Research investigating the use of noninvasive electrical stimulation (e.g., transcranial direct current stimulation (tDCS)), for neurologic and psychiatric disorders has provided compelling evidence that such stimulation can modulate behavior and cognition, and even facilitate recovery of function after focal brain injury, with effects typically outlasting the stimulation period. It is known that these effects are achieved by altering excitability in targeted brain regions, but our understanding of the mechanisms that lead to such changes is limited, and the influence of variables such as current strength, duration, and electrode montage remains unexplained. To increase our understanding of the neurobiological and behavioral effects of tDCS, and optimize procedures for clinical applications, we propose a more extensive series of studies to characterize brain and behavioral responses to tDCS. During magnetic resonance imaging (MRI), tDCS will be delivered by an MRI-compatible, constant-current stimulator. A dynamic imaging technique (arterial spin labeling (ASL)) used to measure perfusion will be coupled with resting state functional MRI (using BOLD contrast imaging) to relate the distribution of brain activity in response to tDCS -- both directly under the electrode and in remote brain regions (using ASL)-- with functional connectivity between those regions (using resting state BOLD fmri).
Our aims are to (1) measure the brain's blood flow response (a surrogate for neuronal activity) to increases in current strength and duration of stimulation to establish dose-response curves, then relate that response to observed behavioral changes, (2) compare the behavioral and neural effects of different electrode montages/geometries, and (3) examine direct and remote network effects of tDCS in two model systems (motor and language) using functional connectivity analysis. The innovation of the proposed study centers on (a) the use of a state-of-the-art functional imaging technique that provides a quantitative measure of functional brain response, and (b) simultaneous tDCS and functional imaging that allows both dynamic tracking of tDCS' effects across the brain and detection of its short- and intermediate- term effects on local and network-connected regions. Expected Results of this novel research include the identification of the neural and physiological bases for tDCS' effect, better-defined functional brain effects in response to various stimulation parameters, and improved understanding of how therapies can be specifically targeted for a broad range of brain disorders. Outcomes from this investigation will provide future studies with an established method for imaging and quantifying neural responses to tDCS. Results of our studies can be used to optimize and quantify modulations of brain regions and neural networks implicated in various neurologic and psychiatric disorders using a non-invasive, safe, and cost-effective method that has the potential to positively affect a large number of patients.

Public Health Relevance

Non-invasive brain stimulation has been shown to affect brain function and behavior. However, the influence of stimulation parameters (current strength and stimulation duration) and stimulation sites are unknown. The proposed study will examine these issues by determining correlations between stimulation parameters and cerebral Blood Flow changes and behavioral effects with the ultimate goal to improve interventions for various neurologic and psychiatric disorders.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
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Special Emphasis Panel (ZMH1)
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Friedman, Fred K
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Beth Israel Deaconess Medical Center
United States
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