Search bioRxiv⌕ Search

Biology subjects

Amber N. V. Ruigrok

Publications and source records attributed to Amber N. V. Ruigrok.

3 recordsLinked to original sources

Examining the boundary sharpness coefficient as an index of cortical microstructure and its relationship to age and sex in autism spectrum disorder

Autism spectrum disorder (ASD) is associated with atypical brain development. However, the phenotype of regionally specific increased cortical thickness observed in ASD may be driven by several independent biological processes that influence the gray/white matter boundary, such as synaptic pruning, myelination, or atypical migration. Here, we propose to use the boundary sharpness coefficient (BSC), a proxy for alterations in microstructure at the cortical gray/white matter boundary, to investigate brain differences in individuals with ASD, including factors that may influence ASD-related heterogeneity (age, sex, and intelligence quotient). Using a vertex-based meta-analysis and a large multi-center magnetic resonance structural imaging (MRI) dataset, with a total of 1136 individuals, 415 with ASD (112 female; 303 male) and 721 controls (283 female; 438 male), we observed that individuals with ASD had significantly greater BSC in the bilateral superior temporal gyrus and left inferior frontal gyrus indicating an abrupt transition (high contrast) between white matter and cortical intensities. Increases were observed in different brain regions in males and females, with larger effect sizes in females. Individuals with ASD under 18 had significantly greater BSC in the bilateral superior temporal gyrus and right postcentral gyrus; individuals with ASD over 18 had significantly increased BSC in the bilateral precuneus and superior temporal gyrus. BSC correlated with ADOS-2 CSS in individuals with ASD in the right medial temporal pole. Importantly, there was a significant spatial overlap between maps of the effect of diagnosis on BSC when compared to cortical thickness. These results invite studies to use BSC as a possible new measure of cortical development in ASD and to further examine the microstructural underpinnings of BSC-related differences and their impact on measures of cortical morphology.

neuroscience↗

Unsupervised data-driven stratification of mentalizing heterogeneity in autism

Individuals affected by autism spectrum conditions (ASC) are considerably heterogeneous. Novel approaches are needed to parse this heterogeneity to enhance precision in clinical and translational research. Applying a clustering approach taken from genomics and systems biology on two large independent cognitive datasets of adults with and without ASC (n=715; n=251), we find replicable evidence for 5 discrete ASC subgroups that are highly differentiated in item-level performance on an explicit mentalizing task tapping ability to read complex emotion and mental states from the eye region of the face (Reading the Mind in the Eyes Test; RMET). Three subgroups comprising 42-65% of ASC adults show evidence for large impairments (Cohens d = -1.03 to -11.21), while other subgroups are effectively unimpaired. These findings delineate robust natural subdivisions within the ASC population that may allow for more individualized inferences and accelerate research towards precision medicine goals.

Animal Behavior and Cognition↗

Improving effect size estimation and statistical power with multi-echo fMRI and its impact on understanding the neural systems supporting mentalizing

Functional magnetic resonance imaging (fMRI) research is routinely criticized for being statistically underpowered due to characteristically small sample sizes and much larger sample sizes are being increasingly recommended. Additionally, various sources of artifact inherent in fMRI data can have detrimental impact on effect size estimates and statistical power. Here we show how specific removal of non-BOLD artifacts can improve effect size estimation and statistical power in task-fMRI contexts, with particular application to the social-cognitive domain of mentalizing/theory of mind. Non-BOLD variability identification and removal is achieved in a biophysical and statistically principled manner by combining multi-echo fMRI acquisition and independent components analysis (ME-ICA). Group-level effect size estimates on two different mentalizing tasks were enhanced by ME-ICA at a median rate of 24% in regions canonically associated with mentalizing, while much more substantial boosts (40-149%) were observed in non-canonical cerebellar areas. This effect size boosting is primarily a consequence of reduction of non-BOLD noise at the subject-level, which then translates into consequent reductions in between-subject variance at the group-level. Power simulations demonstrate that enhanced effect size enables highly-powered studies at traditional sample sizes. Cerebellar effects observed after applying ME-ICA may be unobservable with conventional imaging at traditional sample sizes. Thus, ME-ICA allows for principled design-agnostic non-BOLD artifact removal that can substantially improve effect size estimates and statistical power in task-fMRI contexts. ME-ICA could help issues regarding statistical power and non-BOLD noise and enable potential for novel discovery of aspects of brain organization that are currently under-appreciated and not well understood.

Neuroscience↗