24038
Early Developing Functional Connectivity Between Default Mode, Salience, Attention, and Visual Networks Underpins Autism and a Subgroup with Preference for Geometric Images and Lack of Social Orienting
The way in which a toddler with autism (ASD) may atypically sample the social environment during the first years of life may play an important role in shaping experience-dependent neurobiological processes. Most typically-developing (TD) toddlers as well as some toddlers with ASD show early a visual preference for social images when given the choice to look at social versus non-social geometric visual displays. However, we have consistently found that there is a subgroup within early developing ASD toddlers (GeoASD) who atypically lack this preference for social stimuli in their first 4 years of life and instead prefer geometric images (Pierce et al., 2011, 2016). We predicted that this atypical lack of early social orienting may be underpinned by hypoconnectivity between large-scale neural circuits developing early specialization for visual, attention, salience, social cognition/communication functions.
Objectives:
To examine how ASD subgroups defined by early social or non-social geometric visual preferences measured via the GeoPref eye tracking test (Pierce et al., 2011, 2016) are differentiated in intrinsic functional connectivity measured with resting state fMRI (rsfMRI). We predicted hypoconnectivity in an ASD subgroup with preference for non-social geometric displays (GeoASD), particularly between visual, attention, salience, and default mode neural circuits.
Methods:
n=78 ASD (GeoASD n=16, nonGeoASD n = 62) and n=55 scan age and sex-matched TD individuals (age 12-48 months) were evaluated using the GeoPref eye tracking test and also had a 6 min 25 seconds rsfMRI scan during natural sleep. Data were preprocessed using AFNI and denoised by regressing out 6 motion parameters and their derivatives, CSF signal, as well as removal of further noise-related variability identified with wavelet denoising techniques (Patel et al., 2014, Neuroimage). Groups did not differ in mean framewise displacement or DVARS before and after denoising. FSL MELODIC Group Independent Components Analysis (ICA) and dual regression were utilized to identify networks as components. Nine components were identified as default mode, attention, salience, or visual networks and connectivity between these components was estimated with robust regression to be insensitive to outliers. Group differences were examined with ANOVA and multiple comparison correction (FDR q<0.05).
Results:
Confirming our hypotheses, we found significant effects of group for 7 of the total 36 comparisons (all F>8.84, all p<0.0035, all survive FDR q<0.05), involving default mode-visual, default mode-attention, and salience network connections. All effects followed an ordinal rank pattern of GeoPref<nonGeoPref<TD. Default mode-visual connections were significantly reduced in GeoASD compared to nonGeoASD or TD (i.e. GeoASD<nonGeoASD or GeoASD<TD) and for nonGeoASD compared to TD (all p<0.05). Group differences in default mode-attention connectivity as well as connectivity between salience components were driven primarily by more generalized hypoconnectivity in ASD compared to TD.
Conclusions:
ASD within the first 4 years of life is characterized by decreased functional connectivity between default mode subsystems and early developing visual and attention circuits as well as connectivity within the salience network. The main feature differentiating socially oriented nonGeoASD versus non-socially oriented GeoASD toddlers with ASD is further dampening of functional connections between the default mode subsystems and visual cortices.