Altered functional connectivity of the amygdaloid input nuclei in adolescents and young adults with autism spectrum disorder: a resting state fMRI study

Abstract

Background: Amygdala dysfunction is hypothesized to underlie the social deficits observed in autism spectrum disorders (ASD). However, the neurobiological basis of this hypothesis is underspecified because it is unknown whether ASD relates to abnormalities of the amygdaloid input or output nuclei. Here, we investigated the functional connectivity of the amygdaloid social-perceptual input nuclei and emotion-regulation output nuclei in ASD versus controls.

Methods: We collected resting state functional magnetic resonance imaging (fMRI) data, tailored to provide optimal sensitivity in the amygdala as well as the neocortex, in 20 adolescents and young adults with ASD and 25 matched controls. We performed a regular correlation analysis between the entire amygdala (EA) and the whole brain and used a partial correlation analysis to investigate whole-brain functional connectivity uniquely related to each of the amygdaloid subregions.

Results: Between-group comparison of regular EA correlations showed significantly reduced connectivity in visuospatial and superior parietal areas in ASD compared to controls. Partial correlation analysis revealed that this effect was driven by the left superficial and right laterobasal input subregions, but not the centromedial output nuclei.

Conclusions: These results indicate reduced connectivity of specifically the amygdaloid sensory input channels in ASD, suggesting that abnormal amygdalo-cortical connectivity can be traced down to the socio-perceptual pathways.

Keywords: Amygdala; Autism spectrum disorder; Centromedial; Connectivity; Input-output; Laterobasal; Nuclei; Social perception; Superficial.

Fig. 1

Anatomically defined amygdala regions of interest and its dominant full correlation patterns throughout the cortex. a The Juelich cytoarchitectonic histological probability masks of the amygdaloid subregions. Red areas depict the laterobasal subregions, green areas the superficial subregions, and blue areas the centromedial subregions. Areas in light red, light green, and dark blue indicate the 50 % probability mask of each subdivision. Areas in dark red, dark green, and light blue depict the >70 % subregion probability masks that were used for the seed-based analysis. b Dominant functional correlations of the left and right amygdala subregions in controls using statistical mean testing. A threshold-free cluster enhancement statistic tested the following contrasts: SF > LB + CM, LB > CM + SF, and CM > LB + SF; (p < 0.05, FWE corrected). Green areas indicate dominant superficial connectivity networks, red areas depict dominant laterobasal networks, and blue areas indicate dominant centromedial networks

Fig. 2

Intrinsic positive connectivity networks of the entire amygdala and its individual subregions in controls and patients. a Significant results (p < 0.05 FWE corrected) of entire amygdalo-cortical full correlation analyses are delineated for the ASD group (EA patients) and controls (EA controls). Yellow and red areas depict results from the left and right amygdala seeds, respectively, with orange regions illustrating its overlap. Positive main effects (p < 0.05 FWE corrected) of the subregion-specific correlation analyses are shown in the same color code for the b superficial amygdala in patients (SF patients) and controls (SF controls), c the laterobasal amygdala in patients (LB patients) and controls (LB controls) and d the centromedial amygdala in patients (CM patients) and controls (CM controls)

Fig. 3

Areas of reduced functional connectivity in ASD. a Significant (p < 0.05; FWE corrected) reduced connectivity with the entire amygdala (EA) ROI. Yellow areas show between-group differences in connectivity with left amygdala seeds, while red areas show connectivity with right amygdala seeds. b Conventions are depicted as in panel (a) but with yellow regions illustrating the left superficial ROI and red indicating the right laterobasal subcompartment. The results from the partial correlation analysis revealed that the between-group difference in EA was driven by the left SF and right LB. Bilateral CM, right SF, and left LB did not yield significant between-group differences