Executive dysfunction in cocaine addiction: evidence for discordant frontal, cingulate, and cerebellar activity

Abstract

Using a GO-NOGO response inhibition task in which working memory (WM) demands can be varied, we demonstrate that the compromised abilities of cocaine users to exert control over strong prepotent urges are associated with reduced activity in anterior cingulate and right prefrontal cortices, two regions thought to be critical for implementing cognitive control. Furthermore, unlike drug-naive controls, and opposite to the anterior cingulate pattern, cocaine users showed an over-reliance on the left cerebellum, a compensatory pattern previously seen in alcohol addiction. The results indicate that cocaine users find it difficult to inhibit their own actions, particularly when WM demands, which have been shown previously to increase during cue-induced craving for the drug, are increased. The results reveal a neuroanatomical basis for this dysexecutive component to addiction, supporting the suggested importance cognitive functions may play in prolonging abuse or predisposing users toward relapse.

Figure 1.

WM load inhibition task design. The design of the task requires participants to withhold a prepotent response to an increasing number of items currently held in WM. At the beginning of the task, a memory list of one, three, or five items was presented. A series of single letters was then presented, and participants were told to press a button if the item had not been part of the memory list (88% of trials) and withhold their response if it had.

Figure 2.

Control and cocaine users' performance on the GO-NOGO inhibition task with different WM loads.

Figure 3.

The cortical regions that indicated significantly greater levels of activation for control subjects when compared with cocaine users include the right superior frontal gyrus (A, BAs 10/9; Talairach coordinates, 25, 48, 26), right pre-SMA (Bi, BA 6; Talairach coordinates, 7, 5, 57), and left ACC (Bii, BAs 32/24; Talairach coordinates, -2, 32, 22). The cortical regions showing significant interactions between load and group include the ACC (Bii) and two regions in the left cerebellum (Ci, Talairach coordinates, -33, -49, -25; Cii, Talairach coordinates, -12, -68, -25).