White matter integrity disparities between normal-weight and overweight/obese adolescents: an automated fiber quantification tractography study

  • Kaylie A. Carbine
  • Kara M. Duraccio
  • Ariana Hedges-Muncy
  • Kimberly A. Barnett
  • C. Brock Kirwan
  • Chad D. JensenEmail author


Obese adults have been shown to have poorer white brain matter integrity relative to normal-weight peers, but few studies have tested whether white matter integrity is compromised in overweight and obese adolescents. Also, it is unclear if age interacts with body mass to affect white matter integrity in adolescents. We used Automated Fiber Quantification, a tractography method, to compare fractional anisotropy between normal-weight and overweight/obese adolescents in the corpus callosum, corticospinal tract, cingulum, inferior fronto-occipital fasciculus, and uncinate fasciculus. Further, we tested whether any differences were moderated by age. Forty-seven normal-weight and forty overweight/obese adolescents were scanned using a diffusion tensor imaging (DTI) scan sequence. Overweight/obese compared to normal-weight adolescents had decreased white matter integrity in the superior frontal corpus callosum, left and right uncinate fasciculi, left inferior fronto-occipital fasciculus, and left corticospinal tract, which may be related to heightened reward processing. Overweight/obese compared to normal-weight adolescents had increased white matter integrity in the orbital and anterior frontal corpus callosum, right inferior fronto-occipital fasciculus, left cingulum, and left corticospinal tract, which may be related to heightened attentional processing. As age increased, six tracts showed poorer white matter integrity as body mass index percentile (BMI%) increased, but three tracts showed greater white matter integrity as BMI% increased. Future research examining associations between white matter integrity and neural indices of food-related reward and attention are needed to clarify the functional significance of white matter integrity discrepancies between normal-weight and overweight/obese adolescents.


Diffusion tensor imaging (DTI) Automated fiber quantification (AFQ) Fractional anisotropy (FA) White matter integrity Adolescents Overweight/obesity 



We thank Naomi Goodrich-Hunsaker, Ph.D., for assistance with data analysis.


This study was funded by a Brigham Young University Mentoring Environment Grant.

Compliance with ethical standards

Conflict of interest

The authors have no conflicts of interest to report.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.


  1. Ackard, D. M., Neumark-Sztainer, D., Story, M., & Perry, C. (2003). Overeating among adolescents: Prevalence and associations with weight-related characteristics and psychological health. Pediatrics, 111(1), 67–74.Google Scholar
  2. Alexander, A. L., Hurley, S. A., Samsonov, A. A., Adluru, N., Hosseinbor, A. P., Mossahebi, P., Tromp, D., et al. (2012). Characterization of cerebral white matter properties using quantitative magnetic resonance imaging stains. Brain Connectivity, 1(6), 423–446.Google Scholar
  3. Alosco, M. L., Stanek, K. M., Galioto, R., Korgaonkar, M. S., Grieve, S. M., Brickman, A. M., et al. (2014). Body mass index and brain structure in healthy children and adolescents. International Journal of Neuroscience, 124(1), 49–55.Google Scholar
  4. Beaulieu, C. (2002). The basis of anisotropic water diffusion in the nervous system–a technical review. NMR in Biomedicine, 15(7–8), 435–455.Google Scholar
  5. Bjørnebekk, A., Westlye, L. T., Fjell, A. M., Grydeland, H., & Walhovd, K. B. (2011). Social reward dependence and brain white matter microstructure. Cerebral Cortex, 22(11), 2672–2679.Google Scholar
  6. Black, W. R., Lepping, R. J., Bruce, A. S., Powell, J. N., Bruce, J. M., Martin, L. E., et al. (2014). Tonic hyper-connectivity of reward neurocircuitry in obese children. Obesity, 22(7), 1590–1593. Scholar
  7. Bookstein, F. L. (2001). Registration error and functional image analysis. Paper presented at the Workshop on Biomedical Statistics.Google Scholar
  8. Bruce, A. S., Holsen, L. M., Chambers, R. J., Martin, L. E., Brooks, W. M., Zarcone, J. R., et al. (2010). Obese children show hyperactivation to food pictures in brain networks linked to motivation, reward and cognitive control. International Journal of Obesity, 34(10), 1494–1500.Google Scholar
  9. Catani, M. (2006). Diffusion tensor magnetic resonance imaging tractography in cognitive disorders. Current Opinion in Neurology, 19, 599–606.Google Scholar
  10. Catani, M., & De Schotten, M. T. (2008). A diffusion tensor imaging tractography atlas for virtual in vivo dissections. Cortex, 44(8), 1105–1132.Google Scholar
  11. Center for Disease Control and Prevention. (2016). Defining childhood obesity. BMI for Children and Teens. Retrieved September 2018 from
  12. Chechlacz, M., Humphreys, G. W., Sotiropoulos, S. N., Kennard, C., & Cazzoli, D. (2015). Structural organization of the corpus callosum predicts attentional shifts after continuous theta burst stimulation. Journal of Neuroscience, 35(46), 15353–15368.Google Scholar
  13. Chenevert, T. L., Stegman, L. D., Taylor, J. M., Robertson, P. L., Greenberg, H. S., Rehemtulla, A., & Ross, B. D. (2000). Diffusion magnetic resonance imaging: An early surrogate marker of therapeutic efficacy in brain tumors. JNCI: Journal of the National Cancer Institute, 92(24), 2029–2036.Google Scholar
  14. Deng, F., Wang, Y., Huang, H., Niu, M., Zhong, S., Zhao, L., et al. (2018). Abnormal segments of right uncinate fasciculus and left anterior thalamic radiation in major and bipolar depression. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 81, 340–349.Google Scholar
  15. Doricchi, F., Thiebaut De Schotten, M., Tomaiuolo, F., & Bartolomeo, P. (2008). White matter (dis) connections and gray matter (dys) functions in visual neglect: Gaining insights into the brain networks of spatial awareness. Cortex, 44(8), 983–995.Google Scholar
  16. Feldman, H. M., Yeatman, J. D., Lee, E. S., Barde, L. H., & Gaman-Bean, S. (2010). Diffusion tensor imaging: A review for pediatric researchers and clinicians. Journal of Developmental & Behavioral Pediatrics, 31(4), 346–356.Google Scholar
  17. Giorgio, A., Watkins, K. E., Chadwick, M., James, S., Winmill, L., Douaud, G., et al. (2010). Longitudinal changes in grey and white matter during adolescence. NeuroImage, 49(1), 94–103.Google Scholar
  18. Goodrich-Hunsaker, N. J., Abildskov, T. J., Black, G., Bigler, E. D., Cohen, D. M., Mihalov, L. K., et al. (2018). Age-and sex-related effects in children with mild traumatic brain injury on diffusion magnetic resonance imaging properties: A comparison of voxelwise and tractography methods. Journal of Neuroscience Research, 96(4), 626–641.Google Scholar
  19. Gunning-Dixon, F. M., & Raz, N. (2000). The cognitive correlates of white matter abnormalities in normal aging: A quantitative review. Neuropsychology, 14(2), 224–232.Google Scholar
  20. Hastie, T., Tibshirani, R., & Friedman, J. (2009). The elements of statistical learning: Data mining, inference, and prediction (2nd ed.). New York: Springer.Google Scholar
  21. Hua, K., Zhang, J., Wakana, S., Jiang, H., Li, X., Reich, D. S., Calabresi, P. A., Pekar, J. J., van Zijl, P. C. M., & Mori, S. (2008). Tract probability maps in stereotaxic spaces: Analyses of white matter anatomy and tract-specific quantification. Neuroimage, 39(1), 336–347.Google Scholar
  22. Jensen, C. D., & Kirwan, C. B. (2015). Functional brain response to food images in successful adolescent weight losers compared with normal-weight and overweight controls. Obesity, 23(3), 630–636.Google Scholar
  23. Jensen, C. D., Duraccio, K. M., Barnett, K. A., Carbine, K. A., Stevens, K. S., Muncy, N. M., & Kirwan, C. B. (2019). Sleep duration differentially affects brain activation in response to food images in adolescents with overweight/obesity compared to adolescents with normal weight. Sleep.
  24. Karlsson, H. K., Tuulari, J. J., Hirvonen, J., Lepomaki, V., Parkkola, R., Hiltunen, J., et al. (2013). Obesity is associated with white matter atrophy: A combined diffusion tensor imaging and voxel-based morphometric study. Obesity, 21(12), 2530–2537.Google Scholar
  25. Klarborg, B., Skak Madsen, K., Vestergaard, M., Skimminge, A., Jernigan, T. L., & Baaré, W. F. (2013). Sustained attention is associated with right superior longitudinal fasciculus and superior parietal white matter microstructure in children. Human Brain Mapping, 34(12), 3216–3232.Google Scholar
  26. Kullmann, S., Schweizer, F., Veit, R., Fritsche, A., & Preissl, H. (2015). Compromised white matter integrity in obesity. Obesity Reviews, 16(4), 273–281.Google Scholar
  27. Lenroot, R. K., & Giedd, J. N. (2010). Sex differences in the adolescent brain. Brain and Cognition, 72(1), 46–55.Google Scholar
  28. Lebel, C., Benner, T., & Beaulieu, C. (2012). Six is enough? Comparison of diffusion parameters mesured using six or more diffusion-encoding gradient directions with deterministric tractography. Magnetic Resonance in Medicine, 68(20), 474–483.Google Scholar
  29. Marks, B. L., Katz, L. M., Styner, M., & Smith, J. K. (2010). Aerobic fitness and obesity: Relationship to cerebral white matter integrity in the brain of active and sedentary older adults. British Journal of Sports Medicine, 45(15), 1208–1215.Google Scholar
  30. Mesulam, M. (1981). A cortical network for directed attention and unilateral neglect. Annals of Neurology, 10(4), 309–325.Google Scholar
  31. Mori, S., Crain, B. J., Chacko, V. P., & van Zijl, P. C. (1999). Three-dimensional tracking of axonal projections in the brain by magnetic resonance imaging. Annals of Neurology, 45, 265–269.Google Scholar
  32. Moseley, M. (2002). Diffusion tensor imaging and aging–a review. NMR in Biomedicine, 15(7–8), 553–560.Google Scholar
  33. Mueller, K., Anwander, A., Moller, H. E., Horstmann, A., Lepsien, J., Busse, F., et al. (2011). Sex-dependent influences of obesity on cerebral white matter investigated by diffusion-tensor imaging. PLoS One, 6(4), e18544.Google Scholar
  34. Ogden, C. L., Carroll, M. D., Fryar, C. D., & Flegal, K. M. (2015). Prevalence of obesity among adults and youth: United States, 2011–2014. NCHS Data Brief, 219(219), 1–8.Google Scholar
  35. Olson, E. A., Collins, P. F., Hooper, C. J., Muetzel, R., Lim, K. O., & Luciana, M. (2009). White matter integrity predicts delay discounting behavior in 9-to 23-year-olds: A diffusion tensor imaging study. Journal of Cognitive Neuroscience, 21(7), 1406–1421.Google Scholar
  36. Olson, I. R., Von Der Heide, R. J., Alm, K. H., & Vyas, G. (2015). Development of the uncinate fasciculus: Implications for theory and developmental disorders. Developmental Cognitive Neuroscience, 14, 50–61.Google Scholar
  37. Ou, X., Andres, A., Pivik, R., Cleves, M. A., & Badger, T. M. (2015). Brain gray and white matter differences in healthy normal weight and obese children. Journal of Magnetic Resonance Imaging, 42(5), 1205–1213.Google Scholar
  38. Pierpaoli, C., & Basser, P. J. (1996). Toward a quantitative assessment of diffusion anisotropy. Magnetic Resonance in Medicine, 36(6), 893–906.Google Scholar
  39. Pierpaoli, C., Jezzard, P., Basser, P. J., Barnett, A., & Di Chiro, G. (1996). Diffusion tensor MR imaging of the human brain. Radiology, 201(3), 637–648.Google Scholar
  40. Pollmann, S. (2004). Anterior prefrontal cortex contributions to attention control. Journal of Experimental Psychology, 51(4), 270–278.Google Scholar
  41. R Core Team (2017). R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. Retrieved February 2018 from
  42. Reilly, J. J., & Kelly, J. (2011). Long-term impact of overweight and obesity in childhood and adolescence on morbidity and premature mortality in adulthood: Systematic review. International Journal of Obesity, 35(7), 891–898.Google Scholar
  43. Rohde, G. K., Barnett, A. S., Basser, P. J., Marenco, S., & Pierpaoli C. (2004). Comprehensive approach for correction of motion and distortion in diffusion-weighted MRI. Magnetic Resonance in Medicine, 51(1), 103–114.Google Scholar
  44. Rothemund, Y., Preuschhof, C., Bohner, G., Bauknecht, H. C., Klingebiel, R., Flor, H., & Klapp, B. F. (2007). Differential activation of the dorsal striatum by high-calorie visual food stimuli in obese individuals. NeuroImage, 37(2), 410–421.Google Scholar
  45. Rudrauf, D., Mehta, S., & Grabowski, T. J. (2008). Disconnection's renaissance takes shape: Formal incorporation in group-level lesion studies. Cortex, 44(8), 1084–1096.Google Scholar
  46. Rueckert, L., & Levy, J. (1996). Further evidence that the callosum is involved in sustaining attention. Neuropsychologia, 34(9), 927–935.Google Scholar
  47. Song, S.-K., Sun, S.-W., Ramsbottom, M. J., Chang, C., Russell, J., & Cross, A. H. (2002). Dysmyelination revealed through MRI as increased radial (but unchanged axial) diffusion of water. NeuroImage, 17(3), 1429–1436.Google Scholar
  48. Song, S.-K., Sun, S.-W., Ju, W.-K., Lin, S.-J., Cross, A. H., & Neufeld, A. H. (2003). Diffusion tensor imaging detects and differentiates axon and myelin degeneration in mouse optic nerve after retinal ischemia. NeuroImage, 20(3), 1714–1722.Google Scholar
  49. Sotak, C. H. (2002). The role of diffusion tensor imaging in the evaluation of ischemic brain injury–a review. NMR in Biomedicine, 15(7–8), 561–569.Google Scholar
  50. Stanek, K. M., Grieve, S. M., Brickman, A. M., Korgaonkar, M. S., Paul, R. H., Cohen, R. A., & Gunstad, J. J. (2011). Obesity is associated with reduced white matter integrity in otherwise healthy adults. Obesity, 19(3), 500–504.Google Scholar
  51. Stice, E., Spoor, S., Bohon, C., Veidhuizen, M. G., & Small, D. M. (2008). Relation of reward from food intake and anticipated food intake to obesity: A functional magnetic resonance imaging study. Journal of Abnormal Psychology, 117(4), 924–935.Google Scholar
  52. Stice, E., Yokum, S., Burger, K. S., Epstein, L. H., & Small, D. M. (2011). Youth at risk for obesity show greater activation of striatal and somatosensory regions to food. Journal of Neuroscience, 31(12), 4360–4366.Google Scholar
  53. Stoeckel, L. E., Weller, R. E., Cook, E. W., Twieg, D. B., Knowlton, R. C., & Cox, J. E. (2008). Widespread reward-system activation in obese women in response to pictures of high-calorie foods. NeuroImage, 41(2), 636–647.Google Scholar
  54. Thiebaut De Schotten, M., Dell'Acqua, F., Forkel, S. J., Simmons, A., Vergani, F., Murphy, D. G., & Catani, M. (2011). A lateralized brain network for visuospatial attention. Nature Neuroscience, 14(10), 1245–1246.Google Scholar
  55. Verstynen, T. D., Weinstein, A. M., Schneider, W. W., Jakicic, J. M., Rofey, D. L., & Erickson, K. I. (2012). Increased body mass index is associated with a global and distributed decrease in white matter microstructural integrity. Psychosomatic Medicine, 74(7), 682–690.Google Scholar
  56. Von Der Heide, R. J., Skipper, L. M., Klobusicky, E., & Olson, I. R. (2013). Dissecting the uncinate fasciculus: Disorders, controversies and a hypothesis. Brain, 136(6), 1692–1707.Google Scholar
  57. Wakana, S., Caprihan, A., Panzenboeck, M. M., Fallon, J. H., Perry, M., Gollub, R. L., Hua, K., Zhang, J., Jiang, H., Dubey, P., Blitz, A., van Zijl, P., & Mori, S. (2007). Reproducibility of quantitative tractography methods applied to cerebral white matter. Neuroimage, 36(3), 630–644.Google Scholar
  58. Weber, B., Treyer, V., Oberholzer, N., Jaermann, T., Boesiger, P., Brugger, P., et al. (2005). Attention and interhemispheric transfer: A behavioral and fMRI study. Journal of Cognitive Neuroscience, 17(1), 113–123.Google Scholar
  59. Werring, D., Clark, C., Barker, G., Thompson, A., & Miller, D. (1999). Diffusion tensor imaging of lesions and normal-appearing white matter in multiple sclerosis. Neurology, 52(8), 1626–1626.Google Scholar
  60. Xu, J., Li, Y., Lin, H., Sinha, R., & Potenza, M. N. (2013). Body mass index correlates negatively with white matter integrity in the fornix and corpus callosum: A diffusion tensor imaging study. Human Brain Mapping, 34(5), 1044–1052.Google Scholar
  61. Yau, P., Javier, D., Ryan, C., Tsui, W., Ardekani, B., Ten, S., & Convit, A. (2010). Preliminary evidence for brain complications in obese adolescents with type 2 diabetes mellitus. Diabetologia, 53(11), 2298–2306.Google Scholar
  62. Yeatman, J. D., Dougherty, R. F., Myall, N. J., Wandell, B. A., & Feldman, H. M. (2012). Tract profiles of white matter properties: Automating fiber-tract quantification. PLoS One, 7(11), e49790.Google Scholar
  63. Yokum, S., Ng, J., & Stice, E. (2011). Attentional bias to food images associated with elevated weight and future weight gain: An fMRI study. Obesity, 19(9), 1775–1783.Google Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Kaylie A. Carbine
    • 1
  • Kara M. Duraccio
    • 1
  • Ariana Hedges-Muncy
    • 1
  • Kimberly A. Barnett
    • 1
  • C. Brock Kirwan
    • 1
    • 2
  • Chad D. Jensen
    • 1
    Email author
  1. 1.Department of PsychologyBrigham Young UniversityProvoUSA
  2. 2.Department of NeuroscienceBrigham Young UniversityProvoUSA

Personalised recommendations