NSF EPSCoR: Modulating Functional Connectivity in Cannabis Abusers to Improve Cognitive and Behavioral Outcomes

This project will establish a formal collaboration between two junior investigators at the University of Kentucky (Dr. Michael Wesley) and the University of Oklahoma (Dr. Han Yuan). It is designed to leverage Dr. Wesley¡¦s expertise in human clinical pharmacology and Dr. Yuan¡¦s expertise in computational modeling of neuroimaging data to produce results for competitive co-authored manuscripts and extramural grants. Specifically, funds will be used to add a neuroimaging component to an ongoing study in Dr. Wesley¡¦s lab examining the ability of noninvasive brain stimulation to modulate cognitive and behavioral impairment due to cannabis use in emerging adults. In Aim 1 (the ongoing study), placebo and real psychoactive drug is administered to emerging adults in combination with sham and active transcranial direct current stimulation (tDCS). Emerging adults are targeted because they are a ¡§high-risk¡¨ drug-abusing group and tDCS may serve as a clinical treatment for them. The left dorsal lateral prefrontal cortex (DLPFC) is targeted for stimulation because its function is known to contribute to cognitive and behavioral outcomes impaired by acute ƒ´9-tetrahydrocannabinol (THC), the major psychoactive chemical in cannabis. The same cognitive and behavioral outcomes impaired by THC are also predictive of failed clinical treatment of drug abuse (e.g., increased risky decision-making and impaired working memory performance). Additionally, tDCS targeting the left DLPFC in controls has been shown to differentially impact these outcomes (i.e., decreased risk taking and improved working memory performance). Aim 1 will test the hypothesis that altering left DLPFC functionality with transcranial direct current stimulation (tDCS) will impact cannabinoid-impaired cognitive and behavioral processes in emerging adults who are chronically using cannabis. Aim 2 of the proposed project (the new study), subjects who completed Aim 1 will be invited to undergo a unique and innovative within-subject double-blinded and sham-controlled neuroimaging protocol combining simultaneous brain stimulation with tDCS and neuroimaging with functional magnetic resonance imaging (fMRI). This study is designed to measure individual sensitivity to the acute effects of tDCS in brain measured by task-based functional connectivity (TBFC) and resting state functional connectivity (RSFC). TBFC and RSFC have also been shown to be modulated by tDCS and have been linked to clinical outcomes. TBFC outcomes will be connectivity profiles and behavioral performance during risky decision-making and working memory tasks. RSFC outcomes will be connectivity profiles before and after tDCS and behavioral tasks. The relationship between individual differences in functional connectivity profiles associated with sham and real tDCS will be related to cognitive and behavioral outcomes from Aims 1 and 2. Dr. Wesley and Dr. Yuan, who are both established neuroimaging researchers, will work together to process and analyze these multimodal data. Results from this project will inform our understanding of the ability to acutely modulate brain function, cognition and behavior in a drug-abusing population and will inform new interventions and treatments for drug abuse. They will also lead to the successful submission of collaborative publications and grant proposals to extramural funding agencies.