Resting-State Brain Network Dysfunctions Associated With Visuomotor Impairments in Autism Spectrum Disorder

This work is licensed under a Creative Commons Attribution 4.0 International License.Background: Individuals with autism spectrum disorder (ASD) show elevated levels of motor variability that are associated with clinical outcomes. Cortical–cerebellar networks involved in visuomotor control have been implicated in postmortem and anatomical imaging studies of ASD. However, the extent to which these networks show intrinsic functional alterations in patients, and the relationship between intrinsic functional properties of cortical–cerebellar networks and visuomotor impairments in ASD have not yet been clarified. Methods: We examined the amplitude of low-frequency fluctuation (ALFF) of cortical and cerebellar brain regions during resting-state functional MRI (rs-fMRI) in 23 individuals with ASD and 16 typically developing (TD) controls. Regions of interest (ROIs) with ALFF values significantly associated with motor variability were identified for for patients and controls respectively, and their functional connectivity (FC) to each other and to the rest of the brain was examined. Results: For TD controls, greater ALFF in bilateral cerebellar crus I, left superior temporal gyrus, left inferior frontal gyrus, right supramarginal gyrus, and left angular gyrus each were associated with greater visuomotor variability. Greater ALFF in cerebellar lobule VIII was associated with less visuomotor variability. For individuals with ASD, greater ALFF in right calcarine cortex, right middle temporal gyrus (including MT/V5), left Heschl's gyrus, left post-central gyrus, right pre-central gyrus, and left precuneus was related to greater visuomotor variability. Greater ALFF in cerebellar vermis VI was associated with less visuomotor variability. Individuals with ASD and TD controls did not show differences in ALFF for any of these ROIs. Individuals with ASD showed greater posterior cerebellar connectivity with occipital and parietal cortices relative to TD controls, and reduced FC within cerebellum and between lateral cerebellum and pre-frontal and other regions of association cortex. Conclusion: Together, these findings suggest that increased resting oscillations within visuomotor networks in ASD are associated with more severe deficits in controlling variability during precision visuomotor behavior. Differences between individuals with ASD and TD controls in the topography of networks showing relationships to visuomotor behavior suggest atypical patterns of cerebellar–cortical specialization and connectivity in ASD that underlies previously documented visuomotor deficits.NIMH K23 (MH092696)NIMH R01 (MH112734)Kansas Center for Autism Research and Training (K-CART) Research Investment Council Strategic Initiative GrantNICHD U54 Kansas Intellectual and Developmental Disabilities Research Center Award (U54HD090216)National Natural Science Foundation of China Award (grant no. 81371527

Neuroanatomical abnormalities in first-episode psychosis across independent samples: a multi-centre mega-analysis

Background. Neuroanatomical abnormalities in first-episode psychosis (FEP) tend to be sub tle and widespread. The vast majority of previous studies have used small samples, and there fore may have been underpowered. In addition, most studies have examined participants at a single research site, and therefore the results may be specific to the local sample investigated. Consequently, the findings reported in the existing literature are highly heterogeneous. This study aimed to overcome these issues by testing for neuroanatomical abnormalities in indivi duals with FEP that are expressed consistently across several independent samples. Methods. Structural Magnetic Resonance Imaging data were acquired from a total of 572 FEP and 502 age and gender comparable healthy controls at five sites. Voxel-based morphometry was used to investigate differences in grey matter volume (GMV) between the two groups. Statistical inferences were made at p < 0.05 after family-wise error correction for multiple comparisons. Results. FEP showed a widespread pattern of decreased GMV in fronto-temporal, insular and occipital regions bilaterally; these decreases were not dependent on anti-psychotic medication. The region with the most pronounced decrease – gyrus rectus – was negatively correlated with the severity of positive and negative symptoms. Conclusions. This study identified a consistent pattern of fronto-temporal, insular and occipi tal abnormalities in five independent FEP samples; furthermore, the extent of these alterations is dependent on the severity of symptoms and duration of illness. This provides evidence for reliable neuroanatomical alternations in FEP, expressed above and beyond site-related differ ences in anti-psychotic medication, scanning parameters and recruitment criteri

Conjoint and dissociated structural and functional abnormalities in first-episode drug-naive patients with major depressive disorder: a multimodal meta-analysis

Published MRI evidence of structural and resting-state functional brain abnormalities in MDD has been inconsistent. To eliminate interference by repeated disease episodes and antidepressant treatment, we conducted the first multimodal voxel-wise meta-analysis of studies of voxel-based morphometry (VBM) and the amplitude of low-frequency fluctuation (ALFF) in first-episode drug-naive MDD patients, using the Seed-based d Mapping method (SDM). Fifteen VBM data sets and 11 ALFF data sets were included. SDM-based multimodal meta-analysis was used to highlight brain regions with both structural and functional abnormalities. This identified conjoint structural and functional abnormalities in left lateral orbitofrontal cortex and right supplementary motor area, and also dissociated abnormalities of structure (decreased grey matter in right dorsolateral prefrontal cortex and right inferior temporal gyrus; increased grey matter in right insula, right putamen, left temporal pole, and bilateral thalamus) and function (increased brain activity in left supplementary motor area, left parahippocampal gyrus, and hippocampus; decreased brain activity in right lateral orbitofrontal cortex). This study reveals a complex pattern of conjoint and dissociated structural and functional abnormalities, supporting the involvement of basal ganglia-thalamocortical circuits, representing emotional, cognitive and psychomotor abnormalities, in the pathophysiology of early-stage MDD. Specifically, this study adds to Psychoradiology, an emerging subspecialty of radiology, which seems primed to play a major clinical role in guiding diagnostic and treatment planning decisions in patients with mental disorder

Polysaccharide-based nanomedicines for cancer immunotherapy: a review

Cancer immunotherapy is an effective antitumor approach through activating immune systems to eradicate tumors by immunotherapeutics. However, direct administration of “naked” immunotherapeutic agents (such as nucleic acids, cytokines, adjuvants or antigens without delivery vehicles) often results in: (1) an unsatisfactory efficacy due to suboptimal pharmacokinetics; (2) strong toxic and side effects due to low targeting (or off-target) efficiency. To overcome these shortcomings, a series of polysaccharide-based nanoparticles have been developed to carry immunotherapeutics to enhance antitumor immune responses with reduced toxicity and side effects. Polysaccharides are a family of natural polymers that hold unique physicochemical and biological properties, as they could interact with immune system to stimulate an enhanced immune response. Their structures offer versatility in synthesizing multifunctional nanocomposites, which could be chemically modified to achieve high stability and bioavailability for delivering therapeutics into tumor tissues. This review aims to highlight recent advances in polysaccharide-based nanomedicines for cancer immunotherapy and propose new perspectives on the use of polysaccharide-based immunotherapeutics.info:eu-repo/semantics/publishedVersio

Microstructural Abnormalities in Children with Post-traumatic Stress Disorder: A Diffusion Tensor Imaging Study at 3.0T

Posttraumatic stress disorder (PTSD) is a severe anxiety disorder characterized by re-experiencing, avoidance and hyperarousal. Brain microstructure abnormalities in PTSD, especially in children, are not yet well characterized. The aim of this study was to use MR diffusion tensor imaging (DTI) to identify brain microstructure alterations in children with PTSD compared to non-PTSD controls who experienced the same time-limited trauma. We studied 27 children with PTSD and 24 age- and gender-matched traumatized controls without PTSD, who all experienced the 2008 Sichuan major earthquake. DTI data were acquired and analyzed in terms of fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity (AD). Children with PTSD showed an abnormal pattern, not only of FA, but also of the diffusivity measures MD, AD and RD. Most of the abnormal brain regions belonged to two important networks: the default-mode network, including precuneus and angular gyrus and the salience network, including insula, putamen and thalamus. This DTI study identifies microstructural abnormalities of children with PTSD after a major earthquake, our results are consistent with the suggestion that pediatric PTSD is accompanied by a connectivity disequilibrium between the salience and default-mode networks, a finding of potential pathophysiological significance

Altered Functional Connectivity in an Aged Rat Model of Postoperative Cognitive Dysfunction: A Study Using Resting-State Functional MRI

BACKGROUND: Postoperative cognitive impairment is a common complication after cardiac and major non-cardiac surgery in the elderly, but its causes and mechanisms remain unclear. The purpose of the current study was to use resting-state functional magnetic resonance imaging (fMRI) to explore changes in the functional connectivity, i.e. the synchronization of low frequency fluctuation (LFF), in an animal model of cognitive impairment in aged rats. METHODS: Aged (22 months) rats were anaesthetized with 40 µg/kg fentanyl and 500 µg/kg droperidol (intraperitoneal) for splenectomy. Cognitive function was assessed using Y maze prior to operation and on postoperative days 1, 3 and 9. To evaluate functional connectivity, resting-state fMRI data were acquired using a 3T MR imaging system with a 4 channel phase array rat head coil. RESULTS: Cognitive function was impaired at postoperative days 1 and 3 compared with preoperative. Significant synchronized LFF was detected bilaterally in the primary somatosensory cortex and hippocampus preoperatively. By contrast, no significant LFF synchronization was detected in the right primary somatosensory cortex and right hippocampus on postoperative days 1 and 3, although the pattern of functional connectivity had become almost normal by day 9. CONCLUSION: Splenectomy performed under neuroleptic anaesthesia triggers a cognitive decline that is associated with altered spontaneous neuronal activity in the cortex and hippocampus

Brain grey matter volume alterations associated with antidepressant response in major depressive disorder

Not all patients with major depressive disorder respond to adequate pharmacological therapy. Psychoradiological studies have reported that antidepressant responders and nonresponders show different alterations in brain grey matter, but the findings are inconsistent. The present study reports a meta-analysis of voxel-based morphometric studies of patients with major depressive disorder, both antidepressant responders and nonresponders, using the anisotropic effect size version of Seed-based D Mapping to identify brain regions correlated to clinical response. A systematic search was conducted up to June 2016 to identify studies focussing on antidepressant response. In responders across 9 datasets grey matter volume (GMV) was significantly higher in the left inferior frontal gyrus and insula, while GMV was significantly lower in the bilateral anterior cingulate cortex (ACC) and the right superior frontal gyrus (SFG). In nonresponders across 5 datasets GMV was significantly lower in the bilateral ACC, median cingulate cortex (MCC) and right SFG. Conjunction analysis confirmed significant differences in the bilateral ACC and right SFG, where GMV was significantly lower in nonresponders but higher in responders. The current study adds to psychoradiology, an evolving subspecialty of radiology mainly for psychiatry and clinical psychology

Large-scale dysfunctional white matter and grey matter networks in patients with social anxiety disorder.

Dysfunction of large-scale brain networks has been implicated in social anxiety disorder (SAD); most work has focused on grey matter (GM) functional connectivity (FC) abnormalities, whereas white matter (WM) FC alterations remain unclear. Here, using a K-means clustering algorithm, we obtained 8 GM and 10 WM functional networks from a cohort dataset (48 SAD patients and 48 healthy controls). By calculating and comparing FC matrices between SAD group and healthy controls, we demonstrated disrupted connections between the limbic and dorsal prefrontal, lateral temporal, and sensorimotor networks, and between the visual and sensorimotor networks. Furthermore, there were negative correlations between HAMD scores and limbic-dorsal prefrontal and limbic-sensorimotor networks, and between illness duration and sensorimotor-visual networks. These findings reflect the critical role of limbic network, with its extensive connections to other networks, and the neurobiology of disordered cognition processing and emotional regulation in SAD