Toward a conceptual framework for early brain and behavior development in autism

Abstract

Studies of infant siblings of older autistic probands, who are at elevated risk for autism, have demonstrated that the defining features of autism are not present in the first year of life but emerge late in the first and into the second year. A recent longitudinal neuroimaging study of high-risk siblings revealed a specific pattern of brain development in infants later diagnosed with autism, characterized by cortical surface area hyper-expansion in the first year followed by brain volume overgrowth in the second year that is associated with the emergence of autistic social deficits. Together with new observations from genetically defined autism risk alleles and rodent model, these findings suggest a conceptual framework for the early, post-natal development of autism. This framework postulates that an increase in the proliferation of neural progenitor cells and hyper-expansion of cortical surface area in the first year, occurring during a pre-symptomatic period characterized by disrupted sensorimotor and attentional experience, leads to altered experience-dependent neuronal development and decreased elimination of neuronal processes. This process is linked to brain volume overgrowth and disruption of the refinement of neural circuit connections and is associated with the emergence of autistic social deficits in the second year of life. A better understanding of the timing of developmental brain and behavior mechanisms in autism during infancy, a period which precedes the emergence of the defining features of this disorder, will likely have important implications for designing rational approaches to early intervention.

Genetic correlates of evolutionary adaptations in cognitive functional brain networks and their relationship to human cognitive functioning and disease

“…The cortical expression patterns of HAR-BRAIN and DMN genes show significant overlap with the pattern of cortical involvement across five mental brain disorders, with large involvement observed in lateral and medial prefrontal cortices, key 'brain hubs' and components of high-order networks and identified to be generally implicated in the anatomy of a wide range of brain disorders 55,56 . These brain regions also show a hyper-expansion of surface area in the developing brain of autistic children 57 , which is in line with our findings of associated HAR gene expression and evolutionary cortical expansion. Furthermore, HAR and DMN genes are observed to be significantly associated with the genetic architecture for schizophrenia and ASD, disorders that are often reported to involve disturbed DMN functional connectivity 58 .…”

Increased electroencephalography connectivity precedes epileptic spasm onset in infants with tuberous sclerosis complex

“…It may also result from a pathologic increase in neural connectivity due to excessive activity‐dependent plasticity, predisposing to epilepsy . Increased EEG connectivity may demonstrate a neurophysiologic correlate of early brain overgrowth seen in infants later diagnosed with autism …”

“…36,37 Increased EEG connectivity may demonstrate a neurophysiologic correlate of early brain overgrowth seen in infants later diagnosed with autism. 38,39 Time from the first EEG to ES onset ranged from 24 to 197 days. We did not find a correlation between graph measures and time from EEG to ES onset.…”

Efficacy of early interventions for infants and young children with, and at risk for, autism spectrum disorders

“…Over time, the formation of distributed networks of brain regions and the interaction between these regions is hampered, affecting cognitive and sensorimotor functioning as the ASD symptom complex emerges. The brain abnormality in children with ASD changes across the first 2 years, likely the result of a dynamic interaction between neurobiological and cascading effects of atypical developmental processes (Karmiloff-Smith, Casey, Massand, Tomalski, & Thomas, 2014), with cumulative effects that further contribute to shifting phenotypic features (Piven, Elison, & Zylka, 2017). This highlights the importance of early access to intervention, the need for intervention to address multiple aspects of development, and for ongoing intervention that addresses developmental delays and atypicalities as these unfold over time (Karmiloff-Smith et al, 2014).…”