Functional Connectivity of the Amygdala Is Disrupted in Preschool-Aged Children With Autism Spectrum Disorder

Abstract

Objective The objective of the current study was to determine whether functional connectivity of the amygdala is altered in preschool-aged children with autism spectrum disorder (ASD) and to assess the clinical relevance of observed alterations in amygdala connectivity. Method We conducted a resting-state functional connectivity magnetic resonance imaging (MRI) study of the amygdala (and a parallel study of primary visual cortex) in 72 male children (mean age: 3.5 years; n=43 with ASD; n=29 age-matched controls). Results The ASD group showed significantly weaker connectivity between amygdala and several brain regions involved in social communication and repetitive behaviors, including bilateral medial prefrontal cortex, temporal lobes, and striatum (p < .05, corrected). Weaker connectivity between the amygdala and frontal and temporal lobes was significantly correlated with increased autism severity in the ASD group (p < .05). In a parallel analysis examining the functional connectivity of primary visual cortex, the ASD group showed significantly weaker connectivity between visual cortex and sensorimotor regions (p<.05, corrected). Weaker connectivity between visual cortex and sensorimotor regions was not correlated with core autism symptoms, but instead was correlated with increased sensory hypersensitivity in the visual/auditory domain (p<.05). Conclusion These findings indicate that preschool-aged children with ASD have disrupted functional connectivity between the amygdala and regions of the brain important for social communication and language, which may be clinically relevant since weaker connectivity was associated with increased autism severity. Moreover, whereas amygdala connectivity was associated with behavioral domains that are diagnostic of ASD, altered connectivity of primary visual cortex was related to sensory hypersensitivity.

The journey to autism: Insights from neuroimaging studies of infants and toddlers

“…Seed-based, resting-state functional connectivity between the amygdala and canonical targets is reduced in preschool-aged children with ASD (Shen et al, 2016), consistent with what might be expected given increased amygdala volumes and atypical FA in limbic regions such as the uncinate and the inferior longitudinal fasciculi (Conti et al, 2017; Solso et al, 2016; Wolff et al, 2012; Xiao et al, 2014). A series of studies from Courchesne et al also indicates atypical connectivity in language areas, patterns of which have been associated with measures of receptive and expressive language function (Dinstein et al, 2011; Eyler et al, 2012; Lombardo et al, 2015; Redcay & Courchesne, 2008).…”

“…Findings from Shen et al (2016) concerning diminished cortical and subcortical amygdala connectivity compliment neuroimaging reports of atypical amygdala structure among young preschool-aged children (Mosconi et al, 2009; Munson et al, 2006; Schumann et al, 2009). Evidence that whole-brain functional connectivity patterns could serve as a sensitive and specific presymptomatic biomarker of autism in high-risk sibs will very likely catalyze future work.…”

Protracted dendritic growth in the typically developing human amygdala and increased spine density in young ASD brains

“…Amygdala volume of children with ASD is significantly larger than in typically developing children (Sparks et al, ; Schumann et al, ; Mosconi et al, ; Kim et al, ; Nordahl et al, ). This relative overgrowth correlates with symptom severity, providing further evidence for the structure–function relationship of the amygdala in ASD (Munson et al, ; Mosconi et al, ; Schumann, Barnes, Lord, & Courchesne, ; Iidaka, Miyakoshi, Harada, & Nakai, ; Elison et al, ; Shen et al, ). However, the volume difference in ASD dissipates during adolescence as the amygdala continues to grow in TD (Schumann et al, ).…”

Hyperexcitability and loss of feedforward inhibition in the Fmr1KO lateral amygdala

“…Thus, increased plasticity in the circuits responsible for fear-learning may underpin the pathophysiology of anxiety disorders in FXS and ASDs in early life. However, anxiety and fear-related disorders in FXS and ASDs in later life may be mediated by other mechanisms including changes in brain-wide functional connectivity (Haberl et al , 2015; Shen et al , 2016) or changes in neuromodulation (Hessl et al , 2002; Ghilan et al , 2015).…”