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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...

Individuals with current cocaine use disorders (CUD) form a heterogeneous group, making sensitive neuropsychological (NP) comparisons with healthy individuals difficult. The current study examined the effects on NP functioning of four factors that commonly vary among CUD: urine status for cocaine (positive vs negative on study day), cigarette smoking, alcohol consumption, and dysphoria. Sixty-four cocaine abusers were matched to healthy comparison subjects on gender and race; the groups also did not differ in measures of general intellectual functioning. All subjects were administered an extensive NP battery measuring attention, executive function, memory, facial and emotion recognition, and motor function. Compared with healthy control subjects, CUD exhibited performance deficits on tasks of attention, executive function, and verbal memory (within one standard deviation of controls). Although CUD with positive urine status, who had higher frequency and more recent cocaine use, reported greater symptoms of dysphoria, these cognitive deficits were most pronounced in the CUD with negative urine status. Cigarette smoking, frequency of alcohol consumption, and dysphoria did not alter these results. The current findings replicate a previously reported statistically significant, but relatively mild NP impairment in CUD as compared with matched healthy control individuals and further suggest that frequent/recent cocaine may mask underlying cognitive (but not mood) disturbances. These results call for development of pharmacological agents targeted to enhance cognition, without negatively impacting mood in individuals addicted to cocaine.

Event-related potentials (ERPs) are a direct measure of neural activity and are ideally suited to study the time-course of attentional engagement with emotional and drug-related stimuli in addiction. In particular, the late positive potential (LPP) appears enhanced following cocainerelated compared to neutral stimuli in individuals with cocaine use disorders (CUD). However, previous studies have not directly compared cocaine-related to emotional stimuli while examining potential differences between abstinent and current cocaine users. The present study examined ERPs in 55 CUD (27 abstinent and 28 current users) and 29 matched healthy controls while they passively viewed pleasant, unpleasant, neutral, and cocaine-related pictures. To examine the timecourse of attention to these stimuli, we analyzed both an early and later window in the LPP as well as the early posterior negativity (EPN), established in assessing motivated attention. Cocaine pictures elicited increased electrocortical measures of motivated attention in ways similar to affectively pleasant and unpleasant pictures in all CUD, an effect that was no longer discernible during the late LPP window for the current users. This group also exhibited deficient processing of the other emotional stimuli (early LPP window: pleasant pictures; late LPP window: pleasant and unpleasant pictures). Results were unique to the LPP and not EPN. Taken together, results support a relatively early attention bias to cocaine stimuli in cocaine addicted individuals further suggesting that recent cocaine use decreases such attention bias during later stages of processing but at the expense of deficient processing of other emotional stimuli. KeywordsCocaine addiction; motivated attention; emotional processing; late positive potential Drug-related compared to neutral stimuli elicit increases in physiological reactivity in drug addicted individuals (Carter & Tiffany, 1999). Similar research demonstrates unique reactions to emotional compared to neutral stimuli in healthy individuals (Lang et al., 1997;Vuilleumier, 2005;Schupp et al., 2007). Termed 'motivated attention', it is hypothesized that motivational systems automatically allocate attention to, and enhance the salience of, emotional stimuli (Lang et al., 1997). Two event-related potentials (ERP), the early posterior negativity (EPN) and the late positive potential (LPP), are larger for both pleasant and unpleasant compared to neutral visual stimuli, interpreted as reflecting increased * Corresponding Author: Rita Z. Goldstein, Medical Research, Brookhaven National Laboratory, 30 Bell Ave., Bldg. 490, Upton, NY, 11973-5000; tel. (631) 344-2657; fax (631) Schupp et al., 2000;Schupp et al., 2003a;2004b;Hajcak et al., 2007;Hajcak & Olvet, 2008;Foti et al., 2009). These ERPs capture different stages within emotional processing; specifically, the EPN reflects early selective attentional processing, while the LPP reflects continued processing of motivationally significant stimuli. Also, evidence suggests that the LPP is...