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Attention and Regional Gray Matter Development in Very Preterm Children at Age 12 Years

  • Rachel E. Lean (a1), Tracy R. Melzer (a2) (a3), Samudragupta Bora (a4), Richard Watts (a5) and Lianne J. Woodward (a6) (a7)...


Objectives: This study examines the selective, sustained, and executive attention abilities of very preterm (VPT) born children in relation to concurrent structural magnetic resonance imaging (MRI) measures of regional gray matter development at age 12 years. Methods: A regional cohort of 110 VPT (≤32 weeks gestation) and 113 full term (FT) born children were assessed at corrected age 12 years on the Test of Everyday Attention-Children. They also had a structural MRI scan that was subsequently analyzed using voxel-based morphometry to quantify regional between-group differences in cerebral gray matter development, which were then related to attention measures using multivariate methods. Results: VPT children obtained similar selective (p=.85), but poorer sustained (p=.02) and executive attention (p=.01) scores than FT children. VPT children were also characterized by reduced gray matter in the bilateral parietal, temporal, prefrontal and posterior cingulate cortices, bilateral thalami, and left hippocampus; and increased gray matter in the occipital and anterior cingulate cortices (family-wise error–corrected p<.05). Poorer sustained auditory attention was associated with increased gray matter in the anterior cingulate cortex (p=.04). Poor executive shifting attention was associated with reduced gray matter in the right superior temporal cortex (p=.04) and bilateral thalami (p=.05). Poorer executive divided attention was associated with reduced gray matter in the occipital (p=.001), posterior cingulate (p=.02), and left temporal (p=.01) cortices; and increased gray matter in the anterior cingulate cortex (p=.001). Conclusions: Disturbances in regional gray matter development appear to contribute, at least in part, to the poorer attentional performance of VPT children at school age. (JINS, 2017, 23, 539–550)


Corresponding author

Correspondence and reprint requests to: Lianne Woodward, Department of Pediatric Newborn Medicine, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115. E-mail:


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Aarnoudse-Moens, C., Weisglas-Kuperus, N., van Goudoever, B., & Oosterlaan, J. (2009). Meta-analysis of neurobehavioral outcomes in very preterm and/or very low birth weight children. Pediatrics, 124, 717728.
Anderson, P.J., & Doyle, L.W. (2004). Executive Functioning in School-Aged Children Who Were Born Very Preterm or With Extremely Low Birth Weight in the 1990s. Pediatrics, 114(1), 5057.
Anderson, P.J., De Luca, C., Hutchinson, E., Spencer-Smith, M., Roberts, G., & Doyle, L. (2011). Attention problems in a representative sample of extremely preterm/extremely low birth weight children. Developmental Neuropsychology, 36, 5773.
Ashburner, J. (2007). A fast diffeomorphic image registration algorithm. Neuroimage, 38, 95113.
Ashburner, J. (2009). Computational Anatomy with the SPM Software. Magnetic Resonance Imaging, 27, 11631174.
Ashburner, J., & Friston, K.J. (2000). Voxel-based morphometry--The methods. Neuroimage, 11, 805821.
Bayless, S., & Stevenson, J. (2007). Executive functions in school age children born very prematurely. Early Human Development, 83, 247254.
Berg, R.W., Alaburda, A., & Hounsgaard, J. (2007). Balanced inhibition and excitation drive spike activity in spinal half-centers. Science, 315(5810), 390393.
Bhutta, A.T., Cleves, M.A., Casey, P.H., Cradock, M.M., & Ananad, K.J.S. (2002). Cognitive and behavioral outcomes of school aged children who were born preterm. Journal of the American Medical Association, 288, 728737.
Boardman, J., Counsell, S., Rueckert, D., Kapellou, O., Bhatia, K., Aljabar, P., & Edwards, D. (2006). Abnormal deep grey matter development following very preterm birth detected using deformation-based morphometry. Neuroimage, 32, 7078.
Bora, S., Pritchard, V., Chen, Z., Inder, T., & Woodward, L. (2014). Neonatal cerebral morphometry and later risk of persistent inattention/hyperactivity in children born very preterm. Journal of Child Psychology and Psychiatry, 55, 828838.
Cohen, R. (2014). The neuropsychology of attention (2nd ed.), New York: Springer.
Davidesco, I., Harel, M., Ramot, M., Kramer, U., Kipervasser, S., Andelman, F., & Malach, R. (2013). Spatial and object-based attention modulates broadband high-frequency responses across the human visual cortical hierarchy. The Journal of Neuroscience, 33, 12281240.
de Kieviet, J., van Elburg, R., Lafeber, H., & Oosterlaan, J. (2012). Attention problems of very preterm children compared with age-matched term controls at school age. Journal of Pediatrics, 161, 824829.
De Pisapia, N., & Braver, T. (2006). A model of dual control mechanisms through anterior cingulate and prefrontal cortex interactions. Neurocomputing, 69, 13221326.
Dosenbach, N.U.F., Fair, D.A., Cohen, A.L., Schlaggar, B.L., & Petersen, S.E. (2008). A dual-networks architecture of top-down control. Trends in Cognitive Sciences, 12, 99105.
Elley, W.B., & Irving, J.C. (2003). The Elley-Irving Socio-Economic Index: 2001 Census Revision. New Zealand Journal of Educational Studies, 38, 317.
Fan, J., McCandliss, B., Sommer, T., Raz, A., & Posner, M. (2002). Testing the efficiency and independence of attentional networks. Journal of Cognitive Neuroscience, 14, 340347.
Giedd, J., Blumenthal, J., Jeffries, N., Castellanos, F., Liu, H., Zijdenbos, A., & Rapoport, J. (1999). Brain development during childhood: A longitudinal MRI study. Nature Neuroscience, 2, 861863.
Good, C., Johnsrude, J., Ashburner, J., Henson, R., Friston, K., & Frackowiak, R. (2001). A voxel-based morphometric study of ageing in 465 normal adult human brains. Neuroimage, 14, 2136.
Greicius, M.D., Krasnow, B., Reiss, A.L., & Menon, V. (2003). Functional connectivity in the resting brain: A network analysis of the default mode hypothesis. Proceedings of the National Academy of Sciences of the United States of America, 100(1), 253258.
Heinze, H.J., Mangun, G.R., Burchert, W., Hinrichs, H., Scholz, M., Munte, T.F., & Hillyard, S.A. (1994). Combined spatial and temporal imaging of brain activity during visual selective attention in humans. Nature, 272, 543546.
Iwata, S., Nakamura, T., Kihara, H., Takashima, S., Matsushi, T., & Iwata, O. (2012). Qualitative brain MRI at term and cognitive outcomes at 9 years after very preterm birth. Pediatrics, 129, e1138e1147.
Jaekel, J., Wolke, D., & Bartmann, P. (2013). Poor attention rather than hyperactivity/ impulsivity predicts academic achievement in very preterm and full-term adolescents. Psychological Medicine, 43, 183196.
Kastner, S., Saalmann, Y., & Schneider, K. (2012). Thalamic control of visual attention. In G. Mangun (Ed.), The neuroscience of attention: Attention control and selection. Oxford: Oxford University Press.
Kesler, S., Ment, L., Vohr, B., Pajot, S., Schneider, K., Katz, K., & Reiss, A. (2004). Volumetric analysis of regional cerebral development in preterm children. Pediatric Neurology, 31, 318325.
Kesler, S., Reiss, L., Vohr, B., Watson, C., Schneider, K., Katz, K., & Ment, L. (2008). Brain volume reductions within multiple cognitive systems in male preterm children at age twelve. Journal of Pediatrics, 152, 513520.
Kinomura, S., Larsson, J., Gulyás, B., & Roland, P.E. (1996). Activation by attention of the human reticular formation and thalamic intralaminar nuclei. Science, 271, 512515.
Konrad, K., Neufang, S., Thiel, C., Specht, K., Hanisch, C., Fan, J., & Fink, G. (2005). Development of attentional networks: An fMRI study with children and adults. Neuroimage, 28, 429439.
Leech, R., Braga, R., & Sharp, D. (2012). Echoes of the brain within the posterior cingulate cortex. Journal of Neuroscience, 32, 215222.
Leech, R., Kamourieh, S., Beckmann, C.F., & Sharp, D.J. (2011). Fractionating the default mode network: Distinct contributions of the ventral and dorsal posterior cingulate cortex to cognitive control. Journal of Neuroscience, 31, 32173224.
Leviton, A., & Gressens, P. (2007). Neuronal damage accompanies perinatal white matter damage. Trends in Neurosciences, 30, 473478.
Manly, T., Anderson, V., Nimmo-Smith, I., Turner, A., Watson, P., & Robertson, I. (2001). The differential assessment of children’s attention: The Test of Everyday Attention for Children (TEA-Ch), normative sample and ADHD performance. Journal of Child Psychology and Psychiatry, 42, 10651081.
Marshall, W.A., & Tanner, J.M. (1969). Variations in pattern of pubertal changes in girls. Archives of Disease in Childhood, 44, 291303.
Marshall, W.A., & Tanner, J.M. (1970). Variations in the pattern of pubertal changes in boys. Archives of Disease in Childhood, 45, 1323.
Mechelli, A., Price, C., Friston, K., & Ashburner, J. (2005). Voxel-based morphometry of the human brain: Methods and applications. Current Medical Imaging Reviews, 1, 19.
Mulder, H., Pitchford, N., Hagger, M., & Marlow, N. (2009). Development of executive function and attention in preterm children: A systematic review. Developmental Neuropsychology, 34, 393421.
Mulder, H., Pitchford, N., & Marlow, N. (2011). Processing speed mediates executive function difficulties in very preterm children in middle childhood. Journal of the International Neuropsychological Society, 17, 445454.
Murner-Lavanchy, I., Steinlin, M., Nelle, C., Rummel, W, Perrig, G., Schroth, G., & Everts, R. (2014). Delay of cortical thinning in very preterm born children. Early Human Development, 90, 443450.
Murray, A., Scratch, S., Thompson, D., Inder, T., Doyle, L., Anderson, J., & Anderson, P. (2014). Neonatal brain pathology predicts adverse attention and processing speed outcomes in very preterm children and/or very low birth weight children. Neuropsychology, 28, 552562.
Murray, A., Thompson, D., Pascoe, L., Leemans, A., Inder, T., Doyle, L., & Anderson, P. (2016). White matter abnormalities and impaired attention abilities in children born very preterm. Neuroimage, 124, 7584.
Nagy, Z., Ashburner, J., Andersson, J., Jbabdi, S., Draganski, B., Skare, S., & Largercrantz, H. (2009). Structural correlates of preterm birth in the adolescent brain. Pediatrics, 214, 964972.
Nosarti, C., Giouroukou, E., Healy, E., Rifkin, L., Walshe, M., Reichenberg, A., & Murray, R. (2008). Gray and white matter distribution in very preterm adolescents mediates neurodevelopmental outcome. Brain, 131, 205217.
Nosarti, C., Mechelli, A., Herrera, A., Walshe, M., Shergill, S., Murray, R., & Allin, P. (2011). Structural covariance in the cortex of very preterm adolescents: A voxel-based morphometry study. Human Brain Mapping, 32, 16151625.
Petersen, S., & Posner, M. (2012). The attention system of the human brain: 20 years after. Annual Review of Neuroscience, 35, 7389.
Peterson, B., Vohr, B., Staib, L., Cannistraci, C., Dolberg, A., Schneider, K., & Ment, L. (2000). Regional volume abnormalities and long-term cognitive outcome in preterm infants. Journal of American Medical Association, 284, 19391947.
Posner, M., & Petersen, S. (1990). The attention system of the human brain. Annual Review of Neuroscience, 13, 2542.
Power, J.D., Cohen, A.L., Nelson, S.M., Wig, G.S., Barnes, K.A., Church, J.A., & Petersen, S.E. (2011). Functional network organization of the human brain. Neuron, 72(4), 665678.
Reuter, M., Tisdall, M., Qureshi, A., Buckner, R., van der Kouwe, A., & Fischl, B. (2015). Head motion during MRI acquisition reduces gray matter volume and thickness estimates. Neuroimage, 107, 107115.
Sadaghiani, S., & D’Esposito, M. (2014). Functional characterization of the cingulo-opercular network in the maintenance of tonic alertness. Cerebral Cortex, 25, 27632773.
Sarter, M., Givens, B., & Bruno, J. (2001). The cognitive neuroscience of sustained attention: Where top-down meets bottom-up. Brain Research Reviews, 35, 146160.
Shah, D.K., Guinane, C., August, P., Austin, N.C., Woodward, L.J., Thompson, D.K., & Inder, T.E. (2006). Reduced occipital regional volumes at term predict impaired visual function in early childhood in very low birth weight infants. Investigative Ophthalmology & Visual Science, 47, 33663373.
Shapiro, K., Hillstrom, A.P., & Husain, M. (2002). Control of visuotemporal attention by inferior parietal and superior temporal cortex. Current Biology, 12, 13201325.
Shenhav, A., Botvinick, M.M., & Cohen, J.D. (2013). The expected value of control: An integrative theory of anterior cingulate cortex function. Neuron, 79, 217240.
Shum, D., Neulinger, K., O’Callaghn, M., & Mohay, H. (2008). Attentional problems in children born very preterm or with extremely low birth weight at 7 – 9 years. Archives of Clinical Neuropsychology, 23, 103112.
Soria-Pastor, S., Padilla, N., Zubiaurre-Elorza, L., Ibarretxe-Bilbao, N., Botet, F., Costas-Moragas, C., & Junque, C. (2009). Decreased regional brain volume and cognitive impairment in preterm children at low risk. Pediatrics, 124, e1161e1170.
Statistics New Zealand. (2001). 2001 Census: Regional Summary. Retrieved from
Thompson, D.K., Chen, J., Beare, R., Adamson, C., Ellis, R., Ahmadzai, Z., & Anderson, P.J. (2016). Structural connectivity relates to perinatal factors and functional impairments at 7 years in children born very preterm. Neuroimage, 134, 328337.
Thompson, D.K., Lee, K.J., van Bijnen, L., Leemans, A., Pascoe, L., Scratch, S.E., & Anderson, P.J. (2015). Accelerated corpus callosum development in prematurity predicts improved outcome: Longitudinal corpus callosum development. Human Brain Mapping, 36, 37333748.
Urben, S., Van Hanswijck De Jonge, L., Barishnikov, R., Pizzo, R., Monnier, M., Lazeyras, F., & Hüppi, P. (2015). Gestational age and gender influence on executive control and its related neural structures in preterm-born children at age 6 years. Child Neuropsychology, 23, 188207.
Volpe, J. (2009a). Brain injury in premature infants: A complex amalgam of destructive and developmental disturbances. Lancet Neurology, 8, 110124.
Volpe, J. (2009b). The encephalopathy of prematurity—Brain injury and impaired brain development inextricably intertwined. Seminars in Pediatric Neurology, 16, 167178.
Vossel, S., Geng, J.J., & Fink, G.R. (2014). Dorsal and ventral attention systems. The Neuroscientist, 20, 150159.
Waber, D., Moor, C., Forbes, P., Almli, C., Botteron, K., Leonard, G., & Rumsey, J. (2007). The NIH MRI study of normal brain development: Performance of a population based sample of healthy children aged 6 to 18 years on a neuropsychological test battery. Journal of the International Neuropsychological Society, 13, 118.
Wilson-Ching, M., Molloy, C., Anderson, V., Burnett, A., Roberts, G., Cheong, J., & Anderson, P.J. (2013). Attention difficulties in a contemporary geographic cohort of adolescents born extremely preterm/extremely low birth weight. Journal of the International Neuropsychology Society, 19, 10971108.
Woldorff, M.G., Liotti, M., Seabolt, M., Busse, L., Lancaster, J.L., & Fox, P.T. (2002). The temporal dynamics of the effects in occipital cortex of visual-spatial selective attention. Cognitive Brain Research, 15, 115.
Woodward, L.J., Anderson, P.J., Austin, N.C., Howard, K., & Inder, T.E. (2006). Neonatal MRI to predict neurodevelopmental outcomes in preterm infants. New England Journal of Medicine, 355, 685694.
Woodward, L.J., Clark, C., Bora, S., & Inder, T.E. (2012). Neonatal white matter abnormalities. An Important predictor of neurocognitive outcome for very preterm children. PLoS One, 7, e51879.
Zhang, Y., Inder, T.E., Neil, J., Dierker, D., Alexopoulos, D., Anderson, P.J., & Van Essen, D. (2015). Cortical structural abnormalities in very preterm children at 7 years of age. Neuroimage, 109, 469479.


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Attention and Regional Gray Matter Development in Very Preterm Children at Age 12 Years

  • Rachel E. Lean (a1), Tracy R. Melzer (a2) (a3), Samudragupta Bora (a4), Richard Watts (a5) and Lianne J. Woodward (a6) (a7)...


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