Content area
Full Text
REVIEWS
REVIEWS
Dysfunction of the prefrontal cortex in addiction: neuroimaging findings and clinical implications
Rita Z.Goldstein* and Nora D.Volkow
Abstract | The loss of control over drug intake that occurs in addiction was initially believed to result from disruption of subcortical reward circuits. However, imaging studies in addictive behaviours have identified a key involvement of the prefrontal cortex (PFC) both through its regulation of limbic reward regions and its involvement in higher-order executive function (for example, self-control, salience attribution and awareness). This Review focuses on functional neuroimaging studies conducted in the past decade that have expanded our understanding of the involvement of the PFC in drug addiction. Disruption of the PFC in addiction underlies not only compulsive drug taking but also accounts for the disadvantageous behaviours that are associated with addiction and the erosion of free will.
Drug addiction encompasses a relapsing cycle of intoxication, bingeing, withdrawal and craving that results in excessive drug use despite adverse consequences (FIG.1). Drugs that are abused by humans increase dopamine in the reward circuit and this is believed to underlie their rewarding effects. Therefore, most clinical studies in addiction have focused on the midbrain dopamine areas (the ventral tegmental area and substantia nigra) and the basal ganglia structures to which they project (the ventral striatum, where the nucleus accumbens is located, and the dorsal striatum), which are known to be involved in reward, conditioning and habit formation13.
However, preclinical and clinical studies have more recently brought to light and started to clarify the role of the prefrontal cortex (PFC) in addiction4. A number of processes are ascribed to the PFC that are fundamental for healthy neuropsychological function encompassing emotion, cognition and behaviour and that help to explain why PFC disruption in addiction could negatively affect a wide range of behaviours (TABLE1).
On the basis of imaging findings and emerging preclinical studies5,6, we proposed 10years ago that disrupted function of the PFC leads to a syndrome of impaired response inhibition and salience attribution (iRISA) in addiction (FIG.1) a syndrome that is characterized by attributing excessive salience to the drug and drug-related cues, decreased sensitivity to non-drug reinforcers and decreased ability to inhibit maladaptive or disadvantageous behaviours7. As a result of these core deficits, drug seeking and taking become a...