Phase-specific manipulation of rhythmic brain activity by transcranial alternating current stimulation

Synchronized neuronal activity in the cortex generates weak electric fields that are routinely measured in humans and animal models by electroencephalography and local field potential recordings. Traditionally, these endogenous electric fields have been considered to be an epiphenomenon of brain activity. Recent work has demonstrated that active cortical networks are surprisingly susceptible to weak perturbations of the membrane voltage of a large number of neurons by electric fields. Simultaneously, noninvasive brain stimulation with weak, exogenous electric fields (transcranial current stimulation, TCS) has undergone a renaissance due to the broad scope of its possible applications in modulating brain activity for cognitive enhancement and treatment of brain disorders. This review aims to interface the recent developments in the study of both endogenous and exogenous electric fields, with a particular focus on rhythmic stimulation for the modulation of cortical oscillations. The main goal is to provide a starting point for the use of rational design for the development of novel mechanism-based TCS therapeutics based on transcranial alternating current stimulation, for the treatment of psychiatric illnesses.

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Changes in TMS measures of cortical excitability induced by transcranial direct and alternating current stimulation

The Oxford Handbook of Transcranial Stimulation, Second Edition ◽

10.1093/oxfordhb/9780198832256.013.20 ◽

2021 ◽

Author(s):

Michael A. Nitsche ◽

Walter Paulus ◽

Gregor Thut

Keyword(s):

Brain Stimulation ◽

Cortical Excitability ◽

Brain Activity ◽

Alternating Current ◽

Transcranial Electrical Stimulation ◽

Electrical Currents ◽

After Effects ◽

Brain Physiology ◽

Transcranial Alternating Current Stimulation ◽

Oscillatory Brain Activity

Brain stimulation with weak electrical currents (transcranial electrical stimulation, tES) is known already for about 60 years as a technique to generate modifications of cortical excitability and activity. Originally established in animal models, it was developed as a noninvasive brain stimulation tool about 20 years ago for application in humans. Stimulation with direct currents (transcranial direct current stimulation, tDCS) induces acute cortical excitability alterations, as well as neuroplastic after-effects, whereas stimulation with alternating currents (transcranial alternating current stimulation, tACS) affects primarily oscillatory brain activity but has also been shown to induce neuroplasticity effects. Beyond their respective regional effects, both stimulation techniques have also an impact on cerebral networks. Transcranial magnetic stimulation (TMS) has been pivotal to helping reveal the physiological effects and mechanisms of action of both stimulation techniques for motor cortex application, but also for stimulation of other areas. This chapter will supply the reader with an overview about the effects of tES on human brain physiology, as revealed by TMS.

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Motor Learning Based on Oscillatory Brain Activity Using Transcranial Alternating Current Stimulation: A Review

Brain Sciences ◽

10.3390/brainsci11081095 ◽

2021 ◽

Vol 11 (8) ◽

pp. 1095

Author(s):

Naoyuki Takeuchi ◽

Shin-Ichi Izumi

Keyword(s):

Motor Learning ◽

Brain Activity ◽

Alternating Current ◽

Social Effects ◽

Motor Deficits ◽

Noninvasive Brain Stimulation ◽

Transcranial Alternating Current Stimulation ◽

Oscillatory Brain Activity ◽

Teaching Learning ◽

The Relationship

Developing effective tools and strategies to promote motor learning is a high-priority scientific and clinical goal. In particular, motor-related areas have been investigated as potential targets to facilitate motor learning by noninvasive brain stimulation (NIBS). In addition to shedding light on the relationship between motor function and oscillatory brain activity, transcranial alternating current stimulation (tACS), which can noninvasively entrain oscillatory brain activity and modulate oscillatory brain communication, has attracted attention as a possible technique to promote motor learning. This review focuses on the use of tACS to enhance motor learning through the manipulation of oscillatory brain activity and its potential clinical applications. We discuss a potential tACS–based approach to ameliorate motor deficits by correcting abnormal oscillatory brain activity and promoting appropriate oscillatory communication in patients after stroke or with Parkinson’s disease. Interpersonal tACS approaches to manipulate intra- and inter-brain communication may result in pro-social effects and could promote the teaching–learning process during rehabilitation sessions with a therapist. The approach of re-establishing oscillatory brain communication through tACS could be effective for motor recovery and might eventually drive the design of new neurorehabilitation approaches based on motor learning.

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Dose-Dependent Effects of Transcranial Alternating Current Stimulation on Spike Timing in Awake Nonhuman Primates

10.1101/696344 ◽

2019 ◽

Cited By ~ 6

Author(s):

Luke Johnson ◽

Ivan Alekseichuk ◽

Jordan Krieg ◽

Alex Doyle ◽

Ying Yu ◽

...

Keyword(s):

Electric Fields ◽

Nonhuman Primates ◽

Brain Activity ◽

Alternating Current ◽

Spike Timing ◽

Novel Treatments ◽

Dose Dependent Fashion ◽

Transcranial Alternating Current Stimulation ◽

Dose Dependent

ABSTRACTWeak extracellular electric fields can influence spike timing in neural networks. Approaches to impose such fields on the brain in a noninvasive manner have high potential for novel treatments of neurological and psychiatric disorders. One of these methods, transcranial alternating current stimulation (TACS), is hypothesized to affect spike timing and cause neural entrainment. However, the conditions under which these effects occur in-vivo are unknown. Here, we show that TACS modulates spike timing in awake nonhuman primates (NHPs) in a dose-dependent fashion. Recording single-unit activity from pre-and post-central gyrus regions in NHPs during TACS, we found that a larger population of neurons became entrained to the stimulation waveform for higher stimulation intensities. Performing a cluster analysis of changes in interspike intervals, we identified two main types of neural responses to TACS – increased burstiness and phase entrainment. Our results demonstrate the ability of TACS to affect spike-timing in the awake primate brain and identify fundamental neural mechanisms. Concurrent electric field recordings demonstrate that spike-timing changes occur with stimulation intensities readily achievable in humans. These results suggest that novel TACS protocols tailored to ongoing brain activity may be a potent tool to normalize spike-timing in maladaptive brain networks and neurological disease.

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Effects of Transcranial Alternating Current Stimulation and Neurofeedback on Alpha (EEG) Dynamics: A Review

Frontiers in Human Neuroscience ◽

10.3389/fnhum.2021.628229 ◽

2021 ◽

Vol 15 ◽

Author(s):

Mária Orendáčová ◽

Eugen Kvašňák

Keyword(s):

Brain Activity ◽

Alternating Current ◽

Homeostatic Plasticity ◽

Brain Functioning ◽

Eeg Activity ◽

Non Invasive ◽

Current State ◽

Transcranial Alternating Current Stimulation ◽

Stimulation Period ◽

New Research

Transcranial alternating current stimulation (tACS) and neurofeedback (NFB) are two different types of non-invasive neuromodulation techniques, which can modulate brain activity and improve brain functioning. In this review, we compared the current state of knowledge related to the mechanisms of tACS and NFB and their effects on electroencephalogram (EEG) activity (online period/stimulation period) and on aftereffects (offline period/post/stimulation period), including the duration of their persistence and potential behavioral benefits. Since alpha bandwidth has been broadly studied in NFB and in tACS research, the studies of NFB and tACS in modulating alpha bandwidth were selected for comparing the online and offline effects of these two neuromodulation techniques. The factors responsible for variability in the responsiveness of the modulated EEG activity by tACS and NFB were analyzed and compared too. Based on the current literature related to tACS and NFB, it can be concluded that tACS and NFB differ a lot in the mechanisms responsible for their effects on an online EEG activity but they possibly share the common universal mechanisms responsible for the induction of aftereffects in the targeted stimulated EEG band, namely Hebbian and homeostatic plasticity. Many studies of both neuromodulation techniques report the aftereffects connected to the behavioral benefits. The duration of persistence of aftereffects for NFB and tACS is comparable. In relation to the factors influencing responsiveness to tACS and NFB, significantly more types of factors were analyzed in the NFB studies compared to the tACS studies. Several common factors for both tACS and NFB have been already investigated. Based on these outcomes, we propose several new research directions regarding tACS and NFB.

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Transcranial Alternating Current Stimulation Differently Modulates Brain Activity in Depressed Patients and Healthy Controls

Biological Psychiatry ◽

10.1016/j.biopsych.2020.02.1158 ◽

2020 ◽

Vol 87 (9) ◽

pp. S455

Author(s):

Justin Riddle ◽

Morgan Alexander ◽

Trevor McPherson ◽

Crystal Schiller ◽

David Rubinow ◽

...

Keyword(s):

Brain Activity ◽

Alternating Current ◽

Healthy Controls ◽

Depressed Patients ◽

Transcranial Alternating Current Stimulation

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Dose-dependent effects of transcranial alternating current stimulation on spike timing in awake nonhuman primates

Science Advances ◽

10.1126/sciadv.aaz2747 ◽

2020 ◽

Vol 6 (36) ◽

pp. eaaz2747 ◽

Cited By ~ 7

Author(s):

Luke Johnson ◽

Ivan Alekseichuk ◽

Jordan Krieg ◽

Alex Doyle ◽

Ying Yu ◽

...

Keyword(s):

Electric Fields ◽

Nonhuman Primates ◽

Therapeutic Potential ◽

Brain Activity ◽

Alternating Current ◽

Spike Timing ◽

Transcranial Alternating Current Stimulation ◽

Neural Entrainment ◽

Dose Dependent

Weak extracellular electric fields can influence spike timing in neural networks. Approaches to noninvasively impose these fields on the brain have high therapeutic potential in neurology and psychiatry. Transcranial alternating current stimulation (TACS) is hypothesized to affect spike timing and cause neural entrainment. However, the conditions under which these effects occur in vivo are unknown. Here, we recorded single-unit activity in the neocortex in awake nonhuman primates during TACS and found dose-dependent neural entrainment to the stimulation waveform. Cluster analysis of changes in interspike intervals identified two main types of neural responses to TACS—increased burstiness and phase entrainment. Our results uncover key mechanisms of TACS and show that the stimulation affects spike timing in the awake primate brain at intensities feasible in humans. Thus, novel TACS protocols tailored to ongoing brain activity may be a tool to normalize spike timing in maladaptive brain networks and neurological disease.

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Transcranial alternating current stimulation attenuates BOLD adaptation and increases functional connectivity

10.1101/630368 ◽

2019 ◽

Author(s):

Kohitij Kar ◽

Takuya Ito ◽

Michael Cole ◽

Bart Krekelberg

Keyword(s):

Functional Connectivity ◽

Human Subjects ◽

Brain Activity ◽

Full Range ◽

Alternating Current ◽

Human Motion ◽

Bold Imaging ◽

Dorsal Attention Network ◽

Transcranial Alternating Current Stimulation ◽

The Brain

Transcranial alternating current stimulation (tACS) is used as a non-invasive tool for cognitive enhancement and clinical applications. The physiological effects of tACS, however, are complex and poorly understood (Liu et al. 2018). Most studies of tACS focus on its ability to entrain brain oscillations (Herrmann et al. 2013), but our behavioral results in humans (Kar and Krekelberg 2014a) and extracellular recordings in nonhuman primates (Kar et al. 2017) support the view that tACS at 10 Hz additionally affects brain function by reducing sensory adaptation. Our primary goal here was to test this hypothesis using BOLD imaging in human subjects. Using a motion adaptation paradigm developed to quantify BOLD adaptation (Huk et al. 2001) and concurrent fMRI and tACS, we found that tACS significantly attenuated adaptation in the human motion area (hMT+). In addition, an exploratory analysis showed that tACS increased functional connectivity between the stimulated hMT+ and the rest of the brain, in particular the dorsal attention network. We conclude that weak 10 Hz currents applied to the scalp affect both local and global measures of brain activity.New and NoteworthyConcurrent transcranial alternating current stimulation (tACS) and fMRI show that tACS affects the human brain by attenuating adaptation and increasing functional connectivity. This work is important for our basic understanding of what tACS does, but also for therapeutic applications, which need insight into the full range of ways in which tACS affects the brain.

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Transcranial alternating current stimulation at theta frequency to the parietal cortex impairs associative, but not perceptual, memory encoding

10.1101/2020.11.19.387407 ◽

2020 ◽

Author(s):

Alyssa Meng ◽

Max Kaiser ◽

Tom de Graaf ◽

Felix Duecker ◽

Alexander T. Sack ◽

...

Keyword(s):

Associative Memory ◽

Parietal Cortex ◽

Brain Stimulation ◽

Brain Activity ◽

Memory Performance ◽

Alternating Current ◽

Theta Oscillations ◽

Memory Encoding ◽

Transcranial Alternating Current Stimulation ◽

Hippocampal Network

AbstractNeural oscillations in the theta range (4-6 Hz) are thought to underlie associative memory function in the hippocampal-cortical network. While there is ample evidence supporting a role of theta oscillations in animal and human memory, most evidence is correlational. Non-invasive brain stimulation (NIBS) can be employed to modulate cortical oscillatory activity to influence brain activity, and possibly modulate deeper brain regions, such as hippocampus, through strong and reliable cortico-hippocampal functional connections. We applied high-definition transcranial alternating current stimulation (HD-tACS) at 6 Hz over left parietal cortex to modulate brain activity in the putative cortico-hippocampal network to influence associative memory encoding. After encoding and brain stimulation, participants completed an associative memory and a perceptual recognition task. Results showed that theta tACS significantly decreased associative memory performance but did not affect perceptual memory performance. These results show that parietal theta tACS modulates associative processing separately from perceptual processing, and further substantiate the hypothesis that theta oscillations are implicated in the cortico-hippocampal network and associative encoding.

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