Review. Parallel studies of cocaine-related neural and cognitive impairment in humans and monkeys

Abstract

Cocaine users display profound impairments in executive function. Of all the components of executive function, inhibition, or the ability to withhold responding, has been studied the most extensively and may be most impaired. Consistent with these deficits, evidence from imaging studies points to dysregulation in medial and ventromedial prefrontal cortices, areas activated during performance of inhibition tasks. Other aspects of executive function including updating, shifting and decision making are also deficient in cocaine users, and these deficits are paralleled by abnormalities in patterns of prefrontal cortical activation. The extent to which cocaine plays a role in these effects, however, is not certain, and cannot be determined solely on the basis of human studies. Investigations using a non-human primate model of increasing durations of cocaine exposure revealed that initially the effects of cocaine were restricted to ventromedial and orbital prefrontal cortices, but as exposure was extended the intensity and spatial extent of the effects on functional activity also expanded rostrally and laterally. Given the spatial overlap in prefrontal pathology between human and monkey studies, these longitudinal mapping studies in non-human primates provide a unique window of understanding into the dynamic neural changes that are occurring early in human cocaine abuse.

Figure 1

Impaired performance on two tests of executive function by cocaine users (n=37) and healthy controls (n=57). (a) Per cent correct on the delayed match to sample task (working memory) at three delay intervals for cocaine users (dashed line) and controls (solid line). (b) Total errors on the intra- and extra-dimensional set shifting task (attentional set shifting) in cocaine users (grey bars) and controls (black bars). ^*p<0.05, ^**p<0.005, t-test for independent groups. ID, intra-dimensional; ED, extra-dimensional.

Figure 2

Time course of the effects on local cerebral glucose metabolism in prefrontal cortex of non-human primate brain. Schematic illustrating the spatial extent of the effects of increasing durations of cocaine self-administration histories on functional activity: (a) initial, 5 days; (b) chronic, 3.3 months and (c) prolonged, 1.2 years ((i) rostral, (ii) middle and (iii) caudal). Areas shaded in grey represent regions exhibiting significant decreases in functional activity. Numbers represent Brodmann areas.