Metacognitive impairment in active cocaine use disorder is associated with individual differences in brain structure

Abstract

Dysfunctional self-awareness has been posited as a key feature of drug addiction, contributing to compromised control over addictive behaviors. In the present investigation, we showed that, compared with healthy controls (n=13) and even individuals with remitted cocaine use disorder (n=14), individuals with active cocaine use disorder (n=8) exhibited deficits in basic metacognition, defined as a weaker link between objective performance and self-reported confidence of performance on a visuo-perceptual accuracy task. This metacognitive deficit was accompanied by gray matter volume decreases, also most pronounced in individuals with active cocaine use disorder, in the rostral anterior cingulate cortex, a region necessary for this function in health. Our results thus provide a direct unbiased measurement - not relying on long-term memory or multifaceted choice behavior - of metacognition deficits in drug addiction, which are further mapped onto structural deficits in a brain region that subserves metacognitive accuracy in health and self-awareness in drug addiction. Impairments of metacognition could provide a basic mechanism underlying the higher-order self-awareness deficits in addiction, particularly among recent, active users.

Keywords: Anterior cingulate cortex; Drug addiction; Magnetic resonance imaging; Metacognition; Self-awareness; Voxel-based morphometry.

Figure 1

Behavioral effects on the metacognitive accuracy task in CUD+ (n=8), CUD− (n=14), and controls (n=13). (A) Task schematic. (B–C) Although not differing on task accuracy and staircase-adjusted task difficulty, (D) CUD+ had lower metacognitive accuracy than the other groups.

Figure 2

Metacognitive accuracy associations with gray matter volume (GMV). (A–B) CUD+ had reduced GMV in the bilateral rACC. (C–D) The higher the GMV deficit, the lower the metacognitive accuracy in all participants; these correlations further appeared to be driven by CUD+.

Figure 3

Mediation analyses. First, we established an effect of positive urine status (i.e., CUD+ versus controls) on metacognitive accuracy (c-paths). Second, we found an effect of positive urine status on the bilateral rACC GMV (a-paths). Third, controlling for positive urine status (where effects of CUD+ fell below significance: c′-paths), the (A) left rACC and (B) right rACC ROIs remained significant predictors of metacognitive accuracy (b-paths). Both indirect effects were significant, tested with bootstrapping, indicating mediation (see Results for statistics).

Figure 4

Exploratory whole-brain correlations of GMV with metacognitive accuracy across the entire study sample. At a reduced threshold of p<0.001 uncorrected (T=3.38) (though not at a corrected family-wise error threshold), there was a positive whole-brain correlation in the rostral anterior cingulate cortex (rACC), supporting the ROI analyses. Other regions observed at this reduced threshold included the precuneus; temporal and occipital cortices; and parahippocampal, fusiform, and precentral gyri. There were no whole-brain negative correlations with metacognitive accuracy, at either the corrected or uncorrected thresholds.