Biology subjects

Shanmugan, S.

Publications and source records attributed to Shanmugan, S..

3 recordsLinked to original sources

bioRxiv2021

Linking Individual Differences in Personalized Functional Network Topography to Psychopathology in Youth

The spatial layout of large-scale functional brain networks differs between individuals and is particularly variable in association cortex that has been implicated in a broad range of psychiatric disorders. However, it remains unknown whether this variation in functional topography is related to major dimensions of psychopathology in youth. Capitalizing on a large sample with 27-minutes of high-quality functional MRI data (n=790, ages 8-23 years) and advances in machine learning, we examined associations between functional topography and four correlated dimensions of psychopathology (fear, psychosis, externalizing, anxious-misery) as well as an overall psychopathology factor. We found that functional topography significantly predicted individual differences in dimensions of psychopathology, driven mainly by robust associations between topography and overall psychopathology. Reduced cortical representations of association networks were among the most important features of the model. Our results emphasize the value of considering systematic differences in functional neuroanatomy for personalized diagnostics and therapeutics in psychiatry.

neuroscience↗

bioRxiv2021

Dissociable Multi-scale Patterns of Development in Personalized Brain Networks

The brain is organized into networks at multiple resolutions, or scales, yet studies of functional network development typically focus on a single scale. Here, we derived personalized functional networks across 29 scales in a large sample of youths (n=693, ages 8-23 years) to identify multi-scale patterns of network re-organization related to neurocognitive development. We found that developmental shifts in inter-network coupling systematically adhered to and strengthened a functional hierarchy of cortical organization. Furthermore, we observed that scale-dependent effects were present in lower-order, unimodal networks, but not higher-order, transmodal networks. Finally, we found that network maturation had clear behavioral relevance: the development of coupling in unimodal and transmodal networks dissociably mediated the emergence of executive function. These results delineate maturation of multi-scale brain networks, which varies according to a functional hierarchy and impacts cognitive development.

neuroscience↗

bioRxiv2021

Sex Differences in Functional Topography of Association Networks

Prior work has shown that there is substantial interindividual variation in the spatial distribution of functional networks across the cerebral cortex, or functional topography. However, it remains unknown whether there are sex differences in the topography of individualized networks in youth. Here we leveraged an advanced machine learning method (sparsity-regularized nonnegative matrix factorization) to define individualized functional networks in 693 youth (ages 8-23 years) who underwent functional magnetic resonance imaging as part of the Philadelphia Neurodevelopmental Cohort. Multivariate pattern analysis using support vector machines classified participant sex based on functional topography with 83% accuracy (p<0.0001). Brain regions most effective in classifying participant sex belonged to association networks, including the ventral attention and default mode networks. Mass-univariate analyses using generalized additive models with penalized splines provided convergent results. Comparative analysis using transcriptomic data from the Allen Human Brain Atlas revealed that sex differences in multivariate patterns of functional topography correlated with the expression of genes on the X-chromosome. These results identify normative developmental sex differences in the functional topography of association networks and highlight the role of sex as a biological variable in shaping brain development in youth. SIGNIFICANCE STATEMENTWe identify normative developmental sex differences in the functional topography of personalized association networks including the ventral attention network and default mode network. Furthermore, chromosomal enrichment analyses revealed that sex differences in multivariate patterns of functional topography were spatially coupled to the expression of X-linked genes as well as astrocytic and excitatory neuronal cell-type signatures. These results highlight the role of sex as a biological variable in shaping functional brain development in youth.

neuroscience↗