Prematurity as a risk factor for long-term cognitive impairment is increasingly important, as the rate of prematurity has risen and infants are surviving at progressively lower gestational ages. Although anatomical abnormalities, identified with ultrasound and MRI, have been shown to lead to poor long-term outcomes, it is not clear why infants with an uncomplicated course and no brain lesions after premature birth are still at higher risk for cognitive impairment relative to infants born at term, and conversely why some infants with brain lesions do not suffer from impaired abilities. Therefore, the long-term goal is o identify a complimentary set of functional brain markers to help clinicians recognize which infants will need additional intervention to achieve improved outcomes. Sensorimotor mu rhythm activity has been associated with a cortical network which is important for imitation skills, understanding other's intentions, and additional theory of mind abilities. The objective of the current project is to characterize the sensorimotor mu rhythm and mu rhythm suppression in preterm relative to term infants longitudinally, at 3 and 6 months adjusted age. The central hypothesis is that infants with atypical brain development will present with impaired sensorimotor mu rhythm development and these delays will correspond with impaired cognitive development. This hypothesis was developed based on literature demonstrating motor delays and anatomical abnormalities in the sensorimotor region in prematurely born infants. Furthermore, our published results provide evidence for a rapid progression of the frequency of the mu rhythm at very young ages providing a measure to track brain development. This hypothesis will be tested through the following specific aim: To characterize and compare the development of the mu rhythm associated with motor activity in young infants at 3 and 6 months corrected-age in two participant groups: a) healthy full-term infants and b) premature infants (<28 weeks gestational age) without evidence of brain abnormalities or lesions. This project will use simultaneous magnetoencephalography (MEG) and electroencephalography (EEG), to monitor spontaneous mu rhythm activity and mu rhythm suppression using three conditions: rest, infant hand squeeze, and infant observation of investigator hand squeeze. The preliminary results provide evidence that this paradigm can be performed quickly and without the need for infants to understand task instruction. Comparison of the three conditions allows one to: a) identify the frequency of mu rhythm activity; and b) quantify mu rhythm suppression in the action (squeeze) and observation conditions. This approach is innovative because we are using a multimodal functional neuroimaging approach, drawing on the strengths of each technique, to test a novel paradigm for preterm infants, which has been linked to imitation and higher cognitive abilities. This project is significant because it will evaluate a characteristic of the preterm brain that develops rapidly in term infants, providing a potential marker of atypical brain development in preterm infants, to help identify children in need of early intervention. PUBLIC HEALTH RELEVANCE: Prematurity as a risk factor for long-term cognitive impairment is relevant to public health because of the high incidence of premature birth and significant neurodevelopmental abnormalities occurring after premature birth. This project will characterize a functional measure of brain development in term and preterm infants, which could be used to identify the infants at the greatest risk of impairment in order to optimize opportunities for intervention. This project is relevant to the component of the NIH mission that calls for methods to help all children to achieve their full potential.