Naltrexone engages a brain reward network in the presence of reward-predictive distractor stimuli in males.

The non-selective opioid receptor antagonist, naltrexone is one of the most prescribed medications for treating alcohol and opioid addiction. Despite decades of clinical use, the mechanism(s) by which naltrexone reduces addictive behavior remains unclear. Pharmaco-fMRI studies to date have largely focused on naltrexone's impact on brain and behavioral responses to drug or alcohol cues or on decision-making circuitry. We hypothesized that naltrexone's effects on reward-associated brain regions would associate with reduced attentional bias (AB) to non-drug, reward-conditioned cues. Twenty-three adult males, including heavy and light drinkers, completed a two-session, placebo-controlled, double-blind study testing the effects of acute naltrexone (50 mg) on AB to reward-conditioned cues and neural correlates of such bias measured via fMRI during a reward-driven AB task. While we detected significant AB to reward-conditioned cues, naltrexone did not reduce this bias in all participants. A whole-brain analysis found that naltrexone significantly altered activity in regions associated with visuomotor control regardless of whether a reward-conditioned distractor was present. A region-of-interest analysis of reward-associated areas found that acute naltrexone increased BOLD signal in the striatum and pallidum. Moreover, naltrexone effects in the pallidum and putamen predicted individual reduction in AB to reward-conditioned distractors. These findings suggest that naltrexone's effects on AB primarily reflect not reward processing per se, but rather top-down control of attention. Our results suggest that the therapeutic actions of endogenous opioid blockade may reflect changes in basal ganglia function enabling resistance to distraction by attractive environmental cues, which could explain some variance in naltrexone's therapeutic efficacy.

Ethical decision-making climate, moral distress, and intention to leave among ICU professionals in a tertiary academic hospital center.

BACKGROUND: Commentators believe that the ethical decision-making climate is instrumental in enhancing interprofessional collaboration in intensive care units (ICUs). Our aim was twofold: (1) to determine the perception of the ethical climate, levels of moral distress, and intention to leave one's job among nurses and physicians, and between the different ICU types and (2) determine the association between the ethical climate, moral distress, and intention to leave. METHODS: We performed a cross-sectional questionnaire study between May 2021 and August 2021 involving 206 nurses and physicians in a large urban academic hospital. We used the validated Ethical Decision-Making Climate Questionnaire (EDMCQ) and the Measure of Moral Distress for Healthcare Professionals (MMD-HP) tools and asked respondents their intention to leave their jobs. We also made comparisons between the different ICU types. We used Pearson's correlation coefficient to identify statistically significant associations between the Ethical Climate, Moral Distress, and Intention to Leave. RESULTS: Nurses perceived the ethical climate for decision-making as less favorable than physicians (p < 0.05). They also had significantly greater levels of moral distress and higher intention to leave their job rates than physicians. Regarding the ICU types, the Neonatal/Pediatric unit had a significantly higher overall ethical climate score than the Medical and Surgical units (3.54 ± 0.66 vs. 3.43 ± 0.81 vs. 3.30 ± 0.69; respectively; both p ≤ 0.05) and also demonstrated lower moral distress scores (both p < 0.05) and lower "intention to leave" scores compared with both the Medical and Surgical units. The ethical climate and moral distress scores were negatively correlated (r = -0.58, p < 0.001); moral distress and "intention to leave" was positively correlated (r = 0.52, p < 0.001); and ethical climate and "intention to leave" were negatively correlated (r = -0.50, p < 0.001). CONCLUSIONS: Significant differences exist in the perception of the ethical climate, levels of moral distress, and intention to leave between nurses and physicians and between the different ICU types. Inspecting the individual factors of the ethical climate and moral distress tools can help hospital leadership target organizational factors that improve interprofessional collaboration, lessening moral distress, decreasing turnover, and improved patient care.

Addiction history moderates the effect of prefrontal 10-Hz transcranial alternating current stimulation on habitual action selection.

Individuals with substance use disorders (SUDs) transition more quickly from goal-directed to habitual action-selection, but the neural mechanisms underlying this phenomenon remain unclear. Data from animal models suggest that drugs of abuse can modify the neurocircuits that regulate action-selection, enhancing circuits that drive inflexible, habit-based stimulus-response (S-R) action-selection and weakening circuits that drive flexible, goal-directed actions. Here, we tested the effect of bilateral 10-Hz transcranial alternating current stimulation (10Ηz-tACs) of the dorsolateral prefrontal cortex on action-selection in men and women with a SUD history and an age- and sex-matched control group. We tested the hypothesis that true 10Ηz-tACS versus active sham stimulation would reduce perseverative errors after changed response contingencies for well-learned S-R associations, reflecting reduced habit-based action-selection, specifically in the SUD group. We found that 10 Hz-tACS increased perseverative errors in the control group, but in the SUD group, 10 Hz-tACS effects on perseverative errors depended on substance abuse duration: a longer addiction history was associated with a greater reduction of perseverative errors. These results suggest that 10Ηz-tACs altered circuit level dynamics regulating behavioral flexibility, and provide a foundation for future studies to test stimulation site, frequency, and timing specificity. Moreover, these data suggest that chronic substance abuse is associated with altered circuit dynamics that are ameliorated by 10Ηz-tACs. Determining the generalizability of these effects and their duration merits investigation as a direction for novel therapeutic interventions. These findings are timely based on growing interest in transcranial stimulation methods for treating SUDs.NEW & NOTEWORTHY Treating the executive dysfunction associated with addiction is hampered by redundancies in pharmacological regulation of different behavioral control circuits. Thus, nonpharmacological interventions hold promise for addiction treatment. Here, we show that, among people with an addiction history, 10-Hz transcranial alternating current stimulation (10Hz-tACS) of the dorsolateral prefrontal cortex can reduce habitual actions. The fact that 10Hz-tACS can regulate behavioral flexibility suggests its possible utility in reducing harmful habitual actions.

Naltrexone Acutely Enhances Connectivity Between the Ventromedial Prefrontal Cortex and a Left Frontoparietal Network.

BACKGROUND: Naltrexone, an opioid receptor antagonist that is Food and Drug Administration approved for treating alcohol use disorder (AUD), reduces alcohol craving and intake. Despite known pharmacological properties, little is known regarding the effects of naltrexone on neural circuit function. Thus, a data-driven examination of the neural effects of naltrexone in human subjects may offer novel insight into its treatment mechanisms. METHODS: Twenty-one alcohol using males (22 to 39) participated in a double-blind, placebo-controlled crossover study of the effects of naltrexone on brain voxel-wise functional connectivity (FC) using intersubject FC correlation mapping. We first cross-correlated the time series from each gray matter voxel to produce a 6,356 × 6,356 FC matrix for each subject and session. We then subtracted the placebo FC matrix from the naltrexone FC matrix. To identify brain regions demonstrating significant reconfiguration of whole-brain FC patterns following naltrexone treatment, we statistically quantified the consistency of patterns of voxel FC changes across subjects. Permutation testing identified significant clusters of voxels undergoing significant reconfiguration. Using the identified clusters in a seed-based FC analysis, we then compared the FC patterns of affected brain areas on placebo versus naltrexone in a paired t-test. Ridge regression analyses identified self-report measures, including substance use, that significantly predicted individual differences in FC among naltrexone-modulated regions. RESULTS: Two clusters in the rostral anterior cingulate cortex (rACC)/ventromedial prefrontal cortex (vmPFC) demonstrated significant modulation of FC by naltrexone. Using these 2 proximal clusters as a single seed, specific FC changes were identified in regions associated with a left frontoparietal network (increasing), as well as visual and motor regions (decreasing). Stronger FC between the rACC/vmPFC and this set of regions on placebo was associated with more external locus of control, whereas weaker connectivity was associated with greater substance use problems. Naltrexone strengthened these connections most among individuals who reported greater drinking to cope. CONCLUSIONS: Enhancing connectivity between the rACC/vmPFC, implicated in alcohol craving, and components of a left frontoparietal network involved in executive control may represent an effective strategy for the treatment of AUD.

Prison health-care wings: psychiatry's forgotten frontier?

BACKGROUND: There is worldwide evidence of high rates of mental disorder among prisoners, with significant co-morbidity. In England and Wales, mental health services have been introduced from the National Health Service to meet the need, but prison health-care wings have hardly been evaluated. AIMS/HYPOTHESES: To conduct a service evaluation of the health-care wing of a busy London remand (pre-trial) prison and examine the prevalence and range of mental health problems, including previously unrecognised psychosis. METHODS: Service-use data were collected from prison medical records over a 20-week period in 2006-2007, and basic descriptive statistics were generated. RESULTS: Eighty-eight prisoners were admitted (4.4 per week). Most suffered from psychosis, a third of whom were not previously known to services. Eleven men were so ill that they required emergency compulsory treatment in the prison under Common Law before hospital transfer could take place. Over a quarter of the men required hospital transfer. Problem behaviours while on the prison health-care wing were common. CONCLUSIONS AND IMPLICATIONS: Prison health-care wings operate front-line mental illness triaging and recognition functions and also provide care for complex individuals who display behavioural disturbance. Services are not equivalent to those in hospitals, nor the community, but instead reflect the needs of the prison in which they are situated. There is a recognised failure to divert at earlier points in the criminal justice pathway, which may be a consequence of national failure to fund services properly. Hospital treatment is often delayed.