A Comprehensive Review of the 1H-MRS Metabolite Spectrum in Autism Spectrum Disorder

Neuroimaging studies of neuropsychiatric behaviour biomarkers across spectrum disorders are typically based on diagnosis, thus failing to account for the heterogeneity of multi-dimensional spectrum disorders such as autism (ASD). Control group trait phenotypes are also seldom reported. Proton magnetic resonance spectroscopy (1H-MRS) measures the abundance of neurochemicals such as neurotransmitters and metabolites and hence can probe disorder phenotypes at clinical and sub-clinical levels. This detailed review summarises and critiques the current 1H-MRS research in ASD. The literature reports reduced N-acetylaspartate (NAA), glutamate and glutamine (Glx), gamma-aminobutyric acid (GABA), creatine and choline, and increased glutamate for children with ASD. Adult studies are few and results are inconclusive. Overall, the literature has several limitations arising from differences in 1H-MRS methodology and sample demographics. We argue that more consistent methods and greater emphasis on phenotype studies will advance understanding of underlying cortical metabolite disturbance in ASD, and the detection, diagnosis and treatment of ASD and other multi-dimensional psychiatric disorders

Surround-Masking Affects Visual Estimation Ability

Visual estimation of numerosity involves the discrimination of magnitude between two distributions or perceptual sets that vary in number of elements. How performance on such estimation depends on peripheral sensory stimulation is unclear, even in typically developing adults. Here, we varied the central and surround contrast of stimuli that comprised a visual estimation task in order to determine whether mechanisms involved with the removal of unessential visual input functionally contributes toward number acuity. The visual estimation judgments of typically developed adults were significantly impaired for high but not low contrast surround stimulus conditions. The center and surround contrasts of the stimuli also differentially affected the accuracy of numerosity estimation depending on whether fewer or more dots were presented. Remarkably, observers demonstrated the highest mean percentage accuracy across stimulus conditions in the discrimination of more elements when the surround contrast was low and the background luminance of the central region containing the elements was dark (black center). Conversely, accuracy was severely impaired during the discrimination of fewer elements when the surround contrast was high and the background luminance of the central region was mid level (gray center). These findings suggest that estimation ability is functionally related to the quality of low-order filtration of unessential visual information. These surround masking results may help understanding of the poor visual estimation ability commonly observed in developmental dyscalculia

Screening vs. Confinement in 1+1 Dimensions

We show that, in 1+1 dimensional gauge theories, a heavy probe charge is screened by dynamical massless fermions both in the case when the source and the dynamical fermions belong to the same representation of the gauge group and, unexpectedly, in the case when the representation of the probe charge is smaller than the representation of the massless fermions. Thus, a fractionally charged heavy probe is screened by dynamical fermions of integer charge in the massless Schwinger model, and a colored probe in the fundamental representation is screened in $QCD_2$ with adjoint massless Majorana fermions. The screening disappears and confinement is restored as soon as the dynamical fermions are given a non-zero mass. For small masses, the string tension is given by the product of the light fermion mass and the fermion condensate with a known numerical coefficient. Parallels with 3+1 dimensional $QCD$ and supersymmetric gauge theories are discussed.Comment: 29 pages, latex, no figures. slight change in the wording on page 2, references adde

A note on the power divergence in lattice calculations of ΔI=1/2\Delta I = 1/2 K→ππK\to\pi\pi amplitudes at MK=MπM_{K}=M_{\pi}

In this note, we clarify a point concerning the power divergence in lattice calculations of $\Delta I = 1/2$ $K\to\pi\pi$ decay amplitudes. There have been worries that this divergence might show up in the Minkowski amplitudes at $M_{K}=M_{\pi}$ with all the mesons at rest. Here we demonstrate, via an explicit calculation in leading-order Chiral Perturbation Theory, that the power divergence is absent at the above kinematic point, as predicted by CPS symmetry.Comment: 5 pages, 2 figure

Greater magnocellular saccadic suppression in high versus low autistic tendency suggests a causal path to local perceptual style.

Saccadic suppression-the reduction of visual sensitivity during rapid eye movements-has previously been proposed to reflect a specific suppression of the magnocellular visual system, with the initial neural site of that suppression at or prior to afferent visual information reaching striate cortex. Dysfunction in the magnocellular visual pathway has also been associated with perceptual and physiological anomalies in individuals with autism spectrum disorder or high autistic tendency, leading us to question whether saccadic suppression is altered in the broader autism phenotype. Here we show that individuals with high autistic tendency show greater saccadic suppression of low versus high spatial frequency gratings while those with low autistic tendency do not. In addition, those with high but not low autism spectrum quotient (AQ) demonstrated pre-cortical (35-45 ms) evoked potential differences (saccade versus fixation) to a large, low contrast, pseudo-randomly flashing bar. Both AQ groups showed similar differential visual evoked potential effects in later epochs (80-160 ms) at high contrast. Thus, the magnocellular theory of saccadic suppression appears untenable as a general description for the typically developing population. Our results also suggest that the bias towards local perceptual style reported in autism may be due to selective suppression of low spatial frequency information accompanying every saccadic eye movement

I RAN Fast and I Remembered What I Read: The Relationship between Reading, Rapid Automatic Naming, and Auditory and Visual Short-Term Memory

Although rapid automatic naming (RAN) speed and short-term auditory memory are widely recognised as good predictors of reading ability in most age groups, the predictive value of short-term memory for visually presented digits for reading and RAN in young typically developing learner readers (mean age 91.5 months) has seldom been investigated. We found that visual digit span is a better predictor of reading ability than auditory digit span in learner readers. A significant correlation has also been found between RAN speed and visual, but not auditory digit span. These results suggests that RAN speed may be a good predictor of a child's future reading ability and eventual fluency because like visual digit span, it is a measure of rate of access to memory for the visual icons and their semantic name and meaning. The results also suggest that auditory memory is not an important factor in young children learning to read

Fish oil supplementation associated with decreased cellular degeneration and increased cellular proliferation 6 weeks after middle cerebral artery occlusion in the rat

Anti-inflammatory long-chain omega-3 polyunsaturated fatty acids (n-3-LC-PUFAs) are both neuroprotective and have antidepressive effects. However the influence of dietary supplemented n-3-LC-PUFAs on inflammation-related cell death and proliferation after middle cerebral artery occlusion (MCAo)-induced stroke is unknown. We have previously demonstrated that anxiety-like and hyperactive locomotor behaviors are reduced in n-3-LC-PUFA-fed MCAo animals. Thus in the present study, male hooded Wistar rats were exposed to MCAo or sham surgeries and examined behaviorally 6 weeks later, prior to euthanasia and examination of lesion size, cell death and proliferation in the dentate gyrus, cornu ammonis region of the hippocampus of the ipsilesional hemispheres, and the thalamus of the ipsilesional and contralesional hemispheres. Markers of cell genesis and cell degeneration in the hippocampus or thalamus of the ipsilesional hemisphere did not differ between surgery and diet groups 6 weeks post MCAo. Dietary supplementation with n-3-LC-PUFA decreased cell degeneration and increased cell proliferation in the thalamic region of the contralesional hemisphere. MCAo–associated cell degeneration in the hippocampus and thalamus positively correlated with anxiety-like and hyperactive locomotor behaviors previously reported in these animals. These results suggest that anti-inflammatory n-3-LC-PUFA supplementation appears to have cellular protective effects after MCAo in the rat, which may affect behavioral outcomes

Parietal function in good and poor readers

BACKGROUND: While there are many psychophysical reports of impaired magnocellular pathway function in developmental dyslexia (DD), few have investigated parietal function, the major projection of this pathway, in good and poor readers closely matched for nonverbal intelligence. In view of new feedforward-feedback theories of visual processing, impaired magnocellular function raises the question of whether all visually-driven functions or only those associated with parietal cortex functions are equally impaired and if so, whether parietal performance is more closely related to general ability levels than reading ability. METHODS: Reading accuracy and performance on psychophysical tasks purported to selectively activate parietal cortex such as motion sensitivity, attentional tracking, and spatial localization was compared in 17 children with DD, 16 younger reading-age matched (RA) control children, and 46 good readers of similar chronological-age (CA) divided into CA-HighIQ and a CA-LowIQ matched to DD group nonverbal IQ. RESULTS: In the age-matched groups no significant differences were found between DD and CA controls on any of the tasks relating to parietal function, although performance of the DD group and their nonverbal IQ scores was always lower. As expected, CA and RA group comparisons indicated purported parietal functioning improves with age. No difference in performance was seen on any of the parietally driven tasks between the DD and age-nonverbal IQ matched groups, whereas performance differentiated the DD group from the age-matched, higher nonverbal IQ group on several such tasks. An unexpected statistical difference in performance between lower reading age (DD and RA children) and all higher reading age (CA) children was seen on a test of chromatic sensitivity, whereas when high and low nonverbal IQ normal readers were compared performance was not different CONCLUSION: The results indicate that performance on purported parietal functions improves with age and may be more associated with nonverbal mentation than reading accuracy. Performance on a cognitively demanding task, traditionally considered to rely on ventral stream functions, was more related to reading accuracy

Flicker fusion thresholds as a clinical identifier of a magnocellular-deficit dyslexic subgroup.

The magnocellular-dorsal system is well isolated by high temporal frequency. However, temporal processing thresholds have seldom been explored in developmental dyslexia nor its subtypes. Hence, performances on two, four-alternative forced-choice achromatic flicker fusion threshold tasks modulated at low (5%) and high (75%) temporal contrast were compared in dyslexic and neurotypical children individually matched for age and intelligence (8-12 years, n = 54 per group). As expected, the higher modulation resulted in higher flicker fusion thresholds in both groups. Compared to neurotypicals, the dyslexic group displayed significantly lower ability to detect flicker at high temporal frequencies, both at low and high temporal contrast. Yet, discriminant analysis did not adequately distinguish the dyslexics from neurotypicals, on the basis of flicker thresholds alone. Rather, two distinct dyslexic subgroups were identified by cluster analysis - one characterised by significantly lower temporal frequency thresholds than neurotypicals (referred to as 'Magnocellular-Deficit' dyslexics; 53.7%), while the other group ('Magnocellular-Typical' dyslexics; 46.3%) had comparable thresholds to neurotypicals. The two dyslexic subgroups were not differentially associated with phonological or naming speed subtypes and showed comparable mean reading rate impairments. However, correlations between low modulation flicker fusion threshold and reading rate for the two subgroups were significantly different (p = .0009). Flicker fusion threshold performances also showed strong classification accuracy (79.3%) in dissociating the Magnocellular-Deficit dyslexics and neurotypicals. We propose that temporal visual processing impairments characterize a previously unidentified subgroup of dyslexia and suggest that measurement of flicker fusion thresholds could be used clinically to assist early diagnosis and appropriate treatment recommendations for dyslexia