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INTRODUCTION: Increased salience of drug-related cues over non-drug reinforcers can drive drug use and contribute to tobacco use disorder (TUD). An important scientific and clinical goal is to effectively measure this elevated drug-seeking behavior in TUD. However, most TUD assessments rely on self-reported cravings and cigarette consumption, not providing an objective measure of the impact of drug-cues on biasing behavior towards drugs. The probabilistic image choice (PIC) task investigates the choice of viewing drug-related pictures as compared to other salient pictures (e.g., pleasant and unpleasant). This study aimed to develop and validate the PIC task for TUD and evaluate the associations between behavioral choice and tobacco craving, daily cigarette consumption, quit attempts and motivation to quit, and nicotine dependence (the Fagerström score). METHODS: We recruited 468 smokers and 121 nonsmokers using the Prolific online platform. Participants performed the PIC task twice (at a one-month interval) and completed other measures relevant to TUD. RESULTS: compared to nonsmokers, tobacco smokers selected to view significantly more tobacco images and less pleasant (non-drug reinforcer) images, a profile that remained stable at retest. Individual differences in choice of tobacco as compared to pleasant images on the PIC task were associated with craving but not with the other tobacco dependence measures, suggesting that the task may serve as a behavioral proxy measure of drug "wanting" rather than of cumulative nicotine exposure or physical dependence. CONCLUSIONS: these results suggest that the PIC task can be a valuable tool for objectively assessing craving-associated tobacco seeking in TUD. IMPLICATIONS SECTION: which should provide a brief description about what the study addsMost of the current measures of tobacco use disorder (TUD) rely on self-reports of consumption, dependence and craving and do not take into consideration the role of drug-related cues in driving tobacco seeking. This study shows that the probabilistic image choice (PIC) task provides an objective, reliable proxy measure of tobacco image seeking behavior in people who smoke cigarettes that is linked to craving (desire) for smoking but not to other measures of TUD. Therefore, the PIC task may be a useful complementary tool for the classification, diagnosis, and prognosis of TUD.
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BACKGROUND: Despite longstanding interest in the central cholinergic system in schizophrenia (SCZ), cholinergic imaging studies with patients have been limited to receptors. Here, we conducted a proof-of-concept positron emission tomography study using [18F]-VAT, a new radiotracer that targets the vesicular acetylcholine transporter as a proxy measure of acetylcholine transmission capacity, in patients with SCZ and explored relationships of vesicular acetylcholine transporter with clinical symptoms and cognition. METHODS: A total of 18 adult patients with SCZ or schizoaffective disorder (the SCZ group) and 14 healthy control participants underwent a positron emission tomography scan with [18F]-VAT. Distribution volume (VT) for [18F]-VAT was derived for each region of interest, and group differences in VT were assessed with 2-sample t tests. Functional significance was explored through correlations between VT and scores on the Positive and Negative Syndrome Scale and a computerized neurocognitive battery (PennCNB). RESULTS: No group differences in [18F]-VAT VT were observed. However, within the SCZ group, psychosis symptom severity was positively associated with VT in multiple regions of interest, with the strongest effects in the hippocampus, thalamus, midbrain, cerebellum, and cortex. In addition, in the SCZ group, working memory performance was negatively associated with VT in the substantia innominata and several cortical regions of interest including the dorsolateral prefrontal cortex. CONCLUSIONS: In this initial study, the severity of 2 important features of SCZ-psychosis and working memory deficit-was strongly associated with [18F]-VAT VT in several cortical and subcortical regions. These correlations provide preliminary evidence of cholinergic activity involvement in SCZ and, if replicated in larger samples, could lead to a more complete mechanistic understanding of psychosis and cognitive deficits in SCZ and the development of therapeutic targets.
Assuntos
Tomografia por Emissão de Pósitrons , Transtornos Psicóticos , Esquizofrenia , Proteínas Vesiculares de Transporte de Acetilcolina , Humanos , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/metabolismo , Masculino , Feminino , Adulto , Proteínas Vesiculares de Transporte de Acetilcolina/metabolismo , Transtornos Psicóticos/diagnóstico por imagem , Transtornos Psicóticos/metabolismo , Pessoa de Meia-Idade , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Radioisótopos de Flúor , Compostos RadiofarmacêuticosRESUMO
BACKGROUND: Individuals with substance use disorder show impaired self-awareness of ongoing behavior. This deficit suggests problems with metacognition, operationalized in the cognitive neuroscience literature as the ability to monitor and evaluate the success of one's own cognition and behavior. However, the neural mechanisms of metacognition have not been characterized in a drug-addicted population. METHODS: Community samples of participants with opioid use disorder (OUD) (N=27) and healthy controls (N=29) performed a previously-validated fMRI metacognition task (perceptual decision-making task along with confidence ratings of performance). Measures of recent drug use and addiction severity were also acquired. RESULTS: Individuals with OUD had lower metacognitive sensitivity than controls (i.e., disconnection between task performance and task-related confidence). Trial-by-trial analyses showed that this overall group difference was driven by (suboptimally) low confidence in OUD during correct trials. In fMRI analyses, the task engaged an expected network of brain regions (e.g., rostrolateral prefrontal cortex and dorsal anterior cingulate/supplementary motor area, both previously linked to metacognition); group differences emerged in a large ventral anterior cluster that included the medial and lateral orbitofrontal cortex and striatum (higher activation in OUD). Trial-by-trial fMRI analyses showed group differences in rostrolateral prefrontal cortex activation, which further correlated with metacognitive behavior across all participants. Exploratory analyses suggested that the behavioral and neural group differences were exacerbated by recent illicit opioid use and unexplained by general cognition. CONCLUSIONS: With confirmation and extension of these findings, metacognition and its associated neural circuits could become new, promising therapeutic targets in addiction.