Longitudinal functional brain connectivity maturation in premature newborn infants: Modulatory influence of early music enrichment.

Premature birth affects brain maturation, illustrated by altered brain functional connectivity at term equivalent age (TEA) and alters neurobehavioral outcome. To correct early developmental differences and improve neurological outcome, music during the neonatal intensive care unit (NICU) stay has been proposed as an auditory enrichment with modulatory effects on functional and structural brain development, but longitudinal effects of such interventions have not been studied so far. We longitudinally investigated resting-state functional connectivity (RS-FC) maturation in preterm infants (n = 43). Data-driven Independent Component Analyses (ICA) were performed on scans obtained at 33- and 40-week gestational age (GA), determining the presence of distinct resting-state networks (RSNs). Connectome analysis "accordance measure" quantitively examined the RS-FC both at 33- and 40-week GA. Further comparing the internetwork RS-FC at 33- and 40-week GA provided a circuitry of interest (COI) for significant maturational changes in which the effects on the RS-FC of a music intervention were tested. The connectome analyses resulted in a COI of RS-FC connections significantly maturing from 33 to 40 weeks GA, namely between the thalamic/brainstem and prefrontal-limbic, salience, sensorimotor, auditory, and prefrontal cortical networks; between the prefrontal-limbic and cerebellar, visual and left hemispheric precuneus networks; between the salience and visual, and cerebellar networks; and between the sensorimotor and auditory, and posterior cingulate/precuneus networks. The infants exposed to music exhibited significantly increased maturation in RS-FC between the thalamic/brainstem and salience networks, compared with controls. This study exemplifies that preterm infant RS-FC maturation is modulated through NICU music exposure, highlighting the importance of environmental enrichment for neurodevelopment in premature newborns.