Evaluation of two methods to isolate Schwann cells from murine sciatic nerve.

Background: Schwann cells (SC) and macrophages play key roles in the response to peripheral nerve injury (PNI). Accurate isolation of such cells is essential for further analyses that can lead to better understanding of the repair process after PNI. Separation of live SC from the injury site without culture enrichment is necessary for targeted gene expression analysis.

Flexible combination of reward information across primates.

A fundamental but rarely contested assumption in economics and neuroeconomics is that decision-makers compute subjective values of risky options by multiplying functions of reward probability and magnitude. By contrast, an additive strategy for valuation allows flexible combination of reward information required in uncertain or changing environments. We hypothesized that the level of uncertainty in the reward environment should determine the strategy used for valuation and choice.

Motor thalamus supports striatum-driven reinforcement.

Reinforcement has long been thought to require striatal synaptic plasticity. Indeed, direct striatal manipulations such as self-stimulation of direct-pathway projection neurons (dMSNs) are sufficient to induce reinforcement within minutes. However, it's unclear what role, if any, is played by downstream circuitry.

Volatility Facilitates Value Updating in the Prefrontal Cortex.

Adaptation of learning and decision-making might depend on the regulation of activity in the prefrontal cortex. Here we examined how volatility of reward probabilities influences learning and neural activity in the primate prefrontal cortex. We found that animals selected recently rewarded targets more often when reward probabilities of different options fluctuated across trials than when they were fixed.

Metaplasticity as a Neural Substrate for Adaptive Learning and Choice under Uncertainty.

Value-based decision making often involves integration of reward outcomes over time, but this becomes considerably more challenging if reward assignments on alternative options are probabilistic and non-stationary. Despite the existence of various models for optimally integrating reward under uncertainty, the underlying neural mechanisms are still unknown. Here we propose that reward-dependent metaplasticity (RDMP) can provide a plausible mechanism for both integration of reward under uncertainty and estimation of uncertainty itself.

A Direct Path to Action Initiation.

In this issue of Neuron, Sippy et al. (2015) provide the clearest evidence to date that information is differentially encoded in the direct and indirect pathways of the striatum. The results support the classical notion that the direct pathway plays a critical role in initiating actions.

Dynamic routing of task-relevant signals for decision making in dorsolateral prefrontal cortex.

Neurons in the dorsolateral prefrontal cortex (DLPFC) encode a diverse array of sensory and mnemonic signals, but little is known about how this information is dynamically routed during decision making. We analyzed the neuronal activity in the DLPFC of monkeys performing a probabilistic reversal task where information about the probability and magnitude of reward was provided by the target color and numerical cues, respectively. The location of the target of a given color was randomized across trials and therefore was not relevant for subsequent choices.

Neural correlates of strategic reasoning during competitive games.

Although human and animal behaviors are largely shaped by reinforcement and punishment, choices in social settings are also influenced by information about the knowledge and experience of other decision-makers. During competitive games, monkeys increased their payoffs by systematically deviating from a simple heuristic learning algorithm and thereby countering the predictable exploitation by their computer opponent. Neurons in the dorsomedial prefrontal cortex (dmPFC) signaled the animal's recent choice and reward history that reflected the computer's exploitative strategy.

A randomized, placebo-controlled trial of N-acetylcysteine plus imaginal desensitization for nicotine-dependent pathological gamblers.

Objective: Pathological gambling is associated with elevated proportions of nicotine dependence, and tobacco smoking in pathological gamblers has been associated with increased problem-gambling severity. This study examined the addition of N-acetylcysteine to imaginal desensitization in adults with co-occurring nicotine dependence and pathological gambling.

Method: Twenty-eight individuals with co-occurring DSM-IV nicotine dependence and pathological gambling who were receiving behavioral therapy were recruited from December 2009 to February 2012 and randomized to augmentation with N-acetylcysteine or placebo in an 12-week, double-blind trial.

Cortical signals for rewarded actions and strategic exploration.

In stable environments, decision makers can exploit their previously learned strategies for optimal outcomes, while exploration might lead to better options in unstable environments. Here, to investigate the cortical contributions to exploratory behavior, we analyzed single-neuron activity recorded from four different cortical areas of monkeys performing a matching-pennies task and a visual search task, which encouraged and discouraged exploration, respectively. We found that neurons in multiple regions in the frontal and parietal cortex tended to encode signals related to previously rewarded actions more reliably than unrewarded actions.

Adolescent stealing treated with motivational interviewing and imaginal desensitization - Case report.

Background Adolescent shoplifting occurs in an estimated 15% of the United States population. Although adolescent stealing is associated with significant psychosocial consequences there is limited research concerning efficacious treatments. Case study A 17-year-old male with a history of compulsive stealing was treated using a six-session, individualized cognitive-behavioral therapy protocol which included motivational interviewing, psycho-education, behavioral modification, and an exposure script using imaginal desensitization.

Genome-wide profiling of H3K56 acetylation and transcription factor binding sites in human adipocytes.

The growing epidemic of obesity and metabolic diseases calls for a better understanding of adipocyte biology. The regulation of transcription in adipocytes is particularly important, as it is a target for several therapeutic approaches. Transcriptional outcomes are influenced by both histone modifications and transcription factor binding.

A 6-month follow-up of imaginal desensitization plus motivational interviewing in the treatment of pathological gambling.

Background: Pathological gambling (PG), a disabling disorder experienced by approximately 1% of adults, has few empirically validated treatments. A recent study demonstrated that 6 sessions of imaginal desensitization plus motivational interviewing (IDMI) was effective in achieving abstinence for a majority of individuals with PG. This study sought to examine whether those benefits were maintained 6 months post-treatment.

Somatosensory responses in normal aging, mild cognitive impairment, and Alzheimer's disease.

As a part of a larger study of normal aging and Alzheimer's disease (AD), which included patients with mild cognitive impairment (MCI), we investigated the response to median nerve stimulation in primary and secondary somatosensory areas. We hypothesized that the somatosensory response would be relatively spared given the reported late involvement of sensory areas in the progression of AD. We applied brief pulses of electric current to left and right median nerves to test the somatosensory response in normal elderly (NE), MCI, and AD.

Imaginal desensitisation plus motivational interviewing for pathological gambling: randomised controlled trial.

Sixty-eight individuals were randomised to either six sessions of imaginal desensitisation plus motivational interviewing (IDMI) or Gamblers Anonymous. Individuals assigned to IDMI had significantly greater reductions in Yale-Brown Obsessive Compulsive Scale Modified for Pathological Gambling total scores, gambling urges and gambling behaviour. People who failed to respond to Gamblers Anonymous reported significantly greater reduction in pathological gambling symptoms following later assignment to IDMI.

Cognitive-behavioral therapy for panic disorder in patients being treated for alcohol dependence: Moderating effects of alcohol outcome expectancies.

Anxiety disorders commonly co-occur with alcohol use disorders and reliably mark a poor response to substance abuse treatment. However, treating a co-occurring anxiety disorder does not reliably improve substance abuse treatment outcomes. Failure to account for individual differences in the functional dynamic between anxiety symptoms and drinking behavior might impede the progress and clarity of this research program.

Effect of quetiapine vs. placebo on response to two virtual public speaking exposures in individuals with social phobia.

Objective: Clinical practice and open-label studies suggest that quetiapine (an atypical anti-psychotic) might improve symptoms for individuals with social anxiety disorder (SAD). The purpose of this study was to provide a rigorous test of the acute impact of a single dose of quetiapine (25mg) on SAD symptoms.

Method: Individuals with SAD (N=20) were exposed to a 4-min virtual reality (VR) public speaking challenge after having received quetiapine or placebo (double-blind) 1h earlier.

Physiological response to a speech stressor presented in a virtual reality environment.

The feasibility of using virtual reality (VR) technology to induce a physiological response to stress was assessed in 12 volunteers during a laboratory session in which each participant completed a speech task within a VR environment and a math task outside the VR environment. Both tasks were effective in eliciting a physiological response with significant increases observed in response to each stress task in systolic and diastolic blood pressure and heart rate. Increases in plasma epinephrine and norepinephrine concentrations were observed during the speech task and in plasma epinephrine concentrations during the math task although these differences did not reach statistical significance.

Development of a robust GABA(B) calcium signaling cell line using beta-lactamase technology and sorting.

The GABA(B) receptor is a member of the "family 3" G protein coupled receptors. The GABA(B) receptors modulate activity inwardly rectifying potassium channels and high voltage activated calcium channels. The GABA(B) receptors require heterodimerization between two subunits, GABA(B1) and GABA(B2), for functional expression.

D-cycloserine augmented exposure therapy for obsessive-compulsive disorder.

Background: D-cycloserine (DCS), a glutamatergic partial N-methyl-d-aspartate (NMDA) agonist, can facilitate extinction learning related to cued fear in animals and humans. We predicted that DCS would accelerate obsession-related distress reduction in patients with obsessive-compulsive disorder (OCD) undergoing extinction-based exposure therapy.

Methods: We administered DCS (125 mg) or placebo in a double-blind fashion to individuals with OCD approximately 2 hours before each exposure session.

Urge to gamble in problem gamblers exposed to a casino environment.

Cue-reactivity has received increased attention in addiction research, though not for gambling in particular. We examined cue reactivity in 18 problem gamblers by accompanying them to a gaming casino and measuring their subjective urge to gamble over a 1-h period. Half of the sample was additionally exposed to a gambling-specific negative mood induction (NMI) manipulation via guided imagery.

Cell surface expression of the melanocortin-4 receptor is dependent on a C-terminal di-isoleucine sequence at codons 316/317.

Loss-of-function mutations in the human melanocortin-4 receptor (MC4R) are associated with obesity. Previous work has implicated a C-terminal di-isoleucine motif at residues 316/317 in MC4R cell surface targeting. It was therefore of interest to examine function and cell surface expression of an MC4R mutation found in an obese proband in which one of these isoleucines was substituted by threonine (I317T).