Biology subjects

Al-Sharif, N. B.

Publications and source records attributed to Al-Sharif, N. B..

4 recordsLinked to original sources

bioRxiv2021

A critical role of brain network architecture in a continuum model of autism spectrum disorders spanning from healthy individuals with genetic liability to individuals with ASD

Studies have shown cortical alterations in individuals with autism spectrum disorders (ASD) as well as in individuals with high polygenic risk for ASD. An important addition to the study of altered cortical anatomy is the investigation of the underlying brain network architecture that may reveal brain-wide mechanisms in ASD and in polygenic risk for ASD. Such an approach has been proven useful in other psychiatric disorders by revealing that brain network architecture shapes (to an extent) the disorder-related cortical alterations. This study uses data from a clinical dataset - 560 male subjects (266 individuals with ASD and 294 healthy individuals, CTL, mean age at 17.2 years) from the Autism Brain Imaging Data Exchange database, and data of 391 healthy individuals (207 males, mean age at 12.1 years) from the Pediatric Imaging, Neurocognition and Genetics database. ASD-related cortical alterations (group difference, ASD-CTL, in cortical thickness) and cortical correlates of polygenic risk for ASD were assessed, and then statistically compared with structural connectome-based network measures (such as hubs) using spin permutation tests. Next, we investigated whether polygenic risk for ASD could be predicted by network architecture by building machine-learning based prediction models, and whether the top predictors of the model were identified as disease epicenters of ASD. We observed that ASD-related cortical alterations as well as cortical correlates of polygenic risk for ASD implicated cortical hubs more strongly than non-hub regions. We also observed that age progression of ASD-related cortical alterations and cortical correlates of polygenic risk for ASD implicated cortical hubs more strongly than non-hub regions. Further investigation revealed that structural connectomes predicted polygenic risk for ASD (r=0.30, p<0.0001), and two brain regions (the left inferior parietal and left suparmarginal) with top predictive connections were identified as disease epicenters of ASD. Our study highlights a critical role of network architecture in a continuum model of ASD spanning from healthy individuals with genetic risk to individuals with ASD. Our study also highlights the strength of investigating polygenic risk scores in addition to multi-modal neuroimaging measures to better understand the interplay between genetic risk and brain alterations associated with ASD.

neuroscience↗

bioRxiv2021

Schizophrenia polygenic risk during typical development reflects multiscale cortical organization

Schizophrenia is widely recognized as a neurodevelopmental disorder. Abnormal cortical development may by revealed using polygenic risk scoring for schizophrenia (PRS-SCZ). We assessed PRS-SCZ and cortical morphometry in typically developing children (3-21 years) using whole genome genotyping and T1-weighted MRI (n=390) from the Pediatric Imaging, Neurocognition and Genetics (PING) cohort. We contextualise the findings using (i) age-matched transcriptomics, (ii) histologically-defined cytoarchitectural types and functionally-defined networks, (iii) case-control differences of schizophrenia and other major psychiatric disorders. Higher PRS-SCZ was associated with greater cortical thickness, which was most prominent in areas with heightened gene expression of dendrites and synapses. PRS-SCZ related increases in vertex-wise cortical thickness were especially focused in the ventral attention network, while koniocortical type cortex (i.e. primary sensory areas) was relatively conserved from PRS-SCZ related differences. The large-scale pattern of cortical thickness increases related to PRS-SCZ mirrored the pattern of cortical thinning in schizophrenia and mood-related psychiatric disorders. Age group models illustrate a possible trajectory from PRS-SCZ associated cortical thickness increases in early childhood towards thinning in late adolescence, which resembles the adult brain phenotype of schizophrenia. Collectively, combining imaging-genetics with multi-scale mapping, our work provides novel insight into how genetic risk for schizophrenia impacts the cortex early in life.

neuroscience↗

bioRxiv2021

Structural connectome fingerprinting and age prediction in pediatric development: assessing voxel- and surface-based white matter connectivity

Mapping structural white matter connectivity is a challenge, with many barriers to accurate representation. Here, we assessed the replicability and reliability of two connectome-generating methods, voxel- or surface-based, using test-retest analyses, fingerprinting and age prediction. The two connectomic methods are initiated by the same state-of-the-art dMRI processing pipeline before diverging at the tractography and connectome-generating steps using either voxels or surfaces. While both methods performed very well across all analyses, voxel-based connectomes performed marginally better than surface-based connectomes. Notably, structural connectomes derived from either method demonstrate reliably accurate representations of both individuals and their chronological age, comparable to similar analyses employing multi-modal features. The difference in methodological performance could be attributed to a number of method-specific features but ultimately show that cutting-edge tractography with robust dMRI processing produces reliable white matter connectivity measures.

neuroscience↗

bioRxiv2020

Processing the diffusion-weighted magnetic resonance imaging of the PING dataset

Diffusion-weighted magnetic resonance imaging (dMRI) allows for the in-vivo assessment of anatomical white matter in the brain, thus allowing the depiction of structural connectivity. Using structural processing techniques and related methods, a growing body of literature has illustrated that connectomics is a crucial aspect to assessing the brain in health and disease. The Pediatric Imaging Neurocognition and Genetics (PING) dataset was collected and released openly to contribute to the assessment of typical brain development in a pediatric sample. This current work details the processing of diffusion-weighted images from the PING dataset, including rigorous quality assessment and fine-tuning of parameters at every step, to increase the accessibility of these data for connectomic analysis. This processing provides state-of-the-art diffusion measures, both classical diffusion tensor imaging (DTI) and more advanced HARDI-based metrics, enabling the evaluation not only of structural white matter but also of integrated multimodal analyses, i.e. combining structural information from dMRI with functional or gray matter analyses.

neuroscience↗