Functional idiosyncrasy has a shared topography with group-level connectivity alterations in autism

Abstract

Autism spectrum disorder (ASD) is commonly understood as a network disorder, yet case-control analyses against typically-developing controls (TD) have yielded somewhat inconsistent patterns of results. The current work was centered on a novel approach to profile functional network idiosyncrasy, the inter-individual variability in the association between functional network organization and brain anatomy, and we tested the hypothesis that idiosyncrasy contributes to connectivity alterations in ASD. Studying functional network idiosyncrasy in a multi-centric dataset with 157 ASD and 172 TD, our approach revealed higher idiosyncrasy in ASD in the default mode, somatomotor and attention networks together with reduced idiosyncrasy in the lateral temporal lobe. Idiosyncrasy was found to increase with age in both ASD and TD, and was significantly correlated with symptom severity in the former group. Association analysis with structural and molecular brain features indicated that patterns of functional network idiosyncrasy were not correlated with ASD-related cortical thickness alterations, but closely with the spatial expression patterns of intracortical ASD risk genes. In line with our main hypothesis, we could demonstrate that idiosyncrasy indeed plays a strong role in the manifestation of connectivity alterations that are measurable with conventional case-control designs and may, thus, be a principal driver of inconsistency in the autism connectomics literature. These findings support important interactions between the heterogeneity of individuals with an autism diagnosis and group-level functional signatures, and help to consolidate prior research findings on the highly variable nature of the functional connectome in ASD. Our study promotes idiosyncrasy as a potential individualized diagnostic marker of atypical brain network development.

An expanding manifold in transmodal regions characterizes adolescent reconfiguration of structural connectome organization

“…The structural connectome was built by mapping the reconstructed cross-section streamlines onto the Schaefer 7-network based atlas with 200 parcels (Schaefer et al, 2018) then log-transformed to adjust for the scale (Fornito et al, 2016). We opted for this atlas as it (i) allows contextualization of our findings within macroscale intrinsic functional communities (Yeo et al, 2011), (ii) incorporates the option to assess results across different granularities, and (iii) aligns the current study with previous work from our group (Benkarim et al, 2020; Paquola et al, 2020; Park et al, 2021, 2020a; Rodríguez-Cruces et al, 2020) and others (Baum et al, 2020; Betzel et al, 2019; Osmanlıoğlu et al, 2019).…”

An expanding manifold in transmodal regions characterizes adolescent reconfiguration of structural connectome organization

“…The structural connectome was built by mapping the reconstructed cross-section streamlines onto the Schaefer 7-network based atlas with 200 parcels (Schaefer et al, 2018) then log-transformed to adjust for the scale (Fornito et al, 2016). We opted for this atlas as it (i) allows contextualization of our findings within macroscale intrinsic functional communities (Yeo et al, 2011), (ii) incorporates the option to assess results across different granularities, and (iii) aligns the current study with previous work from our group (Benkarim et al, 2020;Paquola et al, 2020;Park et al, 2021Park et al, , 2020aRodríguez-Cruces et al, 2020) and others (Baum et al, 2020;Betzel et al, 2019;Osmanlıoğlu et al, 2019).…”

Standardizing workflows in imaging transcriptomics with the abagen toolbox

“…We introduce the abagen toolbox, an open-access software package designed to streamline processing and preparation of the AHBA for integration with neuroimaging data , available at https: //github.com/rmarkello/abagen). Supporting several workflows, abagen offers functionality for an array of analyses and has already been used in several peerreviewed publications and preprints (Benkarim et al 2020, Ding et al 2021, Hansen et al 2021, Lariviere et al 2020, Martins et al 2021, 2020, 2020, Valk et al 2021, Zhao et al 2020. The primary workflow, used to generate regional gene expression matrices, integrates 17 distinct processing steps that have previously been employed by research groups throughout the published literature (Table 1).…”

“…Creation of the toolbox has followed best-practices in software development, including version control, continuous integration testing, and modular code design. abagen has already been successfully used in many peer-reviewed publications (Benkarim et al 2020, Ding et al 2021, Hansen et al 2021, Lariviere et al 2020, Martins et al 2021, 2020, 2020, Valk et al 2021, Zhao et al 2020), and we continue to integrate new features as community needs emerge. To encourage further use by new research groups we provide comprehensive documentation on installing and working with the abagen toolbox online (https://abagen.readthedocs.io/).…”