A core challenge for treating drug addiction is the high propensity for relapse. The neuropsychological mechanisms of relapse remain poorly understood, but include the experience of intense craving for the drug elicited by cues or contexts previously associated with the drug.¹ Gawin and Kleber² first proposed that response to drug cues increases after some delay (which they termed as withdrawal) during abstinence. This seemingly counterintuitive notion was later empirically validated by preclinical studies showing a progressive increase in drug seeking during an individual’s early days of abstinence,^3,4 followed by a decline after approximately 6 months of abstinence.⁵ Mechanistic studies have invoked abstinence-induced early adaptations in the ventral tegmental area^6,7 and synaptic transmission changes in the nucleus accumbens,⁸ mediated via changes in composition of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor subunit and silent synapse–based remodeling^9,10 that strengthen the excitatory transmission to the medium spiny neurons, resulting in heightened reactivity to drug cues.¹¹ In addition, selective gene expression in the striatal dopamine system has been implicated in incubation of drug seeking.¹² In humans, incubation of craving (the subjectively assessed urge to use drugs) has been reported for methamphetamine,¹³ nicotine,¹⁴ and alcohol,¹⁵ but not for heroin,¹⁶ whereas the time-dependent trajectory of cue-induced craving in individuals addicted to cocaine is not known. More important, self-reported assessments of craving, as performed in these studies, are recognized for crucial pitfalls that affect their reliability and validity, including the influence of demand characteristics,¹⁷ social desirability bias,¹⁸ and compromised self-awareness.¹⁹ Moreover, subjective craving lacks direct translation to preclinical studies in which craving was defined by behavior and could not invoke introspection.

Neuropsychiatric disorders are often characterized by impaired insight into behaviour. Such an insight deficit has been suggested, but never directly tested, in drug addiction. Here we tested for the first time this impaired insight hypothesis in drug addiction, and examined its potential association with drug-seeking behaviour. We also tested potential modulation of these effects by cocaine urine status, an individual difference known to impact underlying cognitive functions and prognosis. Sixteen cocaine addicted individuals testing positive for cocaine in urine, 26 cocaine addicted individuals testing negative for cocaine in urine, and 23 healthy controls completed a probabilistic choice task that assessed objective preference for viewing four types of pictures (pleasant, unpleasant, neutral and cocaine). This choice task concluded by asking subjects to report their most selected picture type; correspondence between subjects’ self-reports with their objective choice behaviour provided our index of behavioural insight. Results showed that the urine positive cocaine subjects exhibited impaired insight into their own choice behaviour compared with healthy controls; this same study group also selected the most cocaine pictures (and fewest pleasant pictures) for viewing. Importantly, however, it was the urine negative cocaine subjects whose behaviour was most influenced by insight, such that impaired insight in this subgroup only was associated with higher cocaine-related choice on the task and more severe actual cocaine use. These findings suggest that interventions to enhance insight may decrease drug-seeking behaviour, especially in urine negative cocaine subjects, potentially to improve their longer-term clinical outcomes.

In this review, we highlight the role of neuroimaging techniques in studying the emotional and cognitive-behavioral components of the addiction syndrome by focusing on the neural substrates subserving them. The phenomenology of drug addiction can be characterized by a recurrent pattern of subjective experiences that includes drug intoxication, craving, bingeing, and withdrawal with the cycle culminating in a persistent preoccupation with obtaining, consuming, and recovering from the drug. In the past two decades, imaging studies of drug addiction have demonstrated deficits in brain circuits related to reward and impulsivity. The current review focuses on studies employing positron emission tomography (PET), functional magnetic resonance imaging (fMRI), and electroencephalography (EEG) to investigate these behaviors in drug-addicted human populations. We begin with a brief account of drug addiction followed by a technical account of each of these imaging modalities. We then discuss how these techniques have uniquely contributed to a deeper understanding of addictive behaviors.

Electrocortical activity, typically used to track the effectsof cognitive reappraisal on the processing of emotional stimuli, has not been used to index the prefrontal-cortex-mediated regulatory...