Rethinking Autism as an Acquired Disorder: The Hippocampal Neuronal Overflow Hypothesis

AbstractNeuroanatomical studies of autism spectrum disorder (ASD) reveal abnormally increased cortical neuron numbers in affected children, with cortical thickness and weight significantly exceeding normal controls, some accompanied by macrocephaly. Concurrently, severe damage to cortical neuronal axons and columnar structures has been observed, with pronounced cellular accumulation in specific regions and long-range connectivity dysfunction. Most children develop symptoms between 1.5-2 years of age, yet the pathological mechanisms remain unclear.Mammalian hippocampi exhibit sustained neurogenesis peaks during the first postnatal months, with hippocampal neuronal survival significantly increasing in response to learning tasks and information stimulation. The intensity of learning tasks and information stimulation that human infants receive far exceeds conditions in animal experiments. Research demonstrates large-scale neuronal migration phenomena in human infant cortex, with the cortex potentially containing cells from diverse origins.We propose the hippocampal neuronal overflow hypothesis: massive surviving neurons within the infant hippocampus overcome hippocampal capacity limitations and, during critical time windows, overflow from the hippocampus to white matter, migrating into cortical layers to form synaptic connections and construct unique network circuits related to human cognition, language, and memory functions.We propose that ASD etiology involves children receiving excessive learning tasks and information stimulation during the hippocampal neurogenesis peak period, leading to excessive neuronal overflow and migration into the cortex. During intensive synapse formation processes, migrating neurons physically disrupt existing cortical axonal structures, causing cortical functional damage manifested as social deficits, communication impairments, and stereotypical behaviors.Based on extensive literature analysis, this study proposes that some ASD cases may result from this acquired neurodevelopmental abnormality mechanism, providing a new theoretical framework for ASD etiology research.