Prefrontal response and frontostriatal functional connectivity to monetary reward in abstinent alcohol-dependent young adults

Although altered function in neural reward circuitry is widely proposed in models of addiction, more recent conceptual views have emphasized the role of disrupted response in prefrontal regions. Changes in regions such as the orbitofrontal cortex, medial prefrontal cortex, and dorsolateral prefrontal cortex are postulated to contribute to the compulsivity, impulsivity, and altered executive function that are central to addiction. In addition, few studies have examined function in these regions during young adulthood, when exposure is less chronic than in typical samples of alcohol-dependent adults. To address these issues, we examined neural response and functional connectivity during monetary reward in 24 adults with alcohol dependence and 24 psychiatrically healthy adults. Adults with alcohol dependence exhibited less response to the receipt of monetary reward in a set of prefrontal regions including the medial prefrontal cortex, lateral orbitofrontal cortex, and dorsolateral prefrontal cortex. Adults with alcohol dependence also exhibited greater negative correlation between function in each of these regions and that in the nucleus accumbens. Within the alcohol-dependent group, those with family history of alcohol dependence exhibited lower mPFC response, and those with more frequent drinking exhibited greater negative functional connectivity between the mPFC and the nucleus accumbens. These findings indicate that alcohol dependence is associated with less engagement of prefrontal cortical regions, suggesting weak or disrupted regulation of ventral striatal response. This pattern of prefrontal response and frontostriatal connectivity has consequences for the behavior patterns typical of addiction. Furthermore, brain-behavior findings indicate that the potential mechanisms of disruption in frontostriatal circuitry in alcohol dependence include family liability to alcohol use problems and more frequent use of alcohol. In all, these findings build on the extant literature on reward-circuit function in addiction and suggest mechanisms for disrupted function in alcohol dependence. © 2014 Forbes et al

Ge/Si nanowire mesoscopic Josephson junctions

The controlled growth of nanowires (NWs) with dimensions comparable to the Fermi wavelengths of the charge carriers allows fundamental investigations of quantum confinement phenomena. Here, we present studies of proximity-induced superconductivity in undoped Ge/Si core/shell NW heterostructures contacted by superconducting leads. By using a top gate electrode to modulate the carrier density in the NW, the critical supercurrent can be tuned from zero to greater than 100 nA. Furthermore, discrete sub-bands form in the NW due to confinement in the radial direction, which results in stepwise increases in the critical current as a function of gate voltage. Transport measurements on these superconductor-NW-superconductor devices reveal high-order (n = 25) resonant multiple Andreev reflections, indicating that the NW channel is smooth and the charge transport is highly coherent. The ability to create and control coherent superconducting ordered states in semiconductor-superconductor hybrid nanostructures allows for new opportunities in the study of fundamental low-dimensional superconductivity

Different Verbal Learning Strategies in Autism Spectrum Disorder: Evidence from the Rey Auditory Verbal Learning Test

The Rey Auditory Verbal Learning Test, which requires the free recall of the same list of 15 items over 5 trials, was administered to a group of highfunctioning adolescents and adults with autism spectrum disorder (PDD) and a group of matched typical individuals. Overall levels of free recall were comparable in the two groups, as were the rates of learning over trials. Both groups also subjectively organised their recall to a similar extent. However, the serial position curve of the PDD participants, although similar to that of the comparison group on the first trial, became flatter on subsequent trials and was characterised by a slower growth in the primacy effect. Growth in the middle and recency portions of the curve was comparable in both groups. The findings are discussed in the light of current models of serial position effects and their implications for memory in ASD

A Transient Transgenic RNAi Strategy for Rapid Characterization of Gene Function during Embryonic Development

RNA interference (RNAi) is a powerful strategy for studying the phenotypic consequences of reduced gene expression levels in model systems. To develop a method for the rapid characterization of the developmental consequences of gene dysregulation, we tested the use of RNAi for “transient transgenic” knockdown of mRNA in mouse embryos. These methods included lentiviral infection as well as transposition using the Sleeping Beauty (SB) and PiggyBac (PB) transposable element systems. This approach can be useful for phenotypic validation of putative mutant loci, as we demonstrate by confirming that knockdown of Prdm16 phenocopies the ENU-induced cleft palate (CP) mutant, csp1. This strategy is attractive as an alternative to gene targeting in embryonic stem cells, as it is simple and yields phenotypic information in a matter of weeks. Of the three methodologies tested, the PB transposon system produced high numbers of transgenic embryos with the expected phenotype, demonstrating its utility as a screening method

Transabdominal Preperitoneal Repair for Obturator Hernia

信州大学博士（医学）・学位論文・平成23年3月31日授与（甲第889号）・横山隆秀Background A laparoscopic surgical approach for obturator hernia (OH) repair is uncommon. The aim of the present study was to assess the effectiveness of laparoscopic transabdominal preperitoneal (TAPP) repair for OH. Methods From 2001 to May 2010, 659 patients with inguinal hernia underwent TAPP repair at in our institutes. Among these, the eight patients with OH were the subjects of this study. Results Three of the eight patients were diagnosed as having occult OH, and the other five were diagnosed preoperatively, by ultrasonography and/or computed tomography, as having strangulated OH. Bilateral OH was found in five patients (63%), and combined groin hernias, either unilaterally or bilaterally, were observed in seven patients (88%), all of whom had femoral hernia. Of the five patients with bowel obstruction at presentation, four were determined not to require resection after assessment of the intestinal viability by laparoscopy. There was one case of conversion to a two-stage hernia repair performed to avoid mesh contamination: addition of mini-laparotomy, followed by extraction of the gangrenous intestine for resection and anastomosis with simple peritoneal closure of the hernia defect in the first stage, and a Kugel hernia repair in the second stage. There was no incidence of postoperative morbidity, mortality, or recurrence. Conclusions Because TAPP allows assessment of not only the entire groin area bilaterally but also simultaneous assessment of the viability of the incarcerated intestine with a minimum abdominal wall defect, we believe that it is an adequate approach to the treatment of both occult and acutely incarcerated OH. Two-stage hernia repair is technically feasible in patients requiring resection of the incarcerated intestine.ArticleWORLD JOURNAL OF SURGERY. 35(10):2323-2327 (2011)journal articl

Reward-Related Dorsal Striatal Activity Differences between Former and Current Cocaine Dependent Individuals during an Interactive Competitive Game

Cocaine addiction is characterized by impulsivity, impaired social relationships, and abnormal mesocorticolimbic reward processing, but their interrelationships relative to stages of cocaine addiction are unclear. We assessed blood-oxygenation-level dependent (BOLD) signal in ventral and dorsal striatum during functional magnetic resonance imaging (fMRI) in current (CCD; n = 30) and former (FCD; n = 28) cocaine dependent subjects as well as healthy control (HC; n = 31) subjects while playing an interactive competitive Domino game involving risk-taking and reward/punishment processing. Out-of-scanner impulsivity-related measures were also collected. Although both FCD and CCD subjects scored significantly higher on impulsivity-related measures than did HC subjects, only FCD subjects had differences in striatal activation, specifically showing hypoactivation during their response to gains versus losses in right dorsal caudate, a brain region linked to habituation, cocaine craving and addiction maintenance. Right caudate activity in FCD subjects also correlated negatively with impulsivity-related measures of self-reported compulsivity and sensitivity to reward. These findings suggest that remitted cocaine dependence is associated with striatal dysfunction during social reward processing in a manner linked to compulsivity and reward sensitivity measures. Future research should investigate the extent to which such differences might reflect underlying vulnerabilities linked to cocaine-using propensities (e.g., relapses)

Risky Decisions and Their Consequences: Neural Processing by Boys with Antisocial Substance Disorder

Adolescents with conduct and substance problems ("Antisocial Substance Disorder" (ASD)) repeatedly engage in risky antisocial and drug-using behaviors. We hypothesized that, during processing of risky decisions and resulting rewards and punishments, brain activation would differ between abstinent ASD boys and comparison boys.We compared 20 abstinent adolescent male patients in treatment for ASD with 20 community controls, examining rapid event-related blood-oxygen-level-dependent (BOLD) responses during functional magnetic resonance imaging. In 90 decision trials participants chose to make either a cautious response that earned one cent, or a risky response that would either gain 5 cents or lose 10 cents; odds of losing increased as the game progressed. We also examined those times when subjects experienced wins, or separately losses, from their risky choices. We contrasted decision trials against very similar comparison trials requiring no decisions, using whole-brain BOLD-response analyses of group differences, corrected for multiple comparisons. During decision-making ASD boys showed hypoactivation in numerous brain regions robustly activated by controls, including orbitofrontal and dorsolateral prefrontal cortices, anterior cingulate, basal ganglia, insula, amygdala, hippocampus, and cerebellum. While experiencing wins, ASD boys had significantly less activity than controls in anterior cingulate, temporal regions, and cerebellum, with more activity nowhere. During losses ASD boys had significantly more activity than controls in orbitofrontal cortex, dorsolateral prefrontal cortex, brain stem, and cerebellum, with less activity nowhere.Adolescent boys with ASD had extensive neural hypoactivity during risky decision-making, coupled with decreased activity during reward and increased activity during loss. These neural patterns may underlie the dangerous, excessive, sustained risk-taking of such boys. The findings suggest that the dysphoria, reward insensitivity, and suppressed neural activity observed among older addicted persons also characterize youths early in the development of substance use disorders

What Do We Really Know about Cognitive Inhibition? Task Demands and Inhibitory Effects across a Rang

Our study explores inhibitory control across a range of widely recognised memory and behavioural tasks. Eighty-seven never-depressed participants completed a series of tasks designed to measure inhibitory control in memory and behaviour. Specifically, a variant of the selective retrieval-practice and the Think/No-Think tasks were employed as measures of memory inhibition. The Stroop-Colour Naming and the Go/No-Go tasks were used as measures of behavioural inhibition. Participants completed all 4 tasks. Task presentation order was counterbalanced across 3 separate testing sessions for each participant. Standard inhibitory forgetting effects emerged on both memory tasks but the extent of forgetting across these tasks was not correlated. Furthermore, there was no relationship between memory inhibition tasks and either of the main behavioural inhibition measures. At a time when cognitive inhibition continues to gain acceptance as an explanatory mechanism, our study raises fundamental questions about what we actually know about inhibition and how it is affected by the processing demands of particular inhibitory tasks

RECAPP-XPR: A smartphone application for presenting and recalling experimentally controlled stimuli over longer timescales

We report two experiments that used smartphone applications for presenting and recalling verbal stimuli over extended timescales. In Experiment 1, we used an iPhone application that we had developed, called RECAPP-XPR, to present 76 participants with a single list of eight words presented at a rate of one word every hour, followed by a test of free recall an hour later. The experiment was exceptionally easy to schedule, taking only between 5 and 10 min to set up using a web-based interface. RECAPP-XPR randomly samples the stimuli, presents the stimuli, and collects the free recall data. The stimuli disappear shortly after they have been presented, and RECAPP-XPR collects data on when each stimulus was viewed. In Experiment 2, the study was replicated using the widely used image-sharing application Snapchat. A total of 197 participants were tested by 38 student experimenters, who manually presented the stimuli as “snaps” of experimentally controlled stimuli using the same experimental rates that had been used in Experiment 1. Like all snaps, these stimuli disappeared from view after a very short interval. In both experiments, we observed significant recall advantages for the first and last list items (primacy and recency effects, respectively), and there were clear tendencies to make more transitions at output between near-neighboring items, with a forward-ordered bias, consistent with temporal contiguity effects. The respective advantages and disadvantages of RECAPP-XPR and Snapchat as experimental software packages are discussed, as is the relationship between single-study-list smartphone experiments and long-term recency studies of real-world events