Background and ObjectiveTo investigate the relation of early brain activity with structural (growth of the cortex and cerebellum) and white matter microstructural brain development.MethodsA total of 33 preterm neonates (gestational age 26±1 weeks) without major brain abnormalities were continuously monitored with electroencephalography during the first 48 h of life. Rate of spontaneous activity transients per minute (SAT rate) and inter-SAT interval (ISI) in seconds per minute were calculated. Infants underwent brain magnetic resonance imaging ∼30 (mean 30.5; min: 29.3-max: 32.0) and 40 (41.1; 40.0-41.8) weeks of postmenstrual age. Increase in cerebellar volume, cortical gray matter volume, gyrification index, fractional anisotropy (FA) of posterior limb of the internal capsule, and corpus callosum (CC) were measured.ResultsSAT rate was positively associated with cerebellar growth (P=0.01), volumetric growth of the cortex (P=0.027), increase in gyrification (P=0.043), and increase in FA of the CC (P=0.037). ISI was negatively associated with cerebellar growth (P=0.002).ConclusionsIncreased early brain activity is associated with cerebellar and cortical growth structures with rapid development during preterm life. Higher brain activity is related to FA microstructural changes in the CC, a region responsible for interhemispheric connections. This study underlines the importance of brain activity for microstructural brain development.