Biology subjects

Chawarska, K.

Publications and source records attributed to Chawarska, K..

9 recordsLinked to original sources

bioRxiv2025

Functional connectivity in the social perception pathway at birth is linked with attention to faces at 4 months

BackgroundProcessing faces and speech is supported by the right-lateralized social visual perception pathway (social pathway) involving medial temporal/visual 5 area (MT/V5) and superior temporal sulcus (STS). Little is known about development of the social pathway and its links with later social outcomes. We examined intrinsic functional connectivity (iFC) in the right social pathway in neurotypical neonates, compared it with iFC in the left social and bilateral dorsal attention pathways, and interrogated prospective links between iFC and social attention in neurodiverse neonates. MethodsiFC in the social and dorsal pathways was measured in 517 full-term neonates from the developing Human Connectome Project (dHCP) and 73 full-term Yale neonates [Mage=41.5 weeks (SD=1.9)]. Social attention was assessed in 36 Yale neonates at Mage=4.2 months (SD=0.4) months. ResultsIn the dHCP sample, the iFC indices were positive in all the pathways (all p-values < 0.001) and did not vary by sex [all p>0.275], but the iFC in the right-lateralized social pathway was higher than in the remaining pathways [all p<0.001] and was positively associated with age at scan [r(517)=0.251, p<0.011]. In the prospective neurodiverse Yale sample, the iFC in the right social pathway was positively associated with social attention at 4 months [p=0.007], and greater social attention at 4 months predicted better social functioning in the second year [p=0.010]. ConclusionsThe early development of intrinsic functional connectivity in the right social perception pathway represents an area of interest for identifying neural mechanisms underlying emergence of atypical social attention associated with autism.

neuroscience↗

bioRxiv2025

White-matter controllability at birth predicts social engagement and language outcomes in toddlerhood

Social engagement and language are connected through early development. Alterations in their development can have a prolonged impact on childrens lives. However, the role of white matter at birth in this ongoing connection is less well-known. Here, we investigate how white matter at birth jointly supports social engagement and language outcomes in 642 infants. We use edge-centric network control theory to quantify edge controllability, or the ability of white-matter connections to drive transitions between diverse brain states, at 1 month. Next, we used connectome-based predictive modeling (CPM) to predict the Quantitative Checklist for Autism in Toddlers (Q-CHAT) for social engagement risks and the Bayley Scales of Infant and Toddler Development (BSID-III) for language skills at 18 months from edge controllability. We created the social engagement network (SEN) to predict Q-CHAT scores and the language network (LAN) to predict BSID-III scores. The SEN and LAN were complex, spanning the whole brain. They also significantly overlapped in anatomy and generalized across measures. Controllability in the SEN at 1 month partially mediated associations between Q-CHAT and BSID-III language scores at 18 months. Further, controllability in the SEN significantly differed between term and preterm infants and predicted Q-CHAT scores in an external sample of preterm infants. Together, our results suggest that the intertwined nature of social engagement and language development is rooted in an infants white-matter controllability. Significance StatementDuring infancy and toddlerhood, social engagement and language emerge together. Delays are often observed in both simultaneously. These interactions persist into later childhood, potentially affecting life quality. We reveal that the interplay between social engagement and language milestones in toddlerhood is rooted in the infants structural connectivity, which may assist in early risk identification of developmental delays. Insights into the early brain foundations for emerging social engagement and language skills may open opportunities for individualized interventions to improve developmental outcomes.

neuroscience↗

bioRxiv2024

Disruption of the Social Visual Pathway in Autism Spectrum Disorder

The social visual pathway, which diverges from the dorsal pathway at the visual motion area (MT/V5) and runs from posterior down to anterior portions of the superior temporal sulcus (STS), specializes in processing dynamic social information. This study examined resting-state functional connectivity within this pathway in children with autism spectrum disorder (ASD) and typically developing (TD) children. Using data from the ABIDE (Autism Brain Imaging Data Exchange) repository, we found significant underconnectivity between the posterior and middle STS (pSTS-mSTS) in the right hemisphere in children with ASD compared to TD children. Weaker connectivity in this region of the pathway correlated with more severe social impairment symptoms in ASD and reduced social function across both ASD and TD groups. These findings suggest a specific disruption in the right hemisphere social visual pathway in ASD, potentially contributing to social deficits observed in the disorder.

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

Developmental trajectories of the default mode, executive control, and salience networks from the third trimester through the newborn period

Social cognition is critical to early learning. Functional imaging studies in adults and older children suggest the involvement of the default mode (DMN), executive control (ECN), and salience (SAL) networks in social cognition. These networks are vulnerable to environmental insults, and abnormalities of intra- and inter-network connectivity of the three are emerging as biomarkers of neurobehavioral disorders. However, the developmental trajectories of the DMN, ECN, and SAL across the third trimester of gestation and perinatal transition remain largely unknown. Employing resting-state functional MRI studies at 30-32, 34-36, and 40-44 weeks postmenstrual age (PMA), we tested the hypothesis that both intra- and inter-network functional connectivity in the DMN, ECN, and SAL develop across the 30-46 weeks PMA time interval in a longitudinal/cross-sectional sample of 84 fetuses and neonates. A secondary analysis addressed the impact of maternal mental health assessed at 28 weeks PMA on tri-network development from 30-46 weeks PMA. The DMN, ECN, and SAL develop across the third trimester of gestation and the first postnatal month. At the intra-network level, significant increases occurred between 36 to 44 weeks PMA for all three, with network strength values significantly different from 0 beginning at 40 weeks PMA for all. Functional connectivity increased less rapidly in the DMN than in the ECN and SAL networks, suggesting slower maturation of the network subserving social interactions. In contrast, significant inter-network DMN - ECN connectivity greater than 0 was found from 36 weeks PMA through the first postnatal month, suggesting the emergence of inter-network functional connectivity in the fetal brain. Finally, higher maternal mental health symptoms measured at the beginning of the third trimester negatively affected the developmental trajectory of the SAL network across the critical time interval of 30 weeks to 44 weeks PMA. Together, these data provide a framework to compare fetuses and neonates at risk for neurobehavioral disorders and assess the impact of the environment on the developing brain.

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↗

bioRxiv2022

Hypoconnectivity between anterior insula and amygdala in neonates with familial history of autism

BackgroundAltered resting state functional connectivity (FC) involving the anterior insula (aINS), a key node in the salience network, has been reported consistently in autism. MethodHere we examined, for the first time, FC between the aINS and the whole brain in a sample of full-term, postmenstrual age (PMA) matched neonates (mean 44.0 weeks, SD=1.5) who due to family history have high likelihood (HL) for developing autism (n=12) and in controls (n=41) without family history of autism (low likelihood, LL). Behaviors associated with autism were evaluated between 12 and 18 months (M=17.3 months, SD=2.5) in a subsample (25/53) of participants using the First Year Inventory (FYI). ResultsCompared to LL controls, HL neonates showed hypoconnectivity between left aINS and left amygdala. Lower connectivity between the two nodes was associated with higher FYI risk scores in the social domain (r(25) = -.561, p=.003) and this association remained robust when maternal mental health factors were considered. Considering that a subsample of LL participants (n=14/41) underwent brain imaging during the fetal period at PMA 31 and 34 weeks, in an exploratory analysis, we evaluated prospectively development of the LaINS-Lamy connectivity and found that the two areas strongly coactivate throughout the third trimester of pregnancy. ConclusionsThe study identifies left lateralized anterior insula - amygdala connectivity as a potential target of further investigation into neural circuitry that enhances likelihood of future onset of social behaviors associated with autism during neonatal and potentially prenatal periods.

neuroscience↗

bioRxiv2020

Implementation of a pre- and in-scan system to minimize head motion in pediatric participants undergoing fMRI scans

BackgroundPerforming fMRI scans of children can be a difficult task, as participants tend to move while being scanned. Head motion represents a significant confound in functional magnetic resonance imaging (fMRI) connectivity analyses, and methods to limit the impact of movement on data quality are needed. One approach has been to use shorter MRI protocols, though this potentially reduces the reliability of the results. ObjectiveHere we describe steps we have taken to limit head motion in an ongoing fMRI study of children undergoing a 60 minute MRI scan protocol. Specifically, we have used a mock scan protocol that trains participants to lie still while being scanned. We provide a detailed protocol and describe other in-scanner measures we have implemented, including an incentive system and the use of a weighted blanket. Materials and methodsParticipants who received a formal mock scan (n = 12) were compared to participants who had an informal mock scan (n = 7). A replication group of participants (n = 16), including five with autism spectrum disorder, who received a formal mock scan were also compared to the informal mock scan group. The primary measure of interest was the mean frame-to-frame displacement across eight functional runs during the fMRI protocol. ResultsParticipants in the formal mock scan and replication group tended to exhibit more low-motion functional scans than the informal mock scan group (P < 0.05). Across different functional scan conditions (i.e. while watching movie clips, performing an attention task, and during resting-state scans), effect sizes tended to be large (Hedges g > 0.8). ConclusionResults indicate that with appropriate measures, it is possible to achieve low-motion fMRI data in younger participants undergoing a long scan protocol.

neuroscience↗

bioRxiv2019

Within Visit Test-Retest Reliability of EEG Profiles in Children with Autism Spectrum Disorder and Typical Development

Biomarker development is currently a high priority in neurodevelopmental disorder research. For many types of biomarkers (particularly biomarkers of diagnosis), reliability over short time periods is critically important. In the field of autism spectrum disorder (ASD), resting electroencephalography (EEG) power spectral densities (PSD) are well-studied for their potential as biomarkers. Classically, such data have been decomposed into pre-specified frequency bands (e.g., delta, theta, alpha, beta, and gamma). Recent technical advances, such as the Fitting Oscillations and One-Over-F (FOOOF) algorithm, allow for targeted characterization of the features that naturally emerge within an EEG PSD, permitting a more detailed characterization of the frequency band-agnostic shape of each individuals EEG PSD. Here, using two resting EEGs collected a median of 6 days apart from 22 children with ASD and 25 typically developing (TD) controls during the Feasibility Visit of the Autism Biomarkers Consortium for Clinical Trials, we estimate within visit test-retest reliability based on characterization of the PSD shape in two ways: (1) Using the FOOOF algorithm we estimate six parameters (offset, slope, number of peaks, and amplitude, center frequency and bandwidth of the largest alpha peak) that characterize the shape of the EEG PSD; and (2) using nonparametric functional data analyses, we decompose the shape of the EEG PSD into a reduced set of basis functions that characterize individual power spectrum shapes. We show that individuals exhibit idiosyncratic PSD signatures that are stable over recording sessions using both characterizations. Our data show that EEG activity from a brief two-minute recording provides an efficient window into understanding brain activity at the single-subject level with desirable psychometric characteristics that persist across different analytical decomposition methods. This is a necessary step towards analytical validation of biomarkers based on the EEG PSD, and provides insights into parameters of the PSD that offer short-term reliability (and thus promise as potential biomarkers of trait or diagnosis) versus those that are more variable over the short term (and thus may index state or other rapidly dynamic measures of brain function). Future research should address longer-term stability of the PSD, for purposes such as monitoring development or response to treatment.

neuroscience↗