Four Social Brain Regions, Their Dysfunctions, and Sequelae, Extensively Explain Autism Spectrum Disorder Symptomatology

Abstract

Autism spectrum disorder (ASD) is a challenging neurodevelopmental disorder with symptoms in social, language, sensory, motor, cognitive, emotional, repetitive behavior, and self-sufficient living domains. The important research question examined is the elucidation of the pathogenic neurocircuitry that underlies ASD symptomatology in all its richness and heterogeneity. The presented model builds on earlier social brain research, and hypothesizes that four social brain regions largely drive ASD symptomatology: amygdala, orbitofrontal cortex (OFC), temporoparietal cortex (TPC), and insula. The amygdala’s contributions to ASD largely derive from its major involvement in fine-grained intangible knowledge representations and high-level guidance of gaze. In addition, disrupted brain regions can drive disturbance of strongly interconnected brain regions to produce further symptoms. These and related effects are proposed to underlie abnormalities of the visual cortex, inferior frontal gyrus (IFG), caudate nucleus, and hippocampus as well as associated symptoms. The model is supported by neuroimaging, neuropsychological, neuroanatomical, cellular, physiological, and behavioral evidence. Collectively, the model proposes a novel, parsimonious, and empirically testable account of the pathogenic neurocircuitry of ASD, an extensive account of its symptomatology, a novel physiological biomarker with potential for earlier diagnosis, and novel experiments to further elucidate the mechanisms of brain abnormalities and symptomatology in ASD.

An Automated Functional Annotation Pipeline That Rapidly Prioritizes Clinically Relevant Genes for Autism Spectrum Disorder

“…While we chose to use the GTEx resource, as these data are more readily accessible—and likely more generalizable to other conditions—compared to resources containing data generated from ASD brain tissue, this may limit the ability to understand genetic differences that may be unique to the brains of individuals with ASD. Specifically, it is hypothesized that brain regions involved in social behavior drive ASD symptomatology; these include the amygdala, orbitofrontal cortex, temporoparietal cortex and insula [ 48 ]. With the exception of the amygdala, gene expression in the precise brain regions that are proposed biomarkers for ASD are not quantified in the GTEx resource potentially explaining why our results were limited to the pituitary.…”

Neuronal Circuits for Social Decision-Making and Their Clinical Implications

“…Perception of animacy is disturbed in some children with ASD (Congiu et al, 2010). On top of communicative challenges, individuals with ASD face additional difficulties such as having a lack of understanding of social cues and conventions, disinterest in forming new relationships, and difficulties in conversation such as interpreting jokes, sarcasm, or understanding metaphors (Weston, 2019). These impairments tend to result in anxiety, social withdrawal, dysphoric emotions, and high-stress levels.…”

Dynamics of age-related structural and functional changes in the brain of patients with autism spectrum disorders

“…Наряду с увеличением общего размера мозга обнаружено увеличение гиппокампа, миндалины и мозжечка [5,23]. Нейроны в глубоких ядрах мозжечка (n. fastigeal, n. globose, n. emboliform) отличались большими размерами и их количество было больше [24].…”

“…У детей старше 4 лет размеры миндалины и гиппокампа либо не отличались от таковых у НРД, либо были несколько меньше [5,14]. Вместе с тем другие авторы выявили увеличение гиппокампа, особенно в группе больных РАС без когнитивных нарушений [37], а также билатеральное увеличение хвостатых и прилежащих ядер [28,38]; уменьшение мозолистого тела [36].…”

“…Расстройства аутистического спектра (РАС) включают заболевания и состояния со сходными клиническими проявлениями в виде качественных нарушений социального взаимодействия и показателей коммуникабельности, а также ограниченных повторяющихся паттернов поведения, интересов или действий [1]. У больных РАС наблюдаются коморбидные состояния, включая эпилепсию, желудочно-кишечную дисфункцию, психические расстройства, бессонницу, нарушения мышечного тонуса и двигательных навыков, внимания и эмоций, разной степени выраженности когнитивные и речевые расстройства [2][3][4][5].…”