title: Cocaine dependence and thalamic functional connectivity: a multivariate pattern analysis.
abstract: Cocaine dependence is associated with deficits in cognitive control. Previous studies demonstrated that chronic cocaine use affects the activity and functional connectivity of the thalamus, a subcortical structure critical for cognitive functioning. However, the thalamus contains nuclei heterogeneous in functions, and it is not known how thalamic subregions contribute to cognitive dysfunctions in cocaine dependence. To address this issue, we used multivariate pattern analysis (MVPA) to examine how functional connectivity of the thalamus distinguishes 100 cocaine-dependent participants (CD) from 100 demographically matched healthy control individuals (HC). We characterized six task-related networks with independent component analysis of fMRI data of a stop signal task and employed MVPA to distinguish CD from HC on the basis of voxel-wise thalamic connectivity to the six independent components. In an unbiased model of distinct training and testing data, the analysis correctly classified 72% of subjects with leave-one-out cross-validation (p < 0.001), superior to comparison brain regions with similar voxel counts (p < 0.004, two-sample t test). Thalamic voxels that form the basis of classification aggregate in distinct subclusters, suggesting that connectivities of thalamic subnuclei distinguish CD from HC. Further, linear regressions provided suggestive evidence for a correlation of the thalamic connectivities with clinical variables and performance measures on the stop signal task. Together, these findings support thalamic circuit dysfunction in cognitive control as an important neural marker of cocaine dependence.
authors.affiliation: Department of Psychiatry, Yale University, New Haven, CT 06519, USA; Connecticut Mental Health Center, New Haven, CT 06519, USA.
authors.forename: Sheng
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Psychiatry, Yale University, New Haven, CT 06519, USA; Connecticut Mental Health Center, New Haven, CT 06519, USA.
authors.forename: Sien
authors.initials: S
authors.lastname: Hu
authors.affiliation: Department of Psychiatry, Yale University, New Haven, CT 06519, USA; Child Study Center, Yale University, New Haven, CT 06520, USA; Department of Neuroscience, Yale University, New Haven, CT 06520, USA; Interdepartmental Neuroscience Program, Yale University, New Haven, CT 06520, USA.
authors.forename: Rajita
authors.initials: R
authors.lastname: Sinha
authors.affiliation: Department of Psychiatry, Yale University, New Haven, CT 06519, USA; Connecticut Mental Health Center, New Haven, CT 06519, USA; Child Study Center, Yale University, New Haven, CT 06520, USA; Department of Neuroscience, Yale University, New Haven, CT 06520, USA; Interdepartmental Neuroscience Program, Yale University, New Haven, CT 06520, USA; CASAColumbia, Yale University, New Haven, CT 06519, USA.
authors.forename: Marc N
authors.initials: MN
authors.lastname: Potenza
authors.affiliation: Department of Psychiatry, Yale University, New Haven, CT 06519, USA; Connecticut Mental Health Center, New Haven, CT 06519, USA.
authors.forename: Robert T
authors.initials: RT
authors.lastname: Malison
authors.affiliation: Department of Psychiatry, Yale University, New Haven, CT 06519, USA; Connecticut Mental Health Center, New Haven, CT 06519, USA; Department of Neuroscience, Yale University, New Haven, CT 06520, USA; Interdepartmental Neuroscience Program, Yale University, New Haven, CT 06520, USA.
authors.forename: Chiang-Shan R
authors.initials: CS
authors.lastname: Li
mesh_terms: D000328:Adult; D001921:Brain / Q000187:drug effects / Q000503:physiopathology*; D001931:Brain Mapping / Q000379:methods*; D019970:Cocaine-Related Disorders / Q000503:physiopathology* / Q000523:psychology; D056344:Executive Function / Q000502:physiology; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D015999:Multivariate Analysis; D009434:Neural Pathways / Q000187:drug effects / Q000503:physiopathology; D013788:Thalamus / Q000187:drug effects / Q000503:physiopathology*
keywords: Cocaine; Cognitive control; Functional connectivity; Independent component analysis; Multivariate pattern analysis; Thalamus