perturb oscillatory neural activity in brain-wide networks, including deeper structures not directly accessed by stimulation itself.

Repetitive pulsed-wave ultrasound stimulation suppresses neural activity by modulating ambient GABA levels via effects on astrocytes.

Ultrasound is highly biopermeable and can non-invasively penetrate deep into the brain. Stimulation with patterned low-intensity ultrasound can induce sustained inhibition of neural activity in humans and animals, with potential implications for research and therapeutics. Although mechanosensitive channels are involved, the cellular and molecular mechanisms underlying neuromodulation by ultrasound remain unknown. To investigate the mechanism of action of ultrasound stimulation, we studied the effects of two types of patterned ultrasound on synaptic transmission and neural network activity using whole-cell recordings in primary cultured hippocampal cells. Single-shot pulsed-wave (PW) or continuous-wave (CW) ultrasound had no effect on neural activity. By contrast, although repetitive CW stimulation also had no effect, repetitive PW stimulation persistently reduced spontaneous recurrent burst firing. This inhibitory effect was dependent on extrasynaptic-but not synaptic-GABAA receptors, and the effect was abolished under astrocyte-free conditions. Pharmacological activation of astrocytic TRPA1 channels mimicked the effects of ultrasound by increasing the tonic GABAA current induced by ambient GABA. Pharmacological blockade of TRPA1 channels abolished the inhibitory effect of ultrasound. These findings suggest that the repetitive PW low-intensity ultrasound used in our study does not have a direct effect on neural function but instead exerts its sustained neuromodulatory effect through modulation of ambient GABA levels via channels with characteristics of TRPA1, which is expressed in astrocytes.

Consistent spectro-spatial features of human ECoG successfully decode naturalistic behavioral states.

Understanding the neural correlates of naturalistic behavior is critical for extending and confirming the results obtained from trial-based experiments and designing generalizable brain-computer interfaces that can operate outside laboratory environments. In this study, we aimed to pinpoint consistent spectro-spatial features of neural activity in humans that can discriminate between naturalistic behavioral states. We analyzed data from five participants using electrocorticography (ECoG) with broad spatial coverage. Spontaneous and naturalistic behaviors such as "Talking" and "Watching TV" were labeled from manually annotated videos. Linear discriminant analysis (LDA) was used to classify the two behavioral states. The parameters learned from the LDA were then used to determine whether the neural signatures driving classification performance are consistent across the participants. Spectro-spatial feature values were consistently discriminative between the two labeled behavioral states across participants. Mainly, θ, α, and low and high γ in the postcentral gyrus, precentral gyrus, and temporal lobe showed significant classification performance and feature consistency across participants. Subject-specific performance exceeded 70%. Combining neural activity from multiple cortical regions generally does not improve decoding performance, suggesting that information regarding the behavioral state is non-additive as a function of the cortical region. To the best of our knowledge, this is the first attempt to identify specific spectro-spatial neural correlates that consistently decode naturalistic and active behavioral states. The aim of this work is to serve as an initial starting point for developing brain-computer interfaces that can be generalized in a realistic setting and to further our understanding of the neural correlates of naturalistic behavior in humans.

Physical exercise for brain plasticity promotion an overview of the underlying oscillatory mechanism.

The global recognition of the importance of physical exercise (PE) for human health has resulted in increased research on its effects on cortical activity. Neural oscillations, which are prominent features of brain activity, serve as crucial indicators for studying the effects of PE on brain function. Existing studies support the idea that PE modifies various types of neural oscillations. While EEG-related literature in exercise science exists, a comprehensive review of the effects of exercise specifically in healthy populations has not yet been conducted. Given the demonstrated influence of exercise on neural plasticity, particularly cortical oscillatory activity, it is imperative to consolidate research on this phenomenon. Therefore, this review aims to summarize numerous PE studies on neuromodulatory mechanisms in the brain over the past decade, covering (1) effects of resistance and aerobic training on brain health via neural oscillations; (2) how mind-body exercise affects human neural activity and cognitive functioning; (3) age-Related effects of PE on brain health and neurodegenerative disease rehabilitation via neural oscillation mechanisms; and (4) conclusion and future direction. In conclusion, the effect of PE on cortical activity is a multifaceted process, and this review seeks to comprehensively examine and summarize existing studies' understanding of how PE regulates neural activity in the brain, providing a more scientific theoretical foundation for the development of personalized PE programs and further research.

Neural effects of TMS trains on the human prefrontal cortex

How does a train of TMS pulses modify neural activity in humans? Despite adoption of repetitive TMS (rTMS) for the treatment of neuropsychiatric disorders, we still do not understand how rTMS changes the human brain. This limited understanding stems in part from a lack of methods for noninvasively measuring the neural effects of a single TMS train—a fundamental building block of treatment—as well as the cumulative effects of consecutive TMS trains. Gaining this understanding would provide foundational knowledge to guide the next generation of treatments. Here, to overcome this limitation, we developed methods to noninvasively measure causal and acute changes in cortical excitability and evaluated this neural response to single and sequential TMS trains. In 16 healthy adults, standard 10 Hz trains were applied to the dorsolateral prefrontal cortex in a randomized, sham-controlled, event-related design and changes were assessed based on the TMS-evoked potential (TEP), a measure of cortical excitability. We hypothesized that single TMS trains would induce changes in the local TEP amplitude and that those changes would accumulate across sequential trains, but primary analyses did not indicate evidence in support of either of these hypotheses. Exploratory analyses demonstrated non-local neural changes in sensor and source space and local neural changes in phase and source space. Together these results suggest that single and sequential TMS trains may not be sufficient to modulate local cortical excitability indexed by typical TEP amplitude metrics but may cause neural changes that can be detected outside the stimulation area or using phase or source space metrics. This work should be contextualized as methods development for the monitoring of transient noninvasive neural changes during rTMS and contributes to a growing understanding of the neural effects of rTMS.

Recent Advancements in Graphene-Based Implantable Electrodes for Neural Recording/Stimulation.

Implantable electrodes represent a groundbreaking advancement in nervous system research, providing a pivotal tool for recording and stimulating human neural activity. This capability is integral for unraveling the intricacies of the nervous system's functionality and for devising innovative treatments for various neurological disorders. Implantable electrodes offer distinct advantages compared to conventional recording and stimulating neural activity methods. They deliver heightened precision, fewer associated side effects, and the ability to gather data from diverse neural sources. Crucially, the development of implantable electrodes necessitates key attributes: flexibility, stability, and high resolution. Graphene emerges as a highly promising material for fabricating such electrodes due to its exceptional properties. It boasts remarkable flexibility, ensuring seamless integration with the complex and contoured surfaces of neural tissues. Additionally, graphene exhibits low electrical resistance, enabling efficient transmission of neural signals. Its transparency further extends its utility, facilitating compatibility with various imaging techniques and optogenetics. This paper showcases noteworthy endeavors in utilizing graphene in its pure form and as composites to create and deploy implantable devices tailored for neural recordings and stimulations. It underscores the potential for significant advancements in this field. Furthermore, this paper delves into prospective avenues for refining existing graphene-based electrodes, enhancing their suitability for neural recording applications in in vitro and in vivo settings. These future steps promise to revolutionize further our capacity to understand and interact with the neural research landscape.

Human Sensorimotor Beta Event Characteristics and Aperiodic Signal Are Highly Heritable.

Individuals' phenotypes, including the brain's structure and function, are largely determined by genes and their interplay. The resting brain generates salient rhythmic patterns that can be characterized noninvasively using functional neuroimaging such as magnetoencephalography (MEG). One of these rhythms, the somatomotor (rolandic) beta rhythm, shows intermittent high amplitude "events" that predict behavior across tasks and species. Beta rhythm is altered in neurological disease. The aperiodic (1/f) signal present in electrophysiological recordings is also modulated by some neurological conditions and aging. Both sensorimotor beta and aperiodic signal could thus serve as biomarkers of sensorimotor function. Knowledge about the extent to which these brain functional measures are heritable could shed light on the mechanisms underlying their generation. We investigated the heritability and variability of human spontaneous sensorimotor beta rhythm events and aperiodic activity in 210 healthy male and female adult siblings' spontaneous MEG activity. The most heritable trait was the aperiodic 1/f signal, with a heritability of 0.87 in the right hemisphere. Time-resolved beta event amplitude parameters were also highly heritable, whereas the heritabilities for overall beta power, peak frequency, and measures of event duration remained nonsignificant. Human sensorimotor neural activity can thus be dissected into different components with variable heritability. We postulate that these differences partially reflect different underlying signal-generating mechanisms. The 1/f signal and beta event amplitude measures may depend more on fixed, anatomical parameters, whereas beta event duration and its modulation reflect dynamic characteristics, guiding their use as potential disease biomarkers.

Prediction underlying comprehension of human motion: an analysis of Deaf signer and non-signer EEG in response to visual stimuli.

Sensory inference and top-down predictive processing, reflected in human neural activity, play a critical role in higher-order cognitive processes, such as language comprehension. However, the neurobiological bases of predictive processing in higher-order cognitive processes are not well-understood. This study used electroencephalography (EEG) to track participants' cortical dynamics in response to Austrian Sign Language and reversed sign language videos, measuring neural coherence to optical flow in the visual signal. We then used machine learning to assess entropy-based relevance of specific frequencies and regions of interest to brain state classification accuracy. EEG features highly relevant for classification were distributed across language processing-related regions in Deaf signers (frontal cortex and left hemisphere), while in non-signers such features were concentrated in visual and spatial processing regions. The results highlight functional significance of predictive processing time windows for sign language comprehension and biological motion processing, and the role of long-term experience (learning) in minimizing prediction error.

End-to-end translation of human neural activity to speech with a dual–dual generative adversarial network

In a recent study of auditory evoked potential (AEP) based brain–computer interface (BCI), it was shown that, with an encoder–decoder framework, it is possible to translate human neural activity to speech (T-CAS). Current encoder–decoder-based methods achieve T-CAS often with a two-step approach where the information is passed between the encoder and decoder with a shared vector of reduced dimension, which, however, may result in information loss. In this paper, we propose an end-to-end model to translate human neural activity to speech (ET-CAS) by introducing a dual–dual generative adversarial network (Dual-DualGAN) for cross-domain mapping between electroencephalogram (EEG) and speech signals. In this model, we bridge the EEG and speech signals by introducing transition signals which are obtained by cascading the corresponding EEG and speech signals in a certain proportion. We then learn the mappings between the speech/EEG signals and the transition signals. We also develop a new EEG dataset where the attention of the participants is detected before the EEG signals are recorded to ensure that the participants have good attention in listening to speech utterances. The proposed method can translate word-length and sentence-length sequences of neural activity to speech. Experimental results show that the proposed method significantly outperforms state-of-the-art methods on both words and sentences of auditory stimulus.

Spatio-temporal evolution of human neural activity during visually cued hand movements.

Making hand movements in response to visual cues is common in daily life. It has been well known that this process activates multiple areas in the brain, but how these neural activations progress across space and time remains largely unknown. Taking advantage of intracranial electroencephalographic (iEEG) recordings using depth and subdural electrodes from 36 human subjects using the same task, we applied single-trial and cross-trial analyses to high-frequency iEEG activity. The results show that the neural activation was widely distributed across the human brain both within and on the surface of the brain, and focused specifically on certain areas in the parietal, frontal, and occipital lobes, where parietal lobes present significant left lateralization on the activation. We also demonstrate temporal differences across these brain regions. Finally, we evaluated the degree to which the timing of activity within these regions was related to sensory or motor function. The findings of this study promote the understanding of task-related neural processing of the human brain, and may provide important insights for translational applications.

High-density scalp electroencephalogram dataset during sensorimotor rhythm-based brain-computer interfacing

Real-time functional imaging of human neural activity and its closed-loop feedback enable voluntary control of targeted brain regions. In particular, a brain-computer interface (BCI), a direct bridge of neural activities and machine actuation is one promising clinical application of neurofeedback. Although a variety of studies reported successful self-regulation of motor cortical activities probed by scalp electroencephalogram (EEG), it remains unclear how neurophysiological, experimental conditions or BCI designs influence variability in BCI learning. Here, we provide the EEG data during using BCIs based on sensorimotor rhythm (SMR), consisting of 4 separate datasets. All EEG data were acquired with a high-density scalp EEG setup containing 128 channels covering the whole head. All participants were instructed to perform motor imagery of right-hand movement as the strategy to control BCIs based on the task-related power attenuation of SMR magnitude, that is event-related desynchronization. This dataset would allow researchers to explore the potential source of variability in BCI learning efficiency and facilitate follow-up studies to test the explicit hypotheses explored by the dataset.

Omission responses in local field potentials in rat auditory cortex

BackgroundNon-invasive recordings of gross neural activity in humans often show responses to omitted stimuli in steady trains of identical stimuli. This has been taken as evidence for the neural coding of prediction or prediction error. However, evidence for such omission responses from invasive recordings of cellular-scale responses in animal models is scarce. Here, we sought to characterise omission responses using extracellular recordings in the auditory cortex of anaesthetised rats. We profiled omission responses across local field potentials (LFP), analogue multiunit activity (AMUA), and single/multi-unit spiking activity, using stimuli that were fixed-rate trains of acoustic noise bursts where 5% of bursts were randomly omitted.ResultsSignificant omission responses were observed in LFP and AMUA signals, but not in spiking activity. These omission responses had a lower amplitude and longer latency than burst-evoked sensory responses, and omission response amplitude increased as a function of the number of preceding bursts.ConclusionsTogether, our findings show that omission responses are most robustly observed in LFP and AMUA signals (relative to spiking activity). This has implications for models of cortical processing that require many neurons to encode prediction errors in their spike output.

Dimension-wise Sequential Update for Learning a Multidimensional Environment in Humans.

When confronted with multidimensional environment problems, humans may need to jointly update multiple state-action-outcome associations across various dimensions. Computational modeling of human behavior and neural activities suggests that such updates are implemented based upon Bayesian update principle. However, it is unclear whether humans perform these updates individually or sequentially. If the update occurs sequentially, the order in which the associations are updated matters and can influence the updated results. To address this question, we tested a few computational models with different update orders using both human behavior and EEG data. Our results indicated that a model undertaking dimension-wise sequential updates was the best fit to human behavior. In this model, ordering the dimensions was decided using entropy, which indexed the uncertainty of associations. Simultaneously collected EEG data revealed evoked potentials that were correlated to the proposed timing of this model. These findings provide new insights into the temporal processes underlying Bayesian update in multidimensional environments.

0610 The effects of wakefulness promoting agents on neuronal activity in nucleus accumbens

Abstract Introduction Both modafinil and methylphenidate are frequently utilized for maintenance of wakefulness in narcolepsy and other sleep disorders. Both have been demonstrated to affect dopamine transporter, leading to an increase extracellular dopamine. Subsequent functional connectivity changes between nucleus accumbens and pallidum are noted. Animal studies demonstrate changes in neuronal activity with methylphenidate in nucleus accumbens. To our knowledge there has been no direct examination of human neural activity in nucleus accumbens after administration of modafinil or methylphenidate, compared to baseline. Methods Two subjects with placement of stereotactic electroencephalographic (sEEG) electrodes to identify optimal location for permanent deep brain stimulation electrodes in nucleus accumbens were given wakefulness promoting agents to optimize testing of stimulation sites during inpatient hospitalization. Assessment occurred at least 48 hours following surgical electrode insertion under inhaled general anesthesia. Retrospective analysis was performed on neural activity in nucleus accumbens during rest on and off medication. Frequency content was calculated in the following bands: delta (1-3 Hz), theta (4-7 Hz), alpha (8-12 Hz), beta (13-30 Hz), gamma (30-50 Hz), and high gamma (70-100 Hz). Power in each band is reported as the percentage contribution of each band to summed power across all bands. Results Total power was noted to be lower with both modafinil and methylphenidate. With modafinil, the beta band ratio was decreased (22.3% vs. 30.5%), the gamma band ratio was increased (24% vs. 22.4%), and the high gamma band was increased (39.5% vs. 32.9%). With methylphenidate, only the high gamma band was increased (40.3% vs. 22.9%). Conclusion Both methylphenidate and modafinil increase high gamma band neural activity in nucleus accumbens, while modafinil has additional effects on beta and gamma bands. Further assessment of modafinil and methylphenidate’s effects on neural activity are indicated to help better understand their mechanism of action and appropriate use as wakefulness promoting agents. Support (if any)

Human neural network activity reacts to gravity changes in vitro.

During spaceflight, humans experience a variety of physiological changes due to deviations from familiar earth conditions. Specifically, the lack of gravity is responsible for many effects observed in returning astronauts. These impairments can include structural as well as functional changes of the brain and a decline in cognitive performance. However, the underlying physiological mechanisms remain elusive. Alterations in neuronal activity play a central role in mental disorders and altered neuronal transmission may also lead to diminished human performance in space. Thus, understanding the influence of altered gravity at the cellular and network level is of high importance. Previous electrophysiological experiments using patch clamp techniques and calcium indicators have shown that neuronal activity is influenced by altered gravity. By using multi-electrode array (MEA) technology, we advanced the electrophysiological investigation covering single-cell to network level responses during exposure to decreased (micro-) or increased (hyper-) gravity conditions. We continuously recorded in real-time the spontaneous activity of human induced pluripotent stem cell (hiPSC)-derived neural networks in vitro. The MEA device was integrated into a custom-built environmental chamber to expose the system with neuronal cultures to up to 6 g of hypergravity on the Short-Arm Human Centrifuge at the DLR Cologne, Germany. The flexibility of the experimental hardware set-up facilitated additional MEA electrophysiology experiments under 4.7 s of high-quality microgravity (10-6 to 10-5 g) in the Bremen drop tower, Germany. Hypergravity led to significant changes in activity. During the microgravity phase, the mean action potential frequency across the neural networks was significantly enhanced, whereas different subgroups of neurons showed distinct behaviors, such as increased or decreased firing activity. Our data clearly demonstrate that gravity as an environmental stimulus triggers changes in neuronal activity. Neuronal networks especially reacted to acute changes in mechanical loading (hypergravity) or de-loading (microgravity). The current study clearly shows the gravity-dependent response of neuronal networks endorsing the importance of further investigations of neuronal activity and its adaptive responses to micro- and hypergravity. Our approach provided the basis for the identification of responsible mechanisms and the development of countermeasures with potential implications on manned space missions.

A 2D CNN-LSTM hybrid algorithm using time series segments of EEG data for motor imagery classification

Motor imagery-based brain–computer interaction (MI-BCI) converts human neural activity into computational information, often used as commands, by recognizing electroencephalogram (EEG) patterns in different MI tasks. Owing to the poor accuracy and stability of classification algorithms, MI systems remain challenging to employ in practice. Therefore, we proposed a two-dimensional convolutional neural network-long short-term memory (2D CNN-LSTM) hybrid algorithm to classify EEG in MI tasks. We converted EEG signals into time series segments, and then extracted the connectivity features between the different EEG channels in each segment through 2D CNN, finally sent the feature vectors to LSTM network for training. The experimental results showed that the 2D CNN-LSTM algorithm had an average accuracy of 98.5% in the validation set, and a 93.3% average accuracy in the test set, and compared with existing algorithm, such as 1D CNN-LSTM algorithm in the test set, the average accuracy of our algorithm was improved by 3.1% and the F1-score by 0.04, while the loss of the verification set decreased by more than 0.1 in multi-person modeling (general model) in the test set, which was the largest decrease among the algorithms being compared.

Neurocognitive, physiological, and biophysical effects of transcranial alternating current stimulation.

Transcranial alternating current stimulation (tACS) can modulate human neural activity and behavior. Accordingly, tACS has vast potential for cognitive research and brain disorder therapies. The stimulation generates oscillating electric fields in the brain that can bias neural spike timing, causing changes in local neural oscillatory power and cross-frequency and cross-area coherence. tACS affects cognitive performance by modulating underlying single or nested brain rhythms, local or distal synchronization, and metabolic activity. Clinically, stimulation tailored to abnormal neural oscillations shows promising results in alleviating psychiatric and neurological symptoms. We summarize the findings of tACS mechanisms, its use for cognitive applications, and novel developments for personalized stimulation.