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

2020 ◽  
Vol 6 (36) ◽  
pp. eaaz2747 ◽  
Author(s):  
Luke Johnson ◽  
Ivan Alekseichuk ◽  
Jordan Krieg ◽  
Alex Doyle ◽  
Ying Yu ◽  
...  

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.

2019 ◽  
Author(s):  
Luke Johnson ◽  
Ivan Alekseichuk ◽  
Jordan Krieg ◽  
Alex Doyle ◽  
Ying Yu ◽  
...  

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.


2019 ◽  
Author(s):  
Ehsan Negahbani ◽  
Iain M. Stitt ◽  
Marshall Davey ◽  
Thien T. Doan ◽  
Moritz Dannhauer ◽  
...  

SummaryModeling studies predict that transcranial alternating current stimulation (tACS) entrains brain oscillations, yet direct examination has been lacking or potentially contaminated by stimulation artefact. Here we first demonstrate how the posterior parietal cortex drives primary visual cortex and thalamic LP in the alpha-band in head-fixed awake ferrets. The spike-field synchrony is maximum within alpha frequency, and more prominent for narrow-spiking neurons than broad-spiking ones. Guided by a validated model of electric field distribution, we produced electric fields comparable to those in humans and primates (< 0.5 mV/mm). We found evidence to support the model-driven predictions of how tACS entrains neural oscillations as explained by the triangular Arnold tongue pattern. In agreement with the stronger spike-field coupling of narrow-spiking cells, tACS more strongly entrained this cell population. Our findings provide the firstin vivoevidence of how tACS with electric field amplitudes used in human studies entrains neuronal oscillators.


2014 ◽  
Vol 16 (1) ◽  
pp. 93-102 ◽  

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.


Author(s):  
Michael A. Nitsche ◽  
Walter Paulus ◽  
Gregor Thut

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.


2020 ◽  
Vol 32 (8) ◽  
pp. 1428-1437
Author(s):  
Anne Kösem ◽  
Hans Rutger Bosker ◽  
Ole Jensen ◽  
Peter Hagoort ◽  
Lars Riecke

Recent neuroimaging evidence suggests that the frequency of entrained oscillations in auditory cortices influences the perceived duration of speech segments, impacting word perception [Kösem, A., Bosker, H. R., Takashima, A., Meyer, A., Jensen, O., & Hagoort, P. Neural entrainment determines the words we hear. Current Biology, 28, 2867–2875, 2018]. We further tested the causal influence of neural entrainment frequency during speech processing, by manipulating entrainment with continuous transcranial alternating current stimulation (tACS) at distinct oscillatory frequencies (3 and 5.5 Hz) above the auditory cortices. Dutch participants listened to speech and were asked to report their percept of a target Dutch word, which contained a vowel with an ambiguous duration. Target words were presented either in isolation (first experiment) or at the end of spoken sentences (second experiment). We predicted that the tACS frequency would influence neural entrainment and therewith how speech is perceptually sampled, leading to a perceptual overestimation or underestimation of the vowel's duration. Whereas results from Experiment 1 did not confirm this prediction, results from Experiment 2 suggested a small effect of tACS frequency on target word perception: Faster tACS leads to more long-vowel word percepts, in line with the previous neuroimaging findings. Importantly, the difference in word perception induced by the different tACS frequencies was significantly larger in Experiment 1 versus Experiment 2, suggesting that the impact of tACS is dependent on the sensory context. tACS may have a stronger effect on spoken word perception when the words are presented in continuous speech as compared to when they are isolated, potentially because prior (stimulus-induced) entrainment of brain oscillations might be a prerequisite for tACS to be effective.


2015 ◽  
Vol 87 (2 suppl) ◽  
pp. 1397-1408 ◽  
Author(s):  
GABRIELA L. DA SILVA ◽  
CAROLINA LUFT ◽  
ADROALDO LUNARDELLI ◽  
ROBSON H. AMARAL ◽  
DENIZAR A. DA SILVA MELO ◽  
...  

Several studies have investigated the antinociceptive, immunomodulatory and anti-inflammatory properties of compounds found in the lavender essential oil (LEO), however to date, there is still lack of substantial data. The objective of this study was to assess the antioxidant, anti-inflammatory and antinociceptive effects of lavender essential oil. The 1,1-diphenyl-2-picrylhydrazyl radical decolorization assay was used for antioxidant activity evaluation. The anti-inflammatory activity was tested using two models of acute inflammation: carrageenan-induced pleurisy and croton oil-induced ear edema. The antinociceptive activity was tested using the pain model induced by formalin. LEO has antioxidant activity, which is dose-dependent response. The inflammatory response evoked by carrageenan and by croton oil was reduced through the pre-treatment of animals with LEO. In the pleurisy model, the drug used as positive control, dexamethasone, was more efficacious. However, in the ear swelling, the antiedematogenic effect of the oil was similar to that observed for dexamethasone. In the formalin test, LEO consistently inhibited spontaneous nociception and presented a similar effect to that of tramadol. The results of this study reveal (in vivo) the analgesic and anti-inflammatory activities of LEO and demonstrates its important therapeutic potential.


2020 ◽  
Vol 123 (1) ◽  
pp. 428-438 ◽  
Author(s):  
Kohitij Kar ◽  
Takuya Ito ◽  
Michael W. Cole ◽  
Bart Krekelberg

Transcranial alternating current stimulation (tACS) is used as a noninvasive tool for cognitive enhancement and clinical applications. The physiological effects of tACS, however, are complex and poorly understood. Most studies of tACS focus on its ability to entrain brain oscillations, but our behavioral results in humans and extracellular recordings in nonhuman primates support the view that tACS at 10 Hz also affects brain function by reducing sensory adaptation. Our primary goal in the present study is to test this hypothesis using blood oxygen level-dependent (BOLD) imaging in human subjects. Using concurrent functional magnetic resonance imaging (fMRI) and tACS, and a motion adaptation paradigm developed to quantify BOLD adaptation, we show that tACS significantly attenuates adaptation in the human motion area (hMT+). In addition, an exploratory analysis shows that tACS increases functional connectivity of the stimulated hMT+ with the rest of the brain and the dorsal attention network in particular. Based on field estimates from individualized head models, we relate these changes to the strength of tACS-induced electric fields. Specifically, we report that functional connectivity (between hMT+ and any other region of interest) increases in proportion to the field strength in the region of interest. These findings add support for the claim that weak 10-Hz currents applied to the scalp modulate both local and global measures of brain activity. NEW & NOTEWORTHY Concurrent transcranial alternating current stimulation (tACS) and functional MRI show that tACS affects the human brain by attenuating adaptation and increasing functional connectivity in a dose-dependent manner. 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.


2020 ◽  
Vol 32 (2) ◽  
pp. 226-240 ◽  
Author(s):  
Benedikt Zoefel ◽  
Isobella Allard ◽  
Megha Anil ◽  
Matthew H. Davis

Several recent studies have used transcranial alternating current stimulation (tACS) to demonstrate a causal role of neural oscillatory activity in speech processing. In particular, it has been shown that the ability to understand speech in a multi-speaker scenario or background noise depends on the timing of speech presentation relative to simultaneously applied tACS. However, it is possible that tACS did not change actual speech perception but rather auditory stream segregation. In this study, we tested whether the phase relation between tACS and the rhythm of degraded words, presented in silence, modulates word report accuracy. We found strong evidence for a tACS-induced modulation of speech perception, but only if the stimulation was applied bilaterally using ring electrodes (not for unilateral left hemisphere stimulation with square electrodes). These results were only obtained when data were analyzed using a statistical approach that was identified as optimal in a previous simulation study. The effect was driven by a phasic disruption of word report scores. Our results suggest a causal role of neural entrainment for speech perception and emphasize the importance of optimizing stimulation protocols and statistical approaches for brain stimulation research.


2021 ◽  
Vol 11 (8) ◽  
pp. 1095
Author(s):  
Naoyuki Takeuchi ◽  
Shin-Ichi Izumi

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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