Alcohol dependence is a global societal problem, yet current avenues for its treatment are largely ineffective in slowing its chronic-relapsing trajectory. Animal studies of alcohol dependence have described neuroadaptations in the amygdala that may play a central role in mechanisms of relapse. In this thesis, spontaneous amygdala network function was examined in abstinent alcohol dependent patients (ADP) using functional magnetic resonance imaging within the framework of a multi-site neuroimaging platform: ICCAM. Participants underwent five scans that included baseline, as well as scans under placebo, acute antagonism of μ-opioid, Dopamine D3 (DRD3) and Neurokinin-1 (NK1) receptor systems previously implicated in mechanisms of addiction.
At baseline, amygdala – substantia nigra/ventral tegmental area (SN/VTA) resting state functional connectivity (RSFC) was elevated in abstinent ADP, despite widespread grey-matter (GM) volumetric atrophy, in both amygdala and SN/VTA, compared with age-matched healthy controls (HC). The strength of amygdala – SN/VTA RSFC in ADP was primarily associated with years of cumulative alcohol exposure, but not with amygdala or SN/VTA GM volume, length of abstinence, smoking status, or head motion.
Amygdala RSFC with other regions showed sensitivity to core clinical features of ADP at baseline. Amygdala – frontoparietal (FPN) RSFC was inversely associated with abstinence length, with ADP in the first two months of abstinence showing significantly reduced amygdala – FPN RSFC compared with HC.
Voxelwise comparison of amygdala RSFC between each drug session and placebo, did not reveal differential effects of receptor blockade on ADP and HC. Across both groups, however, the three drugs exhibited both overlapping and differential effects on distinct brain networks. Notably, amygdala RSFC in the superior temporal gyrus showed increases under NK1-antagonism, and decreases under naltrexone compared with placebo. Finally, amygdala – SN/VTA was significantly elevated in ADP relative to HC across all four sessions, suggesting that it may represent a stable neurophysiological feature of alcohol dependence.