Brain default mode network functional connectivity in polysubstance using emerging adults during opioid dependence treatment

s / Drug and Alcohol Dependence 156 (2015) e102–e182 e181 Dynamic causal modeling in humans offers a novel approach to delineate prefrontal-striatal serotonergic drivers of impulsivity in rats Amanda E. Price1, Harshini Neelakantan1, Liangsuo Ma2, Joel L. Steinberg3, Scott D. Lane4, James M. Bjork3, P.A. Narayana5, Thomas Kosten6, Antoine Bechara7, Noelle C. Anastasio1,8, F. Gerard Moeller3,9, Kathryn A. Cunningham1,8 1 Ctr Addiction Res, University of Texas Medical Branch, Galveston, TX, United States 2 Dep Radiology, Virginia Commonwealth University, Richmond, VA, United States 3 Dep Psych, Virginia Commonwealth University, Richmond, VA, United States 4 Dep Psych & Behav Sci, University of Texas Health Science Center, Houston, TX, United States 5 Dep Diag & Intervent Img, University of Texas Health Science Center, Houston, TX, United States 6 Dep Psych, Baylor College of Medicine, Houston, TX, United States 7 Dep Psych, University of Southern California, Los Angeles, CA, United States 8 Dep Pharm, University of Texas Medical Branch, Galveston, TX, United States 9 Dep Pharm, Virginia Commonwealth University, Richmond, VA, United States Aims: The prefrontal-striatal network is a major driver of impulsivity and altered neurotransmission in this circuit may underlie heightened impulsivity in cocaine use disorder (CUD). Serotonin transmission through 5-HT2A receptors (5-HT2AR) and 5HT2CR governs prefrontal-striatal networks. This study employed fMRI based DCM to investigate prefrontal-striatal effective connectivity underlying impulsivity in CUD. We also aim to translate our human findings to rodentmodels to analyze themodulatory role of the 5-HT systemwithin the prefrontal-striatal network that drives impulsivity. Methods: Ten control and 13 CUD subjects underwent fMRI while performing Go/NoGo tasks with Easy and Hard NoGo difficulty. Connectivity was determined via DCM analyses. Results: There were no differences in overall performance (p=0.9) or modulation effects on Easy NoGo (p=0.4) between groups. Hard NoGo influenced right dorsoand ventrolateral prefrontal connectivity to left caudate in controls but left anterior cingulate connectivity to left caudate in CUD subjects (p<0.05). Conclusions: CUD subjects utilize different connectivity during impulsive responding to perform similarly to controls. Altered topdown control may be mediated by impaired 5-HT transmission at 5-HT2AR and 5-HT2CR. Ongoing studies are testing if 5-HT2AR:5HT2CR imbalance in the prefrontal-striatal circuit shifts effective connectivity governing impulsivity in CUD. Financial support: DA020087, DA033935, DA034131, DA033374. http://dx.doi.org/10.1016/j.drugalcdep.2015.07.674 Brain default mode network functional connectivity in polysubstance using emerging adults during opioid dependence treatment Jenessa S. Price2, Marc L. Copersino2, Gordana Vitaliano3, Scott E. Lukas3, Roger Weiss1, Amy Janes2 1 Harvard Medical School, Belmont, MA, United States 2 McLean Hospital/Harvard Medical School, Belmont, MA, United States 3 Psychiatry, McLean Hospital/Harvard Medical School, Belmont, MA, United States Aims: The default mode network (DMN) is an interconnected set of brain regions typically active at rest and during low cognitive demand conditions. Heroin-dependent adults show DMN connectivity abnormalities correlated with lifetime heroin use. Functional organization abnormalities are especially pertinent to younger substance-using persons who have ongoing neurodevelopment, higher risk of relapse and lower treatment completion rates. This study examined brain connectivity indices and associations with acute drug use in ten emerging adult patients (ages 18–27) in partial relapse prevention treatment for opioid dependence. Methods: Patients who met DSM-IV criteria for current opioid dependence and used opiates in the past month received restingstate functional magnetic resonance imaging (fMRI) scans within 24hours of admission. Potential participants were not excluded for other drug use or dependence; in most cases this included marihuana, sedatives and/or nicotine. Seven participants also met dependence criteria for at least one other substance. Imaging data wereanalyzedusingan independent componentsanalysis followed by dual regression to identify subject-specific spatial maps of the DMN. A non-parametric permutation testing method was used to correlate DMN with total days of any substance use in the past 30 days. Results: Increased drug use over the past 30 days was correlated with less connectivity between the DMN and insula, dorsal striatum and post central gyrus (cluster corrected Z=2.3, p<0.05, 5000 permutations). Conclusions: These findings provide evidence that polysubstance use is associated with functional adaptations in the DMN of emerging adults seeking treatment for opiate dependence. Further research is needed to delineate if these connectivity changes are related to recent detoxification. Financial support: T32 DA015036, K23 DA027045, K01 DA029645. http://dx.doi.org/10.1016/j.drugalcdep.2015.07.675 Current drug scheduling reviews of synthetic cathinones by the U.S. drug enforcement administration Cassandra Prioleau, Srihari R. Tella, Michelle Walker, Sandy Ghozland, Li Fang, Jordan Trecki, Ambuja S. Bale, Artisha R. Polk, Daniel Willenbring, Liqun L. Wong, Terrence L. Boos Office of Diversion Control, Drug Enforcement Administration, Springfield, VA, United States Aims: In accordance with the Controlled Substances Act (CSA), DEA collects and reviews scientific, medical and other data for substances with abuse potential to evaluate them for possible control under the CSA. Numerous synthetic cathinones have become