[A neurologic model of early infantile autism]

Based on the abnormalities in sleep-wakefulness cycle of early infantile autism, the author discussed its pathophysiology focusing on its main lesion in the raphe nuclei. These neurons, located in the midline portion of the brainstem send their axons to various neurons of the upper and lower nervous systems, including the locus coeruleus and the dopamine neurons of the tegmentum, the former having a broad innervation and the latter a restricted area in the central nervous system. These monoaminergic neurons modulate the functions of the involved neurons and regulate their functional and structural maturation in the early developmental course. The early lesion of the raphe nuclei causes poor adaptation to environment which develops as abnormal circadian oscillation and pervasive lack of responsiveness. Combined hypofunction of the locus ceruleus, particularly of its dorsal bundle, results in the failure of extinction of acquired memory in mice which relates clinically to the excellent memory and resistance to change peculiar interests and attachments in humans. From early childhood, the disturbance of dopaminergic neurons becomes apparent clinically, and causes hyperkinesia and stereotyped activities. With the other two monoaminergic neurons, dopaminergic neurons cause occasional aggressiveness or self-mutilation. The latter behaviors are like those of pampered children and are simulated to "muricide" and "friendliness" observed in rats with these monoaminergic lesions. The particular language disturbance with echolalia is due to the right hemispheric dominance, which might have been caused by a delayed functional lateralization of the hemisphere resulting also from the delayed development of the circadian oscillation in infancy. The motor disturbances consisting of hypotonia and impaired locomotion might be due to decreased tonic innervations of the locus ceruleus and the raphe nuclei to the spinal locomotion center. CT examination of symptomatic autism showed the amygdala as one of the causative nuclei for the autistic behavior.