Transcranial direct current stimulation (tDCS) is a popular brain stimulation technique used by clinical and nonclinical researchers because it is noninvasive and relatively simple to implement. This fact is reflected by over 250 active clinical trials1 to treat various neurological2?4 and psychiatric diseases, as well as innumerable studies with healthy human subjects. The motor system is a common target in these studies, and research suggests that tDCS can improve recovery following stroke2?6, boost motor learning7?10, and increase motor cortex excitability11,12. In addition, tDCS is now being used to probe the brain on the assumption that it can modulate specific networks depending upon the electrode montage13. Despite its popularity, tDCS remains controversial because results are highly variable14,15, and basic understanding about the mechanism of action is lacking16. Due to overwhelming adoption in human trials and basic research, it is more important than ever to understand the physiological effects of tDCS. Some animal experiments have worked towards this goal by pairing tDCS with intracortical recordings17?19. However, these studies apply tDCS in rodents at currents far outside the range seen in human trials, and often under general anesthesia. We plan to build on this with two basic improvements: we will use monkeys trained in a motor task to study the effects of tDCS on the active and resting cortex, and we will deliver tDCS at levels similar to those used in human studies. Our experiments are designed to explore three fundamental physiological predictions drawn from behavioral effects. 1) We will test the hypothesis that cathodal and anodal tDCS have opposite modulatory effects on cortical activity, and that these effects persist for hours after tDCS is turned off. To measure these changes, we will record the spike activity of dozens of single neurons (single unit activity, SUA) and 96 channels of network activity (local field potential, LFP) in the motor cortex before, during, after tDCS. We will also use a novel, battery- powered computer called the NeuroChip to record SUA and LFP for at least 12 hours after tDCS is turned off. 2) We will test whether different tDCS electrode montages can alter functional connectivity of the cortex by measuring the responses, called the cortically-evoked potential (cEP), across cortical sites during tDCS. 3) We will determine whether tDCS enhances cortical plasticity by tracking Hebbian changes in cEP induced by paired- pulse conditioning of two cortical sites. This question is important because tDCS modulation of plasticity is presumed to be the main way that tDCS boosts efficacy of traditional therapy for neurological disease20. Confirmation of these predictions stemming from human trials would not only encourage the continued use of tDCS, but provide critical information about its mechanism of action and inform future human studies.

Public Health Relevance

Commercially available and non-invasive, a brain stimulation technique called transcranial direct current stimulation (tDCS) is a hotly contested topic of research and popular science because it appears to have beneficial effects, yet we do not fully understand how it works. This project will provide critical insights to what happens inside the brain during and after tDCS.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Individual Predoctoral NRSA for M.D./Ph.D. Fellowships (ADAMHA) (F30)
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Neurological Sciences Training Initial Review Group (NST)
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Chen, Daofen
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University of Washington
Schools of Medicine
United States
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