Greater functional connectivity between sensory networks is related to symptom severity in toddlers with autism spectrum disorder

Abstract

Background: Symptoms of autism spectrum disorder (ASD) emerge in the first years of life. Yet, little is known about the organization and development of functional brain networks in ASD proximally to the symptom onset. Further, the relationship between brain network connectivity and emerging ASD symptoms and overall functioning in early childhood is not well understood.

Methods: Resting-state fMRI data were acquired during natural sleep from 24 young children with ASD and 23 typically developing (TD) children, aged 17-45 months. Intrinsic functional connectivity (iFC) within and between resting-state functional networks was derived with independent component analysis (ICA).

Results: Increased iFC between visual and sensorimotor networks was found in young children with ASD compared to TD participants. Within the ASD group, the degree of overconnectivity between visual and sensorimotor networks was associated with greater autism symptoms. Age-related weakening of the visual-auditory between-network connectivity was observed in the ASD but not the TD group.

Conclusions: Taken together, these results provide evidence for disrupted functional network maturation and differentiation, particularly involving visual and sensorimotor networks, during the first years of life in ASD. The observed pattern of greater visual-sensorimotor between-network connectivity associated with poorer clinical outcomes suggests that disruptions in multisensory brain circuitry may play a critical role for early development of behavioral skills and autism symptomatology in young children with ASD.

Keywords: Brain networks; autism spectrum disorders; early childhood; functional connectivity; neuroimaging.

Figure 1

Intrinsic functional connectivity networks in toddlers with and without ASD. Results of the 20-dimensional group ICA; images are z statistics thresholded at z = 3.0 (p < .001) grouped into functional-domain categories as depicted. IC labels: Vis1 = occipital pole visual, Vis2 = medial visual, Vis3 = lateral visual, Vis4 = higher-order visual, SM1 = primary motor, SM2 = lateral sensorimotor, SM3 = medial sensorimotor, Aud = auditory, MSen = multimodal sensory, SN = salience. Images are presented in the Montreal Neurological Institute (MNI) space, in neurological convention (with the left side of the brain represented on the left)

Figure 2

Connectivity matrices between RFN cluster item courses. (A) Normalized pairwise ROI-ROI (RFN clusters) correlation coefficients (z-values) are presented separately for the ASD (upper triangle) and TD (lower triangle) groups. Both axes represent the 20 RFN clusters (see Table S1 for detailed cluster description). Pixel color of each cell represents the magnitude of correlation for each region of interest (ROI) pair, with warmer colors indicating greater correlation coefficient values. (B) Difference connectivity matrix for ASD versus TD (ASD> TD) comparison. * denotes ROI-ROI pairs with significantly stronger connections at FDR corrected p < .05, after controlling for mean RMSD

Figure 3

Relationship between autism symptomatology and visual-sensorimotor connectivity in the ASD group. Partial correlation between connectivity (z-scores) between all-visual and sensorimotor networks and ADOS-2 Total scores (p_FDR < .05). Increasing ADOS-2 Total values indicate greater symptom count and, hence, greater impairment. The values on the X and Y axes reflect residuals of ADOS-2 and z-scores, respectively, after controlling for RMSD, MSEL ELC, and ADOS-2 Module