Biology subjects

Pelphrey, K.

Publications and source records attributed to Pelphrey, K..

6 recordsLinked to original sources

bioRxiv2026

Sex-Dependent Alterations in Fusiform Face Area Activation During Emotional Face Processing in Autism

Atypical processing of emotional faces has been proposed as a characteristic of Autism Spectrum Disorder (ASD), but functional neuroimaging research has yielded inconsistent findings. Prior work is limited in generalizability due to methodological heterogeneity, imbalanced or small sample sizes, and underrepresentation of females. The present study examined functional brain activation during the Hariri Emotional Face-Matching Task (EFMT) in a large, sex-balanced sample of both typically developing and ASD participants (n=295, 8-18 years old) from the multi-site Autism Center of Excellence GENDAAR project. Using an ROI-driven approach, we targeted the right FFA, right OFA, right pSTS, and bilateral amygdala, we investigated whether ASD diagnosis was associated with atypical regional activation when viewing emotional faces, and if these differences were generalizable across sexes. Results revealed a group-by-sex interaction in the right FFA, driven by divergence of ASD males from the ASD female and typically developing participants. Generally, ASD females did not diverge greatly from typically developing populations. These findings suggest that atypical face processing is present, but meaningfully modulated by sex, underscoring the importance of sex-balanced, well-powered developmental samples in autism.

neuroscience↗

bioRxiv2025

Altered aperiodic EEG spectral power during speech perception task is associated with verbal communication in youths with Autism Spectrum Disorder

Most children with Autism Spectrum Disorder (ASD) have co-occurring language impairment, but its neural mechanisms are not well known. Excitation (E) / inhibition (I) imbalance is considered as a key neurobiological mechanism of ASD, and several electroencephalography (EEG)-based E/I balance metrics have been proposed in the previous studies. The goal of the present research was to focus on these metrics abstracted from the speech perception task to investigate their relation to language/communication in autistic youths. We used a high-density 128-channel EEG to register neural responses during speech perception task in the sex- and age-matched groups of youths with ASD (N = 162) and typically developing (TD) controls (N = 144), aged 7-18 years old. The results revealed alterations in the E/I measures in the ASD group, pointing to a higher level of excitation or neural noise in the cortex as well as broadband reduction of spectral power during speech perception. A greater neural noise reflected in the reduction of aperiodic exponent and offset was associated with lower verbal communication skills in youths with ASD. The findings suggested that the higher noisiness in the cortical systems may be a relevant marker to monitor in relation to language/communication in ASD.

neuroscience↗

bioRxiv2023

Enhancer-driven regulatory network of forebrain human development provides insights into autism

Cell differentiation is orchestrated by transcription factors (TFs) binding to enhancers, shaping gene regulatory networks that drive neuronal lineage specification. Deciphering these enhancer-driven networks in human forebrain development is essential for understanding the genetic basis of neurodevelopmental disorders. Through integrative epigenomic and transcriptomic analyses of human forebrain organoids derived from 10 individuals with autism spectrum disorder (ASD) and their neurotypical fathers, we constructed a comprehensive enhancer-driven gene regulatory network (GRN) of early neurodevelopment. This GRN revealed hierarchical regulatory transitions guiding neuronal differentiation and was experimentally validated via CRISPR interference (CRISPRi) and loss-of-function analyses. A subnetwork linked ASD-associated transcriptomic alterations to dysregulated TF activity, implicating FOXG1, BHLHE22, EOMES, and NEUROD2 as key regulators of excitatory neuron specification in macrocephalic ASD. These findings suggest that ASD disrupts enhancer-driven regulatory frameworks, altering neuronal cell fate decisions in the developing fetal brain.

genomics↗

bioRxiv2022

Intrinsic Neural Timescales in Autism Spectrum Disorder and Schizophrenia. A Replication and Direct Comparison Study

Intrinsic neural timescales (INT) reflect the duration for which brain areas store information. A posterior - anterior hierarchy of increasingly longer INT has been revealed in both typically developed individuals (TD), as well as patients diagnosed with autism spectrum disorder (ASD) and schizophrenia (SZ), though INT are, overall, shorter in both patient groups. In the present study, we attempted to replicate previously reported group differences by comparing INT of TD to ASD and SZ. We replicated the previously reported result showing reduced INT in the left lateral occipital gyrus and the right post-central gyrus in SZ compared to TD. For the first time, we also directly compared the INT of the two patient groups and found that these same two areas show significantly reduced INT in SZ compared to ASD. In ASD, significant correlations were found between INT and their clinical and phenotypic characteristics. Our results point to the left lateral occipital gyrus and the right post-central gyrus as holding potential for further diagnostic refinement of SZ.

neuroscience↗

bioRxiv2022

ASD modelling in organoids reveals imbalance of excitatory cortical neuron subtypes during early neurogenesis

There is no clear genetic etiology or convergent pathophysiology for autism spectrum disorders (ASD). Using cortical organoids and single-cell transcriptomics, we modeled alterations in the formation of the forebrain between sons with idiopathic ASD and their unaffected fathers in thirteen families. Alterations in the transcriptome suggest that ASD pathogenesis in macrocephalic and normocephalic probands involves an opposite disruption of the balance between the excitatory neurons of the dorsal cortical plate and other lineages such as the early-generated neurons from the putative preplate. The imbalance stemmed from a divergent expression of transcription factors driving cell fate during early cortical development. While we did not find probands genomic variants explaining the observed transcriptomic alterations, a significant overlap between altered transcripts and reported ASD risk genes affected by rare variants suggests a degree of gene convergence between rare forms of ASD and developmental transcriptome in idiopathic ASD.

neuroscience↗

bioRxiv2019

Neurocognitive mechanisms of social inferences in typical and autistic adolescents

BackgroundMany of our efforts in social interactions are dedicated to learning about others. Adolescents with autism have core deficits in social learning, but a mechanistic understanding of these deficits and how they relate to neural development is lacking. The current study aimed to specify how adolescents with and with autism represent and acquire social knowledge and how these processes are implemented in neural activity. MethodsTypically developing (TD) adolescents (N=26) and adolescents with autism (N=20) rated in the MR scanner how much three peers liked a variety of items and received trial-by-trial feedback about the peers actual preference ratings. In a separate study, we established the preferences of a new sample of adolescents (N=99), used to examine population preference structures. Using computational models, we tested whether participants in the MR study relied on preference structures during learning and how model predictions were implemented in brain activity. ResultsTD adolescents relied on average population preferences and prediction error (PE) updating. Importantly, PE updating was scaled by the similarity between items. In contrast, preferences of adolescents with autism were best described by a No-learning model that relied only on participants own preferences for each item. Model predictions were encoded in neural activity. TD adolescents encoded PEs in the putamen and adolescents with autism showed greater encoding of own preferences in the angular gyrus. ConclusionsWe specified how adolescents represent and update social knowledge during learning. Our findings indicate that adolescents with ASD rely only on their own preferences when making social inferences.

neuroscience↗