Thalamocortical Dysconnectivity in Autism Spectrum Disorder: An Analysis of the Autism Brain Imaging Data Exchange

Abstract

Background Individuals with autism spectrum disorder (ASD) exhibit differences in basic sensorimotor processing as well as general cortical excitability. These observations converge to implicate thalamocortical connectivity as a potential unifying neural mechanism. The goal of this study was to clarify mixed findings on thalamocortical functional connectivity in a large sample of individuals with ASD. Methods Using the Autism Brain Imaging Data Exchange (ABIDE), we examined thalamocortical functional connectivity in 228 individuals with ASD and a matched comparison group of 228 typically developing individuals. In order to fully characterize thalamocortical functional networks, we employed complementary seed-based approaches that examined connectivity of major cortical divisions (e.g. prefrontal cortex, temporal lobe) with the thalamus and whole-brain connectivity of specific thalamic sub-regions. Results Prefrontal cortex, temporal lobe, and sensorimotor cortex exhibited hyper-connectivity with the thalamus in ASD. In the whole-brain analysis, hyper-connectivity of several thalamic seeds included multiple cortical areas, but tended to converge in temporal cortical areas, including the temporoparietal junction. Follow-up analyses of age effects revealed that the connectivity abnormalities in ASD were more pronounced in adolescents compared to children and adults. Conclusions These results confirm previous findings of temporal and motor thalamocortical hyper-connectivity in ASD, and extend them to include somatosensory and prefrontal cortex. While not directly addressable with the data available in ABIDE, this widespread hyper-connectivity could theoretically account for sensorimotor symptoms and general cortical excitability in ASD. Future studies should target comprehensive clinical and behavioral characterization in combination with functional connectivity in order to explore this possibility.

Aberrant “deep connectivity” in autism: A cortico–subcortical functional connectivity magnetic resonance imaging study

“…Our findings of motor–subcortical connectivity are in line with those from previous thalamocortical studies in ASD (Cerliani et al, ; Mizuno et al, ; Nair et al, ; Woodward et al, ). ASD has been associated with abnormal motor‐related functioning beyond repetitive motor mannerisms such as delays in motor development and impairments of gross and fine motor function (Fournier, Hass, Naik, Lodha, & Cauraugh, ); and impaired connectivity within the motor system has been implicated with these features (Mostofsky et al, ).…”

“…Findings of increased auditory–thalamic functional connectivity in the ASD group relative to TD are in line with previous findings (Linke, Jao Keehn, Pueschel, Fishman, & Muller, ) as well as with increased temporal–thalamic connectivity (Cerliani et al, ; Nair et al, ; Nair et al, ; Woodward et al, ). The auditory network is responsible for modality‐specific imagery of auditory information; and there is evidence of heightened auditory sensitivity (Matsuzaki et al, ) and atypical responses and filtering to complex auditory stimuli in ASD, especially in a social context (Hilton et al, ).…”

“…A key limitation of cortico–subcortical studies in ASD is their relatively small sample sizes (20–50 subjects per group). However, with the introduction of data sharing approaches like the Autism Brain Imaging Data Exchange (ABIDE) initiative (Di Martino et al, ), more groups are overcoming this limitation when examining cortico–subcortical rs‐fcMRI (Cerliani et al, ; Chen, Uddin, Zhang, Duan, & Chen, ; Woodward, Giraldo‐Chica, Rogers, & Cascio, ). The majority of these studies found increased rs‐fcMRI between primary sensory cortices and subcortical regions and reduced rs‐fcMRI between prefrontal and parietal areas with subcortical regions.…”

Nonrapid eye movement sleep and risk for autism spectrum disorder in early development: A topographical electroencephalogram pilot study

“…These electrophysiological differences are congruent with neuroanatomical features associated with ASD (Nair, Treiber, Shukla, Shih, & Müller, 2013). One hypothesis is that the differences in the thalamocortical system between ASD and healthy populations indicate atypical connectivity (Ferradal et al, 2018;Woodward, Giraldo-Chica, Rogers, & Cascio, 2017) and functioning of thalamocortical neural substrates in ASD (Daoust, Limoges, Bolduc, Mottron, & Godbout, 2004;Rochette et al, 2018), and result in atypical processing of cognitive, attentional, and sensorimotor pathways in children and adults with ASD (Nair et al, 2013).…”

“…These electrophysiological differences are congruent with neuroanatomical features associated with ASD (Nair, Treiber, Shukla, Shih, & Müller, ). One hypothesis is that the differences in the thalamocortical system between ASD and healthy populations indicate atypical connectivity (Ferradal et al, ; Woodward, Giraldo‐Chica, Rogers, & Cascio, ) and functioning of thalamocortical neural substrates in ASD (Daoust, Limoges, Bolduc, Mottron, & Godbout, ; Rochette et al, ), and result in atypical processing of cognitive, attentional, and sensorimotor pathways in children and adults with ASD (Nair et al, ). Thalamocortical projections increase over the beginning years of life (Alcauter et al, ), and alterations in the thalamocortical connections such as under connectivity to prefrontal, parieto‐occipital, and temporal regions (Nair et al, ) suggest atypical connectivity of the developing brain.…”