Differential effect of a distractor on primary saccades and perceptual localization

AbstractA distractor presented nearby the target of a goal-directed short latency saccade leads to spatial averaging, that is, the saccade lands between the target and the distractor. This so-called global effect is a characteristic feature of the spatial processing underlying the programming of saccadic eye movements. To determine whether this effect of near distractors on saccade metrics is also reflected in perceptual localization, subjects performed a saccade task and a perceptual localization task using identical, briefly flashed visual stimuli. To make the available visual processing time for saccades and perception more similar, we followed the target with a mask.Without the mask, primary saccades with short latency landed between target and distractor. The distractor had less effect on primary saccades with longer latencies (>200 ms) and did not affect the final eye position after late secondary saccades in the dark. This indicates that the oculomotor system can correctly use information about the target location 200 ms after the target flash even if no visual stimulus is present during this period. Likewise the presence of a distractor did not affect perceptual localization.Under the masking condition a similar global effect occurred for primary saccades with short latencies, but the latency dependence of the global effect was weakened. Secondary saccades and perceptual localization still did not show a global effect. The results suggest that the primary saccade is based on a specific target acquisition process that differs from that used for spatial perception and for the programming of memory-guided corrective saccades

Rigorous elimination of fast stochastic variables from the linear noise approximation using projection operators

The linear noise approximation (LNA) offers a simple means by which one can study intrinsic noise in monostable biochemical networks. Using simple physical arguments, we have recently introduced the slow-scale LNA (ssLNA) which is a reduced version of the LNA under conditions of timescale separation. In this paper, we present the first rigorous derivation of the ssLNA using the projection operator technique and show that the ssLNA follows uniquely from the standard LNA under the same conditions of timescale separation as those required for the deterministic quasi-steady state approximation. We also show that the large molecule number limit of several common stochastic model reduction techniques under timescale separation conditions constitutes a special case of the ssLNA.Comment: 10 pages, 1 figure, submitted to Physical Review E; see also BMC Systems Biology 6, 39 (2012

Phase diagram and phase transitions in ferroelectric tris-sarcosine calcium chloride and its brominated isomorphs

Tris-sarcosine calcium chloride [(TSCC), (CH3NHCH2COOH)3CaCl2] is a uniaxial ferroelectric (FE) with a displacive second-order phase transition near Tc=130 K. A continuous range of solid solutions can be made by substituting Br for Cl, which lowers Tc to 0 K at ∼72% Br. Such a quantum critical point differs from that in pseudocubic FEs, such as O-18 SrTiO3 or doped KTaO3. For many years, this system was thought to have only two phases, paraelectric and FE, at ambient pressure. However, we find from dielectric and resonant ultrasound spectroscopy that there are four phase transitions in TSCC and in TSCC:Br (for 0 < Br < 40%): Order-disorder of the sarcosine methyl group at 185 K; displacive FE transition at 130 K (in pure TSCC); a second FE transition [previously hypothesized to be antiferroelectric (AFE) but probably not] at 64 K; and a new anomaly at ∼45 K which might be due to a phase transition or to Debye-like freezing of orientational disorder of some part of the sarcosine molecule. The probable sequence of structures is (upon cooling): Pnma with Z=4(D2h16) ambient 500 K > T > 185 K, disordered; Pnma with Z=4(D2h16)185 K>T>130 K (ordered); Pn21a with Z=4(C2v9)130 K>T>64 K (FE); P21a (C2h5) with Z =4, 64 K > T > 45 K (not AFE); T < 45 K, unknown structure. A sixth hexagonal structure at high temperatures (>500 K) is hypothesized to be D6h3(P63/mcm) with Z =2, but the samples decompose first at 503 K (230 °C)

Altered top-down and bottom-up processing of fear conditioning in panic disorder with agoraphobia

Background: Although several neurophysiological models have been proposed for panic disorder with agoraphobia (PD/AG), there is limited evidence from functional magnetic resonance imaging (fMRI) studies on key neural networks in PD/AG. Fear conditioning has been proposed to represent a central pathway for the development and maintenance of this disorder; however, its neural substrates remain elusive. The present study aimed to investigate the neural correlates of fear conditioning in PD/AG patients. Method: The blood oxygen level-dependent (BOLD) response was measured using fMRI during a fear conditioning task. Indicators of differential conditioning, simple conditioning and safety signal processing were investigated in 60 PD/AG patients and 60 matched healthy controls. Results: Differential conditioning was associated with enhanced activation of the bilateral dorsal inferior frontal gyrus (IFG) whereas simple conditioning and safety signal processing were related to increased midbrain activation in PD/AG patients versus controls. Anxiety sensitivity was associated positively with the magnitude of midbrain activation. Conclusions: The results suggest changes in top-down and bottom-up processes during fear conditioning in PD/AG that can be interpreted within a neural framework of defensive reactions mediating threat through distal (forebrain) versus proximal (midbrain) brain structures. Evidence is accumulating that this network plays a key role in the aetiopathogenesis of panic disorder

converging evidence from an intermediate phenotype approach

Representing a phylogenetically old and very basic mechanism of inhibitory neurotransmission, glycine receptors have been implicated in the modulation of behavioral components underlying defensive responding toward threat. As one of the first findings being confirmed by genome-wide association studies for the phenotype of panic disorder and agoraphobia, allelic variation in a gene coding for the glycine receptor beta subunit (GLRB) has recently been associated with increased neural fear network activation and enhanced acoustic startle reflexes. On the basis of two independent healthy control samples, we here aimed to further explore the functional significance of the GLRB genotype (rs7688285) by employing an intermediate phenotype approach. We focused on the phenotype of defensive system reactivity across the levels of brain function, structure, and physiology. Converging evidence across both samples was found for increased neurofunctional activation in the (anterior) insular cortex in GLRB risk allele carriers and altered fear conditioning as a function of genotype. The robustness of GLRB effects is demonstrated by consistent findings across different experimental fear conditioning paradigms and recording sites. Altogether, findings provide translational evidence for glycine neurotransmission as a modulator of the brain’s evolutionary old dynamic defensive system and provide further support for a strong, biologically plausible candidate intermediate phenotype of defensive reactivity. As such, glycine-dependent neurotransmission may open up new avenues for mechanistic research on the etiopathogenesis of fear and anxiety disorders

Very late-onset neuromyelitis optica spectrum disorder beyond the age of 75

Aquaporin-4 antibody (AQP4-Ab)-positive neuromyelitis optica spectrum disorder (NMOSD) is a rare but often severe autoimmune disease with median onset around 40 years of age. We report characteristics of three very-late-onset NMOSD (including complete NMO) patients >75 years of age, in whom this diagnosis initially seemed unlikely because of their age and age-associated concomitant diseases, and briefly review the literature. All three patients, aged 79, 82 and 88 years, presented with a spinal cord syndrome as the first clinical manifestation of AQP4-Ab-positive NMOSD. They all had severe relapses unless immunosuppressive therapy was initiated, and one untreated patient died of a fatal NMOSD course. Two patients developed side effects of immunosuppression. We conclude that a first manifestation of NMOSD should be considered even in patients beyond the age of 75 years with a compatible syndrome, especially longitudinally extensive myelitis. Early diagnosis and treatment are feasible and highly relevant. Special attention is warranted in the elderly to recognize adverse effects of immunosuppressive therapies as early as possible

The Potential of Physical Exercise to Mitigate Radiation Damage—A Systematic Review

There is a need to investigate new countermeasures against the detrimental effects of ionizing radiation as deep space exploration missions are on the horizon.Objective: In this systematic review, the effects of physical exercise upon ionizing radiation-induced damage were evaluated.Methods: Systematic searches were performed in Medline, Embase, Cochrane library, and the databases from space agencies. Of 2,798 publications that were screened, 22 studies contained relevant data that were further extracted and analyzed. Risk of bias of included studies was assessed. Due to the high level of heterogeneity, meta-analysis was not performed. Five outcome groups were assessed by calculating Hedges' g effect sizes and visualized using effect size plots.Results: Exercise decreased radiation-induced DNA damage, oxidative stress, and inflammation, while increasing antioxidant activity. Although the results were highly heterogeneous, there was evidence for a beneficial effect of exercise in cellular, clinical, and functional outcomes.Conclusions: Out of 72 outcomes, 68 showed a beneficial effect of physical training when exposed to ionizing radiation. As the first study to investigate a potential protective mechanism of physical exercise against radiation effects in a systematic review, the current findings may help inform medical capabilities of human spaceflight and may also be relevant for terrestrial clinical care such as radiation oncology.</jats:p