Increased Functional Connectivity Between Subcortical and Cortical Resting-State Networks in Autism Spectrum Disorder

Abstract

Importance Individuals with autism spectrum disorder (ASD) exhibit severe difficulties in social interaction, motor coordination, behavioral flexibility, and atypical sensory processing, with considerable interindividual variability. This heterogeneous set of symptoms recently led to investigating the presence of abnormalities in the interaction across large-scale brain networks. To date, studies have focused either on constrained sets of brain regions or whole-brain analysis, rather than focusing on the interaction between brain networks. Objectives To compare the intrinsic functional connectivity between brain networks in a large sample of individuals with ASD and typically developing control subjects and to estimate to what extent group differences would predict autistic traits and reflect different developmental trajectories. Design, Setting, and Participants We studied 166 male individuals (mean age, 17.6 years; age range, 7-50 years) diagnosed as having DSM-IV-TR autism or Asperger syndrome and 193 typical developing male individuals (mean age, 16.9 years; age range, 6.5-39.4 years) using resting-state functional magnetic resonance imaging (MRI). Participants were matched for age, IQ, head motion, and eye status (open or closed) in the MRI scanner. We analyzed data from the Autism Brain Imaging Data Exchange (ABIDE), an aggregated MRI data set from 17 centers, made public in August 2012. Main Outcomes and Measures We estimated correlations between time courses of brain networks extracted using a data-driven method (independent component analysis). Subsequently, we associated estimates of interaction strength between networks with age and autistic traits indexed by the Social Responsiveness Scale. Results Relative to typically developing control participants, individuals with ASD showed increased functional connectivity between primary sensory networks and subcortical networks (thalamus and basal ganglia) (all t ≥ 3.13, P < .001 corrected). The strength of such connections was associated with the severity of autistic traits in the ASD group (all r ≥ 0.21, P < .0067 corrected). In addition, subcortico-cortical interaction decreased with age in the entire sample (all r ≤ −0.09, P < .012 corrected), although this association was significant only in typically developing participants (all r ≤ −0.13, P < .009 corrected). Conclusions and Relevance Our results showing ASD-related impairment in the interaction between primary sensory cortices and subcortical regions suggest that the sensory processes they subserve abnormally influence brain information processing in individuals with ASD. This might contribute to the occurrence of hyposensitivity or hypersensitivity and of difficulties in top-down regulation of behavior.

Differential patterns of age‐related cortical and subcortical functional connectivity in 6‐to‐10 year old children: A connectome‐wide association study

“…MeanTS had a mix of positive and negative associations, while ALPACA had exclusively negative associations with age, adding new insight into the nature of previously observed changes in connectivity with age. The negative associations in ALPACA suggest that focal connectivity between cortical and subcortical regions decreases with age, which is consistent with studies reporting negative associations with age in connections between subcortical and cortical regions in typical development (Cerliani et al., 2015; Greene et al., 2014; Sato et al., 2015; Supekar et al., 2009). However, (Solé‐padullés et al., 2015) found primarily positive as well as some negative age associations between cortico‐subcortical connections, and (Sato et al., 2015) found that the thalamus had both positive and negative association with age in development.…”

“…Such an imbalance in timing of development has been previously proposed for cortical/limbic connectivity (Casey, Jones, & Hare, 2008; Heller, Cohen, Dreyfuss, & Casey, 2016). Given the importance of various subcortical structures and their cortical connections with different psychiatric disorders (e.g., Cortico‐cerebellar‐thalamic‐cortical loop in Schizophrenia, caudate motor in ADHD, thalamus/basal ganglia/primary sensory networks; Cerliani et al., 2015), having a better understanding of differences within and between cortical and subcortical regions is a crucial foundation for future efforts studying connectivity differences related to psychopathology.…”

“…Functional connectivity between subcortical and cortical regions has been shown to decrease with age in children (Cerliani et al., 2015; Greene et al., 2014; Sato et al., 2015; Supekar, Musen, & Menon, 2009). However, other studies have found the opposite pattern (Sato et al., 2015; Solé‐padullés et al., 2015).…”

“…This has not yet been investigated in previous studies. Previous studies examining rs‐fMRI connectivity in typical development included subjects with a broad age range or had small to moderate sample sizes ( n  < 200 in most cases; Cerliani et al., 2015; Fair et al., 2009; Greene et al., 2014; Rubia, 2013; Sato et al., 2015; Solé‐padullés et al., 2015; Supekar et al., 2009). Thus, to reduce heterogeneity, which could contribute to the mixed findings, we used a large sample of 6‐to‐10 year‐old children from a population‐based cohort.…”

Correlatos estructurales de las alteraciones cognitivas en niños con TEA

“…Respecto a la conectividad cortico-estriatal, Cerliani et al (2015), encontraron que dicha conectividad decrecía con la edad en sujetos con desarrollo típico pero no cambiaba con la edad en sujetos con autismo. También demostraron que había una correlación entre el grado de hipoactivación en los circuitos cortico-estriatales y los síntomas propios del TEA (los déficits sociales y de comunicación y los comportamientos restringidos y repetitivos).…”