Title
Mesocorticolimbic circuits are impaired in chronic cocaine users as demonstrated by resting-state functional connectivity.
Abstract
Preclinical models have consistently demonstrated the importance of the mesocorticolimbic (MCL) brain reward system in drug dependence, with critical molecular and cellular neuroadaptations identified within these structures following chronic cocaine administration. Cocaine dependent individuals manifest alterations in reward functioning that may relate to changes induced by cocaine or to pre-existing differences related to vulnerability to addiction. The circuit level manifestations of these drug-induced plastic changes and predispositions to drug dependence are poorly understood in preclinical models and virtually unknown in human drug dependence. Using whole-brain resting-state fMRI connectivity analysis with ‘seed voxels’ placed within individual nodes of the MCL system, we report network-specific functional connectivity strength decreases in cocaine users within distinct circuits of the system, including between ventral tegmental area (VTA) and a region encompassing thalamus/lentiform nucleus/nucleus accumbens, between amygdala and medial prefrontal cortex (mPFC), and between hippocampus and dorsal mPFC. Further, regression analysis on regions showing significant functional connectivity decrease in chronic cocaine users revealed that the circuit strength between VTA and thalamus/lentiform nucleus/nucleus accumbens was negatively correlated with years of cocaine use. This is the first evidence of circuit-related changes in human cocaine dependence and is consistent with the range of cognitive and behavioral disruptions seen in cocaine dependence. As potential circuit level biomarkers of cocaine dependence, these circuit alterations may be usefully applied in treatment development and monitoring treatment outcome.
Year
DOI
Venue
2010
10.1016/j.neuroimage.2010.06.066
NeuroImage
Keywords
Field
DocType
drug dependence,brain mapping,magnetic resonance imaging,rest,resting state,regression analysis,limbic system
Developmental psychology,Neuroscience,Lentiform nucleus,Nucleus accumbens,Addiction,Prefrontal cortex,Resting state fMRI,Psychology,Cocaine dependence,Ventral tegmental area,Limbic system
Journal
Volume
Issue
ISSN
53
2
1053-8119
Citations 
PageRank 
References 
11
0.84
6
Authors
7
Name
Order
Citations
PageRank
Hong Gu1273.42
Betty Jo Salmeron2234.00
Thomas J Ross39810.55
Xiujuan Geng416214.34
Wang Zhan5110.84
Elliot A Stein628338.64
Yihong Yang721821.67