Greater than 37 weeks without perinatal complications. There were a total of 38 pre-adolescent children recruited with a median age of approximately 10 years for late preterms and approximately 10 years for term controls. Thirteen resting-stated BOLD MRI studies were removed for technical reasons (motion-related artifacts) resulting in a total of 25 subjects for final Resiquimod clinical trials functional connectivity analysis (11 preterm and 14 full-term preadolescent children).Neurocognitive AssessmentThe neuropsychological test battery performed by all participants included the Rey-Osterrieth Complex Figure Test (CFT), the Trail Making Test (children’s version), and selected subtests of the NEPSY-II assessing visuospatial, visuo-perceptual, and memory functions: Affect Recognition, Memory for Designs, Block Construction, Geometric Puzzles, and Route Finding. jir.2014.0227 No significant difference in cognitive performance was seen between preterm and term preadolescents after controlling for age (MANCOVA, F (12,27) = 0.735, p > 0.5). A nominally significant difference in the direction of the preterm preadolescents outperforming the term preadolescents was detected only on Block Construction (F (1,37) = 4.131, p = 0.049), not surviving correction for multiple comparisons.Resting State Functional Connectivity ResultsPosteromedial Cortex. Late preterm individuals during preadolescent childhood demonstrate increased functional connectivity when seeding from the PMC as shown in Fig 2. Increased functional connectivity strength was noted within the posterior DMN of the parietal and occipital cortices. Significantly increased anti-correlation was present within the dorsolateral prefrontal cortex for late preterms ?a key component of the central-order PNPP executive network. As shown in Fig 3, the patterns of connectivity increases in late preterm individuals demonstrate similar increased connectivity within the posterior parietal and occipital cortices of the posterior DMN for both precuneus and posterior cingulate seeding. Posterior cingulate seeding demonstrated slightly greater increased connectivity within the posterior DMN. More importantly, the posterior cingulate cortex seeds demonstrated anti-correlation with the salience network components (insular cortex) and central executive network (prefrontal cortex) not observed with precuneus seeding. This finding suggests decreased connectivity involving both the salience and central-executive networks in late preterm children.PLOS ONE | DOI:10.1371/journal.pone.0130686 June jir.2014.0227 22,7 /Altered Brain Connectivity in Late Preterm ChildrenFig 2. Posteromedial Cortex Connectivity Comparison of Late Preterms versus Term Control Children. Representative plots on standard anatomic images demonstrate increases in functional connectivity in late preterms within the posterior DMN components. There is significant decreased connectivity to components of the executive network (right frontal). These findings are consistent with late prematurity-related posterior DMN hyperconnectivity and increased anti-correlation (decreased functional connectivity) to the central-executive network. doi:10.1371/journal.pone.0130686.gStrength of increased functional connectivity within the posterior DMN was greater for the right hemispheric seeds compared to left-sided seeding as displayed in Fig 4 and verified by statistical testing (data not presented). Lateral Parietal Cortex. Hyperconnectivity of the DMN in late preterm children was also demonstrated when seeding from the l.Greater than 37 weeks without perinatal complications. There were a total of 38 pre-adolescent children recruited with a median age of approximately 10 years for late preterms and approximately 10 years for term controls. Thirteen resting-stated BOLD MRI studies were removed for technical reasons (motion-related artifacts) resulting in a total of 25 subjects for final functional connectivity analysis (11 preterm and 14 full-term preadolescent children).Neurocognitive AssessmentThe neuropsychological test battery performed by all participants included the Rey-Osterrieth Complex Figure Test (CFT), the Trail Making Test (children’s version), and selected subtests of the NEPSY-II assessing visuospatial, visuo-perceptual, and memory functions: Affect Recognition, Memory for Designs, Block Construction, Geometric Puzzles, and Route Finding. jir.2014.0227 No significant difference in cognitive performance was seen between preterm and term preadolescents after controlling for age (MANCOVA, F (12,27) = 0.735, p > 0.5). A nominally significant difference in the direction of the preterm preadolescents outperforming the term preadolescents was detected only on Block Construction (F (1,37) = 4.131, p = 0.049), not surviving correction for multiple comparisons.Resting State Functional Connectivity ResultsPosteromedial Cortex. Late preterm individuals during preadolescent childhood demonstrate increased functional connectivity when seeding from the PMC as shown in Fig 2. Increased functional connectivity strength was noted within the posterior DMN of the parietal and occipital cortices. Significantly increased anti-correlation was present within the dorsolateral prefrontal cortex for late preterms ?a key component of the central-executive network. As shown in Fig 3, the patterns of connectivity increases in late preterm individuals demonstrate similar increased connectivity within the posterior parietal and occipital cortices of the posterior DMN for both precuneus and posterior cingulate seeding. Posterior cingulate seeding demonstrated slightly greater increased connectivity within the posterior DMN. More importantly, the posterior cingulate cortex seeds demonstrated anti-correlation with the salience network components (insular cortex) and central executive network (prefrontal cortex) not observed with precuneus seeding. This finding suggests decreased connectivity involving both the salience and central-executive networks in late preterm children.PLOS ONE | DOI:10.1371/journal.pone.0130686 June jir.2014.0227 22,7 /Altered Brain Connectivity in Late Preterm ChildrenFig 2. Posteromedial Cortex Connectivity Comparison of Late Preterms versus Term Control Children. Representative plots on standard anatomic images demonstrate increases in functional connectivity in late preterms within the posterior DMN components. There is significant decreased connectivity to components of the executive network (right frontal). These findings are consistent with late prematurity-related posterior DMN hyperconnectivity and increased anti-correlation (decreased functional connectivity) to the central-executive network. doi:10.1371/journal.pone.0130686.gStrength of increased functional connectivity within the posterior DMN was greater for the right hemispheric seeds compared to left-sided seeding as displayed in Fig 4 and verified by statistical testing (data not presented). Lateral Parietal Cortex. Hyperconnectivity of the DMN in late preterm children was also demonstrated when seeding from the l.