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Computationally guided modulation of cortical-striatal activity: Toward brain stimulation-based treatments for impulsive and risky decision making

Award Number: K08MH117347
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

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ABSTRACT Impulsive and risky decision-making are observed in many psychiatric disorders (e.g., ADHD, bipolar, eating and substance use disorders). Variation in the underlying psychological constructs of choice impulsivity (CI) and risky choice (RC), can be evaluated in both pre-clinical and clinical populations using specific tasks—the delay discounting task for CI and the risky decision-making task for RC. In patients, CI and RC task performance associated with impulsive and risky decision-making, relates prospectively to problematic behaviors—gambling, binge eating, substance use, violence and suicide—and also predicts non-response to treatment and risk of relapse. Thus, treatments that can normalize decision-making, reflected in improved CI or RC task performance, could have a meaningful clinical impact across an array of neuropsychiatric conditions. Previous studies have correlated CI and RC task performance (in both rodents and humans) with specific patterns of cortical-striatal activity, but few approved treatments for neuropsychiatric illness have been developed for the purpose of targeting and therapeutically manipulating these systems-level neural activity patterns. Therefore, this proposal will: (1) identify patterns of cortical-striatal activity correlated with CI and RC task performance; (2) determine how targeting diverse cortical-striatal regions with deep brain stimulation (DBS) alters cortical-striatal activity; and (3) use DBS to modulate activity patterns and correlate these with CI and RC task performance changes. This proposal will identify neural systems-level treatment targets that will aid in the development of circuit-based interventions (e.g., DBS and transcranial magnetic stimulation-TMS) for maladaptive decision-making across an array of psychiatric conditions. My primary goal under this proposal is to establish an independent research program that will address the following questions: What are the neural systems-level activity patterns that are relevant to domains of mental illness?; and How can a neural systems-level understanding of trans-diagnostic domains be leveraged to enable circuit-based interventions to reach their therapeutic potential? I believe that transitioning my pre- clinical research from models of disordered appetitive behavior to common domains of function that are pathologic across many psychiatric conditions will enhance the translational relevance of my research program. To make this transition and be at the forefront of computational psychiatry, I must acquire additional training in advanced behavioral protocols and cutting-edge computational tools for analysis of high dimensional neural data. The training outlined in this K08 complements my existing knowledge base (electrophysiology and circuit-based interventions) and aligns well with the proposed Specific Aims to provide a context to gain experience in these key areas of training through course work and one-on-one mentorship (both internal and external).


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2022 ( Subtotal = $173,016 )
2022	2022	DARTMOUTH-HITCHCOCK CLINIC	ONE MEDICAL CENTER DR	LEBANON	NH	03756	GRAFTON	USA	Mental Health Research Grants	000	4	2/28/2022	NON-COMPETING CONTINUATION	$173,016
														Subtotal = $173,016

Issue Date FY: 2021 ( Subtotal = $173,016 )
2021	2021	DARTMOUTH-HITCHCOCK CLINIC	ONE MEDICAL CENTER DR	LEBANON	NH	03756	GRAFTON	USA	Mental Health Research Grants	000	3	3/5/2021	NON-COMPETING CONTINUATION	$173,016
														Subtotal = $173,016

Issue Date FY: 2020 ( Subtotal = $173,016 )
2020	2020	DARTMOUTH-HITCHCOCK CLINIC	ONE MEDICAL CENTER DR	LEBANON	NH	03756	GRAFTON	USA	Mental Health Research Grants	000	2	3/19/2020	NON-COMPETING CONTINUATION	$173,016
														Subtotal = $173,016

Issue Date FY: 2019 ( Subtotal = $173,016 )
2019	2019	DARTMOUTH-HITCHCOCK CLINIC	ONE MEDICAL CENTER DR	LEBANON	NH	03756	GRAFTON	USA	Mental Health Research Grants	000	1	2/26/2019	NEW	$173,016
														Subtotal = $173,016

Grand Total All Awards = $692,064

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Computationally guided modulation of cortical-striatal activity: Toward brain stimulation-based treatments for impulsive and risky decision making

Award Number: K08MH117347

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

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