Decreased homotopic interhemispheric functional connectivity in children with autism spectrum disorder

Abstract

While several functional and structural changes occur in large‐scale brain networks in autism spectrum disorder (ASD), reduced interhemispheric resting‐state functional connectivity (rsFC) between homotopic regions may be of particular importance as a biomarker. ASD is an early‐onset developmental disorder and neural alterations are often age‐dependent. Although there is some evidence for homotopic interhemispheric rsFC alterations in language processing regions in ASD children, wider analyses using large data sets have not been performed. The present study, therefore, conducted a voxel‐based homotopic interhemispheric rsFC analysis in 146 ASD and 175 typically developing children under‐age 10 and examined associations with symptom severity in the autism brain imaging data exchange data sets. Given the role of corpus callosum (CC) in interhemispheric connectivity and reported CC volume changes in ASD we additionally examined whether there were parallel volumetric changes. Results demonstrated decreased homotopic rsFC in ASD children in the posterior cingulate cortex (PCC) and precuneus of the default mode network, the precentral gyrus of the mirror neuron system, and the caudate of the reward system. Homotopic rsFC of the PCC was associated with symptom severity. Furthermore, although no significant CC volume changes were found in ASD children, there was a significant negative correlation between the anterior CC volumes and homotopic rsFC strengths in the caudate. The present study shows that a reduced pattern of homotopic interhemispheric rsFC in ASD adults/adolescents is already present in children of 5–10 years old and further supports their potential use as a general ASD biomarker. Lay summary Homotopic interhemispheric functional connectivity plays an important role in synchronizing activity between the two hemispheres and is altered in adults and adolescents with autism spectrum disorder (ASD). In the present study focused on children with ASD, we have observed a similar pattern of decreased homotopic connectivity, suggesting that alterations in homotopic interhemispheric connectivity may occur early in ASD and be a useful general biomarker across ages.

Reduced homotopic interhemispheric connectivity in psychiatric disorders: evidence for both transdiagnostic and disorder specific features

“…In a study that only used data from children with ASD (5–10 years old) from both ABIDE I and II, and further controlled for center/scanner variability, a similar pattern of decreased homotopic rsFC was found to that reported by Li et al . ( 2019 ) across different ages in ABIDE I, but positive correlations between strengths of homotopic rsFC in regions of the DMN and visual cortex and ASD symptom severity (Yao et al ., 2021b ). The positive correlation with symptoms in children may reflect abnormal developmental trajectories of homotopic interhemispheric rsFC in ASD (Kozhemiako et al ., 2019 ; Ma et al ., 2022 ).…”

“…Of these VMHC studies, only one has reported associations between homotopic rsFC and CC structure, with a trend for caudate rsFC being negatively correlated with volume of the anterior CC (Yao et al ., 2021b ). Previous studies have consistently revealed reduced CC volume in ASD, although specific subregions vary across studies due to differences in sample size, analysis approaches, and age of participants (see Yao et al ., 2021a ).…”

Connectivity and functional characterization of the mouse contralateral projecting neurons in basolateral amygdala

“…https://mc03.manuscriptcentral.com/sab | Stress and Brain 9 disorders. For example, clinical studies have revealed that homotopic interhemispheric connectivity is significantly reduced in children, adolescents, and adults with an autism spectrum disorder [23,24]. In addition, a recent study showed that unilateral BLA PNs send dense projection to contralateral BLA via the posterior part of the anterior commissure [12].…”

CDKL5 sculpts functional callosal connectivity to promote cognitive flexibility

“…Specifically, structural deficits of the CC have been found in patients with autism spectrum disorder (ASD) [9][10][11][12] and epilepsy [13][14][15] and associated mice models [16][17][18][19]. A growing body of work supports that FC is also disrupted in NDD [13,[20][21][22][23], in fact two studies examining large cohorts of children with ASD (ABIDE I and II) report abnormalities of interhemispheric FC [21], and found evidence of hyperconnectivity in the anterior cingulate/medial prefrontal cortex (ACC/mPFC) [24]. Most importantly, the degree of disrupted interhemispheric connectivity correlates with ASD severity [20,22,24,25].…”