Tobacco Images Choice and Its Association with Craving and Dependence in People who Smoke Cigarettes.

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.

Imaging the Vesicular Acetylcholine Transporter in Schizophrenia: A Positron Emission Tomography Study Using [18F]-VAT.

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.

Tobacco Images Choice and Its Association with Craving and Dependence in Cigarette Smokers.

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.

Reduced neural encoding of utility prediction errors in cocaine addiction.

Influential accounts of addiction posit alterations in adaptive behavior driven by deficient dopaminergic prediction errors (PEs), signaling the discrepancy between actual and expected reward. Dopamine neurons encode these error signals in subjective terms, calibrated by individual risk preferences, as "utility" PEs. It remains unclear, however, whether people with drug addiction have PE deficits or their computational source. Here, using an analogous task to prior single-unit studies with known expectancies, we show that fMRI-measured PEs similarly reflect utility PEs. Relative to control participants, people with chronic cocaine addiction demonstrate reduced utility PEs in the dopaminoceptive ventral striatum, with similar trends in orbitofrontal cortex. Dissecting this PE signal into its subcomponent terms attributed these reductions to weaker striatal responses to received reward/utility, whereas suppression of activity with reward expectation was unchanged. These findings support that addiction may fundamentally disrupt PE signaling and reveal an underappreciated role for perceived reward value in this mechanism.

Whole-brain resting-state connectivity underlying impaired inhibitory control during early versus longer-term abstinence in cocaine addiction.

Lapses in inhibitory control have been linked to relapse in human drug addiction. Evidence suggests differences in inhibitory control depending on abstinence duration, but the underlying neural mechanisms remain unknown. We hypothesized that early abstinence (2-5 days) would be characterized by the strongest impairments of inhibitory control and most wide-spread deviations in resting-state functional connectivity of brain networks, while longer-term abstinence (>30 days) would be characterized by weaker impairments as compared to healthy controls. In this laboratory-based cross-sectional study, we compared individuals with Cocaine Use Disorder (iCUD) during early (cocaine urine-positive: N = 19, iCUD+; 32% female; mean age: 46.8 years) and longer-term abstinence (cocaine urine-negative: N = 29, iCUD-; 15% female; mean age: 46.6 years) to healthy controls (N = 33; 24% female; mean age: 40.9 years). We compared the groups on inhibitory control performance (Stop-Signal Task) and, using a whole-brain graph theory analysis (638 region parcellation) of functional magnetic resonance imaging (fMRI) data, we tested for group differences in resting-state brain function (local/global efficiency). We characterized how resting-state brain function was associated with inhibitory control performance within iCUD. Inhibitory control performance was worst in the early abstinence group, and intermediate in the longer-term abstinence group, as compared to the healthy control group (P < 0.01). More recent use of cocaine (CUD+ > CUD- > healthy controls) was characterized by decreased efficiency in fronto-temporal and subcortical networks (primarily in the salience, semantic, and basal ganglia networks) and increased efficiency in visual networks. Importantly, a similar functional connectivity pattern characterized impaired inhibitory control performance within iCUD (all brain analyses P < 0.05, FWE-corrected). Together, we demonstrated that a similar pattern of systematic and widespread deviations in resting-state brain efficiency, extending beyond the networks commonly investigated in human drug addiction, is linked to both abstinence duration and inhibitory control deficits in iCUD.

Neurophysiological error processing and addiction self-awareness correlates of reduced insight in cannabis use disorder.

BACKGROUND AND AIMS: Cannabis use disorder (CUD) prevalence has increased, while perceived risks of cannabis use and CUD treatment need have decreased. Chronic cannabis use may also impair the neural and behavioral mechanisms of insight, further hampering treatment-seeking. This study aimed to measure whether CUD is characterized by reduced self-monitoring in drug-related contexts (objectively-assessed insight), subserved by functional neural abnormalities in error-processing and manifested clinically as decreased awareness of the need to change. DESIGN: Case-control laboratory study was used. SETTING: University setting was in Alabama, USA. PARTICIPANTS: There were 42 CUD participants and 47 age-, sex-, and nicotine use-matched controls. MEASUREMENTS: Participants completed a probabilistic choice task, adapted for the first time for CUD, in which they selected pleasant, unpleasant, neutral, and cannabis-related images according to their preference. Reduced versus accurate insight was operationalized as the correspondence between self-reported and actual most chosen image type. Neurophysiological error-processing during an inhibitory control task was recorded using electroencephalography. Participants with CUD completed measures of cannabis problem recognition and motivation to change. FINDINGS: Compared with controls, the CUD group made significantly more cannabis selections on the choice task (mean difference [MD] = 8.11, 95% confidence interval [CI] [4.88 11.35], p < 0.001) and had significantly reduced insight into cannabis choice (odds ratio [OR] = 9.69, 95% CI [1.06 88.65], p = 0.04). CUD participants with reduced insight on the choice task had significantly decreased neurophysiological reactivity to errors on the inhibitory control task (error-related negativity) compared with CUD participants with accurate insight (MD = 2.64 µV, 95% CI [0.74 µV 4.54 µV], p = 0.008) and controls (MD = 4.05 µV, 95% CI [1.29 µV 6.80 µV], p = 0.005). Compared with CUD participants with accurate insight on the choice task, CUD participants with reduced insight reported significantly less agreement that they had a cannabis problem (MD = -5.06, 95% CI [-8.49-1.62], p = 0.003). CONCLUSIONS: People with CUD who show reduced insight on a drug-related choice task may also have decreased early neural error-processing and less cannabis problem recognition.

Candidate biomarkers in psychiatric disorders: state of the field.

The field of psychiatry is hampered by a lack of robust, reliable and valid biomarkers that can aid in objectively diagnosing patients and providing individualized treatment recommendations. Here we review and critically evaluate the evidence for the most promising biomarkers in the psychiatric neuroscience literature for autism spectrum disorder, schizophrenia, anxiety disorders and post-traumatic stress disorder, major depression and bipolar disorder, and substance use disorders. Candidate biomarkers reviewed include various neuroimaging, genetic, molecular and peripheral assays, for the purposes of determining susceptibility or presence of illness, and predicting treatment response or safety. This review highlights a critical gap in the biomarker validation process. An enormous societal investment over the past 50 years has identified numerous candidate biomarkers. However, to date, the overwhelming majority of these measures have not been proven sufficiently reliable, valid and useful to be adopted clinically. It is time to consider whether strategic investments might break this impasse, focusing on a limited number of promising candidates to advance through a process of definitive testing for a specific indication. Some promising candidates for definitive testing include the N170 signal, an event-related brain potential measured using electroencephalography, for subgroup identification within autism spectrum disorder; striatal resting-state functional magnetic resonance imaging (fMRI) measures, such as the striatal connectivity index (SCI) and the functional striatal abnormalities (FSA) index, for prediction of treatment response in schizophrenia; error-related negativity (ERN), an electrophysiological index, for prediction of first onset of generalized anxiety disorder, and resting-state and structural brain connectomic measures for prediction of treatment response in social anxiety disorder. Alternate forms of classification may be useful for conceptualizing and testing potential biomarkers. Collaborative efforts allowing the inclusion of biosystems beyond genetics and neuroimaging are needed, and online remote acquisition of selected measures in a naturalistic setting using mobile health tools may significantly advance the field. Setting specific benchmarks for well-defined target application, along with development of appropriate funding and partnership mechanisms, would also be crucial. Finally, it should never be forgotten that, for a biomarker to be actionable, it will need to be clinically predictive at the individual level and viable in clinical settings.

Deep rTMS of the insula and prefrontal cortex in smokers with schizophrenia: Proof-of-concept study.

Patients with schizophrenia have a high prevalence of cigarette smoking and respond poorly to conventional treatments, highlighting the need for new therapies. We conducted a mechanistic, proof-of-concept study using bilateral deep repetitive transcranial magnetic stimulation (dTMS) of insular and prefrontal cortices at high frequency, using the specialized H4 coil. Feasibility of dTMS was tested for disruption of tobacco self-administration, insula target engagement, and insula circuit modulation, all of which were a priori outcomes of interest. Twenty patients completed the study, consisting of weekday dTMS sessions (randomization to active dTMS or sham; double-blind; 10 patients per group), a laboratory tobacco self-administration paradigm (pre/post assessments), and multimodal imaging (three MRI total sessions). Results showed that participants assigned to active dTMS were slower to initiate smoking their first cigarette compared with sham, consistent with smoking disruption. The imaging analyses did not reveal significant Time × Group interactions, but effects were in the anticipated directions. In arterial spin labeling analyses testing for target engagement, an overall decrease in insula blood flow, measured during a post-treatment MRI versus baseline, was numerically more pronounced in the active dTMS group than sham. In fMRI analyses, resting-state connectivity between the insula and default mode network showed a numerically greater change from baseline in the active dTMS group than sham, consistent with a functional change to insula circuits. Exploratory analyses further suggested a therapeutic effect of dTMS on symptoms of psychosis. These initial observations pave the way for future confirmatory studies of dTMS in smoking patients with schizophrenia.

Simulated opioid choice linked to opioid use disorder severity among veterans with chronic pain: initial validation of a novel paradigm.

Background: Modeling addictive behavior among individuals with, or at risk for, opioid use disorder (OUD) in a way that is accurate, ethical, and reproducible presents a pressing concern. OUD risk is elevated among people with chronic pain on long-term opioid therapy (LTOT).Objectives: To provide initial validation of a novel opioid preference task as an index of OUD and its symptomatology among veterans prescribed opioids for chronic pain, a population at high risk for poor opioid-related outcomes. The relative ease by which such a paradigm can be implemented and performed in clinical contexts, including enabling investigation of opioid reinforcement and drug-seeking behavior while avoiding ethical pitfalls associated with direct drug administration, could make this task an attractive approach for potentially tracking OUD symptoms.Methods: We studied 87 veterans (74 males, 13 females) on LTOT for chronic pain - 33 of whom had OUD diagnoses. Participants completed a picture-viewing choice task to assess preference for viewing opioid-related images in comparison with standardized pleasant, unpleasant, neutral, and blank images. Opioid-related choice, measured by vigor of button pressing, was tested for association with OUD severity (measured by symptom counts), as well as craving and anhedonia.Results: Choice for opioid-related images was positively correlated with OUD severity (i.e., number of DSM-5 measured OUD symptoms) (r = 0.38, p < .001), particularly among those meeting diagnostic criteria for OUD (r = 0.47, p = .006). Neither craving nor anhedonia correlated with opioid-related choice.Conclusions: Our results provide initial validation for a new opioid picture-choice paradigm in patients with chronic pain.

Changes in alcohol use by cannabis use status among adolescents and young adults in the United States: Emerging evidence for both substitution and complementarity.

BACKGROUND: The majority of adolescents and young adults (AYA) who use cannabis also use alcohol. Although cannabis use is increasing in the United States (US), it is not known whether the increase contributes to either increased co-use of alcohol and cannabis (e.g., complementarity) or replacement of alcohol with cannabis (e.g., substitution). The current study estimated the prevalence of alcohol use by cannabis use status among US AYA ages 12 to 25 in 2018 and trends in alcohol use by cannabis use status from 2002 to 2018. METHODS: Data were drawn from the 2002 to 2018 National Survey on Drug Use and Health public use data files. The analytic sample included AYA ages 12 to 25 (2018 sample, n = 26,924; total combined sample 2002 to 2018, n = 576,053). Linear and logistic regression models were used to estimate past-month alcohol use, daily alcohol use, and average quantity of alcohol consumed among AYA with and without past-month cannabis use from 2002 to 2018. RESULTS: In 2018, any alcohol use and daily alcohol use were significantly more common among AYA who used cannabis use than those who did not use cannabis. Overall, any alcohol use, daily alcohol use, and average drinks per day declined from 2002 to 2018 among AYA irrespective of recent cannabis use. However, the decline in any alcohol use, daily alcohol use, and average alcohol drinks per day was more rapid among AYA who used cannabis (daily and nondaily) than those who did not use cannabis. The rate of decline in average alcohol drinks per day was also higher among AYA with daily compared to nondaily cannabis use. CONCLUSIONS: Even with declines in alcohol use over time, drinking is much more common among AYA who report cannabis than those without recent cannabis use, which is consistent with complementarity. Yet, because the decline in alcohol use has been more rapid among AYA who use cannabis, there is also evidence of substitution. Thus, the current data on alcohol and cannabis use are consistent with both complementarity and substitution. However, these relationships may change as cannabis legalization expands over time.

Attention bias modification in drug addiction: Enhancing control of subsequent habits.

A relapse in addiction is often precipitated by heightened attention bias to drug-related cues, underpinned by a subcortically mediated transition to habitual/automatized responding and reduced prefrontal control. Modification of such automatized attention bias is a fundamental, albeit elusive, target for relapse reduction. Here, on a trial-by-trial basis, we used electroencephalography and eye tracking with a task that assessed, in this order, drug cue reactivity, its instructed self-regulation via reappraisal, and the immediate aftereffects on spontaneous (i.e., not instructed and automatized) attention bias. The results show that cognitive reappraisal, a facet of prefrontal control, decreased spontaneous attention bias to drug-related cues in cocaine-addicted individuals, more so in those with less frequent recent use. The results point to the mechanisms underlying the disruption of automatized maladaptive drug-related attention bias in cocaine addiction. These results pave the way for future studies to examine the role of such habit disruption in reducing compulsive drug seeking outside the controlled laboratory environment, with the ultimate goal of developing a readily deployable cognitive-behavioral and personalized intervention for drug addiction.

Neural and Behavioral Correlates of Impaired Insight and Self-Awareness in Substance Use Disorder.

Purpose of Review: Clinical insight is an emerging interest in substance use disorder research, but is difficult to study empirically. We reviewed recent research examining the behavioral and neural correlates of several psychological processes tapping into self-awareness that may in turn contribute to insight. Recent Findings: Individuals with substance use disorder exhibit deficits in self-monitoring (especially self-report / behavior dissociations), metacognition, alexithymia, readiness for behavior change, and interoception. Behavioral impairments have been further linked to neural abnormalities in a diverse network of brain regions encompassing cortical midline areas, insula, and frontal cortex, among others. Various treatment modalities may target these deficits, though corresponding effects on neural circuitry remain to be determined. Summary: Compromised insight in substance use disorder may be relevant to a constellation of behaviors that suggest a lack of behavioral awareness linked to drug use. Future work needs to refine and advance the measurements, continuing to investigate insight problems in addiction that may become important therapeutic targets.

The potential role of cocaine and heroin co-use in the opioid epidemic in the United States.

INTRODUCTION: Opioid/heroin use is an epidemic in the United States (US). Polysubstance use dramatically increases risk of adverse overdose outcomes, versus use of a single substance. Co-use of heroin and cocaine, known as "speedballing," is associated with higher risk of overdose than use of either alone. It is not known whether co-use relative to use of either alone has increased in the US in recent years at a national level. If so, this may be one contributing factor to the increasing fatality rate associated with the US opioid epidemic. This study investigated the prevalence of use of each and co-use of heroin and cocaine from 2002 to 2017 in the US. METHODS: Data were drawn from the 2002 to 2017 National Survey on Drug Use and Health (NSDUH) to estimate prevalence of past-month heroin use, cocaine use, and co-use of heroin and cocaine among Americans ages 12 and older. RESULTS: From 2002 to 2017, cocaine use (without heroin) (adjusted odds ratio (AOR) = 0.971, 95% confidence interval (0.963, 0.979)) declined overall, though a subsequent quadratic analysis suggested that it began increasing in 2011. In contrast, heroin and cocaine co-use (AOR = 1.062 (1.027, 1.099)) and heroin use (without cocaine) (AOR = 1.101 (1.070, 1.133)) linearly increased from 2002 to 2017. CONCLUSIONS: Screening, outreach, clinical treatment, and first responders should be aware of increasing patterns of polysubstance use and the potential implications of co-use of heroin and cocaine on first responders' intervention and the potential role of increasing exposure to multiple substances on overdose outcomes in the US.

Human Cognitive Ability Is Modulated by Aromatase Availability in the Brain in a Sex-Specific Manner.

The enzyme aromatase catalyzes the final step in estrogen biosynthesis, converting testosterone to estradiol, and is expressed in the brain of all mammals. Estrogens are thought to be important for maintenance of cognitive function in women, whereas testosterone is thought to modulate cognitive abilities in men. Here, we compare differences in cognitive performance in relation to brain aromatase availability in healthy men and women. Twenty-seven healthy participants were administered tests of verbal learning and memory and perceptual/abstract reasoning. In vivo images of brain aromatase availability were acquired in this sample using positron emission tomography (PET) with the validated aromatase radiotracer [11C]vorozole. Regions of interest were placed bilaterally on the amygdala and thalamus where aromatase availability is highest in the human brain. Though cognitive performance and aromatase availability did not differ as a function of sex, higher availability of aromatase in the amygdala was associated with lower cognitive performance in men. No such relationship was found in women; and the corresponding regression slopes were significantly different between the sexes. Thalamic aromatase availability was not significantly correlated with cognitive performance in either sex. These findings suggest that the effects of brain aromatase on cognitive performance are both region- and sex-specific and may explain some of the normal variance seen in verbal and nonverbal cognitive abilities in men and women as well as sex differences in the trajectory of cognitive decline associated with Alzheimer's disease.

Self-awareness of problematic drug use: Preliminary validation of a new fMRI task to assess underlying neurocircuitry.

BACKGROUND: Multiple psychopathologies feature impaired clinical insight. Emerging evidence suggests that insight problems may similarly characterize addiction, perhaps due to aberrant functioning of self-referential brain circuitry, including the rostral anterior cingulate and ventromedial prefrontal cortices (rACC/vmPFC). We developed a new fMRI task to probe whether rACC/vmPFC abnormalities in cocaine use disorder (CUD) constitute neural correlates of readiness to change, one facet of insight. METHODS: Eighteen individuals with current CUD and 15 healthy controls responded about their own need to change their drug use and eating behavior (control condition) and the need for a named acquaintance to do the same (two additional control conditions). Measures of simulated drug-choice behavior, addiction severity, and neuropsychological function were collected outside the scanner. RESULTS: CUD participants perceived a greater need for behavior change than controls (as expected, given their diagnosis), but fell short of "agreeing" to a need for change; in CUD, lower perceived need correlated with higher simulated drug-choice behavior, a proxy measure of drug-seeking. During drug-related insight judgments, CUD participants had higher activation than controls in an anatomically-defined region of interest (ROI) in the medial orbitofrontal cortex, part of the rACC/vmPFC. Although not showing group differences, activation in an anatomically-defined ACC ROI correlated with insight-related task behavior (in all participants) and memory performance (in CUD). CONCLUSIONS: As a group, individuals with current CUD appear to show mild insight problems and rACC/vmPFC abnormalities vis-à-vis readiness to change behavior. With replication and extension of these results, insight-related circuitry may emerge as a novel therapeutic target.

Perception of treatment need among adults with substance use disorders: Longitudinal data from a representative sample of adults in the United States.

BACKGROUND: Most individuals with substance use disorders (SUDs) do not seek treatment. Lack of perceived treatment need (PTN) is one contributing factor, but little is known about PTN over time. We estimated whether PTN changed over three years among those with SUDs in the United States and identified select variables, including sociodemographics and symptom burden, that predict malleability vs. stability of PTN. METHODS: Data were from Waves 1 (collected 2001-2002) and 2 (collected 2004-2005) of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC); 1695 adults who met DSM criteria for alcohol or non-alcohol SUD at Wave 1 and maintained ≥1 diagnostic symptom at Wave 2 were included. RESULTS: Most individuals with SUDs (77.2%) did not perceive a need for treatment at Wave 1 baseline. Only about 1 in 8 individuals not perceiving a need for treatment in Wave 1 came to perceive a need in Wave 2 (adjusted odds ratio = 0.18, 99% confidence interval = 0.11-0.29). In contrast, about half the individuals who perceived a need for treatment in Wave 1 no longer did so in Wave 2, despite maintaining ≥1 SUD symptom. Married respondents, and respondents with more SUD symptoms, were more likely to transition from low- to high-PTN status three years later. Respondents with incomes >$35,000 were less likely to transition to high-PTN status three years later. CONCLUSIONS: PTN was more likely to decline than increase over time. Low PTN appears to be stable among adults with SUDs in the United States, presenting a potentially enduring barrier to treatment-seeking.

Behavioral preference for viewing drug v. pleasant images predicts current and future opioid misuse among chronic pain patients.

BACKGROUND: The USA is currently enduring an opioid crisis. Identifying cost-effective, easy-to-implement behavioral measures that predict treatment outcomes in opioid misusers is a crucial scientific, therapeutic, and epidemiological goal. METHODS: The current study used a mixed cross-sectional and longitudinal design to test whether a behavioral choice task, previously validated in stimulant users, was associated with increased opioid misuse severity at baseline, and whether it predicted change in opioid misuse severity at follow-up. At baseline, data from 100 prescription opioid-treated chronic pain patients were analyzed; at follow-up, data were analyzed in 34 of these participants who were non-misusers at baseline. During the choice task, participants chose under probabilistic contingencies whether to view opioid-related images in comparison with affectively pleasant, unpleasant, and neutral images. Following previous procedures, we also assessed insight into choice behavior, operationalized as whether (yes/no) participants correctly self-reported the image category they chose most often. RESULTS: At baseline, the higher choice for viewing opioid images in direct comparison with pleasant images was associated with opioid misuse and impaired insight into choice behavior; the combination of these produced especially elevated opioid-related choice behavior. In longitudinal analyses of individuals who were initially non-misusers, higher baseline opioid v. pleasant choice behavior predicted more opioid misuse behaviors at follow-up. CONCLUSIONS: These results indicate that greater relative allocation of behavior toward opioid stimuli and away from stimuli depicting natural reinforcement is associated with concurrent opioid misuse and portends vulnerability toward future misuse. The choice task may provide important medical information to guide opioid-prescribing practices.

Neural mechanisms of extinguishing drug and pleasant cue associations in human addiction: role of the VMPFC.

The neurobiological mechanisms that underlie the resistance of drug cue associations to extinction in addiction remain unknown. Fear extinction critically depends on the ventromedial prefrontal cortex (VMPFC). Here, we tested if this same region plays a role in extinction of non-fear, drug and pleasant cue associations. Eighteen chronic cocaine users and 15 matched controls completed three functional MRI scans. Participants first learned to associate an abstract cue (the conditioned stimulus, CS) with a drug-related (CSD+ ) or pleasant (CSP+ ) image. Extinction immediately followed where each CS was repeatedly presented without the corresponding image. Participants underwent a second identical session 24 hours later to assess retention of extinction learning. Results showed that like fear extinction, non-fear-based extinction relies on the VMPFC. However, extinction-related changes in the VMPFC differed by cue valence and diagnosis. In controls, VMPFC activation to the CSD+ (which was unpleasant for participants) gradually increased as in fear extinction, while it decreased to the CSP+ , consistent with a more general role of the VMPFC in flexible value updating. Supporting a specific role in extinction retention, we further observed a cross-day association between VMPFC activation and skin conductance, a classic index of conditioned responses. Finally, cocaine users showed VMPFC abnormalities for both CSs, which, in the case of the CSD+ , correlated with craving. These data suggest a global deficit in extinction learning in this group that may hinder extinction-based treatment efforts. More broadly, these data show that the VMPFC, when functionally intact, supports extinction learning in diverse contexts in humans.