NMDA Receptors Subserve Persistent Neuronal Firing during Working Memory in Dorsolateral Prefrontal Cortex

SummaryNeurons in the primate dorsolateral prefrontal cortex (dlPFC) generate persistent firing in the absence of sensory stimulation, the foundation of mental representation. Persistent firing arises from recurrent excitation within a network of pyramidal Delay cells. Here, we examined glutamate receptor influences underlying persistent firing in primate dlPFC during a spatial working memory task. Computational models predicted dependence on NMDA receptor (NMDAR) NR2B stimulation, and Delay cell persistent firing was abolished by local NR2B NMDAR blockade or by systemic ketamine administration. AMPA receptors (AMPARs) contributed background depolarization to sustain network firing. In contrast, many Response cells were sensitive to AMPAR blockade and increased firing after systemic ketamine, indicating that models of ketamine actions should be refined to reflect neuronal heterogeneity. The reliance of Delay cells on NMDAR may explain why insults to NMDARs in schizophrenia or Alzheimer’s disease profoundly impair cognition

Association Between Use of Specific Drugs and Antiretroviral Adherence: Findings from MACH 14

To determine the association between individual substances of abuse and antiretroviral adherence, analyses require a large sample assessed using electronic data monitoring (EDM). In this analysis, EDM data from 1636 participants in 12 U.S. adherence-focused studies were analyzed to determine the associations between recent use of various substances and adherence during the preceding four weeks. In bivariate analyses comparing adherence among patients who had used a specific substance to those who had not, adherence was significantly lower among those who had recently used cocaine, other stimulants or heroin but not among those who had used cannabis or alcohol. In multivariate analyses controlling for sociodemographics, amount of alcohol use and recent use of any alcohol, cocaine, other stimulants and heroin each was significantly negatively associated with adherence. The significant associations of cocaine, other stimulants, heroin, and alcohol use with adherence suggest that these are important substances to target with adherence-focused interventions

The statistical neuroanatomy of frontal networks in the macaque

We were interested in gaining insight into the functional properties of frontal networks based upon their anatomical inputs. We took a neuroinformatics approach, carrying out maximum likelihood hierarchical cluster analysis on 25 frontal cortical areas based upon their anatomical connections, with 68 input areas representing exterosensory, chemosensory, motor, limbic, and other frontal inputs. The analysis revealed a set of statistically robust clusters. We used these clusters to divide the frontal areas into 5 groups, including ventral-lateral, ventral-medial, dorsal-medial, dorsal-lateral, and caudal-orbital groups. Each of these groups was defined by a unique set of inputs. This organization provides insight into the differential roles of each group of areas and suggests a gradient by which orbital and ventral-medial areas may be responsible for decision-making processes based on emotion and primary reinforcers, and lateral frontal areas are more involved in integrating affective and rational information into a common framework

Empowering With PrEP (E-PrEP), a Peer-Led Social Media–Based Intervention to Facilitate HIV Preexposure Prophylaxis Adoption Among Young Black and Latinx Gay and Bisexual Men: Protocol for a Cluster Randomized Controlled Trial

Background: Young black and Latinx, gay, bisexual, and other men who have sex with men (YBLGBM, aged 18-29 years) have among the highest rates of new HIV infections in the United States and are not consistently reached by existing prevention interventions. Preexposure prophylaxis (PrEP), an oral antiretroviral regimen taken daily by HIV-uninfected individuals to prevent HIV acquisition, is highly efficacious in reducing HIV acquisition and could help stop the HIV epidemic in YBLGBM. Use of social media (eg, Facebook, Twitter, online dating sites) is ubiquitous among young people, providing an efficient avenue to engage YBLGBM to facilitate PrEP adoption. Objective: Our overall goal was to develop and pilot test a theoretically grounded, social media–based, peer-led intervention to increase PrEP uptake in YBLGBM. We used diffusion of innovation and information-motivation-behavioral skills frameworks to (1) identify potential factors associated with interest in and adoption of PrEP among YBLGBM; (2) develop Empowering with PrEP (E-PrEP), a social media–based, peer-led intervention to increase PrEP uptake in YBLGBM; and (3) pilot test the feasibility and acceptability of E-PrEP, and determine its preliminary efficacy for increasing adoption of PrEP by YBLGBM. We describe the development and protocol for E-PrEP. Methods: Using a participatory research approach, we partnered with YBLGBM intervention development partners to develop a social media–based behavioral intervention to facilitate PrEP uptake, which involved an online messaging campaign disseminated by YBLGBM peer leaders to their existing online networks. We designed the 6-week campaign to provide education about PrEP, increase motivation to use PrEP, and facilitate access to PrEP. We then conducted a cluster-randomized trial of E-PrEP compared with an attention-matched general health control condition (E-Health) among YBLGBM aged 18 to 29 years to assess E-PrEP’s feasibility, acceptability, preliminary efficacy for increasing self-reported intention to use PrEP, PrEP uptake, and impact on knowledge and attitudes about PrEP at 12-week follow-up (6 weeks after the end of the online campaign). Results: From October 2016 to March 2017, we developed, pretested, and refined E-PrEP with 6 YBLGBM intervention development partners. From May to June 2017, we recruited, enrolled, and randomly assigned 10 peer leaders (n=5 for each condition). The 10 peer leaders then recruited and enrolled 152 participants from their existing online networks (range 3-33 per peer leader), during June and July 2017. Intervention follow-up was completed after 12 weeks, in November 2017, with analyses underway. Conclusions: We hypothesize that, compared with E-Health, participants randomly assigned to E-PrEP will be more likely to express intention to use PrEP and greater PrEP uptake, and will also show changes in potential mediators of PrEP uptake (knowledge, attitudes, stigma, and access). A Web-based biobehavioral intervention model such as E-PrEP could be rapidly scaled even with limited resources and have significant population-level impact

Dopaminergic modulation of appetitive trace conditioning: the role of D1 receptors in medial prefrontal cortex

Rationale: Trace conditioning may provide a behavioural model suitable to examine the maintenance of ‘on line’ information and its underlying neural substrates. Objectives: Experiment la was run to establish trace conditioning in a shortened procedure which would be suitable to test the effects of dopamine (DA) D1 receptor agents administered by microinjection directly into the brain. Experiment lb examined the effects of the DA D1 agonist SKF81297 and the DA D1 antagonist SCH23390 following systemic administration in pre-trained animals. Experiment 2 went on to test the effects of systemically administered SKF81297 on the acquisition of trace conditioning. In experiment 3, SKF81297 was administered directly in prelimbic (PL) and infralimbic (IL) sub-regions of medial prefrontal cortex (mPFC) to compare the role of different mPFC sub-regions. Results: Whilst treatment with SCH23390 impaired motor responding and/or motivation, SKF81297 had relatively little effect in the pre-trained animals tested in experiment 1b. However, systemic SKF81297 depressed the acquisition function at the 2-s trace interval in experiment 2. Similarly, in experiment 3, SKF81297 (0.1 μg in 1.0 μl) microinjected into either PL or IL mPFC impaired appetitive conditioning at the 2-s trace interval. Conclusions: Impaired trace conditioning under SKF81297 is likely to be mediated in part (but not exclusively) within the IL and PL mPFC sub-regions. The finding that trace conditioning was impaired rather than enhanced under SKF81297 provides further evidence for the inverse U-function which has been suggested to be characteristic of mPFC DA function

ART adherence changes among patients in community substance use treatment: a preliminary analysis from MACH14

Abstract Background Opiate substitution treatment has been associated with better adherence to lifesaving antiretroviral medications, but the impact of other substance abuse treatment on adherence is unknown. Findings In this study, 215 patients who had been in adherence-focused research studies provided electronically-measured adherence data and a measure of whether the patient had recently been in substance abuse treatment. Recent engagement in substance abuse treatment was independently associated with significantly higher adherence, after covarying for recent substance use and other factors potentially affecting adherence. Conclusions The findings suggest that substance abuse treatment is associated with better adherence. Potential mechanisms by which substance abuse treatment improves adherence, such as more stability or more future-orientation, require further study

Mindfulness-based interventions for young offenders: a scoping review

Youth offending is a problem worldwide. Young people in the criminal justice system have frequently experienced adverse childhood circumstances, mental health problems, difficulties regulating emotions and poor quality of life. Mindfulness-based interventions can help people manage problems resulting from these experiences, but their usefulness for youth offending populations is not clear. This review evaluated existing evidence for mindfulness-based interventions among such populations. To be included, each study used an intervention with at least one of the three core components of mindfulness-based stress reduction (breath awareness, body awareness, mindful movement) that was delivered to young people in prison or community rehabilitation programs. No restrictions were placed on methods used. Thirteen studies were included: three randomized controlled trials, one controlled trial, three pre-post study designs, three mixed-methods approaches and three qualitative studies. Pooled numbers (n = 842) comprised 99% males aged between 14 and 23. Interventions varied so it was not possible to identify an optimal approach in terms of content, dose or intensity. Studies found some improvement in various measures of mental health, self-regulation, problematic behaviour, substance use, quality of life and criminal propensity. In those studies measuring mindfulness, changes did not reach statistical significance. Qualitative studies reported participants feeling less stressed, better able to concentrate, manage emotions and behaviour, improved social skills and that the interventions were acceptable. Generally low study quality limits the generalizability of these findings. Greater clarity on intervention components and robust mixed-methods evaluation would improve clarity of reporting and better guide future youth offending prevention programs

ART adherence changes among patients in community substance use treatment: a preliminary analysis from MACH14

Background: Opiate substitution treatment has been associated with better adherence to lifesaving antiretroviral medications, but the impact of other substance abuse treatment on adherence is unknown. Findings: In this study, 215 patients who had been in adherence-focused research studies provided electronically-measured adherence data and a measure of whether the patient had recently been in substance abuse treatment. Recent engagement in substance abuse treatment was independently associated with significantly higher adherence, after covarying for recent substance use and other factors potentially affecting adherence. Conclusions: The findings suggest that substance abuse treatment is associated with better adherence. Potential mechanisms by which substance abuse treatment improves adherence, such as more stability or more future-orientation, require further study

The Association Between Poor Antiretroviral Adherence and Unsafe Sex: Differences by Gender and Sexual Orientation and Implications for Scale-up of Treatment as Prevention

Non-adherence to safer sex and non-adherence to ART can each have adverse health consequences for HIV-infected individuals and their sex partners, but little is known about the association of these behaviors with each other. This “dual risk” has potential negative public health consequences since non-adherence can lead to the development of resistant virus that can then be transmitted to sex partners