Inhibitory behavioral control: A stochastic dynamic causal modeling study comparing cocaine dependent subjects and controls

Abstract

Cocaine dependence is associated with increased impulsivity in humans. Both cocaine dependence and impulsive behavior are under the regulatory control of cortico-striatal networks. One behavioral laboratory measure of impulsivity is response inhibition (ability to withhold a prepotent response) in which altered patterns of regional brain activation during executive tasks in service of normal performance are frequently found in cocaine dependent (CD) subjects studied with functional magnetic resonance imaging (fMRI). However, little is known about aberrations in specific directional neuronal connectivity in CD subjects. The present study employed fMRI-based dynamic causal modeling (DCM) to study the effective (directional) neuronal connectivity associated with response inhibition in CD subjects, elicited under performance of a Go/NoGo task with two levels of NoGo difficulty (Easy and Hard). The performance on the Go/NoGo task was not significantly different between CD subjects and controls. The DCM analysis revealed that prefrontal-striatal connectivity was modulated (influenced) during the NoGo conditions for both groups. The effective connectivity from left (L) anterior cingulate cortex (ACC) to L caudate was similarly modulated during the Easy NoGo condition for both groups. During the Hard NoGo condition in controls, the effective connectivity from right (R) dorsolateral prefrontal cortex (DLPFC) to L caudate became more positive, and the effective connectivity from R ventrolateral prefrontal cortex (VLPFC) to L caudate became more negative. In CD subjects, the effective connectivity from L ACC to L caudate became more negative during the Hard NoGo conditions. These results indicate that during Hard NoGo trials in CD subjects, the ACC rather than DLPFC or VLPFC influenced caudate during response inhibition.

Keywords: Cocaine dependence; Dynamic casual modeling; Impulsivity; Inhibitory control.

Fig. 1

Flow chart showing subject inclusion/exclusion, and which project (Project 1 and Project 2) the subjects come from. CTL denotes control subject, and CD denotes cocaine dependent subject.

Fig. 2

FWE corrected significant cluster detected by the SPM8 second-level random effects analysis. In the cluster, the control group had significantly greater activation (FWE corrected two-tailed p = 0.038) than the CD group for the E contrast (Easy NoGo BOLD signal minus the Go BOLD signal). The cluster is overlaid in color on axial slices of the MNI brain template image in gray. The number above each slice indicates slice location (mm) of the MNI z coordinate. Scale on color bar represents voxel t values. The reader's left (L) side of each slice is the subjects' left brain hemisphere.

Fig. 3

Schematic diagram representing effective connectivity only modulated by the NoGo conditions. The endogenous connectivities are denoted by line with arrow. The modulation effects are depicted by lines ending with solid dot. The mean strengths (in units of Hz) of the modulation effects exerted by the Easy (E) or Hard (H) NoGo condition are separately shown. For clarity, not all nodes or endogenous connectivities are shown in this figure. The modulation effects showing significant group difference are indicated by asterisks. All the significant group differences in modulation effect occurred during Hard NoGo condition. L =  Left. R = right.