Children born very prematurely (≤32 weeks) often exhibit visual-perceptual difficulties at school-age even in the absence of major neurological impairment. may have heightened vulnerability to neonatal pain. In a cohort of school-age children followed since birth we assessed relations between functional brain activity measured using magnetoencephalogragy (MEG) visual-perceptual abilities and cumulative neonatal pain. We demonstrated alterations in the spectral structure of spontaneous cortical oscillatory activity in ELGA children at school-age. Cumulative neonatal pain-related stress was associated with changes in background cortical rhythmicity in these children and these alterations in spontaneous brain oscillations were negatively correlated with visual-perceptual abilities at school-age and were not driven by potentially confounding neonatal variables. These findings provide the first evidence linking neonatal painrelated stress the development of functional brain activity and school-age cognitive outcome in these vulnerable children. to denote pain-related stress. Thalamocortical connectivity is undergoing various stages of development during the ELGA and VLGA periods and is critical for how sensory information including pain is transmitted and processed in the neonatal brain . The subplate a transient structure critical for development of thalamocortical connectivity reaches peak size during the ELGA period and Cd44 is highly vulnerable to insult . Thalamocortical interactions are critical for cortical oscillations  which are vital for cognition and perception [52 64 Mogroside VI Therefore we compared long-term effects of pain in children born at ELGA compared to those born at VLGA. The spectral structure of cortical oscillations expressed in power ratios among oscillations in different frequency ranges develops throughout childhood [8 28 and is altered in at-risk children [1 9 34 Young adults born at extremely low birth weight display an atypical ratio of low- to high-frequency power in resting brain rhythms  likely reflecting the development of functional brain activity as alpha- and gamma-band oscillations which are understood to play reciprocal roles in cognition and perception [12 15 22 26 29 30 39 51 Very preterm children often display selective difficulties at school age in visual-perceptual abilities [eg 4 21 60 67 We previously found alterations in the spectrum of spontaneous neuromagnetic oscillations in school-age children born very prematurely (≤32 weeks gestational age (GA))  Mogroside VI and demonstrated that such atypicalities are related to Mogroside VI selective difficulties in visual-perceptual abilities in this population . In the present study we used magnetoencephalography (MEG) to investigate spontaneous neuromagnetic activity in schoolage ELGA VLGA and full-term children. Among the preterm children we examined cumulative neonatal pain (adjusted for clinical confounders) in relation to spontaneous neuromagnetic oscillations and to school-age visual-perceptual abilities. Due the distinct phases of thalamocortical development occurring in the ELGA and VLGA periods we hypothesized that neonatal pain-related stress would impact primarily children born at ELGA. 2 Methods 2.1 Subjects We studied 54 preterm children: 22 were born at ELGA (24 to 28 wks) (10 girls 12 boys; mean age 7.74 years SD = 0.39); and 32 were born at VLGA (28 to 32 wks) (21 girls 11 boys; mean age 7.72 years SD = 0.40). They were seen as part of a longitudinal study of the long-term effects of neonatal pain on neurocognitive development in children born very preterm [17 19 21 Neonatal characteristics for the preterm group are provided in Table 1. Twenty-five age-matched full-term control children (17 girls 8 boys; Mogroside VI mean age 7.61 years SD = 0.46) were recruited from the longitudinal study and from the community by advertisement. Informed consent was obtained from each child and parent. Exclusion criteria were major sensory motor or cognitive impairment current psychoactive medications (eg Ritalin for attention deficit hyperactivity disorder) or significant brain injury (periventricular leukomalacia or grade III-IV intraventricular hemorrhage) as evidenced on neonatal cranial ultrasound . As expected ELGA infants had significantly higher scores on all neonatal risk and illness factors (eg gestational age illness severity Supplemental Nutrition Assistance Program (SNAP) II number of skin-breaking procedures and days of.