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.

Keywords: autism pathogenesis; autism spectrum disorders (ASD); congenital blindness; human development; pulvinar; superior colliculus (SC); visual pathways.

FIGURE 1

Levels of compromise in ASD.

FIGURE 2

Two visual pathways.

FIGURE 3

The SC is in the interface of bottom–up/top–down attentional process. Relevant information is sent to higher structures. Motor responses could be conscious or non conscious, limited to eye movement (redirection of the attention) or all body goal oriented response.

FIGURE 4

Indirect bottom–up multisensory input from the SC to the cortex: Almost all sensory inputs (visual, auditory, somatosensory, proprioceptive and nociceptive) converge at the Deep SC. The visual input from the superficial SC is the most massive and leads to the correspondence of the rest (somatosensory, auditory, etc.) Several thalamic nuclei receive deep SC input to further reach the cortex.

FIGURE 5

Emotional circuits triggered by the SC: visual and non-visual stimuli carrying emotional content could be processed exclusively by subcortical circuits or to reach the frontal cortex resulting or not in a motor non-conscious or conscious response respectively. The reward dopaminergic system is mediated by the Susbtantia njgra (SN)and the nucleo accubens (NA); the alerting adrenergic system by the locus ceruleous (LC);the cholinergic system by the substantia innomminata (SI). The hypothalamic-pituitary-adrenal axis (HPA) is reached through the paraventricular nucleus (PVN). Some basic emotions like defensive, reproductive, maternal or pain related behaviors are mediated by connections with the periacueductal gray matter (PAG). Through these ways the SC activates simultaneously several attentional, autonomic, endocrine and cognitive functions.

FIGURE 6

Top–down direct multisensory, motor, and emotion related input from the cortex to the SC. The SC receives direct cortical input mainly from V layer that concentrates all elaborated sensory-motor information from most cortical neurons. Temporal-Parietoccipital (TPO) associated area and frontal lobe regions -premotor mirror networks, emotional networks (OFC) and eye movements areas (FEF-SEF)-should be integrated for mentalize abilities. With this direct input, the SC functions as a contiguous cortical layer. Subcortical nuclei process non-conscious sensory-motor functions and are essential to SC functions.