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Losh, M.

Publications and source records attributed to Losh, M..

3 recordsLinked to original sources

Neurophysiological Evidence for Reduced Use of Prior Sound Patterns to Shape Speech Processing in Autism

Reported perceptual differences in autism may arise from reduced use of prior context to shape incoming sensory input. Speech perception provides a critical test of this account because stable perception requires listeners to integrate variable acoustic signals with contextual expectations. This study examined context-dependent modulation of speech encoding in autistic and non-autistic adults using the frequency-following response (FFR), a neurophysiological measure of phase-locked auditory encoding. Participants heard English intonational pitch contours presented in repetitive and variable contexts while EEG was recorded. Principal component analysis of FFR metrics yielded components indexing neural encoding fidelity and timing. Non-autistic participants showed enhanced encoding fidelity in more predictable contexts, whereas autistic participants showed reduced context-dependent modulation. Neural encoding timing also showed divergent context effects across groups, suggesting altered balance between feedback-based predictive mechanisms and locally driven adaptation processes. Within the autistic group, greater context-related modulation of encoding fidelity was associated with lower ADOS-2 Social Affect severity but poorer speech-in-noise perception, suggesting that the functional impact of contextual modulation depends on input reliability and task demands. These findings indicate that context-dependent modulation of speech encoding is altered in autism and may contribute to individual differences in auditory and social-communicative function. Lay SummaryWhen we listen to speech, the brain often uses sounds it has recently heard to help make sense of new ones, which is especially useful in noisy, everyday settings. In this study, autistic adults brains tended to process speech differently, drawing less on recent sound patterns than non-autistic adults, and this difference was related to their autism domain variability and to understanding speech in background noise. These effects were not simply better or worse but depended on the listening conditions, suggesting that natural differences in how the brain uses recent context may shape some of the ways autistic people listen to speech.

neuroscience↗

Elevated polygenic burden for ASD is associated with the broad autism phenotype

BackgroundAutism spectrum disorder (ASD) is a multifactorial, neurodevelopmental disorder that encompasses a complex and heterogeneous set of traits. Subclinical traits that mirror the core features of ASD, referred to as the broad autism phenotype (BAP) have been documented repeatedly in unaffected relatives and are believed to reflect underlying genetic liability to ASD. The BAP may help inform the etiology of ASD by allowing the stratification of families into more phenotypically and etiologically homogeneous subgroups. This study explored polygenic scores related to the BAP. MethodsPhenotypic and genotypic information were obtained from 2,614 trios from Simons Simplex Sample. Polygenic scores of ASD (ASD-PGS) were generated across the sample to determine the shared genetic overlap between the BAP and ASD. Maternal and Paternal ASD-PGS was explored in relation to BAP traits and their child ASD symptomatology. ResultsMaternal pragmatic language was related to childs social communicative atypicalities. In fathers, rigid personality was related to increased repetitive behaviors in children. Maternal (but not paternal) ASD-PGS was related to the pragmatic language and rigid BAP domains. ConclusionsDomain- and sex-specific associations emerged between parent and child phenotypes. ASD-PGS associations emerged with BAP in mothers only, highlighting the potential for a female protective factor, and implicating the polygenic etiology of ASD-related phenotypes in the BAP.

genetics↗

Common Variant Associations with Fragile X Syndrome

Fragile X syndrome is a common cause of intellectual disability. It is usually caused by a de novo mutation which often occur on multiple haplotypes and should not be detectible using genome-wide association (GWA). We conducted GWA 89 male FXS cases and 266 male controls, and detected multiple genome-wide significant signals near FMR1 (odds ratio=8.10, P=2.5x10-10). These findings withstood robust attempts at falsification. Fine-mapping did not serve to narrow the interval (minimum P=1.13xl0-14), and functional genomic integration (including 5C data we generated for this region) did not provide a mechanistic hypothesis. Controls carrying a risk haplotype had significantly longer and more variable FMR1 CGG repeats than controls with the protective haplotype (P=4.75x10-5) which may predispose toward increases in CGG number to the pre-mutation range over many generations. This is a salutary reminder of the complexity of even \"simple\" monogenetic disorders.

genetics↗