Autism is a neurodevelopmental disorder, and sensorimotor disturbances are among the earliest signs of atypical development in autism, revealing themselves in early infancy. As every parent knows, infants spend most of their time asleep, and about half of that sleep time is spent in rapid eye movement (REM) sleep. One of the defining features of REM sleep is myoclonic twitching, a phenomenon which is thought to play a critical role in sensorimotor development. Twitching — jerky movements of the limbs, head, face and eyes — occurs abundantly and exclusively during REM sleep, with sensory feedback from twitching limbs acting as a primary driver of neural activity throughout the sensorimotor system. This suggests that twitching plays a role in shaping, tuning, and mapping the developing sensorimotor system and that alterations in twitching might serve as a useful model for tracking sensorimotor disturbances in autism.

Mark Blumberg and his colleagues propose to develop a novel neurodevelopmental approach to investigating autism, focusing on the development of the profound sensorimotor impairments in autism. This proposal is predicated on two notions: first, that there is much to be learned about the neurodevelopmental origins of autism by focusing attention on infant motor development; and second, that sleep-related twitching can provide insight into the functional status of the infant sensorimotor system in autism that wake-related movements cannot.

The researchers will initially focus on the neurodevelopmental effects associated with deletion of chromosomal region 16p11.2, one of the most common genetic variants found in autism. In humans with this deletion, there is a high prevalence (>90 percent) of psychiatric and developmental disorders, including deficits in motor coordination. The team will develop a sensitive and high-throughput method for assessing quantitative and qualitative aspects of twitching in newborn mice with and without the 16p11.2 deletion. To form a more complete picture of sensorimotor disturbances in autism, the information the researchers uncover about twitching will be integrated with what is known about related motor deficits in infant mice with this deletion. Ultimately, this approach can be combined with neonatal neurophysiology to identify the neural causes and consequences of deficient twitching in this and other mouse models of autism, with the aim of using these insights to better understand the etiology of autism and develop new conceptual approaches to early diagnosis, prevention and treatment.