Sensing Echoes: Temporal misalignment as the Earliest Marker of Neurodevelopmental Derail

FROM THE PREPRINT: 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.来自预印本：感觉转导（sensory transduction）与传递延迟以不同时间尺度运作并传播。从听觉领域的微秒级，到视觉、动觉领域的数百毫秒级，大脑必须成功对齐源自内源性自发运动与内脏感觉信息流的各类差异延迟，使其与外源性感觉输入相匹配。为了对环境目标产生连贯响应、持续探索适应并构建同时性感知，大脑需要完成这一核心任务，并补偿任意感觉模态中过度的延迟。此类过程的紊乱可能改变对自我与他人的感知，进而无意之中影响社会互动。但此类问题最早何时出现、能否被可靠检测，仍是一项挑战。本研究针对新生儿展开评估，检测声波从耳蜗神经（cochlear nerve）传递至脑干（brainstem）、最终抵达初级听觉皮层（primary auditory cortex）的传输潜伏期。我们发现，在出生时，后续被诊断为自闭症（autism）的新生儿中，该声波传播存在系统性累积延迟。此外，我们还发现，此类时间延迟的分布带宽远窄于未被诊断为自闭症的新生儿。我们鉴定了相关的共调控基因网络，并定义了可在出生时检测到的神经发育脱轨可靠标志物。基于精准自闭症模型（precision autism model），我们提出：脑干中存在一个内源性时钟（endogenous clock），可锚定并对齐对自我与他人的一致感知（congruent percepts）形成与维持至关重要的各类时间尺度。