Exhibit Hall | Forum 6
Purpose: To identify whether striatal changes in functional connectivity (FC) within resting state (RS) brain neural networks is a function of heavy (HD) or non-heavy (NHD) alcohol-drinking status in primates.
Methods: 35 rhesus macaques (F= 18, M= 17) underwent a 2-year longitudinal rsfMRI study acquired under 1% isoflurane at baseline and after six-months of 22-hour/day access to 4% ethanol and water. HD status is defined as consuming >3.0 g/kg ethanol on 20% of days of ethanol access (NHD= 19, HD= 16). Independent component analysis (ICA) was used to generate four group spatial maps corresponding to RS brain networks: IC0- visual, IC1- primary motor, IC2- sensorimotor, and IC3- executive network. Subsequent group-ICA decomposition generated maps of each individual’s FC to each brain network at pre- and post-drinking time points. Brain maps were further segmented using the ONPRC18 macaque atlas for subsequent ROI-based analysis on the effect of drinking status and the effects of brain hemisphere over time.
Results: Dual regression on the paired baseline and post-drinking subjects revealed significant increases in FC post-drinking across all networks (P < 0.01). The putamen (PUT) and caudate (CAU) average voxel FC measurements of individual subjects across all networks found decreased FC between IC2 and the PUT due to drinking (2-factor ANOVA; p < 0.05).
Conclusion: The CAU and PUT are striatal structures involved in addiction-related brain circuitry. The PUT is an important structure heavily associated with habitual behaviors such as chronic heavy drinking. Prior electrophysiological studies found a decrease in inhibitory neural transmission of the PUT in HD primates after prolonged consumption. Our results showcase a selective decrease in FC of the PUT in HD monkeys of the sensorimotor network. The decreased connectivity of the PUT to sensorimotor control over behavior may underlie the chronic habitual intake of ethanol associated with alcohol use disorders.