44 research outputs found

    Preserved white matter microstructure in young patients with anorexia nervosa?

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    A massive but reversible reduction of cortical thickness and subcortical gray matter (GM) volumes in Anorexia Nervosa (AN) has been recently reported. However, the literature on alterations in white matter (WM) volume and microstructure changes in both acutely underweight AN (acAN) and after recovery (recAN) is sparse and results are inconclusive. Here, T1-weighted and diffusion-weighted MRI data in a sizable sample of young and medication-free acAN (n = 35), recAN (n = 32), and age-matched female healthy controls (HC, n = 62) were obtained. For analysis, a well-validated global probabilistic tractography reconstruction algorithm including rigorous motion correction implemented in FreeSurfer: TRACULA (TRActs Constrained by UnderLying Anatomy) were used. Additionally, a clustering algorithm and a multivariate pattern classification technique to WM metrics to predict group membership were applied. No group differences in either WM volume or WM microstructure were detected with standard analysis procedures either in acAN or recAN relative to HC after controlling for the number of performed statistical tests. These findings were not affected by age, IQ, or psychiatric symptoms. While cluster analysis was unsuccessful at discriminating between groups, multivariate pattern classification showed some ability to separate acAN from HC (but not recAN from HC). However, these results were not compatible with a straightforward hypothesis of impaired WM microstructure. The current findings suggest that WM integrity is largely preserved in non-chronic AN. This finding stands in contrast to findings in GM, but may help to explain the relatively intact cognitive performance of young patients with AN and provide the basis for the fast recovery of GM structures. Hum Brain Mapp 37:4069–4083, 2016. © 2016 Wiley Periodicals, Inc

    In Vivo Time- Resolved Microtomography Reveals the Mechanics of the Blowfly Flight Motor

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    Dipteran flies are amongst the smallest and most agile of flying animals. Their wings are driven indirectly by large power muscles, which cause cyclical deformations of the thorax that are amplified through the intricate wing hinge. Asymmetric flight manoeuvres are controlled by 13 pairs of steering muscles acting directly on the wing articulations. Collectively the steering muscles account for <3% of total flight muscle mass, raising the question of how they can modulate the vastly greater output of the power muscles during manoeuvres. Here we present the results of a synchrotron-based study performing micrometre-resolution, time-resolved microtomography on the 145 Hz wingbeat of blowflies. These data represent the first four-dimensional visualizations of an organism's internal movements on sub-millisecond and micrometre scales. This technique allows us to visualize and measure the three-dimensional movements of five of the largest steering muscles, and to place these in the context of the deforming thoracic mechanism that the muscles actuate. Our visualizations show that the steering muscles operate through a diverse range of nonlinear mechanisms, revealing several unexpected features that could not have been identified using any other technique. The tendons of some steering muscles buckle on every wingbeat to accommodate high amplitude movements of the wing hinge. Other steering muscles absorb kinetic energy from an oscillating control linkage, which rotates at low wingbeat amplitude but translates at high wingbeat amplitude. Kinetic energy is distributed differently in these two modes of oscillation, which may play a role in asymmetric power management during flight control. Structural flexibility is known to be important to the aerodynamic efficiency of insect wings, and to the function of their indirect power muscles. We show that it is integral also to the operation of the steering muscles, and so to the functional flexibility of the insect flight motor

    Enhancing studies of the connectome in autism using the autism brain imaging data exchange II

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    The second iteration of the Autism Brain Imaging Data Exchange (ABIDE II) aims to enhance the scope of brain connectomics research in Autism Spectrum Disorder (ASD). Consistent with the initial ABIDE effort (ABIDE I), that released 1112 datasets in 2012, this new multisite open-data resource is an aggregate of resting state functional magnetic resonance imaging (MRI) and corresponding structural MRI and phenotypic datasets. ABIDE II includes datasets from an additional 487 individuals with ASD and 557 controls previously collected across 16 international institutions. The combination of ABIDE I and ABIDE II provides investigators with 2156 unique cross-sectional datasets allowing selection of samples for discovery and/or replication. This sample size can also facilitate the identification of neurobiological subgroups, as well as preliminary examinations of sex differences in ASD. Additionally, ABIDE II includes a range of psychiatric variables to inform our understanding of the neural correlates of co-occurring psychopathology; 284 diffusion imaging datasets are also included. It is anticipated that these enhancements will contribute to unraveling key sources of ASD heterogeneity

    Novel genetic loci associated with hippocampal volume

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    The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg =-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness

    Genetic architecture of subcortical brain structures in 38,851 individuals

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    Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease

    Novel genetic loci underlying human intracranial volume identified through genome-wide association

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    Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five novel loci for intracranial volume and confirmed two known signals. Four of the loci are also associated with adult human stature, but these remained associated with intracranial volume after adjusting for height. We found a high genetic correlation with child head circumference (ρgenetic=0.748), which indicated a similar genetic background and allowed for the identification of four additional loci through meta-analysis (Ncombined = 37,345). Variants for intracranial volume were also related to childhood and adult cognitive function, Parkinson’s disease, and enriched near genes involved in growth pathways including PI3K–AKT signaling. These findings identify biological underpinnings of intracranial volume and provide genetic support for theories on brain reserve and brain overgrowth

    The genetic architecture of the human cerebral cortex

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    The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

    Vision-based flight control and stabilisation in hawkmoths

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    Insects are inherently unstable and therefore rely on sensory feedback in order to maintain flight control and stability. This thesis focuses on how the hawkmoth Manduca sexta uses visual feedback to control and stabilise flight. The analysis is based on extensive sampling of the optomotor responses. I use a virtual reality flight simulator to measure the total moment that the moths generate in response to oscillating wide-field stimuli. The visual stimuli simulate rotations of different amplitudes and frequencies about six different body axes. The moment responses depend upon stimulus amplitude, so are fundamentally non-linear. Nevertheless, for a fixed and suitably small stimulus amplitude, it is possible to fit a linear PID-controller with time delay to each of the optomotor responses. The analysis shows that the moths rely on proportional and integral feedback of angular velocity, with different time delays about different rotation axes. This varying time delay prevents spatial superposition of the optomotor responses to lateral rotational stimuli, meaning that there is no general control law that predicts the responses to an arbitrary lateral stimulus. By combining these empirically derived vision-based flight controllers with linearised flight dynamic models of hovering M. sexta, I evaluate their performance in providing flight stability. This analysis suggests that visual feedback is sufficient to stabilise disturbances associated with rotational stimuli about the horizontal roll and dorso-ventral axes, but is insufficient to stabilise disturbances associated with rotational stimuli about the pitch axis, vertical yaw axis, and longitudinal body axis. The time delay of the optomotor response has a substantial influence on the superposition of the measured optomotor responses, and strongly affects the predicted flight stability. The findings presented in this work have implications for understanding not only the mechanisms and functionality of flight control in hawkmoths, but also the results of past and future investigations into vision-based flight control in insects and flapping-wing air vehicles.</p

    Mineralization pathways of organic matter deposited in a river-lake transition of the Rhone River Delta, Lake Geneva

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    During the éLEMO endeavour (a research project in which the Russian MIR submersibles were used for studying Lake Geneva) four sediment cores were retrieved on a transect from the delta of the Rhone River towards the profundal part of the lake. The degradation pathways of organic material (OM) were investigated considering different electron acceptors. Essentially, OM at the delta sites had a higher fraction of terrestrial material than the lake sites indicated by higher C/N ratios, and higher long-chain n-alkane and alcohol concentrations. The concentrations of chlorins were higher at the distant sites indicating more easily degradable OM in the sediments. However, the chlorin index that was used to determine the degradation state of the OM material indicated that pigment derived OM of deltaic sediments was less degraded than that of the profundal sediments. The fluxes of reduced species from the sediments decreased from the delta to the profundal for CH4 (from 2.3 to 0.5 mmol m−2 d−1) and NH4+ (from 0.31 to 0.13 mmol m−2 d−1). Fluxes of Fe(II) and Mn(II), however, increased although they were generally very low (between 9 × 10−5 and 7.6 × 10−3 mmol m−2 d−1). Oxygen concentration profiles in the pore waters revealed lower fluxes close to the river inflow with 4.3 and 4.1 mmol m−2 d−1 compared to two times higher fluxes at the profundal sites (8.8 and 8.2 mmol m−2 d−1). The rates for totally mineralized OM (Rtotal) at the shallower sites (4.7 mmol C m−2 d−1) were only half of those of the deeper sites (9.7 mmol C m−2 d−1). Accordingly, not only the rates but also the mineralization pathways differed between the shallow and profundal sites. Whereas only 0–6% of the OM was mineralized aerobically at the shallow sites (since almost all O2 was used to oxidize the large flux of CH4 from below) the situation was reversed at the deeper sites and the fraction of aerobically degraded OM was 72–78%. We found a better efficiency in CH4 production per carbon equivalent deposited at the deeper sites as a result of the higher degradability of the mainly autochthonous OM in spite of the lower deposition rate and the higher degradation state of the OM compared to the delta sites.ISSN:2050-7887ISSN:2050-789

    Four-dimensional in vivo X-ray microscopy with projection-guided gating

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    Visualizing fast micrometer scale internal movements of small animals is a key challenge for functional anatomy, physiology and biomechanics. We combine phase contrast tomographic microscopy (down to 3.3 μm voxel size) with retrospective, projection-based gating (in the order of hundreds of microseconds) to improve the spatiotemporal resolution by an order of magnitude over previous studies. We demonstrate our method by visualizing 20 three-dimensional snapshots through the 150 Hz oscillations of the blowfly flight motor.ISSN:2045-232
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