Altered Cortical-Subcortical Functional Connectivity in Autism Spectrum Disorders

Background: Studies examining functional brain networks in autism spectrum disorder (ASD) have risen exponentially over the last decade and have characterized it as a disorder of aberrant brain network connectivity. While a large number of these functional MRI studies have focused on cortico-cortical connectivity in ASD, limited attention has been paid to cortical-subcortical connectivity. Subcortical regions such as thalamus (THAL) and basal ganglia (BG) may play a vital role in ASD neuropathology considering their role in sensory processing and cognition.

Objectives: To assess patterns of cortical-basal ganglia and thalamocortical connectivity in individuals with ASD and to examine the relationship between connectivity and ASD phenotype, such as socio-communicative and repetitive behaviors.

Methods: Resting state fMRI data (TD = 168; ASD = 138; 5-8 minute-long, eyes open scans) from the Autism Brain Imaging Data Exchange (ABIDE II) were used and preprocessed using a standard resting state processing pipeline. Unimodal (motor, auditory, lateral and medial visual) and supramodal ROIs (DMN, posterior DMN, salience, attention, and left and right executive) were defined using MELODIC ICA. Partial correlation maps were obtained for functional connectivity between cortical ROIs with THAL and BG and mean Z’ score obtained for each cortical seed for the ASD group were correlated with clinical measures (ADOS, ADI-R, and RBS-R).

Results: For unimodal connectivity, clusters of overconnectivity (ASD > TD) were found between THAL (auditory and motor) and BG (auditory and lateral visual) while clusters of underconnectivity (ASD < TD) were also found between THAL and BG with medial visual. Conversely, for supramodal connectivity, clusters of underconnectivity (ASD < TD) were found in THAL (salience, left executive, and posterior DMN) and BG (salience and left executive) while clusters of overconnectivity (ASD > TD) were also found in THAL (DMN and posterior DMN) and BG (attention). Positive correlations were found between medial visual-BG connectivity with ADOS-RRB scores and between auditory-BG connectivity with RBS-R stereotyped behavior. Negative correlations were found between DMN-THAL connectivity with ADI-R verbal scores and salience-THAL connectivity with ADOS-Social scores.

Conclusions: Our findings of altered cortical-BG and thalamocortical connectivity in ASD are consistent with previous studies. This study targeted specific brain networks responsible for key cognitive processes, where overconnectivity (ASD > TD) between unimodal and subcortical regions and underconnectivity (ASD < TD) between supramodal and subcortical regions were predominantly detected. These findings may suggest excess crosstalk within unimodal regions and subcortical regions that support basic sensory information based on previous activation fMRI studies of visual, auditory and somatosensory systems. On the other hand, supramodal regions may require increased communication for effective higher cognitive functioning with subcortical regions, which may be reduced in people with ASD. The findings of brain-behavior relationship suggest that connectivity profile of unimodal and supramodal networks in ASD may play a role in sensory sensitivity and social communication respectively.