Network inefficiencies in autism spectrum disorder at 24 months

Abstract

Autism spectrum disorder (ASD) is a developmental disorder defined by behavioral symptoms that emerge during the first years of life. Associated with these symptoms are differences in the structure of a wide array of brain regions, and in the connectivity between these regions. However, the use of cohorts with large age variability and participants past the generally recognized age of onset of the defining behaviors means that many of the reported abnormalities may be a result of cascade effects of developmentally earlier deviations. This study assessed differences in connectivity in ASD at the age at which the defining behaviors first become clear. There were 113 24-month-old participants at high risk for ASD, 31 of whom were classified as ASD, and 23 typically developing 24-month-old participants at low risk for ASD. Utilizing diffusion data to obtain measures of the length and strength of connections between anatomical regions, we performed an analysis of network efficiency. Our results showed significantly decreased local and global efficiency over temporal, parietal and occipital lobes in high-risk infants classified as ASD, relative to both low- and high-risk infants not classified as ASD. The frontal lobes showed only a reduction in global efficiency in Broca's area. In addition, these same regions showed an inverse relation between efficiency and symptom severity across the high-risk infants. The results suggest delay or deficits in infants with ASD in the optimization of both local and global aspects of network structure in regions involved in processing auditory and visual stimuli, language and nonlinguistic social stimuli.

Predicting symptom severity in autism spectrum disorder based on cortical thickness measures in agglomerative data

“…As expected based on existing literature and given that problems with communication are part of the definition of ASD, a number of the strongest predictors are related to language: the left pars triangularis, rolandic operculum, superior temporal gyrus, and angular gyrus. The left pars triangularis is part of Broca's area, which is critical for language production, and has been implicated in autism in numerous studies (Just et al, 2004;Zielinski et al, 2014;Lewis et al, 2014). The left rolandic operculum is involved in the production of prosody, a lack of which is one of the hallmarks of autistic speech, as well the perception of prosody, and shows abnormal levels of activiation in ASD (Paul et al, 2005;Gebauer et al, 2014).…”

Early Intervention for Children With Autism Spectrum Disorder Under 3 Years of Age: Recommendations for Practice and Research

“…Some authors have also argued that the second year of life is a particularly critical developmental period for children with ASD, for various reasons. First, the second year is a dynamic period of brain growth, during which increases in brain volume and atypical connectivity associated with ASD first emerge 6,7 but also a time of substantial neural plasticity providing greater potential to alter developmental course. 8 Second, a proportion of children with ASD reportedly regress in the second year.…”

Brain imaging research in autism spectrum disorders

“…The longitudinal trajectory of fractional anisotropy between 6 and 24 months of age is atypical in 80% of the white matter tracts examined in high-risk infants, suggesting widespread involvement. At the whole-brain neural network level, network inefficiency appears decreased at 24 months of age in high-risk infants who develop ASD [50 ▪▪ ]. The topography of the structural networks appears reduced in spatial extent and number of connections.…”

“…The differences in network efficiency are located primarily in posterior (occipital and temporal) regions of the brain involved in processing auditory, visual, language, and nonverbal social stimuli, rather than in frontal regions. Greater network inefficiency is associated with greater severity of core features of autism [50 ▪▪ ]. …”

“…Elevated levels of brain lactate may develop in localized areas of the brain in some ASD adults [56]. Brain lactate is elevated in mitochondrial disorders, some cases of bipolar disorder, and transiently by subtle hyperventilation and caffeine [50 ▪▪ ]. …”