Targeting corticostriatal synchrony with deep brain stimulation to reduce alcohol drinking

Dartmouth College, Hanover NH

Investigators

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Abstract

Project Summary Although alcohol use disorder (AUD) affects a large segment of American adults and the current treatments are unsuccessful in a significant proportion of patients. Studying the neural underpinnings of AUD has the potential for uncovering target for developing novel treatments. There is mounting evidence that AUD is correlated with dysregulated synchrony within the corticostriatal network. Neuromodulatory therapies, like deep brain stimulation (DBS), have been successful at treating other disorders, like Parkinson's disease, characterized by network dysregulation. Although, DBS has also shown the potential to treat AUD in pre- clinical models and clinical studies, the variable response to treatment (~50% of subject) limits the clinical adoption of these techniques. If we are able to uncover which measures of corticostriatal synchrony are implicated in the therapeutic effects of DBS, then we could target those features to increase response rates and open the door to a new therapeutic approach to AUD. The short-term objective of this research is to uncover the synchrony measure indicative of successful DBS treatment of AUD and then improve outcomes by targeting that measure with a novel DBS approach. The longer-term objective is to develop a novel treatment modality?dual-site DBS?which could be used to target dysregulated synchrony between two brain regions by targeting both of those regions. To achieve both of these objectives, (Aim 1) I will use a rodent model of alcohol drinking and an unbiased computational approach to determine what corticostriatal synchrony measure best correlates with successful single-site DBS. Next (Aim 2a), I will determine if dual-site DBS can be optimized to selectively modulate the measure previously associated with alcohol drinking. Last, (Aim 2b) I will test the ability of dual-site DBS to alter both synchrony and drinking behavior compared to single-site DBS. These aims will not only provide a brain network-based biomarker of successful AUD treatment, but also begin the development of an innovative treatment. To complete these aims I will work with my mentorship team at Dartmouth College on the use of animal models of alcohol use, the analysis of local field potentials, and the implementation of machine learning algorithms. Dartmouth College not only provides cutting-edge facilities which I will use to complete this research, but also has dedicated centers for professional development like the Dartmouth Center for the Advancement of Learning, which I will use over the next two years. Altogether, the training I will receive under this F31 will be integral in my pursuit of a pre-clinical research career.