Anatomical imbalance between cortical networks in autism

Abstract

Influential psychological models of autism spectrum disorder (ASD) have proposed that this prevalent developmental disorder results from impairment of global (integrative) information processing and overload of local (sensory) information. However, little neuroanatomical evidence consistent with this account has been reported. Here, we examined relative grey matter volumes (rGMVs) between three cortical networks, how they changed with age, and their relationship with core symptomatology. Using public neuroimaging data of high-functioning ASD males and age-/sex-/IQ-matched controls, we first identified age-associated atypical increases in rGMVs of the regions of two sensory systems (auditory and visual networks), and an age-related aberrant decrease in rGMV of a task-control system (fronto-parietal network, FPN) in ASD children. While the enlarged rGMV of the auditory network in ASD adults was associated with the severity of autistic socio-communicational core symptom, that of the visual network was instead correlated with the severity of restricted and repetitive behaviours in ASD. Notably, the atypically decreased rGMV of FPN predicted both of the two core symptoms. These findings suggest that disproportionate undergrowth of a task-control system (FPN) may be a common anatomical basis for the two ASD core symptoms, and relative overgrowth of the two different sensory systems selectively compounds the distinct symptoms.

Figure 1

(a) Nine large-scale brain networks. 213 cortical ROIs were defined in previous study, and are categorised into nine brain networks. No ROI was shared between different networks. (b) Analysis procedures. We first extracted grey matter volume (GMV) for each ROI from preprocessed anatomical neuroimaging data, and then classified the ROIs to the nine networks (panel a). After calculating average GMV for each network, we normalised the GMVs and estimated relative GMVs (rGMVs) for the networks. This procedure was repeated for each participant.

Figure 2. Age-associated rGMV changes.

Using the childhood data (age ≤ 18), we found significant correlations between age and rGMV of regions in three of the nine brain networks (P_{Bonferroni-corrected} < 0.05). The rGMVs of auditory and visual networks showed significantly positive correlations with age in ASD children, but not in neurotypical ones (panels a,b). In contrast, the rGMV of FPN was negatively correlated with age in autism, and was positively correlated in neurotypical population (panel c). These correlations were qualitatively preserved after controlling the effects of IQ (Supplementary Table 2) or even when considering effects of recording sites (Table 2).

Figure 3. Comparison of rGMVs between brain networks.

We compared rGMVs between the nine brain networks. In the adult data (18 < age ≤ 40), rGMVs of auditory and visual networks in autism were significantly larger than those in the neurotypical adults, whereas that of FPN was smaller in autism (F_(8,746) = 325.5, P < 0.0001 as interactions in a repeated measure two-way ANOVA; *P_{Bonferroni-corrected} < 0.05 in post-hoc two-sample t-tests). Error bars: std. The abbreviations of network names were spelled out in Fig. 1a.

Figure 4. Correlations between rGMVs and ASD symptoms.

Using data of ASD adults, we estimated associations between rGMVs and severity of autism, which was clinically evaluated with ADIR. Individuals with larger rGMVs of auditory network were likely to have severer deficits in socio-communicational interactions (ADIR Social + Communication) (panel a), whereas those with larger rGMVs of visual network tended to show severer RRB (ADIR-RRB) (panel b) (P_{Bonferroni-corrected} < 0.05). Autistic individuals with smaller rGMVs of FPN had severer symptoms in both core symptoms (panel c).

Figure 5

(a) Using data of ASD adults, we searched ROIs in auditory, visual, and fronto-parietal networks for focal regions whose rGMVs were significantly correlated with ASD severity. The sizes of the circles represent the magnitudes of the symptom-rGMV correlations. (b) In auditory network, rGMVs of bilateral dorsal posterior insulae had significant positive correlations with socio-communicational deficits, whereas rGMV of medial prefrontal cortex (mPFC) in FPN showed a negative correlation. (c) In visual network, rGMVs of three lateral occipital regions in visual network were positively correlated with RRB, and those of two dorso-/ventro-lateral prefrontal cortical regions (DLPFC/VLPFC) in FPN showed negative correlations.