Effect of methamphetamine dependence on inhibitory deficits in a novel human open-field paradigm.

RationaleMethamphetamine (MA) is an addictive psychostimulant associated with neurocognitive impairment, including inhibitory deficits characterized by a reduced ability to control responses to stimuli. While various domains of inhibition such as exaggerated novelty seeking and perseveration have been assessed in rodents by quantifying activity in open-field tests, similar models have not been utilized in human substance abusers. We recently developed a cross-species translational human open-field paradigm, the human behavior pattern monitor (hBPM), consisting of an unfamiliar room containing novel and engaging objects. Previous work demonstrated that manic bipolar subjects exhibit a disinhibited pattern of behavior in the hBPM characterized by increased object interactions.ObjectivesIn the current study, we examined the effect of MA dependence on inhibitory deficits using this paradigm. hBPM activity and object interactions were quantified in 16 abstinent MA-dependent individuals and 18 matched drug-free comparison subjects. The Wisconsin card sorting task (WCST) and the positive and negative syndrome scale (PANSS) were administered to assess executive function and psychopathology.ResultsMA-dependent participants exhibited a significant increase in total object interactions, time spent with objects, and perseverative object interactions relative to comparison subjects. Greater object interaction was associated with impaired performance on the WCST, higher PANSS scores, and more frequent MA use in the past year.ConclusionsAbstinent MA-dependent individuals exhibited impaired inhibition in the hBPM, displaying increased interaction with novel stimuli. Utilization of this measure may enable assessment of inhibitory deficits relevant to drug-seeking behavior and facilitate development of intervention methods to reduce high-risk conduct in this population

Lafora disease offers a unique window into neuronal glycogen metabolism

Lafora disease (LD) is a fatal, autosomal recessive, glycogen-storage disorder that manifests as severe epilepsy. LD results from mutations in the gene encoding either the glycogen phosphatase laforin or the E3 ubiquitin ligase malin. Individuals with LD develop cytoplasmic, aberrant glycogen inclusions in nearly all tissues that more closely resemble plant starch than human glycogen. This Minireview discusses the unique window into glycogen metabolism that LD research offers. It also highlights recent discoveries, including that glycogen contains covalently bound phosphate and that neurons synthesize glycogen and express both glycogen synthase and glycogen phosphorylase

Genome annotation for clinical genomic diagnostics: strengths and weaknesses

The Human Genome Project and advances in DNA sequencing technologies have revolutionized the identification of genetic disorders through the use of clinical exome sequencing. However, in a considerable number of patients, the genetic basis remains unclear. As clinicians begin to consider whole-genome sequencing, an understanding of the processes and tools involved and the factors to consider in the annotation of the structure and function of genomic elements that might influence variant identification is crucial. Here, we discuss and illustrate the strengths and weaknesses of approaches for the annotation and classification of important elements of protein-coding genes, other genomic elements such as pseudogenes and the non-coding genome, comparative-genomic approaches for inferring gene function, and new technologies for aiding genome annotation, as a practical guide for clinicians when considering pathogenic sequence variation. Complete and accurate annotation of structure and function of genome features has the potential to reduce both false-negative (from missing annotation) and false-positive (from incorrect annotation) errors in causal variant identification in exome and genome sequences. Re-analysis of unsolved cases will be necessary as newer technology improves genome annotation, potentially improving the rate of diagnosis

Dissociating anticipation from perception: Acute pain activates default mode network.

Few studies have explored the effect of acute pain on attentional networks and on the default mode network. Moreover, these studies convey conflicting results, seemingly caused by design. To reassess this issue, we studied 20 healthy subjects with functional magnetic resonance imaging while delivering painful electric shocks. The design was purposely constructed to separate rest, anticipation, and pain perception. We found that default mode network activity in response to pain was biphasic. It deactivated during anticipation when the dorsal attentional network was activated. During pain perception, the default mode network was activated, as were attentional networks. The left posterior fusiform gyrus showed the same dynamics as the default mode network, and its activity was negatively correlated to the subject\u27s pain intensity rating. The associative pregenual anterior cingulate cortex seemed to play a key role in these coactivations. These results concur with data from the literature showing that enhanced pain perception results in greater default mode network activity and that the anticorrelation between the default mode network and the dorsal attentional network disappears in chronic pain patients

A High Power Density Power System Electronics for NASA's Lunar Reconnaissance Orbiter

A high power density, modular and state-of-the-art Power System Electronics (PSE) has been developed for the Lunar Reconnaissance Orbiter (LRO) mission. This paper addresses the hardware architecture and performance, the power handling capabilities, and the fabrication technology. The PSE was developed by NASA s Goddard Space Flight Center (GSFC) and is the central location for power handling and distribution of the LRO spacecraft. The PSE packaging design manages and distributes 2200W of solar array input power in a volume less than a cubic foot. The PSE architecture incorporates reliable standard internal and external communication buses, solid state circuit breakers and LiIon battery charge management. Although a single string design, the PSE achieves high reliability by elegantly implementing functional redundancy and internal fault detection and correction. The PSE has been environmentally tested and delivered to the LRO spacecraft for the flight Integration and Test. This modular design is scheduled to flight in early 2009 on board the LRO and Lunar Crater Observation and Sensing Satellite (LCROSS) spacecrafts and is the baseline architecture for future NASA missions such as Global Precipitation Measurement (GPM) and Magnetospheric MultiScale (MMS)

Ariel - Volume 8 Number 3

Executive Editor James W. Lockard, Jr. Business Manager Neeraj K. Kanwal University News Richard J . Perry World News Doug Hiller Opinions Elizabeth A. McGuire Features Patrick P. Sokas Sports Desk Shahab S. Minassian Managing Editor Edward H. Jasper Managing Associate Brenda Peterson Photography Editor Robert D. Lehman. Jr. Graphics Christine M. Kuhnl

Ariel - Volume 8 Number 2

Executive Editor James W. Lockard , Jr. Issue Editor Doug Hiller Business Manager Neeraj K. Kanwal University News Richard J. Perry World News Doug Hiller Opinions Elizabeth A. McGuire Features Patrick P. Sokas Sports Desk Shahab S. Minassian Managing Editor Edward H. Jasper Managing Associate Brenda Peterson Photography Editor Robert D. Lehman, Jr. Graphics Christine M. Kuhnl

The effect of video-guidance on passive movement in patients with cerebral palsy: fMRI study

In patients with cerebral palsy (CP), neuroimaging studies have demonstrated that passive movement and action–observation tasks have in common to share neuronal activation in all or part of areas involved in motor system. Action observation with simultaneous congruent passive movements may have additional effects in the recruitment of brain motor areas. The aim of this functional magnetic resonance imaging (fMRI) study was to examine brain activation in patients with unilateral CP during passive movement with and without simultaneous observation of simple hand movement. Eighteen patients with unilateral CP (fourteen male, mean age 14 years and 2 months) participated in the study. Using fMRI block design, brain activation following passive simple opening–closing hand movement of either the paretic or nonparetic hand with and without simultaneous observation of a similar movement performed by either the left or right hand of an actor was compared. Passive movement of the paretic hand performed simultaneously to the observation of congruent movement activated more “higher motor areas” including contralesional pre-supplementary motor area, superior frontal gyrus (extending to premotor cortex), and superior and inferior parietal regions than nonvideo-guided passive movement of the paretic hand. Passive movement of the paretic hand recruited more ipsilesional sensorimotor areas compared to passive movement of the nonparetic hand. Our study showed that the combination of observation of congruent hand movement simultaneously to passive movement of the paretic hand recruits more motor areas, giving neuronal substrate to propose video-guided passive movement of paretic hand in CP rehabilitation

Classical and Quantum Equations of Motion for a BTZ Black String in AdS Space

We investigate gravitational collapse of a $(3+1)$-dimensional BTZ black string in AdS space in the context of both classical and quantum mechanics. This is done by first deriving the conserved mass per unit length of the cylindrically symmetric domain wall, which is taken as the classical Hamiltonian of the black string. In the quantum mechanical context, we take primary interest in the behavior of the collapse near the horizon and near the origin (classical singularity) from the point of view of an infalling observer. In the absence of radiation, quantum effects near the horizon do not change the classical conclusions for an infalling observer, meaning that the horizon is not an obstacle for him/her. The most interesting quantum mechanical effect comes in when investigating near the origin. First, quantum effects are able to remove the classical singularity at the origin, since the wave function is non-singular at the origin. Second, the Schr\"odinger equation describing the behavior near the origin displays non-local effects, which depend on the energy density of the domain wall. This is manifest in that derivatives of the wavefunction at one point are related to the value of the wavefunction at some other distant point.Comment: 9 pages, 1 figure. Minor Clarification and corrections. Accepted for Publication in JHE