Skip to main content Accessibility help
×
Home

Pediatric Brain Development in Down Syndrome: A Field in Its Infancy

  • Taralee Hamner (a1), Manisha D. Udhnani (a1), Karol Z. Osipowicz (a1) and Nancy Raitano Lee (a1)

Abstract

Objectives: As surprisingly little is known about the developing brain studied in vivo in youth with Down syndrome (DS), the current review summarizes the small DS pediatric structural neuroimaging literature and begins to contextualize existing research within a developmental framework. Methods: A systematic review of the literature was completed, effect sizes from published studies were reviewed, and results are presented with respect to the DS cognitive behavioral phenotype and typical brain development. Results: The majority of DS structural neuroimaging studies describe gross differences in brain morphometry and do not use advanced neuroimaging methods to provide nuanced descriptions of the brain. There is evidence for smaller total brain volume (TBV), total gray matter (GM) and white matter, cortical lobar, hippocampal, and cerebellar volumes. When reductions in TBV are accounted for, specific reductions are noted in subregions of the frontal lobe, temporal lobe, cerebellum, and hippocampus. A review of cortical lobar effect sizes reveals mostly large effect sizes from early childhood through adolescence. However, deviance is smaller in adolescence. Despite these smaller effects, frontal GM continues to be largely deviant in adolescence. An examination of age-frontal GM relations using effect sizes from published studies and data from Lee et al. (2016) reveals that while there is a strong inverse relationship between age and frontal GM volume in controls across childhood and adolescence, this is not observed in DS. Conclusions: Further developmentally focused research, ideally using longitudinal neuroimaging, is needed to elucidate the nature of the DS neuroanatomic phenotype during childhood and adolescence. (JINS, 2018, 24, 966–976)

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Pediatric Brain Development in Down Syndrome: A Field in Its Infancy
      Available formats
      ×

      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      Pediatric Brain Development in Down Syndrome: A Field in Its Infancy
      Available formats
      ×

      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      Pediatric Brain Development in Down Syndrome: A Field in Its Infancy
      Available formats
      ×

Copyright

Corresponding author

*Correspondence and reprint requests to: Taralee Hamner, Department of Psychology, Drexel University, 3141 Chestnut Street, Stratton 119, Philadelphia, PA 19104. E-mail: taralee.hamner@gmail.com

References

Hide All
Anderson, J.S., Nielsen, J.A., Ferguson, M.A., Burback, M.C., Cox, E.T., Dai, L., & Korenberg, J.R. (2013). Abnormal brain synchrony in Down syndrome. Neuroimage: Clinical, 2, 703715. doi: 10.1016/j.nicl.2013.05.006
Blanken, A.E., Hurtz, S., Zarow, C., Biado, K., Honarpisheh, H., Somme, J., & Lo, D. (2017). Associations between hippocampal morphometry and neuropathologic markers of Alzheimer’s disease using 7T MRI. NeuroImage: Clinical, 15, 5661.
Buckner, R.L. (2013). The cerebellum and cognitive function: 25 years of insight from anatomy and neuroimaging. Neuron, 80(3), 807815.
Bunge, S.A., & Kahn, I. (2009). Cognition: An overview of neuroimaging techniques. Encyclopedia of Neuroscience, 2, 10631067.
Carducci, F., Onorati, P., Condoluci, C., Di Gennaro, G., Quarato, P.P., Pierallini, A., & Albertini, G. (2013). Whole-brain voxel-based morphometry study of children and adolescents with Down syndrome. Functional Neurology, 28(1), 1928.
Carter, J.C., Capone, G.T., & Kaufmann, W.E. (2008). Neuroanatomic correlates of autism and stereotypy in children with Down syndrome. Neuroreport, 19(6), 653656.
Clark, C.A.C., Fernandez, F., Sakhon, S., Spano, G., & Edgin, J.O. (2017). The medial temporal memory system in Down syndrome: Translating animal models of hippocampal compromise. Hippocampus, 27(6), 683691. doi: 10.1002/hipo.22724
Cohen, J. (1988). Statistical power analysis for the behavioral sciences. Hilsdale, NJ: Lawrence Earlbaum Associates.
Collins, D.L., Holmes, C.J., Peters, T.M., & Evans, A.C. (1995). Automatic 3‐D model‐based neuroanatomical segmentation. Human Brain Mapping, 3(3), 190208.
Fenoll, R., Pujol, J., Esteba-Castillo, S., De Sola, S., Ribas-Vidal, N., García-Alba, J., & Dierssen, M. (2017). Anomalous white matter structure and the effect of age in Down syndrome patients. Journal of Alzheimer’s Disease, 57(1), 6170.
Fidler, D., Most, D., & Philofsky, A. (2009). The Down syndrome behavioural phenotype: Taking a developmental approach. Retrieved from https://www.researchgate.net/publication/253424551_The_Down_syndrome_behavioural_phenotype_Taking_a_developmental_approach.
Friederici, A.D., & Gierhan, S.M. (2013). The language network. Current Opinion in Neurobiology, 23(2), 250254. doi: 10.1016/j.conb.2012.10.002
Gibson, D. (1978). Down syndrome: The psychology of mongolism. London: Cambridge University Press.
Giedd, J.N. (2008). The teen brain: Insights from neuroimaging. Journal of Adolescent Health, 42(4), 335343. doi: 10.1016/j.jadohealth.2008.01.007
Giedd, J.N., Stockman, M., Weddle, C., Liverpool, M., Alexander-Bloch, A., Wallace, G.L., & Lenroot, R.K. (2010). Anatomic magnetic resonance imaging of the developing child and adolescent brain and effects of genetic variation. Neuropsychology Review, 20(4), 349361. doi: 10.1007/s11065-010-9151-9
Gogtay, N., Giedd, J.N., Lusk, L., Hayashi, K.M., Greenstein, D., Vaituzis, A.C., & Thompson, P.M. (2004). Dynamic mapping of human cortical development during childhood through early adulthood. Proceeding of the National Academy of Sciences of the United States of America, 101(21), 81748179. doi: 10.1073/pnas.0402680101
Gunbey, H.P., Bilgici, M.C., Aslan, K., Has, A.C., Ogur, M.G., Alhan, A., & Lutfi, I. (2017). Structural brain alterations of Down’s syndrome in early childhood evaluation by DTI and volumetric analyses. European Journal of Radiology, 27(7), 30133021.
Gunning‐Dixon, F.M., Brickman, A.M., Cheng, J.C., & Alexopoulos, G.S. (2009). Aging of cerebral white matter: A review of MRI findings. International Journal of Geriatric Psychiatry, 24(2), 109117.
Hickok, G., & Poeppel, D. (2004). Dorsal and ventral streams: A framework for understanding aspects of the functional anatomy of language. Cognition, 92(1-2), 6799. doi: 10.1016/j.cognition.2003.10.011
Huttenlocher, P.R. (1979). Synaptic density in human frontal cortex-developmental changes and effects of aging. Brain Research, 163(2), 195205.
Isaacs, E., Vargha-Khadem, F., Watkins, K., Lucas, A., Mishkin, M., & Gadian, D. (2003). Developmental amnesia and its relationship to degree of hippocampal atrophy. Proceedings of the National Academy of Sciences of the United States of America, 100(22), 1306013063.
Jacola, L.M., Byars, A.W., Chalfonte-Evans, M., Schmithorst, V.J., Hickey, F., Patterson, B., & Holland, S.K. (2011). Functional magnetic resonance imaging of cognitive processing in young adults with Down syndrome. American Journal on Intellectual and Developmental Disabilities, 116(5), 344359.
Jarrold, C., Baddeley, A.D., & Phillips, C. (2007). Long-term memory for verbal and visual information in Down syndrome and Williams syndrome: Performance on the Doors and People test. Cortex, 43(2), 233247.
Jernigan, T.L., & Bellugi, U. (1990). Anomalous brain morphology on magnetic resonance images in Williams syndrome and Down syndrome. Archives of Neurology, 47(5), 529533.
Jernigan, T.L., Bellugi, U., Sowell, E., Doherty, S., & Hesselink, J.R. (1993). Cerebral morphologic distinctions between Williams and Down syndromes. Archives of Neurology, 50(2), 186191.
Jung, R.E., & Haier, R.J. (2007). The Parieto-Frontal Integration Theory (P-FIT) of intelligence: Converging neuroimaging evidence. Behavioral and Brain Sciences, 30(2), 135154. discussion 154–187.
Karmiloff-Smith, A. (2012). Foreward: Development is not about studying children: The importance of longitudinal approaches. American Journal on Intellectual and Developmental Disabilities, 117(2), 8789.
Kates, W.R., Folley, B.S., Lanham, D.C., Capone, G.T., & Kaufmann, W.E. (2002). Cerebral growth in Fragile X syndrome: Review and comparison with Down syndrome. Microscopy Research and Technique, 57(3), 159167.
Kaufmann, W.E., Cooper, K.L., Mostofsky, S.H., Capone, G.T., Kates, W.R., Newschaffer, C.J., & Lanham, D.C. (2003). Specificity of cerebellar vermian abnormalities in autism: A quantitative magnetic resonance imaging study. Journal of Child Neurology, 18(7), 463470.
Krogsrud, S.K., Fjell, A.M., Tamnes, C.K., Grydeland, H., Mork, L., Due-Tønnessen, P., & Johansen-Berg, H. (2016). Changes in white matter microstructure in the developing brain—A longitudinal diffusion tensor imaging study of children from 4 to 11years of age. NeuroImage, 124, 473486.
Lee, N.R., Adeyemi, E.I., Lin, A., Clasen, L.S., Lalonde, F.M., Condon, E., & Giedd, J.N. (2016). Dissociations in cortical morphometry in youth with Down syndrome: Evidence for reduced surface area but increased thickness. Cerebral Cortex, 26(7), 29822990. doi: 10.1093/cercor/bhv107
Martin, G.E., Klusek, J., Estigarribia, B., & Roberts, J.E. (2009). Language characteristics of individuals with Down syndrome. Topics in Language Disorders, 29(2), 112.
McDaniel, M.A. (2005). Big-brained people are smarter: A meta-analysis of the relationship between in vivo brain volume and intelligence. ScienceDirect, 33(4), 337346. doi: https://doi.org/10.1016/j.intell.2004.11.005
Menghini, D., Costanzo, F., & Vicari, S. (2011). Relationship between brain and cognitive processes in Down syndrome. Behavior Genetics, 41(3), 381393. doi: 10.1007/s10519-011-9448-3
Middleton, F.A., & Strick, P.L. (2001). Cerebellar projections to the prefrontal cortex of the primate. Journal of Neuroscience, 21(2), 700712.
Parker, S.E., Mai, C.T., Canfield, M.A., Rickard, R., Wang, Y., Meyer, R.E., & Kirby, R.S. (2010). Updated national birth prevalence estimates for selected birth defects in the United States, 2004–2006. Birth Defects Research Part A: Clinical and Molecular Teratology, 88(12), 10081016.
Pennington, B.F., Moon, J., Edgin, J., Stedron, J., & Nadel, L. (2003). The neuropsychology of Down syndrome: Evidence for hippocampal dysfunction. Child Development, 74(1), 7593.
Pinter, J.D., Brown, W.E., Eliez, S., Schmitt, J.E., Capone, G.T., & Reiss, A.L. (2001). Amygdala and hippocampal volumes in children with Down syndrome: A high-resolution MRI study. Neurology, 56(7), 972974.
Pinter, J.D., Eliez, S., Schmitt, J.E., Capone, G.T., & Reiss, A.L. (2001). Neuroanatomy of Down’s syndrome: A high-resolution MRI study. American Journal of Psychiatry, 158(10), 16591665.
Powell, D., Caban-Holt, A., Jicha, G., Robertson, W., Davis, R., Gold, B.T., & Head, E. (2014). Frontal white matter integrity in adults with Down syndrome with and without dementia. Neurobiology of Aging, 35(7), 15621569. doi: 10.1016/j.neurobiolaging.2014.01.137
Ramnani, N. (2006). The primate cortico-cerebellar system: Anatomy and function. Nature Reviews. Neuroscience, 7(7), 511522.
Raschle, N., Zuk, J., Ortiz-Mantilla, S., Sliva, D.D., Franceschi, A., Grant, P.E., & Gaab, N. (2012). Pediatric neuroimaging in early childhood and infancy: Challenges and practical guidelines. Annals of the New York Academy of Sciences, 1252(1), 4350.
Savage, L.M., Buzzetti, R.A., & Ramirez, D.R. (2004). The effects of hippocampal lesions on learning, memory, and reward expectancies. Neurobiology of Learning and Memory, 82(2), 109119. doi: 10.1016/j.nlm.2004.05.002
Shaw, P., Gogtay, N., & Rapoport, J. (2010). Childhood psychiatric disorders as anomalies in neurodevelopmental trajectories. Human Brain Mapping, 31(6), 917925. doi: 10.1002/hbm.21028
Smigielska-Kuzia, J., Bockowski, L., Sobaniec, W., Sendrowski, K., Olchowik, B., Cholewa, M., & Lebkowska, U. (2011). A volumetric magnetic resonance imaging study of brain structures in children with Down syndrome. Polish Journal of Neurology and Neurosurgery, 45(4), 363369.
Sowell, E.R., Peterson, B.S., Thompson, P.M., Welcome, S.E., Henkenius, A.L., & Toga, A.W. (2003). Mapping cortical change across the human life span. Nature Neuroscience, 6(3), 309315.
Spanò, M., Mercuri, E., Randò, T., Pantò, T., Gagliano, A., Henderson, S., & Guzetta, F. (1999). Motor and perceptual–motor competence in children with Down syndrome: Variation in performance with age. European Journal of Paediatric Neurology, 3(1), 714.
Squire, L.R. (1992). Memory and the hippocampus: A synthesis from findings with rats, monkeys, and humans. Psychology Review, 99(2), 195231.
Stiles, J., & Jernigan, T.L. (2010). The basics of brain development. Neuropsychology Review, 20(4), 327348. doi: 10.1007/s11065-010-9148-4
Thomas, M.S., Annaz, D., Ansari, D., Scerif, G., Jarrold, C., & Karmiloff-Smith, A. (2009). Using developmental trajectories to understand developmental disorders. Journal of Speech, Language, and Hearing Research, 52(2), 336358.
Thompson, P.M., Stein, J.L., Medland, S.E., Hibar, D.P., Vasquez, A.A., Renteria, M.E., & Franke, B. (2014). The ENIGMA Consortium: Large-scale collaborative analyses of neuroimaging and genetic data. Brain Imaging and Behavior, 8(2), 153182.
Tiemeier, H., Lenroot, R.K., Greenstein, D.K., Tran, L., Pierson, R., & Giedd, J.N. (2010). Cerebellum development during childhood and adolescence: A longitudinal morphometric MRI study. NeuroImage, 49(1), 6370. doi: 10.1016/j.neuroimage.2009.08.016
Uematsu, A., Matsui, M., Tanaka, C., Takahashi, T., Noguchi, K., Suzuki, M., & Nishijo, H. (2012). Developmental trajectories of amygdala and hippocampus from infancy to early adulthood in healthy individuals. PLoS One, 7(10), e46970.
van den Heuvel, M.P., & Sporns, O. (2013). Network hubs in the human brain. Trends in Cognitive Sciences, 17(12), 683696.
Vicari, S. (2006). Motor development and neuropsychological patterns in persons with Down syndrome. Behavior Genetics, 36(3), 355364.
Volman, M.J., Visser, J.J., & Lensvelt-Mulders, G.J. (2007). Functional status in 5 to 7-year-old children with Down syndrome in relation to motor ability and performance mental ability. Disability and Rehabilitation, 29(1), 2531.
Webb, S.J., Monk, C.S., & Nelson, C.A. (2001). Mechanisms of postnatal neurobiological development: Implications for human development. Developmental Neuropsychology, 19(2), 147171. doi: 10.1207/S15326942DN1902_2
Weiner, M.W., Veitch, D.P., Aisen, P.S., Beckett, L.A., Cairns, N.J., Green, R.C., & Liu, E. (2013). The Alzheimer’s Disease Neuroimaging Initiative: A review of papers published since its inception. Alzheimer’s & Dementia, 9(5), e111e194.
Zigman, W.B., & Lott, I.T. (2007). Alzheimer’s disease in Down syndrome: Neurobiology and risk. Developmental Disabilities Research Reviews, 13(3), 237246.

Keywords

Pediatric Brain Development in Down Syndrome: A Field in Its Infancy

  • Taralee Hamner (a1), Manisha D. Udhnani (a1), Karol Z. Osipowicz (a1) and Nancy Raitano Lee (a1)

Metrics

Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed