Anterior cingulate cortex hypoactivations to an emotionally salient task in cocaine addiction

Abstract

Anterior cingulate cortex (ACC) hypoactivations during cognitive processing characterize drug addicted individuals as compared with healthy controls. However, impaired behavioral performance or task disengagement may be crucial factors. We hypothesized that ACC hypoactivations would be documented in groups matched for performance on an emotionally salient task. Seventeen individuals with current cocaine use disorders (CUD) and 17 demographically matched healthy controls underwent functional magnetic resonance imaging during performance of a rewarded drug cue-reactivity task previously shown to engage the ACC. Despite lack of group differences in objective or subjective taskrelated performance, CUD showed more ACC hypoactivations throughout this emotionally salient task. Nevertheless, intensity of emotional salience contributed to results: (i) CUD with the largest rostroventral ACC [Brodmann Area (BA) 10, 11, implicated in default brain function] hypoactivations to the most salient task condition (drug words during the highest available monetary reward), had the least task-induced cocaine craving; (ii) CUD with the largest caudal-dorsal ACC (BA 32) hypoactivations especially to the least salient task condition (neutral words with no reward) had the most frequent current cocaine use; and (iii) responses to the most salient task condition in both these ACC major subdivisions were positively intercorrelated in the controls only. In conclusion, ACC hypoactivations in drug users cannot be attributed to task difficulty or disengagement. Nevertheless, emotional salience modulates ACC responses in proportion to drug use severity. Interventions to strengthen ACC reactivity or interconnectivity may be beneficial in enhancing top-down monitoring and emotion regulation as a strategy to reduce impulsive and compulsive behavior in addiction.blood-oxygen-level-dependent fMRI ͉ salience ͉ brain-behavior dissociation ͉ craving ͉ cocaine use I n the impaired response inhibition and salience attribution (I-RISA) model we have emphasized the role of the anterior cingulate (ACC) and orbitofrontal cortices (OFC) in core clinical symptoms of drug addiction that encompass attribution of enhanced salience to drug cues at the expense of the salience attributed to nondrug-related stimuli (1). Supporting this core I-RISA hypothesis, neuroimaging studies in drug addicted individuals demonstrate ACC and OFC hyperactivations during drug-related cue reactivity (2), including craving (3, 4) and hypoactivations during performance of neutrally valenced cognitive tasks (5-9). Because these hypoactivations in addicted individuals could reflect impaired performance (5-8) or decreased engagement (9), in the current study we set out to determine whether ACC hypoactivations in addiction can still be observed in groups matched for overt performance on an emotionally salient task. This is a crucial question because the clinical implications for such hypoactivations even in the absence of overt behavioral group differences may be pronounced. For example, t...

Oral methylphenidate normalizes cingulate activity in cocaine addiction during a salient cognitive task

“…1A). Thus, consistent with our previous results in a larger independent cohort that did not receive any pharmacological intervention (14), during placebo, the cdACC was hypoactive in the CUD. Here, MPH bolstered the cdACC signal in the CUD to a level where there were no longer significant differences between the study groups (note specificity of results in the drug-related context).…”

“…We hypothesized that, compared with placebo, oral MPH will increase function of these two ACC subregions in the CUD, evidenced by reduced group differences (i.e., normalization in CUD) during MPH use. For all subjects compared with a fixation baseline, the fMRI task produced brain-activation and hypoactivation patterns similar to those we previously reported (14) with similar group differences (Table S2). Importantly, an MPH main effect was observed in both our a priori regions of interest (ROIs) as driven by the CUD (Table 1).…”

“…The cdACC is located within the confines of the posterior medial frontal cortex and includes BA 24 as previously described (18) (BA 32 occupies territories within both ACC subdivisions). Similarly to our previous study (14), we were interested in these two major subdivisions of the ACC that are differentially recruited for the regulation of emotion, cognition, and behavior in response to salient stimuli (19); the rvACC/mOFC has been implicated in maintaining a default brain function that needs to be suspended during goal-oriented tasks, including the regulation of autonomic functions (20), and in the adaptive suppression of emotion (21), and the cdACC has been implicated in performance monitoring (22) and cognitive control (18). Functional neuroimaging studies in posttraumatic stress disorder (23,24) and depression (25) have indeed implicated the cdACC in emotional conflict monitoring (26), whereas the rvACC/mOFC has been implicated in emotional conflict resolution (27).…”

“…These whole-brain analyses also revealed correlations between drug use and the dorsolateral PFC, caudate, and inferior parietal lobule (Table 1). Notably, a significant ROI correlation between the rvACC/mOFC and recent cocaine use (SI Text) did not survive whole-brain corrections, and this effect, although echoing our prior correlation between this region with craving (14), needs to be studied further in larger sample sizes. There were also no significant correlations between the selected drug-use variables (Table S1) and any of the task-performance variables (r S < |0.67|, P > 0.01).…”

“…We chose a task that, as previously reported, engaged the PFC in CUD; here, subjects are monetarily remunerated for correct pressing for color of drugrelated and matched neutral words that they have just read (13). Importantly, using this task, despite lack of group differences in self-reported engagement or objective behavioral performance, the CUD participants compared with the healthy controls showed robust anterior cingulate cortex (ACC) hypoactivations (14), encompassing the rostroventral ACC [rvACC; extending to the medial orbitofrontal cortex (mOFC)] and the caudal-dorsal ACC (cdACC). The rvACC/mOFC is based on a functional network known as the orbital and medial PFC (15,16) or the ventromedial PFC (which does not include the central and lateral regions of the OFC) and includes Brodmann Area (BA) 10 (and BAs 11, 13, and 14 but not 47/12 or 45) (17).…”