Neuroimaging of Real-world Audio-visual Sensory Integration in High-functioning Autism

Sensory processing differences are a prevalent aspect of autism spectrum disorder (ASD) that may contribute to core deficits of ASD such as repetitive behaviors as well as comorbidities including anxiety disorders. The ability to integrate information among our senses is required to comprehend the world around us and is crucial for the development of language, motor skills, and social communication. Prior studies have shown that individuals with autism differ from individuals without autism when presented with simple, non-natural audio-visual stimuli such as basic shapes accompanied by pure tones. Because the human brain processes non-natural and natural stimuli differently, more recent studies have used real-world images paired with a sound. However, the stimuli used in many of these studies were static photos paired with a congruent sound and do not reflect the dynamic nature of a real-world environment. The bulk of studies using dynamic real-world stimuli have investigated language processing by pairing human vocalizations with a human face. However, because face and vocalization stimuli are processed in distinct areas of the brain, dynamic stimuli that contain faces and vocalizations confound investigations of multisensory integration. The remaining studies that used dynamic real-world videos to investigate multisensory integration, have primarily used very short video clips of only a few seconds in length. While these stimuli do represent the natural environment, the short length of these videos lacks the continuous nature of what we see and hear in our environment. Only two studies have used dynamic, real-world stimuli that are continuous to investigate multisensory integration in autism. Unfortunately, the stimuli used in both of these studies contained confounding facial and or language processing. Therefore, we currently do not have a good understanding of how individuals with autism integrate multiple real-world sensory inputs that reflect dynamic natural stimuli encountered in the environment outside of our understanding of language and face processing. Considering the gap in the current literature regarding processing of real-world, dynamic stimuli, the goal of this research was to use functional magnetic resonance imaging (fMRI) to investigate how individuals with autism integrate auditory and visual information of a real-world, dynamic scene. We hypothesized that individuals with high-functioning autism would show different levels of brain activation in regions known to process auditory and visual information as well as in brain areas known to integrate audio-visual information. While undergoing an MRI, participants (ASD n=20 and typically developed controls [TD] n=21) watched a video of a person bouncing a basketball. The person was filmed from the neck down to avoid engaging face processing brain regions while viewing the video. To ensure engagement, a simple attention task was used and was easily accomplished by both groups. Analysis of the fMRI data showed that the ASD group had significantly less brain activation in left-lateralized intraparietal sulcus and putamen/globus pallidus. These brain regions are known to be involved in processing human biological motion and regulating motor movements respectively. The hypoactivation seen in the ASD group may reflect underconnectivity between and within the hemispheres for processing this dynamic audio-visual stimulus. These data support the Underconnectivity Theory of Autism which posits long-distance networks are underconnected in individuals with autism contributing to global processing deficits

Meta-analyses support a taxonomic model for representations of different categories of audio-visual interaction events in the human brain

Our ability to perceive meaningful action events involving objects, people and other animate agents is characterized in part by an interplay of visual and auditory sensory processing and their cross-modal interactions. However, this multisensory ability can be altered or dysfunctional in some hearing and sighted individuals, and in some clinical populations. The present meta-analysis sought to test current hypotheses regarding neurobiological architectures that may mediate audio-visual multisensory processing. Reported coordinates from 82 neuroimaging studies (137 experiments) that revealed some form of audio-visual interaction in discrete brain regions were compiled, converted to a common coordinate space, and then organized along specific categorical dimensions to generate activation likelihood estimate (ALE) brain maps and various contrasts of those derived maps. The results revealed brain regions (cortical “hubs”) preferentially involved in multisensory processing along different stimulus category dimensions, including (1) living versus non-living audio-visual events, (2) audio-visual events involving vocalizations versus actions by living sources, (3) emotionally valent events, and (4) dynamic-visual versus static-visual audio-visual stimuli. These meta-analysis results are discussed in the context of neurocomputational theories of semantic knowledge representations and perception, and the brain volumes of interest are available for download to facilitate data interpretation for future neuroimaging studies

Divergent Human Cortical Regions for Processing Distinct Acoustic-Semantic Categories of Natural Sounds: Animal Action Sounds vs. Vocalizations

A major gap in our understanding of natural sound processing is knowledge of where or how in a cortical hierarchy differential processing leads to categorical perception at a semantic level. Here, using functional magnetic resonance imaging (fMRI) we sought to determine if and where cortical pathways in humans might diverge for processing action sounds vs. vocalizations as distinct acoustic-semantic categories of real-world sound when matched for duration and intensity. This was tested by using relatively less semantically complex natural sounds produced by non-conspecific animals rather than humans. Our results revealed a striking double-dissociation of activated networks bilaterally. This included a previously well described pathway preferential for processing vocalization signals directed laterally from functionally defined primary auditory cortices to the anterior superior temporal gyri, and a less well-described pathway preferential for processing animal action sounds directed medially to the posterior insulae. We additionally found that some of these regions and associated cortical networks showed parametric sensitivity to high-order quantifiable acoustic signal attributes and/or to perceptual features of the natural stimuli, such as the degree of perceived recognition or intentional understanding. Overall, these results supported a neurobiological theoretical framework for how the mammalian brain may be fundamentally organized to process acoustically and acoustic-semantically distinct categories of ethologically valid, real-world sounds

Inter-species differences in polychlorinated biphenyls patterns from five sympatric species of odontocetes : Can PCBs be used as tracers of feeding ecology?

The authors gratefully acknowledge the assistance of volunteers from the Galician (CEMMA) and Portuguese (SPVS) stranding networks. The authors would like to thank R. Gallois and C. Trichet for their participation on total lipid content analysis. P. Méndez-Fernandez was supported during the research period through a PhD grant from the Fundação do Ministério de Ciência e Tecnologia de Portugal and ANIMATE project (SFRH/BD/36766/2007) and through a Science Without Borders (CSF) young talent postdoctoral grant of the Brazilian government. G. J. Pierce acknowledges support from the EU ANIMATE project (MEXC-CT-2006-042337), University of Aveiro and Caixa Geral de Depósitos (Portugal).Peer reviewedPostprin

Efficacy and Safety of Vamorolone in Duchenne Muscular Dystrophy: A 30-Month Nonrandomized Controlled Open-Label Extension Trial

Importance: Vamorolone is a synthetic steroidal drug with potent anti-inflammatory properties. Initial open-label, multiple ascending dose-finding studies of vamorolone among boys with Duchenne muscular dystrophy (DMD) found significant motor function improvement after 6 months treatment in higher-dose (ie, ≥2.0 mg/kg/d) groups. / Objective: To investigate outcomes after 30 months of open-label vamorolone treatment. / Design, Setting, and Participants: This nonrandomized controlled trial was conducted by the Cooperative International Neuromuscular Research Group at 11 US and non-US study sites. Participants were 46 boys ages 4.5 to 7.5 years with DMD who completed the 6-month dose-finding study. Data were analyzed from July 2020 through November 2021. / Interventions: Participants were enrolled in a 24-month, long-term extension (LTE) study with vamorolone dose escalated to 2.0 or 6.0 mg/kg/d. / Main Outcomes and Measures: Change in time-to-stand (TTSTAND) velocity from dose-finding baseline to end of LTE study was the primary outcome. Efficacy assessments included timed function tests, 6-minute walk test, and NorthStar Ambulatory Assessment (NSAA). Participants with DMD treated with glucocorticoids from the Duchenne Natural History Study (DNHS) and NorthStar United Kingdom (NSUK) Network were matched and compared with participants in the LTE study receiving higher doses of vamorolone. / Results: Among 46 boys with DMD who completed the dose-finding study, 41 boys (mean [SD] age, 5.33 [0.96] years) completed the LTE study. Among 21 participants treated with higher-dose (ie, ≥2.0 mg/kg/d) vamorolone consistently throughout the 6-month dose-finding and 24-month LTE studies with data available at 30 months, there was a decrease in mean (SD) TTSTAND velocity from baseline to 30 months (0.206 [0.070] rises/s vs 0.189 (0.124) rises/s), which was not a statistically significant change (-0.011 rises/s; CI, -0.068 to 0.046 rises/s). There were no statistically significant differences between participants receiving higher-dose vamorolone and matched participants in the historical control groups receiving glucocorticoid treatment (75 patients in DNHS and 110 patients in NSUK) over a 2-year period in NSAA total score change (0.22 units vs NSUK; 95% CI, -4.48 to 4.04]; P = .92), body mass index z score change (0.002 vs DNHS SD/mo; 95% CI, -0.006 to 0.010; P = .58), or timed function test change. Vamorolone at doses up to 6.0 mg/kg/d was well tolerated, with 5 of 46 participants discontinuing prematurely and for reasons not associated with study drug. Participants in the DNHS treated with glucocorticoids had significant growth delay in comparison with participants treated with vamorolone who had stable height percentiles (0.37 percentile/mo; 95% CI, 0.23 to 0.52 percentile/mo) over time. / Conclusions and Relevance: This study found that vamorolone treatment was not associated with a change in TTSTAND velocity from baseline to 30 months among boys with DMD aged 4 to 7 years at enrollment. Vamorolone was associated with maintenance of muscle strength and function up to 30 months, similar to standard of care glucocorticoid therapy, and improved height velocity compared with growth deceleration associated with glucocorticoid treatment, suggesting that vamorolone may be an attractive candidate for treatment of DMD. Trial Registration: ClinicalTrials.gov Identifier: NCT03038399

Assessment of the toxicological status of small cetacean species from the North West Iberian Peninsula

27th Conference of the European Cetacean Society, Interdisciplinary Approaches in the Study of Marine Mammals, 8th-10th April 2013, Setúbal, PortugalIn order to determine the contamination status and vulnerability of five of the most frequent small cetaceans from the NW Iberian Peninsula (NWIP) (common dolphin Delphinus delphis, harbour porpoise Phocoena phocoena, bottlenose dolphin Tursiops truncatus, striped dolphin Stenella coeruleoalba and long-finned pilot whale Globicephala melas), 32 congeners of polychlorinated biphenyls (PCBs) were analysed in their blubber and 14 trace elements (Ag, As, Cd, Co, Cu, Cr, Fe, Hg, Mn, Ni, Pb, Se, V, Zn) in liver and kidneyN

Taxonomic and Functional Microbial Signatures of the Endemic Marine Sponge Arenosclera brasiliensis

The endemic marine sponge Arenosclera brasiliensis (Porifera, Demospongiae, Haplosclerida) is a known source of secondary metabolites such as arenosclerins A-C. In the present study, we established the composition of the A. brasiliensis microbiome and the metabolic pathways associated with this community. We used 454 shotgun pyrosequencing to generate approximately 640,000 high-quality sponge-derived sequences (∼150 Mb). Clustering analysis including sponge, seawater and twenty-three other metagenomes derived from marine animal microbiomes shows that A. brasiliensis contains a specific microbiome. Fourteen bacterial phyla (including Proteobacteria, Cyanobacteria, Actinobacteria, Bacteroidetes, Firmicutes and Cloroflexi) were consistently found in the A. brasiliensis metagenomes. The A. brasiliensis microbiome is enriched for Betaproteobacteria (e.g., Burkholderia) and Gammaproteobacteria (e.g., Pseudomonas and Alteromonas) compared with the surrounding planktonic microbial communities. Functional analysis based on Rapid Annotation using Subsystem Technology (RAST) indicated that the A. brasiliensis microbiome is enriched for sequences associated with membrane transport and one-carbon metabolism. In addition, there was an overrepresentation of sequences associated with aerobic and anaerobic metabolism as well as the synthesis and degradation of secondary metabolites. This study represents the first analysis of sponge-associated microbial communities via shotgun pyrosequencing, a strategy commonly applied in similar analyses in other marine invertebrate hosts, such as corals and algae. We demonstrate that A. brasiliensis has a unique microbiome that is distinct from that of the surrounding planktonic microbes and from other marine organisms, indicating a species-specific microbiome

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Impaired immune responses in the lungs of aged mice following influenza infection

<p>Abstract</p> <p>Background</p> <p>Each year, influenza virus infection causes severe morbidity and mortality, particularly in the most susceptible groups including children, the elderly (>65 years-old) and people with chronic respiratory diseases. Among the several factors that contribute to the increased susceptibility in elderly populations are the higher prevalence of chronic diseases (<it>e.g</it>. diabetes) and the senescence of the immune system.</p> <p>Methods</p> <p>In this study, aged and adult mice were infected with sublethal doses of influenza virus (A/Puerto Rico/8/1934). Differences in weight loss, morbidity, virus titer and the kinetics of lung infiltration with cells of the innate and adaptive immune responses were analyzed. Additionally, the main cytokines and chemokines produced by these cells were also assayed.</p> <p>Results</p> <p>Compared to adult mice, aged mice had higher morbidity, lost weight more rapidly, and recovered more slowly from infection. There was a delay in the accumulation of granulocytic cells and conventional dendritic cells (cDCs), but not macrophages in the lungs of aged mice compared to adult animals. The delayed infiltration kinetics of APCs in aged animals correlated with alteration in their activation (CD40 expression), which also correlated with a delayed detection of cytokines and chemokines in lung homogenates. This was associated with retarded lung infiltration by natural killer (NK), CD4⁺and CD8⁺T-cells. Furthermore, the percentage of activated (CD69+) influenza-specific and IL-2 producer CD8+ T-cells was higher in adult mice compared to aged ones. Additionally, activation (CD69+) of adult B-cells was earlier and correlated with a quicker development of neutralizing antibodies in adult animals.</p> <p>Conclusion</p> <p>Overall, alterations in APC priming and activation lead to delayed production of cytokines and chemokines in the lungs that ultimately affected the infiltration of immune cells following influenza infection. This resulted in delayed activation of the adaptive immune response and subsequent delay in clearance of virus and prolonged illness in aged animals. Since the elderly are the fastest growing segment of the population in developed countries, a better understanding of the changes that occur in the immune system during the aging process is a priority for the development of new vaccines and adjuvants to improve the immune responses in this population.</p