A meta-analysis of tract-based spatial statistics studies examining white matter integrity in cocaine use disorder.

Tract-based spatial statistics (TBSS) of diffusion tensor imaging (DTI) studies have consistently shown diminished white matter (WM) integrity for individuals with cocaine use disorder (CUD). The present study used seed-based d mapping (SDM) to determine the extent to which a systematic difference in the WM integrity of cocaine users may exist (as compared with that of healthy controls). Articles from 2006 (when TBSS was first developed) to present were reviewed, with eight selected for inclusion. Meta-analysis found lower fractional anisotropy (FA) in the genu of the corpus callosum for cocaine users, with a small-to-moderate peak effect size (Hedge's g = -0.331). Sensitivity analyses mostly supported the robustness of the obtained difference. Differences detected at exploratory thresholds for significance suggested insult to WM integrity extending beyond the corpus callosum. The present results compliment a previous region-of-interest (ROI)-based meta-analysis of DTI studies in individuals with CUD. These findings have significant implications for the potential role of neuroprotective agents in the treatment of CUD and merit additional iteration as more studies accrue in the literature.

Objective analysis of language use in cognitive-behavioral therapy: associations with symptom change in adults with co-occurring substance use disorders and posttraumatic stress.

Substance use disorders (SUD) commonly co-occur with posttraumatic stress disorder (PTSD) symptoms, and the comorbidity is prevalent and difficult-to-treat. Few studies have objectively analyzed language use in psychotherapy as a predictor of treatment outcomes. We conducted a secondary analysis of patient language use during cognitive-behavioral therapy (CBT) in a randomized clinical trial, comparing a novel, integrated CBT for PTSD/SUD with standard CBT for SUD. Participants included 37 treatment-seeking, predominantly African-American adults with SUD and at least four symptoms of PTSD. We analyzed transcripts of a single, matched session across both treatment conditions, using the Linguistic Inquiry and Word Count (LIWC) program. The program measures language use across multiple categories. Compared to standard CBT for SUD, patients in the novel, integrated CBT for PTSD/SUD used more negative emotion words, partially consistent with our hypothesis, but less positive emotion words. Further, exploratory analyses indicated an association between usage of cognitive processing words and clinician-observed reduction in PTSD symptoms, regardless of treatment condition. Our results suggest that language use during therapy may provide a window into mechanisms active in therapy.

Utility of a brief assessment of opioid demand among post-discharge trauma care patients.

Opioid misuse and opioid-related death are a growing public health concern. One population of interest is recent trauma and/or surgery patients, who are at increased risk of developing an opioid use disorder (OUD). Although a variety of assessments have been developed to screen for risk of opioid misuse, each has limitations and prediction needs improvement. One promising measure is drug demand, a behavioral economic measure assessing drug consumption at different price points. In the current proposal, we assessed the utility of a brief assessment of opioid demand. Demand and various pain-related self-report measures among trauma-surgery patients (N = 103) were assessed at 4 weeks post-discharge. Opioid demand was significantly associated with self-report measures of pain and amount of morphine milligram equivalents (MME) received during the hospital stay. The current result support the utility of the opioid demand as an adjunctive and complementary measure to assess risk of opioid misuse. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Dose-response effects of d-amphetamine on effort-based decision-making and reinforcement learning.

Effort-related decision-making and reward learning are both dopamine-dependent, but preclinical research suggests they depend on different dopamine signaling dynamics. Therefore, the same dose of a dopaminergic medication could have differential effects on effort for reward vs. reward learning. However, no study has tested how effort and reward learning respond to the same dopaminergic medication within subjects. The current study aimed to test the effect of therapeutic doses of d-amphetamine on effort for reward and reward learning in the same healthy volunteers. Participants (n = 30) completed the Effort Expenditure for Reward Task (EEfRT) measure of effort-related decision-making, and the Probabilistic Reward Task (PRT) measure of reward learning, under placebo and two doses of d-amphetamine (10 mg, and 20 mg). Secondarily, we examined whether the individual characteristics of baseline working memory and willingness to exert effort for reward moderated the effects of d-amphetamine. d-Amphetamine increased willingness to exert effort, particularly at low to intermediate expected values of reward. Computational modeling analyses suggested this was due to decreased effort discounting rather than probability discounting or decision consistency. Both baseline effort and working memory emerged as moderators of this effect, such that d-amphetamine increased effort more in individuals with lower working memory and lower baseline effort, also primarily at low to intermediate expected values of reward. In contrast, d-amphetamine had no significant effect on reward learning. These results have implications for treatment of neuropsychiatric disorders, which may be characterized by multiple underlying reward dysfunctions.

Electrophysiological responses to appetitive and aversive outcomes: A comparison of college drinkers and non-drinkers.

The current study compared electrophysiological responses (the feedback-related negativity [FRN]) to appetitive and aversive outcomes between a group of college drinkers and non-drinkers. 50 undergraduate students completed a passive, slot machine-like task while their electroencephalographic data was recorded to extract the FRN to unexpected appetitive and aversive outcomes. In the appetitive condition, participants could expectedly or unexpectedly win $1 or not win $1 and in the aversive condition participants could expectedly or unexpectedly be exposed to a loud noise burst or silence. The FRN was recorded in response to a cue indicating the outcome. Participants also reported on the number of drinks they consumed in a typical week to establish drinking status (drinker/non-drinker). Results showed that non-drinkers had a larger FRN in the aversive task compared to the appetitive task while drinkers had similar FRNs between the tasks. Drinkers had a significantly smaller aversive outcome related FRN compared to non-drinkers. Neural sensitivity to aversive outcomes might be a marker of decreased punishment sensitivity in college drinkers compared to non-drinkers, contributing to unhealthy drinking behavior.

Elevated Neutrophil to Lymphocyte Ratio in Older Adults with Cocaine Use Disorder as a Marker of Chronic Inflammation.

OBJECTIVE: The neutrophil to lymphocyte ratio (NLR) is a non-specific, easy-to-obtain marker of inflammation associated with morbidity and mortality in systemic, psychiatric, and age-related inflammatory conditions. Given the growing trend of substance use disorder (SUD) in older adults, and the relationship between inflammation and SUD elevated NLR may serve as a useful inflammatory biomarker of the combined burden of aging and SUD. The present study focused on cocaine use disorder (CUD) to examine if cocaine adds further inflammatory burden among older adults, by comparing NLR values between older adults with CUD and a non-cocaine using, aged-matched, nationally representative sample. METHODS: The dataset included 107 (86% male) participants (aged 50-65 years) with cocaine use disorder. NLR was derived from complete blood count tests by dividing the absolute value of peripheral neutrophil concentration by lymphocyte concentration. For comparison, we extracted data from age-matched adults without CUD using the National Health and Nutrition Examination Survey. Individuals with immunocompromising conditions were excluded (e.g., rheumatoid arthritis and sexually transmitted infections such as HIV). A doubly-robust inverse probability-weighted regression adjustment (IPWRA) propensity score method was used to estimate group differences on NLR while controlling for potential confounding variables (age, gender, race, income, nicotine, marijuana and alcohol use). RESULTS: The IPWRA model revealed that the CUD sample had significantly elevated NLR in comparison to non-cocaine users, with a moderate effect size (ß weight = 0.67). CONCLUSION: Although non-specific, NLR represents a readily obtainable inflammatory marker for SUD research. CUD may add further inflammatory burden to aging cocaine users.

Baseline resting heart rate variability predicts post-traumatic stress disorder treatment outcomes in adults with co-occurring substance use disorders and post-traumatic stress.

Post-traumatic stress disorder (PTSD) symptoms are highly prevalent among individuals with substance use disorders (SUD), presenting a difficult-to-treat, complex comorbidity. Prognostic factors for treatment outcomes may characterize heterogeneity of the treated population and/or implicate mechanisms of action that are salient for improving treatments. High frequency heart rate variability (HF-HRV) is a suggested biomarker for emotion regulation-the ability to generate appropriate emotional responses via the influence of the parasympathetic nervous system on the heart. This initial study investigated the utility of baseline resting HF-HRV for predicting PTSD symptoms and substance use outcomes following treatment of 37 SUD participants with comorbid PTSD symptoms. Participants completed either standard cognitive- behavioral therapy (CBT) for SUD or a novel treatment of integrated post-traumatic stress and substance use that combined CBT for SUD with cognitive processing therapy for PTSD. Analyses demonstrated that higher HF-HRV predicted greater reduction in PTSD symptoms following both types of treatment. This suggests prognostic value of HF-HRV as a predictor of PTSD treatment outcomes; those with poorer autonomic emotional regulation may not respond as well to psychotherapy in general. This hypothesis-generating analysis identifies a putative biomarker that might have utility in treatment prediction.

A test of dopamine hyper- and hyposensitivity in alcohol use.

Biases in outcome processing, mediated by the mesocortical dopaminergic (DA) system, may predict individual differences in the frequency and quantity of alcohol use. We tested the hypothesis that genetic markers associated with increased DA neurotransmission contribute to reduced neural sensitivity to costs and increased alcohol use in an undergraduate sample. We created a DA transmission score using five genetic markers related to DA transmission and assessed neural sensitivity to cost using the feedback-related negativity (FRN), an event-related potential implicated in neural outcome evaluation, on both passive evaluative and active decision-making tasks. Self-reported alcohol use was assessed using the Daily Drinking Questionnaire-Revised. Participants with a higher DA transmission score reported increased alcohol consumption and exhibited a more blunted FRN on both the passive and active tasks. While dopamine hyposensitivity is common among chronic alcohol users, these data provide preliminary evidence that hypersensitivity of the dopamine system may underlie increased alcohol use in those who have not yet developed a chronic alcohol use disorder.

Regional differences in white matter integrity in stimulant use disorders: A meta-analysis of diffusion tensor imaging studies.

BACKGROUND: Converging lines of evidence from diffusion tensor imaging (DTI) studies reveal significant alterations in white matter (WM) microstructure in the prefrontal cortex of chronic stimulant users compared to controls, suggesting compromised axonal microstructure and/or myelin. METHODS: A meta-analysis of DTI-based WM integrity was conducted for white matter regions across the corpus callosum and association fibers. Articles were sourced and selected using PRISMA guidelines for systematic review and meta-analysis. Inclusion and exclusion criteria were determined by the authors in order to best capture WM integrity among individuals with primary stimulant use in comparison to healthy control subjects. RESULTS: Eleven studies that focused on region-of-interest (ROI)-based analysis of WM integrity were extracted from an initial pool of 113 independent studies. Analysis across ROIs indicated significantly lower fractional anisotropy (FA) values in stimulant use groups compared to controls with a small to moderate overall effect (Hedges' g = -0.37, 95% CI [-0.54, -0.20]). Eigenvalues were also analyzed, revealing a significant effect for radial diffusivity (RD; Hedges' g = 0.24, 95% CI [0.01, 0.47]) but not axial diffusivity (AD; Hedges' g = 0.05, 95% CI [-0.20, 0.29]) or mean diffusivity (MD; Hedges' g = 0.20, 95% CI [-0.01, 0.41]). Subgroup analyses based on specific ROIs, primary substance use, poly-substance use, and imaging technology were also explored. CONCLUSION: Results of the present study suggest a consistent effect of compromised WM integrity for individuals with stimulant use disorders. Furthermore, no significant differences were found between cocaine and methamphetamine-based groups.

Medial frontal cortex response to unexpected motivationally salient outcomes.

The medial frontal cortex (MFC) plays a central role allocating resources to process salient information, in part by responding to prediction errors. While there is some recent debate, the feedback-related negativity (FRN) is thought to index a reward prediction error by signaling outcomes that are worse than expected. A recent study utilizing electric shock provided data inconsistent with these accounts and reported that the omission of both appetitive (money) and aversive outcomes (electric shocks) elicited a medial frontal negativity. These data suggest that the ERPs within this time range support a salience prediction error that responds to unexpected events regardless of valence. To compare the reward and salience prediction error models, we employed a design that delivered both appetitive (monetary) and aversive (noise burst) outcomes. Participants completed a passive S1/S2 prediction design where S1 predicted S2 with 80% accuracy and S2 predicted the outcome with 100% accuracy. We compared both earlier and later ERP responses over the medial frontal cortex to compare the salience and reward prediction hypotheses. Considering both time windows, the ERP response to S2 in the early time window was most positive when S2 signaled that an outcome was unexpectedly delivered and in the later time window, was most negative when an outcome was unexpectedly withheld, regardless of outcome valence. Thus, these results are more consistent with a salience prediction error rather than a reward prediction error.

Preliminary evidence that digit length ratio (2D:4D) predicts neural response to delivery of motivational stimuli.

Reduced relative length of the 2nd to 4th digits (2D:4D) is thought to partially reflect fetal testosterone (FT) exposure, a process suspected to promote relatively permanent effects on the brain and behavior via structural and functional neuroadaptations. We examined the effect of 2D:4D on neural response - assessed by P2a and feedback-related negativity (FRN) event-related potentials (ERPs) - to motivational stimuli (reward or punishment) using two counterbalanced conditions of a passive S1/S2 outcome prediction design. P2a to expected and unexpected delivered rewards or punishments ($1 or white noise burst, respectively) and FRN to withheld rewards or punishments ($0 or silence, respectively) were observed in undergraduates. Lower left 2D:4D and greater 2D:4DR-L predicted amplified P2a to the delivery (but not FRN to the omission) of motivationally salient stimuli, regardless of valence and probability. These preliminary findings suggest that FT may organize dopamine neurons to respond more strongly to the delivery of motivational stimuli.

Neural outcome processing of peer-influenced risk-taking behavior in late adolescence: Preliminary evidence for gene × environment interactions.

Adolescent brains are particularly susceptible to the rewarding properties of risky decisions in social contexts. Individual differences in genetic influences on dopamine transmission moderate neural outcome processing of risky decisions and may exert pronounced effects on adolescent risk-taking behavior (RTB) and corresponding neural outcome processing in peer contexts, a process called gene-environment interaction (G × E). Eighty-five undergraduate students completed a behavioral risk task alone and in the presence of a confederate peer providing "risky" feedback. We tested for G × E effects using a polygenic risk index that included 3 candidate genetic variations associated with high dopamine transmission efficiency, as well as the moderating role of family history of behavioral disinhibition. Difference waves for the P300 and FRN (i.e., feedback-related negativity) were examined as indices of neural outcome processing. A G × E effect was observed for RTB and the P300, but not the FRN. Family history of behavioral disinhibition also interacted with peer influence to predict P300 amplitude. These data provide preliminary evidence for G × E for peer-influenced RTB and neural outcome processing during late adolescence. Genetic influences on dopaminergic function may be particularly relevant for attentional and motivational neural systems, as indexed by the P300, which exert downstream effects on peer-influenced RTB. (PsycINFO Database Record

The role of the neural reward system in attention selection.

The prefrontal cortex may play a role in attention selection using motivational information from the mesotelencephalic dopamine system, a neural system that responds to reward prediction violations. If so, neural indices of attention selection and reward prediction violation should have overlapping spatiotemporal distributions. Attention selection elicits a frontal event-related potential component around 200-300 ms, the frontal selection positivity. A component with similar spatiotemporal characteristics, the reward positivity is elicited in reward prediction designs to outcomes that are better than expected. The current study used dense sensor array recording in a sample of 41 participants performing visual oddball (attention) and a reward prediction 'slot machine-like' design to compare the spatiotemporal distributions of the frontal selection positivity and the reward positivity. The components did not differ in their peak latencies and had overlapping scalp topographies, supporting the hypothesis that these positivities represent attachment of incentive salience to perceptual representations in the prefrontal cortex.