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TACS motor system effects can be caused by transcutaneous stimulation of peripheral nerves.

ABSTRACT: Transcranial alternating current stimulation (tACS) is a noninvasive neuromodulation method which has been shown to modulate hearing, motor, cognitive and memory function. However, the mechanisms underpinning these findings are controversial, as studies show that the current reaching the cortex may not be strong enough to entrain neural activity. Here, we propose a new hypothesis to reconcile these opposing results: tACS effects are caused by transcutaneous stimulation of peripheral nerves in the skin and not transcranial stimulation of cortical neurons. Rhythmic activity from peripheral nerves then entrains cortical neurons. A series of experiments in rats and humans isolated the transcranial and transcutaneous mechanisms and showed that the reported effects of tACS on the motor system can be caused by transcutaneous stimulation of peripheral nerves. Whether or not the transcutaneous mechanism will generalize to tACS effects on other systems is debatable but should be investigated.

SUBMITTER: Asamoah B

PROVIDER: S-EPMC6336776 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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tACS motor system effects can be caused by transcutaneous stimulation of peripheral nerves.

Asamoah Boateng B Khatoun Ahmad A Mc Laughlin Myles M

Nature communications 20190117 1

Transcranial alternating current stimulation (tACS) is a noninvasive neuromodulation method which has been shown to modulate hearing, motor, cognitive and memory function. However, the mechanisms underpinning these findings are controversial, as studies show that the current reaching the cortex may not be strong enough to entrain neural activity. Here, we propose a new hypothesis to reconcile these opposing results: tACS effects are caused by transcutaneous stimulation of peripheral nerves in th ...[more]

PMID: 30655523

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Project description:Objective: Reanimation of muscles paralyzed by disease states such as spinal cord injury remains a highly sought therapeutic goal of neuroprosthetic research. Optogenetic stimulation of peripheral motor nerves expressing light-sensitive opsins is a promising approach to muscle reanimation that may overcome several drawbacks of traditional methods such as functional electrical stimulation (FES). However, the utility of these methods has only been demonstrated in rodents to date, while translation to clinical practice will likely first require demonstration and refinement of these gene therapy techniques in non-human primates. Approach: Three rhesus macaques were injected intramuscularly with either one or both of two optogenetic constructs (AAV6-hSyn-ChR2-eYFP and/or AAV6-hSyn-Chronos-eYFP) to transduce opsin expression in the corresponding nerves. Neuromuscular junctions were targeted for virus delivery using an electrical stimulating injection technique. Functional opsin expression was periodically evaluated up to 13 weeks post-injection by optically stimulating targeted nerves with a 472 nm fiber-coupled laser while recording electromyographic (EMG) responses. Main Results: One monkey demonstrated functional expression of ChR2 at 8 weeks post-injection in each of two injected muscles, while the second monkey briefly exhibited contractions coupled to optical stimulation in a muscle injected with the Chronos construct at 10 weeks. A third monkey injected only in one muscle with the ChR2 construct showed strong optically coupled contractions at 5 ½ weeks which then disappeared by 9 weeks. EMG responses to optical stimulation of ChR2-transduced nerves demonstrated graded recruitment relative to both stimulus pulse-width and light intensity, and followed stimulus trains up to 16 Hz. In addition, the EMG response to prolonged stimulation showed delayed fatigue over several minutes. Significance: These results demonstrate the feasibility of viral transduction of peripheral motor nerves for functional optical stimulation of motor activity in non-human primates, a variable timeline of opsin expression in a animal model closer to humans, and fundamental EMG response characteristics to optical nerve stimulation. Together, they represent an important step in translating these optogenetic techniques as a clinically viable gene therapy.

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TACS motor system effects can be caused by transcutaneous stimulation of peripheral nerves.

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tACS motor system effects can be caused by transcutaneous stimulation of peripheral nerves.

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