Prefrontal Cortical Dysfunction in Abstinent Cocaine Abusers

Abstract

The anterior cingulate cortex (ACC) and lateral prefrontal (LPFC) cortex are brain regions important to executive cognitive functions (ECF). We determined ACC and LPFC function in 23-day abstinent cocaine abusers using positron emission tomography (PET H 2 15 O) during performance of a modified version of the Stroop Task. Cocaine abusers showed less activation than non-drug-using comparison subjects in the left ACC and the right LPFC and greater activation in the right ACC. Average amount of cocaine used per week was negatively correlated with activity in the rostral ACC and right LPFC. Disruption of ECF in substance abusers could interfere with attempts to stop drug use and undermine treatment. Since impairment in ECF may be a common feature of various neuropsychiatric disorders, these findings have applicability beyond the neurobiology of addiction.Cocaine abuse is a substantial public health concern, as recent estimates indicate that there are 1.5 million chronic cocaine users in the United States. 1 Societal costs of drug abuse including cocaine abuse are estimated to be $62 billion. 2 The use of cocaine produces changes in brain chemistry with attendant functional consequences. Neuroimaging studies have revealed metabolic 3,4 and structural 5 differences in prefrontal brain regions, including the anterior cingulate cortex (ACC) and lateral prefrontal cortex (LPFC) of cocaine and polydrug abusers relative to non-drug-using comparison subjects. The caudal-dorsal ACC has strong reciprocal interconnections with the LPFC, and this network operates during performance of tasks that involve high levels of mental effort. 6 This neural network also appears to participate in executive cognitive functions (ECF) governing resolution of conflict, response inhibition, performance monitoring, implementation of control, and error monitoring. [7][8][9][10][11] Disruption of these functions could impair an individual's ability to monitor and inhibit inappropriate behavior. In the context of substance abuse, such disruption could impede the discontinuation of self-destructive, drug seeking behavior, thereby undermining treatment.The aim of this investigation was to determine if cocaine abusers have impaired function of the ACC and LPFC. We used water method positron emission tomography (PET H 2 15 O) imaging and a cognitive activation task, a modified version of the Stroop Task. 12 9,10,17,18 The LPFC plays a role in maintaining attentional demands of the Stroop Task whereas the ACC plays a role in conflict monitoring. 10 It is important to study the functional integrity of the ACC and LPFC in cocaine abusers because dysregulation of this prefrontal neural network might contribute to the development and persistence of maladaptive behaviors (e.g., poor response selection) that could sustain addiction or impede abstinence from drug use.In previous neurobehavioral studies of abstinent cocaine abusers, we have shown a dose-related relationship between the amount of cocaine used and performance on tasks associated with ACC ...

Post-Error Behavior in Active Cocaine Users: Poor Awareness of Errors in the Presence of Intact Performance Adjustments

“…The general pattern of poorer inhibitory control in cocaine users is consistent with the extant literature (Bolla et al, 1999;Fillmore and Rush, 2002;Hester and Garavan, 2004), although intact performance has also been reported (Bolla et al, 2004;Goldstein et al, 2001;Hoff et al, 1996). It is possible that some of the cause of inconsistency lies with sampling power, primarily the number of observations, as both current tasks indicate a significant cocaine-related deficit when inhibitory performance is averaged across within-task conditions.…”

“…Previous studies have indicated that cocaine users have a hypoactive error-related neural response (Kaufman et al, 2003;Kubler et al, 2005), particularly in the ACC region. It remains unclear how this hypoactivity might contribute to the more general cognitive control problem identified in this population (Bolla et al, 2004;Di Sclafani et al, 2002;Fillmore and Rush, 2002;Goldstein et al, 2001), which suggests a broader dysfunction in fronto-parietal top-down control networks. Two error-related processes were chosen to examine the potential influence of a hypoactive error-related neural response: error awareness and post-error cognitive control.…”

Performance on the Stroop Predicts Treatment Compliance in Cocaine-Dependent Individuals

“…The improvement in prediction ability of the model after the addition of the HDRS scores suggests that affective state contributes to treatment compliance. This is not surprising as decreased activity in the cingulate cortex and other prefrontal regions has been reported in both depressed individuals and cocaine-dependent individuals with impaired performance on the Stroop (Mayberg, 1997;Bolla et al, 2004). Most reports of neuropsychological testing in cocaine-dependent subjects have been completed when subjects are in varying degrees of abstinence (Manschreck et al, 1990; O'Malley et al, 1992; Mittenberg and Motta, 1993;Beatty et al, 1995;Bolla et al, 1998Bolla et al, , 1999Bolla et al, , 2000.…”

“…An fMRI study of cocaine abusers, using a modified version of the Goldman Stroop task, demonstrated less activation of the left ACC and right lateral PFC and increased activation of the right ACC compared to controls (Bolla et al, 2004). Subjects with the highest cocaine use before the study showed the lowest activation of prefrontal structures suggesting that cocaine use compromises the activation of the prefrontal regions involved in executive function (Bolla et al, 2004).…”

Neuropsychological effects associated with recreational cocaine use

“…These include a depletion, and reduced functioning of D2 receptors in the orbitofrontal cortex, cingulate gyri and striatum (Volkow et al, 1993(Volkow et al, , 1997(Volkow et al, , 1999Martinez et al, 2007Martinez et al, , 2009), dysfunctions in frontal brain regions including orbitofrontal, lateral prefrontal and anterior cingulate cortex (Bolla et al, 2001(Bolla et al, , 2003(Bolla et al, , 2004, as well as anterior cingulate and cerebellum (Hester and Garava, 2004). A reduced uptake of l-dopa (the precursor to dopamine) has also been reported in abstinent cocaine users .…”