Biology subjects

Demopoulos, C.

Publications and source records attributed to Demopoulos, C..

4 recordsLinked to original sources

bioRxiv2026

The Regional Vulnerability Index (RVI) as a Neuroimaging-Based Biomarker for Autism: Associations with Likelihood, Cognition, and Longitudinal Social Outcomes

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition with symptoms spanning cognitive, social and behavioral domains and leading to lifelong challenges. Autism is heritable but specific genetic and environmental factors that shape its early neurodevelopmental trajectory remain unknown. Despite the clinical variability, neuroimaging findings from Enhancing Neuro Imaging Genetics through Meta Analysis (ENIGMA)-ASD consortium identified stable and replicable patterns of cortical and subcortical differences that were consistent with those reported by an independent consortium, the Cognitive Genetics Collaborative Research Organization (COCORO) in Japan. Here we developed and evaluated a regional vulnerability index (RVI), a similarity metric that quantifies how closely a persons brain resembles the specific pattern of an individual with autism. RVI-ASD is based on combining the regional effect sizes for regional brain measurements published by the ENIGMA-ASD group with microstructural white matter integrity differences reported by COCORO. RVI-ASD showed significantly higher effect size for case-control differences relative to any individual brain measure (d=0.30 vs. d=0.01-0.21) in individuals with autism, particularly in the adolescent-to-adult sample (N=2,577; Mean age = 16.1; SD=5.0). We next calculated RVI-ASD in the baseline and follow-up (ages 10 and 12) data from normally developing participants of the ABCD study (N=4,201). We tested the longitudinal stability, heritability, genotype-by-age interaction and sensitivity of RVI-ASD to known factors and cognitive measurements. RVI-ASD were stable on the 2-year follow up (ICC=0.76-0.92); showed significant heritability (h{superscript 2}=0.55-0.83, p<10-16) but was not affected by gene-by-age interaction. RVI-ASD showed significant positive correlation with paternal age, while correlation with maternal age was non-significant. Baseline and follow-up RVI-ASD were negatively correlated with cognitive measures including total, fluid and crystallized intelligence (r=-0.09 to -0.11, p<10-6). RVI-ASD scores tracked with core autism phenotypes including poor eye contact and rigid routines (p < .01). In a sub-sample of children with symptoms of autism (N=20), we found that earlier age of symptom onset was strongly correlated with higher White Matter RVI (r = -0.61), linking early behavioral emergence to the neuroanatomical signature. Longitudinal changes in subcortical RVI-ASD are significantly correlated with change in social functioning. The RVI-ASD is a neuroimaging-based biomarker linked to stable and reproducible brain patterns in autism. RVI-ASD allows researchers to study associations with factors associated with the likelihood for autism and cognition across large and inclusive non-clinical samples, thus moving beyond simple case-control models to understand the biological pathways of autism.

neuroscience↗

bioRxiv2024

Global MEG Resting State Functional Connectivity in Children with Autism and Sensory Processing Dysfunction

Sensory processing dysfunction not only affects most individuals with autism spectrum disorder (ASD), but at least 5% of children without ASD also experience dysfunctional sensory processing. Our understanding of the relationship between sensory dysfunction and resting state brain activity is still emerging. This study compared long-range resting state functional connectivity of neural oscillatory behavior in children aged 8-12 years with autism spectrum disorder (ASD; N=18), those with sensory processing dysfunction (SPD; N=18) who do not meet ASD criteria, and typically developing control participants (TDC; N=24) using magnetoencephalography (MEG). Functional connectivity analyses were performed in the alpha and beta frequency bands, which are known to be implicated in sensory information processing. Group differences in functional connectivity and associations between sensory abilities and functional connectivity were examined. Distinct patterns of functional connectivity differences between ASD and SPD groups were found only in the beta band, but not in the alpha band. In both alpha and beta bands, ASD and SPD cohorts differed from the TDC cohort. Somatosensory cortical beta-band functional connectivity was associated with tactile processing abilities, while higher-order auditory cortical alpha-band functional connectivity was associated with auditory processing abilities. These findings demonstrate distinct long-range neural synchrony alterations in SPD and ASD that are associated with sensory processing abilities. Neural synchrony measures could serve as potential sensitive biomarkers for ASD and SPD.

neuroscience↗

bioRxiv2021

Investigating the Interplay Between Affective, Phonatory and Motoric Subsystems in Autism Spectrum Disorder Using a Multimodal Dialogue Agent

We explore the utility of an on-demand multimodal conversational platform in extracting speech and facial metrics in children with Autism Spectrum Disorder (ASD). We investigate the extent to which these metrics correlate with objective clinical measures, particularly as they pertain to the interplay be-tween the affective, phonatory and motoric subsystems. 22 participants diagnosed with ASD engaged with a virtual agent in conversational affect production tasks designed to elicit facial and vocal affect. We found significant correlations between vocal pitch and loudness extracted by our platform during these tasks and accuracy in recognition of facial and vocal affect, as-sessed via the Diagnostic Analysis of Nonverbal Accuracy-2 (DANVA-2) neuropsychological task. We also found significant correlations between jaw kinematic metrics extracted using our platform and motor speed of the dominant hand assessed via a standardised neuropsychological finger tapping task. These findings offer preliminary evidence for the usefulness of these audiovisual analytic metrics and could help us better model the interplay between different physiological subsystems in individuals with ASD.

neuroscience↗

bioRxiv2017

Abnormal Speech Motor Control in Individuals with 16p11.2 Deletions

Speech and motor deficits are highly prevalent (>70%) in individuals with the 600 kb BP4-BP5 16p11.2 deletion; however, the mechanisms that drive these deficits are unclear, limiting our ability to target interventions and advance treatment. This study examined fundamental aspects of speech motor control in participants with the 16p11.2 deletion. To assess capacity for control of voice, we examined how accurately and quickly subjects changed the pitch of their voice within a trial to correct for a transient perturbation of the pitch of their auditory feedback. When compared to sibling controls, 16p11.2 deletion carriers show an over-exaggerated pitch compensation response to unpredictable mid-vocalization pitch perturbations. We also examined sensorimotor adaptation of speech by assessing how subjects learned to adapt their sustained productions of formants (speech spectral peak frequencies important for vowel identity), in response to consistent changes in their auditory feedback during vowel production. Deletion carriers show reduced sensorimotor adaptation to sustained vowel identity changes in auditory feedback. These results together suggest that 16p11.2 deletion carriers have fundamental impairments in the basic mechanisms of speech motor control and these impairments may partially explain the deficits in speech and language in these individuals.

neuroscience↗