Atypical functional connectome hierarchy in autism

Abstract

One paradox of autism is the co-occurrence of deficits in sensory and higher-order socio-cognitive processing. Here, we examined whether these phenotypical patterns may relate to an overarching system-level imbalance—specifically a disruption in macroscale hierarchy affecting integration and segregation of unimodal and transmodal networks. Combining connectome gradient and stepwise connectivity analysis based on task-free functional magnetic resonance imaging (fMRI), we demonstrated atypical connectivity transitions between sensory and higher-order default mode regions in a large cohort of individuals with autism relative to typically-developing controls. Further analyses indicated that reduced differentiation related to perturbed stepwise connectivity from sensory towards transmodal areas, as well as atypical long-range rich-club connectivity. Supervised pattern learning revealed that hierarchical features predicted deficits in social cognition and low-level behavioral symptoms, but not communication-related symptoms. Our findings provide new evidence for imbalances in network hierarchy in autism, which offers a parsimonious reference frame to consolidate its diverse features.

Stepwise functional connectivity reveals altered sensory‐multimodal integration in medication‐naïve adults with attention deficit hyperactivity disorder

“…Hence, although previous studies using SFC analysis tend to interpret their results in the sensory-to-cognitive direction (Carmona et al, 2015;Hong et al, 2019;Sepulcre et al, 2012), the directionality of the observed alterations should be tested in future studies using methods such as Dynamic Causal Modeling (Friston, Li, Daunizeau, & Stephan, 2011). First, computational constraints required us to downsample data to relatively large voxels (4 mm 3 ).…”

“…If SFC decrease was affecting sensory-to-cognitive functional streams, this would involve a reduced information feed from sensory up to higher level association nodes; if it was affecting cognitive-to-sensory functional streams, this would entail lower cognitive control over incoming perceptual information-thus hindering selective attention. Hence, although previous studies using SFC analysis tend to interpret their results in the sensory-to-cognitive direction (Carmona et al, 2015;Hong et al, 2019;Sepulcre et al, 2012), the directionality of the observed alterations should be tested in future studies using methods such as Dynamic Causal Modeling (Friston, Li, Daunizeau, & Stephan, 2011).…”

Targeting age‐related differences in brain and cognition with multimodal imaging and connectome topography profiling

“…In addition to leveraging surface-based processing and multimodal co-registration techniques, we harnessed a novel analysis reference frame determined by the putative neocortical hierarchy. Initially formulated in nonhuman primates (Mesulam, 1998), the hierarchy follows a "sensory-fugal" gradient from low-level cortices involved in interactions with the external world to higher-order transmodal areas involved in self-generated, abstract cognition (Buckner & Krienen, 2013;Huntenburg, Bazin, & Margulies, 2018;Margulies et al, 2016;Paquola et al, 2019;Hong et al, 2019). Recent application of unsupervised compression techniques applied to cortico-cortical functional connectivity data recapitulated a similar gradient in humans (Margulies et al, 2016).…”

Enhancement of indirect functional connections with shortest path length in the adult autistic brain

“…During early-life development, a time when atypical development is often first diagnosed, rapid changes occur in connectome that is subject to the competing forces of module segregation for functional specialization, and inter-module integration to facilitate behaviors combining specializations (Homae et al, 2010). A reduction in this integration appears to be a key characteristic of autism (Abbott et al, 2016;Duan et al, 2017;Keown et al, 2013Keown et al, , 2017, and in particular the switching between local and global processing (Hong et al, 2019). By virtue of their long-range influence and ubiquity in the connectome, weak links are suggested as a potential substrate for integrative communication, and thus metrics sensitive to their distribution could be informative of neurodevelopmental disorders such as autism.…”