title: Accumbens functional connectivity during reward mediates sensation-seeking and alcohol use in high-risk youth.
abstract: BACKGROUND
  Differences in fronto-striatal connectivity in problem substance users have suggested reduced influence of cognitive regions on reward-salience regions. Youth with a family history of alcoholism (FH+) have disrupted ventral striatal processing compared with controls with no familial risk (FH-). As sensation-seeking represents an additional vulnerability factor, we hypothesized that functional connectivity during reward anticipation would differ by family history, and would mediate the relationship between sensation-seeking and drinking in high-risk subjects.
  
  
  METHODS
  Seventy 18-22 year olds (49 FH+/21 FH-) performed a monetary incentive delay task during functional magnetic resonance imaging. Group connectivity differences for incentive (reward/loss) vs. neutral conditions were evaluated with psychophysiological interaction (PPI) analysis, seeded in nucleus accumbens (NAcc). Indirect effects of sensation-seeking on drinking volume through accumbens connectivity were tested.
  
  
  RESULTS
  NAcc connectivity with paracentral lobule/precuneus and sensorimotor areas was decreased for FH- vs. increased for FH+ during incentive anticipation. In FH+, task-related functional coupling between left NAcc and supplementary sensorimotor area (SSMA) and right precuneus correlated positively with sensation-seeking and drinking volume and mediated their relationship. In FH-, left NAcc-SSMA connectivity correlated negatively with sensation-seeking but was not related to drinking.
  
  
  CONCLUSIONS
  These results suggest preexisting differences in accumbens reward-related functional connectivity in high-risk subjects. NAcc coupling with SSMA, involved in attention and motor networks, and precuneus, a default mode structure, appear to mediate sensation-seeking's effect on drinking in those most at-risk. Differences in accumbens connectivity with attention/motor/default networks, rather than control systems, may influence the reward system's role in vulnerability for substance abuse.
authors.affiliation: Department of Psychiatry, The University of Michigan, Ann Arbor, MI, United States; Addiction Research Center, The University of Michigan, Ann Arbor, MI, USA. bweiland@umich.edu
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Weiland
authors.forename: Robert C
authors.initials: RC
authors.lastname: Welsh
authors.forename: Wai-Ying Wendy
authors.initials: WY
authors.lastname: Yau
authors.forename: Robert A
authors.initials: RA
authors.lastname: Zucker
authors.forename: Jon-Kar
authors.initials: JK
authors.lastname: Zubieta
authors.forename: Mary M
authors.initials: MM
authors.lastname: Heitzeg
mesh_terms: D000293:Adolescent; D000339:Affect / Q000502:physiology; D000428:Alcohol Drinking / Q000503:physiopathology* / Q000523:psychology; D001931:Brain Mapping; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D009415:Nerve Net / Q000503:physiopathology*; D009483:Neuropsychological Tests; D009714:Nucleus Accumbens / Q000503:physiopathology*; D011594:Psychometrics; D011930:Reaction Time / Q000502:physiology; D012201:Reward; D055815:Young Adult