scholarly journals tACS competes with ongoing oscillations for control of spike-timing in the primate brain.

2021 ◽  
Author(s):  
Matthew Ryan Krause ◽  
Pedro Gabrielle Vieira ◽  
Jean-Philippe Thivierge ◽  
Christopher C Pack

Transcranial alternating current stimulation (tACS) is a promising but controversial method for modulating neural activity noninvasively. Much of the controversy revolves around the question of whether tACS can generate electric fields that are strong enough to entrain neuronal spiking activity. Here we show that what matters is not the electric field strength per se, but rather the strength of the stimulation relative to ongoing oscillatory entrainment. We recorded from single neurons in the cortex and subcortex of behaving non-human primates, while applying tACS at different frequencies and amplitudes. When neuronal activity was weakly locked to ongoing oscillations, tACS readily entrained single-neuron activity to specific stimulation phases. In contrast, neurons that were strongly locked to ongoing oscillations usually exhibited decreased entrainment during low-amplitude tACS. As this reduced entrainment is a property of many oscillating systems, attempts to impose an external rhythm on spiking activity may often yield precisely the opposite effect.

2019 ◽  
Vol 116 (12) ◽  
pp. 5747-5755 ◽  
Author(s):  
Matthew R. Krause ◽  
Pedro G. Vieira ◽  
Bennett A. Csorba ◽  
Praveen K. Pilly ◽  
Christopher C. Pack

Spike timing is thought to play a critical role in neural computation and communication. Methods for adjusting spike timing are therefore of great interest to researchers and clinicians alike. Transcranial electrical stimulation (tES) is a noninvasive technique that uses weak electric fields to manipulate brain activity. Early results have suggested that this technique can improve subjects’ behavioral performance on a wide range of tasks and ameliorate some clinical conditions. Nevertheless, considerable skepticism remains about its efficacy, especially because the electric fields reaching the brain during tES are small, whereas the likelihood of indirect effects is large. Our understanding of its effects in humans is largely based on extrapolations from simple model systems and indirect measures of neural activity. As a result, fundamental questions remain about whether and how tES can influence neuronal activity in the human brain. Here, we demonstrate that tES, as typically applied to humans, affects the firing patterns of individual neurons in alert nonhuman primates, which are the best available animal model for the human brain. Specifically, tES consistently influences the timing, but not the rate, of spiking activity within the targeted brain region. Such effects are frequency- and location-specific and can reach deep brain structures; control experiments show that they cannot be explained by sensory stimulation or other indirect influences. These data thus provide a strong mechanistic rationale for the use of tES in humans and will help guide the development of future tES applications.


2010 ◽  
Vol 103 (4) ◽  
pp. 1843-1855 ◽  
Author(s):  
Shunsuke Kobayashi ◽  
Wolfram Schultz ◽  
Masamichi Sakagami

An operant is a behavioral act that has an impact on the environment to produce an outcome, constituting an important component of voluntary behavior. Because the environment can be volatile, the same action may cause different consequences. Thus to obtain an optimal outcome, it is crucial to detect action–outcome relationships and adapt the behavior accordingly. Although prefrontal neurons are known to change activity depending on expected reward, it remains unknown whether prefrontal activity contributes to obtaining reward. We investigated this issue by setting variable relationships between levels of single-neuron activity and rewarding outcomes. Lateral prefrontal neurons changed their spiking activity according to the specific requirements for gaining reward, without the animals making a motor response. Thus spiking activity constituted an operant response. Data from a control task suggested that these changes were unlikely to reflect simple reward predictions. These data demonstrate a remarkable capacity of prefrontal neurons to adapt to specific operant requirements at the single-neuron level.


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.


PLoS Biology ◽  
2020 ◽  
Vol 18 (10) ◽  
pp. e3000931
Author(s):  
Mircea van der Plas ◽  
Simon Hanslmayr

Transcranial Alternating Current Stimulation (tACS) is a method that injects rhythmic currents into the human brain via electrodes attached to the scalp of a participant. This technique allows researchers to control naturally occurring brain rhythms and study their causal relevance for cognition. Recent findings, however, cast doubts on the effectiveness of tACS to stimulate the brain and its mode of action. Two new studies by Vieira and colleagues and Marchesotti and colleagues reported in the current issue report promising new results in showing that tACS can entrain single neuron activity and improve reading abilities in dyslexic individuals.


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.


2021 ◽  
Author(s):  
Harry Tran ◽  
Sina Shirinpour ◽  
Alexander Opitz

AbstractNeural oscillations are a key mechanism for information transfer in brain circuits. Rhythmic fluctuations of local field potentials control spike timing through cyclic membrane de- and hyperpolarization. Transcranial alternating current stimulation (tACS) is a non-invasive neuromodulation method which can directly interact with brain oscillatory activity by imposing an oscillating electric field on neurons. Despite its increasing use, the basic mechanisms of tACS are still not fully understood. Here, we investigate in a computational study the effects of tACS on morphologically realistic neurons with ongoing spiking activity. We characterize the membrane polarization as a function of electric field strength and subsequent effects on spiking activity in a set of 25 neurons from different neocortical layers. We find that tACS does not affect the firing rate of investigated neurons for electric field strengths applicable to human studies. However, we find that the applied electric fields entrain the spiking activity of large pyramidal neurons at < 1mV/mm field strengths. Our model results are in line with recent experimental studies and can provide a mechanistic framework to understand the effects of oscillating electric fields on single neuron activity. They highlight the importance of neuron morphology in responsiveness to electrical stimulation and suggest that large pyramidal neurons are most likely the prime target for tACS.


2021 ◽  
Vol 11 (3) ◽  
pp. 377
Author(s):  
Cheng Chen ◽  
Kai Yuan ◽  
Winnie Chiu-wing Chu ◽  
Raymond Kai-yu Tong

Transcranial alternating current stimulation (tACS) has emerged as a promising technique to non-invasively modulate the endogenous oscillations in the human brain. Despite its clinical potential to be applied in routine rehabilitation therapies, the underlying modulation mechanism has not been thoroughly understood, especially for patients with neurological disorders, including stroke. In this study, we aimed to investigate the frequency-specific stimulation effect of tACS in chronic stroke. Thirteen chronic stroke patients underwent tACS intervention, while resting-state functional magnetic resonance imaging (fMRI) data were collected under various frequencies (sham, 10 Hz and 20 Hz). The graph theoretical analysis indicated that 20 Hz tACS might facilitate local segregation in motor-related regions and global integration at the whole-brain level. However, 10 Hz was only observed to increase the segregation from whole-brain level. Additionally, it is also observed that, for the network in motor-related regions, the nodal clustering characteristic was decreased after 10 Hz tACS, but increased after 20 Hz tACS. Taken together, our results suggested that tACS in various frequencies might induce heterogeneous modulation effects in lesioned brains. Specifically, 20 Hz tACS might induce more modulation effects, especially in motor-related regions, and they have the potential to be applied in rehabilitation therapies to facilitate neuromodulation. Our findings might shed light on the mechanism of neural responses to tACS and facilitate effectively designing stimulation protocols with tACS in stroke in the future.


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