Drug cues play an important role in relapse to drug use. Naltrexone is an opioid antagonist that is used to prevent relapse in opioid dependence. Central opioidergic pathways may be implicated in the heightened drug cue-reactivity, but the effects of the opioid receptors' blockade on the brain responses to drug cues in opioid dependence are unknown. To pursue this question, we studied 17 abstinent i.v. heroin users with brain functional magnetic resonance imaging (fMRI) during exposure to visual heroin-related cues and matched neutral images before and 10-14 days after an injection of extended-release naltrexone (XRNTX). Whole brain analysis of variance of fMRI data showed main effect of XRNTX in the medial frontal gyrus, precentral gyrus, cuneus, precuneus, caudate and the amygdala. fMRI response was decreased in the amygdala, cuneus, caudate and the precentral gyrus and increased in the medial frontal gyrus and the precuneus. Higher plasma levels of naltrexone's major metabolite, 6-beta-naltrexol, were associated with larger reduction in the fMRI response to drug cues after XRNTX in the precentral, caudate and amygdala clusters. The present data suggest that XRNTX pharmacotherapy of opioid-dependent patients may, respectively, decrease and potentiate prefrontal and limbic cortical responses to drug cues and that this effect might be related to the XRNTX metabolism. Our findings call for further evaluation of the brain fMRI response to drug-related cues and of the 6-beta-naltrexol levels as potential biomarkers of XRNTX therapeutic effects in patients with opioid dependence.

Background Opioid neurotransmission mediates hedonic value of sweet tastants; their intake may be exaggerated by the consumption of exogenous opioids (e.g., opioid dependence). Sweet Taste Test (STT) is a validated quantitative instrument assessing taste perception and hedonic features of sugar (sucrose) using a randomized and double-blind administration at five different sucrose concentrations ranging from 0.05 to 0.83 M. Methods The STT and cue-induced craving procedure were administered to opioid dependent patients (n=15) before and one week after the injection of a long-acting depot-naltrexone (XRNT) preparation. Results Analyses of covariance, employing sucrose concentration and its perceived taste as covariates, showed that XRNT therapy significantly reduced the self-reported hedonic and motivational characteristics of sucrose. Greater reductions in both these characteristics were associated with more diminution in the cue-induced opioid craving. Conclusions Opioid antagonism in opioid dependent subjects leads to a smaller sweet taste reward, which, in turn, may be proportional to decreased opioid craving. These pilot results support the heuristic value of the STT as a potential marker of the XRNT treatment response and call for further inquiry into potential clinical applications of the test.

We studied the cognitive basis of the functional magnetic resonance imaging (fMRI) pattern of deception in three participants performing the Concealed Information Test (CIT). In all participants, the prefrontoparietal lie activation was similar to the pattern derived from the meta-analysis (N = 40) of our previously reported fMRI CIT studies and was unchanged when the lie response was replaced with passive viewing of the target items. When lies were replaced with irrelevant responses, only the left inferior gyrus activation was common to all subjects. This study presents a systematic strategy for testing the cognitive basis of deception models, and a qualitative approach to single-subject truth-verification fMRI tests.

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Recent reports of successful fMRI-based discrimination between lie and truth in single subjects raised the interest of prospective users and a public concern about the potential scope of this technology. The increased scrutiny highlighted the lack of controlled "real life", i.e. prospective clinical trials of this technology that conform to the common standards of medical device development. The ethics of conducting such trials given the paucity of data on fMRI-based lie detection has also been questioned. To probe the potential issues of translating the laboratory research into practice, we conducted a case study in which we adapted the standard Guilty Knowledge Test (GKT), a well-established model of producing deception, to the common scenario of lying on a resume. The task consisted of questions about pertinent items on the subject's resume, three of which could be independently verified as truth (KNOWN) and three that could not be verified and were thus termed UNKNOWN. The subject had an incentive to lie on all UNKNOWN items, and on debriefing confirmed that he had done so. Data was preprocessed, masked with a priori regions of interest, thresholded, and qualitatively evaluated for consistency with the previously reported prefronto-parietal Lie > Truth pattern. Deceptive responses to two out of the three UNKNOWN items were associated with the predicted prefronto-parietal fMRI pattern. In the third UNKNOWN this pattern was absent, and instead, increased limbic (amygdala and hippocampus) response was observed. Based on published prefronto-parietal Lie response pattern, only the first two items could be categorized as Lie. If confirmed, this demonstration of amygdala and hippocampus activation in a Lie > Truth contrast illustrates the need to integrate the limbic system and its emotional and cognitive correlates into the existing model of deception. Our experiment suggests an approach to a naturalistic scenario and the research questions that need to be answered in order to set the stage for prospective clinical trials of fMRI-based lie detection.