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Russ J.B.,Rockefeller University | Russ J.B.,Sloan Kettering Institute | Kaltschmidt J.A.,Neuroscience Program | Kaltschmidt J.A.,New York Medical College | Kaltschmidt J.A.,Sloan Kettering Institute
Open Biology | Year: 2014

Every behaviour of an organism relies on an intricate and vastly diverse network of neurons whose identity and connectivity must be specified with extreme precision during development. Intrinsically, specification of neuronal identity depends heavily on the expression of powerful transcription factors that direct numerous features of neuronal identity, including especially properties of neuronal connectivity, such as dendritic morphology, axonal targeting or synaptic specificity, ultimately priming the neuron for incorporation into emerging circuitry. As the neuron's early connectivity is established, extrinsic signals from its pre- and postsynaptic partners feedback on the neuron to further refine its unique characteristics. As a result, disruption of one component of the circuitry during development can have vital consequences for the proper identity specification of its synaptic partners. Recent studies have begun to harness the power of various transcription factors that control neuronal cell fate, including those that specify a neuron's subtype-specific identity, seeking insight for future therapeutic strategies that aim to reconstitute damaged circuitry through neuronal reprogramming. © 2014 The Authors. Published. Source

Pace L.A.,Wake Forest Institute for Regenerative Medicine | Plate J.F.,Neuroscience Program
Tissue Engineering - Part A | Year: 2014

A human hair keratin biomaterial hydrogel scaffold was evaluated as a nerve conduit luminal filler following median nerve transection injury in 10 Macaca fascicularis nonhuman primates (NHP). A 1 cm nerve gap was grafted with a NeuraGen® collagen conduit filled with either saline or keratin hydrogel and nerve regeneration was evaluated by electrophysiology for a period of 12 months. The keratin hydrogel-grafted nerves showed significant improvement in return of compound motor action potential (CMAP) latency and recovery of baseline nerve conduction velocity (NCV) compared with the saline-treated nerves. Histological evaluation was performed on retrieved median nerves and abductor pollicis brevis (APB) muscles at 12 months. Nerve histomorphometry showed a significantly larger nerve area in the keratin group compared with the saline group and the keratin APB muscles had a significantly higher myofiber density than the saline group. This is the first published study to show that an acellular biomaterial hydrogel conduit filler can be used to enhance peripheral nerve regeneration and motor recovery in an NHP model. © 2014 Mary Ann Liebert, Inc. Source

Moussa M.N.,Neuroscience Program
PLoS ONE | Year: 2012

At rest, spontaneous brain activity measured by fMRI is summarized by a number of distinct resting state networks (RSNs) following similar temporal time courses. Such networks have been consistently identified across subjects using spatial ICA (independent component analysis). Moreover, graph theory-based network analyses have also been applied to resting-state fMRI data, identifying similar RSNs, although typically at a coarser spatial resolution. In this work, we examined resting-state fMRI networks from 194 subjects at a voxel-level resolution, and examined the consistency of RSNs across subjects using a metric called scaled inclusivity (SI), which summarizes consistency of modular partitions across networks. Our SI analyses indicated that some RSNs are robust across subjects, comparable to the corresponding RSNs identified by ICA. We also found that some commonly reported RSNs are less consistent across subjects. This is the first direct comparison of RSNs between ICAs and graph-based network analyses at a comparable resolution. © 2012 Moussa et al. Source

Aston E.R.,Neuroscience Program | Liguori A.,Neuroscience Program
Alcohol and Alcoholism | Year: 2013

Breath alcohol concentration (BrAC) estimation training has been effective in increasing estimation accuracy in social drinkers. Predictors of estimation accuracy may identify populations to target for training, yet potential predictors typically are not evaluated. In addition, the therapeutic efficacy of estimation training as a preventive strategy for problematic drinking is unknown. Methods: Forty-six social drinkers with a recent binge history were randomly assigned to an intervention or control group (n = 23 per group). In each of three sessions (pretraining, training, testing), participants consumed alcohol (0.32, 0.24, 0.16 and 0.08 g/kg, in random order) every 30 min (total dose: 0.8 g/kg). Participants provided five BrAC estimates within 3 h of alcohol administration. The intervention group, but not control group, received internal and external training. During testing, participants provided BrAC estimates, but received no feedback. Participants returned for two follow-up visits to complete self-report measures. Results: BrAC estimation training improved intervention group estimation accuracy within the laboratory. Together, training, low trait anxiety and low risk expectancy predicted high testing accuracy. There were no significant group differences in subsequent alcohol consumption, behavior under the influence or risk expectancy regarding potentially hazardous behaviors. Conclusion: BrAC estimation training is effective in the laboratory but may not translate into naturalistic settings. © The Author 2013. Medical Council on Alcohol and Oxford University Press. All rights reserved. Source

Aston E.R.,Neuroscience Program | Aston E.R.,Brown University | Liguori A.,Neuroscience Program
Psychology of Addictive Behaviors | Year: 2014

The current study evaluated the relationships among trait anxiety, subjective response to alcohol, and simulated driving following a simulated alcohol binge. Sixty drinkers with a binge history completed the State Trait Anxiety Inventory (STAI), the Alcohol Use Questionnaire, and subsequently completed a driving simulation. Participants were then administered 0.2 g/kg ethanol at 30-min intervals (cumulative dose 0.8 g/kg). Following alcohol consumption, the Biphasic Alcohol Effects Scale (BAES) and visual analog scales of subjective impairment and driving confidence were administered, after which simulated driving was reassessed. Due to the emphasis on simulated driving after drinking in the current study, subjective response to alcohol (i.e., self-reported sedation, stimulation, impairment, and confidence in driving ability) was assessed once following alcohol consumption, as this is the time when drinkers tend to make decisions regarding legal driving ability. Alcohol increased driving speed, speeding tickets, and collisions. Sedation following alcohol predicted increased subjective impairment and decreased driving confidence. Subjective impairment was not predicted by sensitivity to stimulation or trait anxiety. High trait anxiety predicted low driving confidence after drinking and this relationship was mediated by sedation. Increased speed after alcohol was predicted by sedation, but not by trait anxiety or stimulation. Anxiety, combined with the sedating effects of alcohol, may indicate when consumption should cease. However, once driving is initiated, sensitivity to sedation following alcohol consumption is positively related to simulated driving speed. © 2014 American Psychological Association. Source

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