Sensing Echoes: Temporal Misalignment in Auditory Brainstem Responses as the Earliest Marker of Neurodevelopmental Derailment

Abstract

Sensory transduction and transmission delays operate and propagate along different time scales. From microseconds in the auditory domain, to hundreds of milliseconds in the visual, and kinesthetic domains, the brain must successfully align disparate delays arising from endogenously self-generated streams of motor and visceral sensorial information, with exogenous sensory inputs. To produce a cohesive response to environmental goals, constantly explore, adapt, and develop a sense of simultaneity, the brain must resolve this major feat and compensate for excessive delays in any sensory modality. Disruption in these processes may lead to altered perception of the self and others, and inadvertently affect social interactions. But how early such issues may emerge and be reliably detectable, remains a challenge. Here we assess in neonates, the transmission latencies of a sound wave that travels from the cochlear nerve to the brainstem on its way to the primary auditory cortex. Already at birth, we find systematic and cumulative delays in the propagation of this wave in neonates that later received a diagnosis of autism. Furthermore, we discover that the distributions of such temporal delays have far narrower bandwidth than those from neonates who did not receive the autism diagnosis. We identify associated codependent genes' networks and define a reliable marker of neurodevelopment derail, detectable at birth. Under the precision autism model, we propose that the brainstem contains an endogenous clock anchoring and aligning disparate timescales critical for the emergence and maintenance of congruent percepts of the self and others.