title: Top-Down Network Effective Connectivity in Abstinent Substance Dependent Individuals.
abstract: OBJECTIVE
  We hypothesized that compared to healthy controls, long-term abstinent substance dependent individuals (SDI) will differ in their effective connectivity between large-scale brain networks and demonstrate increased directional information from executive control to interoception-, reward-, and habit-related networks. In addition, using graph theory to compare network efficiencies we predicted decreased small-worldness in SDI compared to controls.
  
  
  METHODS
  50 SDI and 50 controls of similar sex and age completed psychological surveys and resting state fMRI. fMRI results were analyzed using group independent component analysis; 14 networks-of-interest (NOI) were selected using template matching to a canonical set of resting state networks. The number, direction, and strength of connections between NOI were analyzed with Granger Causality. Within-group thresholds were p<0.005 using a bootstrap permutation. Between group thresholds were p<0.05, FDR-corrected for multiple comparisons. NOI were correlated with behavioral measures, and group-level graph theory measures were compared.
  
  
  RESULTS
  Compared to controls, SDI showed significantly greater Granger causal connectivity from right executive control network (RECN) to dorsal default mode network (dDMN) and from dDMN to basal ganglia network (BGN). RECN was negatively correlated with impulsivity, behavioral approach, and negative affect; dDMN was positively correlated with impulsivity. Among the 14 NOI, SDI showed greater bidirectional connectivity; controls showed more unidirectional connectivity. SDI demonstrated greater global efficiency and lower local efficiency.
  
  
  CONCLUSIONS
  Increased effective connectivity in long-term abstinent drug users may reflect improved cognitive control over habit and reward processes. Higher global and lower local efficiency across all networks in SDI compared to controls may reflect connectivity changes associated with drug dependence or remission and requires future, longitudinal studies to confirm.
authors: Department of Radiology, University of Colorado School of Medicine, Aurora, CO, 80045, United States of America.|Department of Bioengineering, University of Colorado College of Engineering and Applied Sciences, Aurora, CO, 80045, United States of America.
authors: Michael F
authors: MF
authors: Regner
authors: Department of Radiology, University of Colorado School of Medicine, Aurora, CO, 80045, United States of America.
authors: Naomi
authors: N
authors: Saenz
authors: Department of Psychiatry, University of Colorado School of Medicine, Aurora, CO, 80045, United States of America.
authors: Keeran
authors: K
authors: Maharajh
authors: Department of Radiology, University of Colorado School of Medicine, Aurora, CO, 80045, United States of America.
authors: Dorothy J
authors: DJ
authors: Yamamoto
authors: Department of Radiology, University of Colorado School of Medicine, Aurora, CO, 80045, United States of America.
authors: Brianne
authors: B
authors: Mohl
authors: Department of Psychiatry, University of Colorado School of Medicine, Aurora, CO, 80045, United States of America.
authors: Korey
authors: K
authors: Wylie
authors: Department of Psychiatry, University of Colorado School of Medicine, Aurora, CO, 80045, United States of America.
authors: Jason
authors: J
authors: Tregellas
authors: Department of Radiology, University of Colorado School of Medicine, Aurora, CO, 80045, United States of America.|Department of Psychiatry, University of Colorado School of Medicine, Aurora, CO, 80045, United States of America.
authors: Jody
authors: J
authors: Tanabe
mesh_terms: D000328:Adult; D001931:Brain Mapping / Q000379:methods*; D055030:Drug Users / Q000523:psychology*; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D009483:Neuropsychological Tests; D055815:Young Adult