Sensory processing in autism spectrum disorders and Fragile X syndrome-From the clinic to animal models.

Brains are constantly flooded with sensory information that needs to be filtered at the pre-attentional level and integrated into endogenous activity in order to allow for detection of salient information and an appropriate behavioral response. People with Autism Spectrum Disorder (ASD) or Fragile X Syndrome (FXS) are often over- or under-reactive to stimulation, leading to a wide range of behavioral symptoms. This altered sensitivity may be caused by disrupted sensory processing, signal integration and/or gating, and is often being neglected. Here, we review translational experimental approaches that are used to investigate sensory processing in humans with ASD and FXS, and in relevant rodent models. This includes electroencephalographic measurement of event related potentials, neural oscillations and mismatch negativity, as well as habituation and pre-pulse inhibition of startle. We outline robust evidence of disrupted sensory processing in individuals with ASD and FXS, and in respective animal models, focusing on the auditory sensory domain. Animal models provide an excellent opportunity to examine common mechanisms of sensory pathophysiology in order to develop therapeutics

Far-UV Emissions of the Sun in Time: Probing Solar Magnetic Activity and Effects on Evolution of Paleo-Planetary Atmospheres

We present and analyze FUSE observations of six solar analogs. These are single, main-sequence G0-5 strs selected as proxies for the Sun at several stages of its main-sequence lifetime. The emission features in the FUSE 920-1180 A wavelength range allow for a critical probe of the hot plasma over three decades in temperature. Using the flux ratio CIII 1176/977 as diagnostics, we investigate the dependence of the electron pressure of the transition region as a function of the rotation period, age and magnetic activity. The results from these solar proxies indicate that the electron pressure of the stellar ~10^5-K plasma decreases by a factor of about 70 between the young, fast-rotating magnetically active star and the old, slow-rotating inactive star. Also, the observations indicate that the average surface fluxes of emission features strongly decrease with increasing stellar age and longer rotation period. The emission flux evolution with age or rotation period is well fitted by power laws, which become steeper from cooler chromospheric (10^4 K) to hotter coronal (10^7 K) plasma. The relationship for the integrated (920-1180 A) FUSE flux indicates that the solar far-ultraviolet emissions were about twice the present value 2.5 Gyr ago and about 4 times the present value 3.5 Gyr ago. Note also that the FUSE/FUV flux of the Zero-Age Main Sequence Sun could have been higher by as much as 50 times. Our analysis suggests that the strong FUV emissions of the young Sun may have played a crucial role in the developing planetary system, in particular through the photoionization, photochemical evolution and possible erosion of the planetary atmospheres. (abridged)Comment: 15 pages, 8 figures, accepted for publication in Ap

Efficacy of different types of cognitive enhancers for patients with schizophrenia. A meta-analysis

Cognitive impairment is a core feature of schizophrenia, which is predictive for functional outcomes and is, therefore, a treatment target in itself. Yet, literature on efficacy of different pharmaco-therapeutic options is inconsistent. This quantitative review provides an overview of studies that investigated potential cognitive enhancers in schizophrenia. We included pharmacological agents, which target different neurotransmitter systems and evaluated their efficacy on overall cognitive functioning and seven separate cognitive domains. In total, 93 studies with 5630 patients were included. Cognitive enhancers, when combined across all different neurotransmitter systems, which act on a large number of different mechanisms, showed a significant (yet small) positive effect size of 0.10 (k = 51, p = 0.023; 95% CI = 0.01 to 0.18) on overall cognition. Cognitive enhancers were not superior to placebo for separate cognitive domains. When analyzing each neurotransmitter system separately, agents acting predominantly on the glutamatergic system showed a small significant effect on overall cognition (k = 29, Hedges’ g = 0.19, p = 0.01), as well as on working memory (k = 20, Hedges’ g = 0.13, p = 0.04). A sub-analysis of cholinesterase inhibitors (ChEI) showed a small effect on working memory (k = 6, Hedges’ g = 0.26, p = 0.03). Other sub-analyses were positively nonsignificant, which may partly be due to the low number of studies we could include per neurotransmitter system. Overall, this meta-analysis showed few favorable effects of cognitive enhancers for patients with schizophrenia, partly due to lack of power. There is a lack of studies involving agents acting on other than glutamatergic and cholinergic systems, especially of those targeting the dopaminergic system

STUDENTS' PERCEPTIONS OF THE INCIDENCE OF BURN-OUT AMONG THEIR TEACHERS

research paperThe aim was to explore students' perceptions of teacher burn-out in relation to the incidence of disruptive student classroom behaviour and teachers' competence to cope with it. A random sample of students from a Regional Training Centre participated. First, it was shown that the Maslach Burnout Inventory, the Coping with Disruptive Behaviour Scale and the Perceived Disruptive Behaviour Scale could be adapted for students to report symptoms of burn-out perceived among their teachers, the occurrence of perceived disruptive student behaviour and the students' perception of their teachers' ability to cope with such behaviour. Second, students' perceptions do not differ according to their age. Third, a significant difference was found between the perceptions of male and female students in respect of emotional exhaustion and depersonalisation, but not in respect of personal achievement. Finally, a considerable percentage of variance on each of the three burn-out dimensions is explained by teachers' ability to cope with student disruptive behaviour and perceived disruptive student behaviour. Students' perceptions of their teachers appear to contribute valid information on the mental health of the latter. It is advisable for future research into teacher burn-out to be based both on the teachers' self-reports and on the students' reports

The Search for Super-saturation in Chromospheric Emission

We investigate if the super-saturation phenomenon observed at X-ray wavelengths for the corona, exists in the chromosphere for rapidly rotating late-type stars. Moderate resolution optical spectra of fast rotating EUV- and X-ray- selected late-type stars were obtained. Stars in alpha Per were observed in the northern hemisphere with the Isaac Newton 2.5 m telescope and IDS spectrograph. Selected objects from IC 2391 and IC 2602 were observe in the southern hemisphere with the Blanco 4m telescope and R-C spectrograph at CTIO. Ca II H & K fluxes were measured for all stars in our sample. We find the saturation level for Ca II K at log(L_CaK/L_bol) = -4.08. The Ca II K flux does not show a decrease as a function of increased rotational velocity or smaller Rossby number as observed in the X-ray. This lack of "super-saturation" supports the idea of coronal-stripping as the cause of saturation and super-saturation in stellar chromospheres and corona, but the detailed underlying mechanism is still under investigation.Comment: 28 Pages, 6 figures, 1 Table; Accepted in ApJ for Aug 201

Preference for biological motion is reduced in ASD: implications for clinical trials and the search for biomarkers.

BACKGROUND: The neurocognitive mechanisms underlying autism spectrum disorder (ASD) remain unclear. Progress has been largely hampered by small sample sizes, variable age ranges and resulting inconsistent findings. There is a pressing need for large definitive studies to delineate the nature and extent of key case/control differences to direct research towards fruitful areas for future investigation. Here we focus on perception of biological motion, a promising index of social brain function which may be altered in ASD. In a large sample ranging from childhood to adulthood, we assess whether biological motion preference differs in ASD compared to neurotypical participants (NT), how differences are modulated by age and sex and whether they are associated with dimensional variation in concurrent or later symptomatology. METHODS: Eye-tracking data were collected from 486 6-to-30-year-old autistic (N = 282) and non-autistic control (N = 204) participants whilst they viewed 28 trials pairing biological (BM) and control (non-biological, CTRL) motion. Preference for the biological motion stimulus was calculated as (1) proportion looking time difference (BM-CTRL) and (2) peak look duration difference (BM-CTRL). RESULTS: The ASD group showed a present but weaker preference for biological motion than the NT group. The nature of the control stimulus modulated preference for biological motion in both groups. Biological motion preference did not vary with age, gender, or concurrent or prospective social communicative skill within the ASD group, although a lack of clear preference for either stimulus was associated with higher social-communicative symptoms at baseline. LIMITATIONS: The paired visual preference we used may underestimate preference for a stimulus in younger and lower IQ individuals. Our ASD group had a lower average IQ by approximately seven points. 18% of our sample was not analysed for various technical and behavioural reasons. CONCLUSIONS: Biological motion preference elicits small-to-medium-sized case-control effects, but individual differences do not strongly relate to core social autism associated symptomatology. We interpret this as an autistic difference (as opposed to a deficit) likely manifest in social brain regions. The extent to which this is an innate difference present from birth and central to the autistic phenotype, or the consequence of a life lived with ASD, is unclear

Haloperidol differentially modulates prepulse inhibition and p50 suppression in healthy humans stratified for low and high gating levels

Schizophrenia patients exhibit deficits in sensory gating as indexed by reduced prepulse inhibition (PPI) and P50 suppression, which have been linked to psychotic symptom formation and cognitive deficits. Although recent evidence suggests that atypical antipsychotics might be superior over typical antipsychotics in reversing PPI and P50 suppression deficits not only in schizophrenia patients, but also in healthy volunteers exhibiting low levels of PPI, the impact of typical antipsychotics on these gating measures is less clear. To explore the impact of the dopamine D2-like receptor system on gating and cognition, the acute effects of haloperidol on PPI, P50 suppression, and cognition were assessed in 26 healthy male volunteers split into subgroups having low vs high PPI or P50 suppression levels using a placebo-controlled within-subject design. Haloperidol failed to increase PPI in subjects exhibiting low levels of PPI, but attenuated PPI in those subjects with high sensorimotor gating levels. Furthermore, haloperidol increased P50 suppression in subjects exhibiting low P50 gating and disrupted P50 suppression in individuals expressing high P50 gating levels. Independently of drug condition, high PPI levels were associated with superior strategy formation and execution times in a subset of cognitive tests. Moreover, haloperidol impaired spatial working memory performance and planning ability. These findings suggest that dopamine D2-like receptors are critically involved in the modulation of P50 suppression in healthy volunteers, and to a lesser extent also in PPI among subjects expressing high sensorimotor gating levels. Furthermore, the results suggest a relation between sensorimotor gating and working memory performance

Macroscale EEG characteristics in antipsychotic-naïve patients with first-episode psychosis and healthy controls

Electroencephalography in patients with a first episode of psychosis (FEP) may contribute to the diagnosis and treatment response prediction. Findings in the literature vary due to small sample sizes, medication effects, and variable illness duration. We studied macroscale resting-state EEG characteristics of antipsychotic naïve patients with FEP. We tested (1) for differences between FEP patients and controls, (2) if EEG could be used to classify patients as FEP, and (3) if EEG could be used to predict treatment response to antipsychotic medication. In total, we studied EEG recordings of 62 antipsychotic-naïve patients with FEP and 106 healthy controls. Spectral power, phase-based and amplitude-based functional connectivity, and macroscale network characteristics were analyzed, resulting in 60 EEG variables across four frequency bands. Positive and Negative Symptom Scale (PANSS) were assessed at baseline and 4–6 weeks follow-up after treatment with amisulpride or aripiprazole. Mann-Whitney U tests, a random forest (RF) classifier and RF regression were used for statistical analysis. Our study found that at baseline, FEP patients did not differ from controls in any of the EEG characteristics. A random forest classifier showed chance-level discrimination between patients and controls. The random forest regression explained 23% variance in positive symptom reduction after treatment in the patient group. In conclusion, in this largest antipsychotic- naïve EEG sample to date in FEP patients, we found no differences in macroscale EEG characteristics between patients with FEP and healthy controls. However, these EEG characteristics did show predictive value for positive symptom reduction following treatment with antipsychotic medication

Resting state EEG power spectrum and functional connectivity in autism: a cross-sectional analysis

BACKGROUND: Understanding the development of the neuronal circuitry underlying autism spectrum disorder (ASD) is critical to shed light into its etiology and for the development of treatment options. Resting state EEG provides a window into spontaneous local and long-range neuronal synchronization and has been investigated in many ASD studies, but results are inconsistent. Unbiased investigation in large and comprehensive samples focusing on replicability is needed. METHODS: We quantified resting state EEG alpha peak metrics, power spectrum (PS, 2-32 Hz) and functional connectivity (FC) in 411 children, adolescents and adults (n = 212 ASD, n = 199 neurotypicals [NT], all with IQ > 75). We performed analyses in source-space using individual head models derived from the participants' MRIs. We tested for differences in mean and variance between the ASD and NT groups for both PS and FC using linear mixed effects models accounting for age, sex, IQ and site effects. Then, we used machine learning to assess whether a multivariate combination of EEG features could better separate ASD and NT participants. All analyses were embedded within a train-validation approach (70%-30% split). RESULTS: In the training dataset, we found an interaction between age and group for the reactivity to eye opening (p = .042 uncorrected), and a significant but weak multivariate ASD vs. NT classification performance for PS and FC (sensitivity 0.52-0.62, specificity 0.59-0.73). None of these findings replicated significantly in the validation dataset, although the effect size in the validation dataset overlapped with the prediction interval from the training dataset. LIMITATIONS: The statistical power to detect weak effects-of the magnitude of those found in the training dataset-in the validation dataset is small, and we cannot fully conclude on the reproducibility of the training dataset's effects. CONCLUSIONS: This suggests that PS and FC values in ASD and NT have a strong overlap, and that differences between both groups (in both mean and variance) have, at best, a small effect size. Larger studies would be needed to investigate and replicate such potential effects