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Goldstein, R. Z.

Publications and source records attributed to Goldstein, R. Z..

5 recordsLinked to original sources

Blunted anterior midcingulate response to reward in opioid users is normalized by prefrontal transcranial magnetic stimulation

IntroductionAbnormalities in goal-directed behavior, mediated by mesocorticolimbic reward function and structure, contribute to worse clinical outcomes including higher risk of treatment dropout and drug relapse in opioid users (OU). Material and MethodIn a sham-controlled randomized study design, we measured whether robot-assisted 10Hz transcranial magnetic stimulation (TMS) applied to the prefrontal cortex was able to modulate anterior midcingulate cortex (MCC) electrophysiological response to rewards, in OU and matched healthy controls. ResultsWe show that OU exhibit a blunted anterior MCC reward response, compared to healthy controls (t(39) = 2.62, p = 0.01, d = 0.84), and that this is normalized following 10-Hz excitatory TMS (t(36) = .82, p = 0.42, d = 0.17). ConclusionsExcitatory TMS modulated the putative reward function of the MCC in OU. Further work with increased sample sizes and TMS sessions is required to determine whether restoring MCC reward function increases reward-directed behaviors, which may enhance treatment success through the maintenance of treatment goals.

neuroscience↗

Dynamic alterations in gene co-expression networks and gene-transcript associations characterize co-morbidities in cocaine use disorder

BackgroundIndividuals with cocaine use disorder (CUD) who attempt abstinence experience craving and relapse, which poses challenges in treatment. Longitudinal studies linking behavioral manifestations in CUD to the blood transcriptome in living individuals are limited. Therefore, we investigated the connection between drug use behaviors during abstinence with blood transcriptomics. MethodsWe conducted a comprehensive longitudinal study involving 12 subjects (9 males, 3 females) with CUD and RNA sequencing on blood collected at a drug-free baseline, and 3, 6 & 9 months thereafter. We categorized subjects into 2 responder groups (high-low) based on scores of drug use variables, and 3 responder groups (low-intermediate-high) on days of abstinence. We investigated differential expression and gene-transcript associations across responder groups at each time point. Lastly, we examined genes that are both co-expressed and showed dynamic expression with time. ResultsGenes with significant transcript associations between high and. intermediate days of abstinence at 9 months were notably enriched for cannabis use disorder, drinks weekly, and coronary artery disease risk genes. Time-specific gene co-expression analysis prioritized transcripts related to immune processes, cell cycle, RNA-protein synthesis, and second messenger signaling for days of abstinence. ConclusionWe demonstrate that abstinence reflects robust changes in drug use behaviors and the blood transcriptome in CUD. We also highlight the importance of longitudinal studies to capture complex biological processes during abstinence in CUD.

genomics↗

Cue-Induced Drug Seeking and Its Association with Craving and Dependence in Cigarette Smokers

IntroductionIncreased 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 Fagerstrom score). MethodsWe 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. Resultscompared 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. Conclusionsthese 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 adds. Most 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 cigarette smokers 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.

neuroscience↗

Speak and you shall predict: speech at initial cocaine abstinence as a biomarker of long-term drug use behavior

ImportanceValid biomarkers that can predict longitudinal clinical outcomes at low cost are a holy grail in psychiatric research, promising to ultimately be used to optimize and tailor intervention and prevention efforts. ObjectiveTo determine if baseline linguistic markers in natural speech, as compared to non-speech clinical and demographic measures, can predict drug use severity measures at future sessions in initially abstinent individuals with cocaine use disorder (iCUD). DesignA longitudinal cohort study (August 2017 - March 2020), where baseline measures were used to predict outcomes collected at three-month intervals for up to one year of follow-up. ParticipantsEighty-eight initially abstinent iCUD were studied at baseline; 57 (46 male, age 50.7+/-7.9 years) came back for at least another session. Main Outcomes and MeasuresOutcomes were self-reported symptoms of withdrawal, craving, abstinence duration and frequency of cocaine use in the past 90 days at each study session. The predictors were derived from 5-min recordings of vocal descriptions of the positive consequences of abstinence and the negative consequences of using cocaine; the baseline cocaine and other common drug use measures, demographic and neuropsychological variables were used for comparison. ResultsModels using the non-speech variables showed the best predictive performance at three(r>0.45, P<2x10-3) and six months follow-up (r>0.37, P<3x10-2). At 12 months, the natural language processing-based model showed significant correlations with withdrawal (r=0.43, P=3x10-2), craving (r=0.72, P=5x10-5), days of abstinence (r=0.76, P=1x10-5), and cocaine use in the past 90 days (r=0.61, P=2x10-3), significantly outperforming the other models for abstinence prediction. Conclusions and RelevanceAt short time intervals, maximal predictive power was obtained with models that used baseline drug use (in addition to demographic and neuropsychological) measures, potentially reflecting a slow rate of change in these measures, which could be estimated by linear functions. In contrast, short speech samples predicted longer-term changes in drug use, implying deeper penetrance by potentially capturing non-linear dynamics over longer intervals. Results suggest that, compared to the common outcome measures used in clinical trials, speech-based measures could be leveraged as better predictors of longitudinal drug use outcomes in initially abstinent iCUD, as potentially generalizable to other substance use disorders and related comorbidity. Key PointsO_ST_ABSQuestionC_ST_ABSCan natural language processing be leveraged to predict longitudinal drug use outcomes in individuals with substance use disorder? FindingsIn this prospective study that included initially abstinent individuals with cocaine use disorder (iCUD), models using demographics, neuropsychological measures and drug use patterns at baseline were compared to those using minimally structured short natural speech samples relating the positive consequences of abstinence and the negative consequences of using drugs, showing a differential prediction of outcomes measured up to one year later. At three and six months, the former outperformed speech models, including approximately 50% of the variability in craving and 40% in abstinence duration. At 12 months from baseline, speech models were superior, predicting 50% of the variability in abstinence duration. MeaningSpeech variables derived through natural language processing can predict clinically meaningful drug use outcome measures in addiction, with greater value at longer intervals. The applicability of language modeling to aid in assessing treatment response and risk in drug addiction warrants further investigation in clinical settings.

neuroscience↗

Microstructural Impairments in a Topologically Distinct Prefrontal-Habenular Connection in Cocaine Addiction

Drug addiction is characterized by neuroadaptations in mesocorticolimbic networks regulating reward and inhibitory control. The habenula (Hb) is central to adaptive reward and aversion-driven behaviors, serving as a hub connecting emotion/cognitive processing regions including the prefrontal cortex (PFC). However, its role in human drug addiction has not been fully explored. Using diffusion tractography, we detailed PFC structural connectivity with three regions, namely the Hb, ventral tegmental area (VTA), and anterior thalamus (AT), and quantified the tract-specific microstructural integrity using diffusion tensor imaging within the anterior limb of the internal capsule (ALIC) in healthy and cocaine-addicted individuals. White matter microstructure in cocaine-addicted individuals was uniquely impaired in PFC-Hb projections in the ALIC, distinguishable from adjacent PFC-VTA and PFC-AT projections, with more pronounced abnormalities in short-term abstinence. These findings extend preclinical evidence of PFC-Hb circuit impairments in addiction and contextualize the plausible existence of a similar PFC-Hb connection in the human brain.

neuroscience↗