Substrates of neuropsychological functioning in stimulant dependence: a review of functional neuroimaging research

Stimulant dependence is associated with neuropsychological impairments. Here, we summarize and integrate the existing neuroimaging literature on the neural substrates of neuropsychological (dys)function in stimulant dependence, including cocaine, (meth‐)amphetamine, ecstasy and nicotine dependence, and excessive caffeine use, comparing stimulant abusers ( SA s) to nondrug using healthy controls ( HC s). Despite some inconsistencies, most studies indicated altered brain activation in prefrontal cortex ( PFC ) and insula in response to reward and punishment, and higher limbic and anterior cingulate cortex ( ACC )/ PFC activation during craving and attentional bias paradigms in SA s compared with HC s. Impulsivity in SA s was associated with lower ACC and presupplementary motor area activity compared with HC s, and related to both ventral (amygdala, ventrolateral PFC , insula) and dorsal (dorsolateral PFC , dorsal ACC , posterior parietal cortex) systems. Decision making in SA s was associated with low dorsolateral PFC activity and high orbitofrontal activity. Finally, executive function in SA s was associated with lower activation in frontotemporal regions and higher activation in premotor cortex compared with HC s. It is concluded that the lower activations compared with HC s are likely to reflect the neural substrate of impaired neurocognitive functions, whereas higher activations in SA s compared with HC s are likely to reflect compensatory cognitive control mechanisms to keep behavioral task performance to a similar level as in HC s. However, before final conclusions can be drawn, additional research is needed using neuroimaging in SA s and HC s using larger and more homogeneous samples as well as more comparable task paradigms, study designs, and statistical analyses.