title: Modeling Causal Relationship Between Brain Regions Within the Drug-Cue Processing Network in Chronic Cocaine Smokers.
abstract: The cues associated with drugs of abuse have an essential role in perpetuating problematic use, yet effective connectivity or the causal interaction between brain regions mediating the processing of drug cues has not been defined. The aim of this fMRI study was to model the causal interaction between brain regions within the drug-cue processing network in chronic cocaine smokers and matched control participants during a cocaine-cue exposure task. Specifically, cocaine-smoking (15M; 5F) and healthy control (13M; 4F) participants viewed cocaine and neutral cues while in the scanner (a Siemens 3 T magnet). We examined whole brain activation, including activation related to drug-cue processing. Time series data extracted from ROIs determined through our General Linear Model (GLM) analysis and prior publications were used as input to IMaGES, a computationally powerful Bayesian search algorithm. During cocaine-cue exposure, cocaine users showed a particular feed-forward effective connectivity pattern between the ROIs of the drug-cue processing network (amygdala → hippocampus → dorsal striatum → insula → medial frontal cortex, dorsolateral prefrontal cortex, anterior cingulate cortex) that was not present when the controls viewed the cocaine cues. Cocaine craving ratings positively correlated with the strength of the causal influence of the insula on the dorsolateral prefrontal cortex in cocaine users. This study is the first demonstration of a causal interaction between ROIs within the drug-cue processing network in cocaine users. This study provides insight into the mechanism underlying continued substance use and has implications for monitoring treatment response.
authors.affiliation: Center of Alcohol Studies, Rutgers University, Piscataway, NJ, USA.
authors.forename: Suchismita
authors.initials: S
authors.lastname: Ray
authors.affiliation: Columbia University Medical Center, New York, NY, USA.
authors.forename: Margaret
authors.initials: M
authors.lastname: Haney
authors.affiliation: Rutgers University Brain Imaging Center, Newark, NJ, USA.
authors.forename: Catherine
authors.initials: C
authors.lastname: Hanson
authors.affiliation: New Jersey Institute of Technology, Newark, NJ, USA.
authors.forename: Bharat
authors.initials: B
authors.lastname: Biswal
authors.affiliation: Rutgers University Brain Imaging Center, Newark, NJ, USA.|Psychology Department, Rutgers University, Newark, NJ, USA.
authors.forename: Stephen José
authors.initials: SJ
authors.lastname: Hanson
mesh_terms: D000328:Adult; D001921:Brain / Q000187:drug effects / Q000503:physiopathology*; D001931:Brain Mapping; D003042:Cocaine / Q000008:administration & dosage; D019970:Cocaine-Related Disorders / Q000503:physiopathology* / Q000523:psychology; D066249:Craving / Q000502:physiology; D003463:Cues; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage; D005260:Female; D006801:Humans; D013287:Illicit Drugs; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D008959:Models, Neurological; D009434:Neural Pathways / Q000187:drug effects / Q000503:physiopathology; D009483:Neuropsychological Tests
chemical_list: D018765:Dopamine Uptake Inhibitors; D013287:Illicit Drugs; D003042:Cocaine