Autism Pathogenesis: The Superior Colliculus

Abstract

After been exposed to the visual input, in the first year of life, the brain experiences subtle but massive changes apparently crucial for communicative/emotional and social human development. Its lack could be the explanation of the very high prevalence of autism in children with total congenital blindness. The present theory postulates that the superior colliculus is the key structure for such changes for several reasons: it dominates visual behavior during the first months of life; it is ready at birth for complex visual tasks; it has a significant influence on several hemispheric regions; it is the main brain hub that permanently integrates visual and non-visual, external and internal information (bottom–up and top–down respectively); and it owns the enigmatic ability to take non-conscious decisions about where to focus attention. It is also a sentinel that triggers the subcortical mechanisms which drive social motivation to follow faces from birth and to react automatically to emotional stimuli. Through indirect connections it also activates simultaneously several cortical structures necessary to develop social cognition and to accomplish the multiattentional task required for conscious social interaction in real life settings. Genetic or non-genetic prenatal or early postnatal factors could disrupt the SC functions resulting in autism. The timing of postnatal biological disruption matches the timing of clinical autism manifestations. Astonishing coincidences between etiologies, clinical manifestations, cognitive and pathogenic autism theories on one side and SC functions on the other are disclosed in this review. Although the visual system dependent of the SC is usually considered as accessory of the LGN canonical pathway, its imprinting gives the brain a qualitatively specific functions not supplied by any other brain structure.

The Brainstem-Informed Autism Framework: Early Life Neurobehavioral Markers

“…The more primal and fast to react dorsal visual stream is highly operational during the first months of life, relaying low-resolution data from the rods with increased sensitivity to changes in the exterior scenery ( Hammarrenger et al, 2003 ; Bridge et al, 2016 ). The role of the superior colliculus (SC) in the dorsal stream has been recently highlighted, suggesting that in the neonatal period, this midbrain structure is pertinent for exercising focal oculomotor operations, receiving and integrating multimodal sensory inputs, and communicating with higher-order visual-neural configurations ( Pitti et al, 2013 ; Jure, 2019 ). The SC is, thus, highly involved in rudimentary social behaviors, including the preference to fixate on human faces and the ability to detect and imitate emotion-resonating facial expressions ( Jure, 2019 ).…”

Single-Cell RNA Sequencing Characterizes the Molecular Heterogeneity of the Larval Zebrafish Optic Tectum

“…The optic tectum, like its mammalian counterpart, the superior colliculus (SC), is a sensory processing hub that receives multimodal stimuli and is responsible for eliciting appropriate behavioral response 1 . Recently, the SC has received attention for a proposed role in autism spectrum disorder (ASD) pathogenesis due the essential role it plays in sensory perception 45 .…”

“…A potential link between the SC and autism spectrum disorder (ASD) has been proposed as congenitally blind children are diagnosed with ASD at a higher rate than those born with no vision impairments 45,52 . As sensory processing impairments typically present in ASD, a structure such as the SC that receives and interprets sensory stimuli poses an interesting avenue for ASD investigations.…”

“…The copyright holder for this preprint this version posted November 5, 2021. ; https://doi.org/10.1101/2021.11.05.467443 doi: bioRxiv preprint vision impairments 45,52 . As sensory processing impairments typically present in ASD, a structure such as the SC that receives and interprets sensory stimuli poses an interesting avenue for ASD investigations.…”

Superior Colliculus to VTA pathway controls orienting response to conspecific stimuli

“…SC is an evolutionary ancient structure organized in functionally and anatomically distinct layers. While the upper layers are exclusively visual, the medial and deeper layers have multisensory and motor functions (27) . It has been suggested that this structure, via different output projections, mediates both orienting and avoidance responses to novel sensory stimuli (15, 17) .…”