Deficits in default mode network activity preceding error in cocaine dependent individuals

Abstract

Background: Cocaine dependence is associated with cognitive deficits and altered task-related cerebral activation in cognitive performance (see Li and Sinha, 2008, for a review). Relatively little is known whether these individuals are also impaired in regional brain activation of the default mode network (DMN). We demonstrated previously that greater activation of the default brain regions precedes errors in a stop signal task performed by healthy controls (SST, Li et al., 2007). We seek to determine whether individuals with cocaine dependence are impaired in DMN activity, specifically activity preceding error, as compared to the healthy people. We also examine the relation to years of cocaine use.

Methods: Individuals with cocaine dependence (CD, n=23) and demographics-matched healthy controls (HC, n=27) performed a SST that employed a tracking procedure to adjust the difficulty of stop trials and elicit errors approximately half of the time. Blood oxygenation level dependent (BOLD) signals of go trials preceding stop error as compared to those preceding stop success trials were extracted with generalized linear models using statistical parametric mapping.

Results: HC showed activation of bilateral precuneus and posterior cingulate cortices and ventromedial prefrontal cortex (vmPFC) preceding errors during the SST. In contrast, despite indistinguishable stop signal performance, CD did not show these error predicting activations. Furthermore, the effect size of error-preceding vmPFC activation was inversely correlated with years of cocaine use.

Conclusions: These findings indicate DMN deficits and could potentially add to our understanding of the effects of chronic cocaine use on cerebral functions in cocaine dependence. Work to further clarify potential changes in functional connectivity and gray matter volume is warranted to understand the relevance of DMN to the pathology of cocaine misuse.

Figure 1

(a) Stop signal paradigm. In “go” trials (75%) observers responded to the go signal (a circle) and in “stop” trials (25%) they had to withhold the response when they saw the stop signal (an X). In both trials the go signal appeared after a randomized time interval between 1 to 5 s (the fore-period or FP, uniform distribution) following the appearance of the fixation point. The stop signal followed the go signal by a time delay – the stop signal delay (SSD). The SSD was updated according to a staircase procedure, whereby it increased and decreased by 64 ms following a stop success and stop error trial, respectively. We distinguished go success (G) and go error (F), and stop success (SS) and stop error (SE) trials during the task. (b) Go successes were further distinguished by their subsequent trial; thus G trials followed by a SS, and SE trial were indicated by pre-SS, and pre-SE trials, respectively.

Figure 2

(a) Brain regions showing greater activation during pre-SE than pre-SS trials (blue) in HC (right panel) but not CD (left panel) in the perigenual and subgenual anterior cingulate cortex and posterior cingulate cortex/precuneus (p<0.005, uncorrected). At the same threshold, no brain regions showed greater activation during pre-SS compared to pre-SE trials (red). T statistic for the contrast was shown for a mid-sagittal section (x=0) of a mean EPI image. (b) Two sample t-test of the contrast pre-SE > pre-SS showing greater error predicting activation in the ventromedial prefrontal cortex and posterior cingulate cortex/precuneus in HC, as compared to CD (p<0.005, uncorrected). T map of the contrast was overlaid on sagittal sections (x=−4, 0, 4) of a mean EPI image. Color bars represent voxel T value.

Figure 3

Brain regions showing greater activation during pre-SE than pre-SS trials in HC, as compared to CD (p<0.005, uncorrected). T statistic was overlaid on a mean EPI image in axial sections from z=−12 to z=48 with adjacent sections 6mm apart. Neurological orientation: Right = right. Color bars represent voxel T value.

Figure 4

Effect size correlation of vmPFC (pre-SE > pre-SS) is inversely correlated with years of cocaine use for 23 CD (R²=0.332, p<0.005, Pearson regression). Each dot represents the data of one subject.