Orbitofrontal cortex dysfunction in abstinent cocaine abusers performing a decision-making task

Abstract

Cocaine abusers demonstrate faulty decision-making as manifested by their inability to discontinue self-destructive drug-seeking behaviors. The orbitofrontal cortex (OFC) plays an important role in decision-making. In this preliminary study we tested whether 25-day-abstinent cocaine abusers show alterations in normalized cerebral blood flow (rCBF) in the OFC using PET with (15)O during the Iowa Gambling Task (a decision-making task). This task measures the ability to weigh short-term rewards against long-term losses. A control task matched the sensorimotor aspects of the task but did not require decision-making. Cocaine abusers (N = 13) showed greater activation during performance of the Iowa Gambling Task in the right OFC and less activation in the right dorsolateral prefrontal cortex (DLPFC) and left medial prefrontal cortex (MPFC) compared to a control group (N = 13). Better Iowa Gambling Task performance was associated with greater activation in the right OFC in both groups. Also, the amount of cocaine used (grams/week) prior to the 25 days of enforced abstinence was negatively correlated with activation in the left OFC. Greater activation in the OFC in cocaine abusers compared to a control group may reflect differences in the anticipation of reward while less activation in the DLPFC and MPFC may reflect differences in planning and working memory. These findings suggest that cocaine abusers show persistent functional abnormalities in prefrontal neural networks involved in decision-making and these effects are related to cocaine abuse. Compromised decision-making could contribute to the development of addiction and undermine attempts at abstinence.

Fig. 1

(A and B) Sagittal and axial views. Cocaine abusers showed more activation than controls in the right OFC (peak located at 34, 35, −8) [BA 47]; (P < 0.001, k = 46 voxels, uncorrected) during performance on the Iowa Gambling Task (active task minus control task). (C) Cocaine abusers showed less activation than controls in the right DLPFC (peak located at 34, 23, 36) [BA 9]; and left MPFC (peak located at −16, 38, 20) [BA 9]; (P < 0.001; right DLPFC, k = 109 voxels and left MPFC, k = 46 voxels, uncorrected) during performance on the Iowa Gambling Task (active task minus control task); (D and E) Sagittal and axial views. Significant correlation between better performance on the Iowa Gambling Task and greater activation in the right medial OFC in the cocaine abusers (blue) (peak located at 20, 38, −17, 223 voxels), [BA 11] and control group (red) (peak located at 20, 42, −19, 94 voxels), [BA 11]; P < 0.001).

Fig. 2

(A) Regression between activation in the 13 cocaine abusers at the epicenter of the left OFC (peak located at −26, 20, −18) and the number of grams of cocaine used per week prior to the 25 days of enforced abstinence (r =−0.89, P < 0.001, k = 59 voxels, uncorrected). (B) Regression between activation in the 11 cocaine abusers at the epicenter of the left OFC (peak located at −22, 40, −18) and the number of grams of cocaine used per week prior to the 25 days of enforced abstinence (r =−0.82, P < 0.005, k = 36 voxels, uncorrected). The two “extreme cases” with respect to the number of grams of cocaine used per week and magnitude of activation intensity were omitted from this analysis. Only 10 data points are readily apparent because two cases with 1 g of cocaine use overlap.