The “Primitive Brain Dysfunction” Theory of Autism: The Superior Colliculus Role

Abstract

A better understanding of the pathogenesis of autism will help clarify our conception of the complexity of normal brain development. The crucial deficit may lie in the postnatal changes that vision produces in the brainstem nuclei during early life. The superior colliculus is the primary brainstem visual center. Although difficult to examine in humans with present techniques, it is known to support behaviors essential for every vertebrate to survive, such as the ability to pay attention to relevant stimuli and to produce automatic motor responses based on sensory input. From birth to death, it acts as a brain sentinel that influences basic aspects of our behavior. It is the main brainstem hub that lies between the environment and the rest of the higher neural system, making continuous, implicit decisions about where to direct our attention. The conserved cortex-like organization of the superior colliculus in all vertebrates allows the early appearance of primitive emotionally-related behaviors essential for survival. It contains first-line specialized neurons enabling the detection and tracking of faces and movements from birth. During development, it also sends the appropriate impulses to help shape brain areas necessary for social-communicative abilities. These abilities require the analysis of numerous variables, such as the simultaneous evaluation of incoming information sustained by separate brain networks (visual, auditory and sensory-motor, social, emotional, etc.), and predictive capabilities which compare present events to previous experiences and possible responses. These critical aspects of decision-making allow us to evaluate the impact that our response or behavior may provoke in others. The purpose of this review is to show that several enigmas about the complexity of autism might be explained by disruptions of collicular and brainstem functions. The results of two separate lines of investigation: 1. the cognitive, etiologic, and pathogenic aspects of autism on one hand, and two. the functional anatomy of the colliculus on the other, are considered in order to bridge the gap between basic brain science and clinical studies and to promote future research in this unexplored area.

Atypical cortical feedback underlies failure to process contextual information in the superior colliculus of Scn2a+/-autism model mice

“…Most importantly, Scn2a +/mice showed impaired neurophysiological and behavioral phenotypes, both due to anomalous signaling from V1 to SC. This highlights a crucial role of the top-down corticotectal pathway in forming perceptual associations to recognize and properly react to visual contexts (Tang and Higley, 2020), and a possible relationship between ASD and dysfunctions of V1 L5 projection neurons (Marco et al, 2011;Johnson et al, 2016;Jure, 2022). SC neurons represent expectations on environmental volatility in WT mice, while those on outcomes in Scn2a +/mice Thus far we have analyzed the overall activity level of SC populations during the implicit visual learning task, and demonstrated that their dynamics were largely consistent with the behavior of the posterior predictability from the Bayesian inference viewpoint (Figs.…”

“…The involvement of SC in these processes highlights its relevance to the neurophysiological mechanisms underlying ASD (Jure, 2022).…”

“…The superior colliculus (SC) is a promising target to address this question. It is a midbrain hub for the visual system, implicated in atypical visual processing in ASD (Marco et al, 2011; Johnson et al, 2016; Jure, 2022). For instance, gaze management and attentional focus are two major functions of SC that are often altered in ASD (Lomber et al, 2002; Kato et al, 2011).…”

“…A growing body of evidence indicates the involvement of subcortical structures in ASD, including SC (Marco et al, 2011;Johnson et al, 2016;Jure, 2022). For instance, gaze management and attentional focus are two major functions of SC that are often altered in ASD (Lomber et al, 2002;Kato et al, 2011).…”

Protein kinase C mediates hypoxia-induced long-term potentiation of NMDA neurotransmission in the visual retinocollicular pathway

“…The retinocollicular pathway, as part of the visual system, is extremely sensitive to oxygen deprivation (Wong-Riley, 2010). Lesions of this pathway lead to navigation, orientation, and visual attention deficits, and also could be involved in several neurological and psychiatric disorders such as attention deficit hyperactivity disorder, and autism (Brace et al, 2015;Mathis et al, 2015;Jure, 2022). In our research, we focus on the very early hypoxia-induced processes and their mechanisms as potential therapeutic targets serving to prevent lesions of the retinocollicular visual transmission.…”