Skip to main content
Log in

Localizing deficits in white matter tracts of patients with narcolepsy with cataplexy: tract-specific statistical analysis

  • ORIGINAL RESEARCH
  • Published:
Brain Imaging and Behavior Aims and scope Submit manuscript

Abstract

White matter alterations related to hypocretin pathway have been less evaluated in patients who have narcolepsy with cataplexy (NC), as compared to the identified exploration of gray matter and have varied among structural brain magnetic resonance imaging studies. The aim of this study was to investigate the disruption of specific white matter tracts in drug-naïve patients with NC, by using a tract-specific statistical analysis (TSSA). Forty drug-naïve NC patients with cataplexy and 42 heathy controls were enrolled in the study. All participants completed diffusion weighted imaging, polysomnography, and neuropsychological testing. At that time, we automatically identified fourteen major fiber tracts using diffusion tensor imaging techniques and analyzed the group comparison of fractional anisotropy (FA) values for each tract between the NC and controls, controlling for the participant’s age and gender. The mean age of the NC patients was 26.9 years and the onset age of daytime sleepiness and cataplexy was 16.7 years and 19.9 years, respectively. Relative to the controls, the NC patients showed that there were identified decreased FA values in the bilateral inferior fronto-occipital fasciculus (IFO). The Epworth sleepiness scale was positively correlated with FA values for the left IFO and right cingulate. The REM sleep latency was positively correlated with FA values for the left IFO, cingulate, and uncinate fasciculus in patients. This TSSA study revealed disintegration of the IFO in the NC patients and suggested that disintegration of WM tracts connected to the frontal cortex contributes to clinical manifestations of narcolepsy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Bayard, S., Croisier Langenier, M., Cochen De Cock, V., Scholz, S., & Dauvilliers, Y. (2012). Executive control of attention in narcolepsy. PLoS One, 7(4), e33525. https://doi.org/10.1371/journal.pone.0033525.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bookstein, F. L. (2001). “Voxel-based morphometry” should not be used with imperfectly registered images. Neuroimage, 14(6), 1454–1462.

    Article  CAS  Google Scholar 

  • Bullmore, E. T., Suckling, J., Overmeyer, S., Rabe-Hesketh, S., Taylor, E., & Brammer, M. J. (1999). Global, voxel, and cluster tests, by theory and permutation, for a difference between two groups of structural MR images of the brain. IEEE Transactions on Medical Imaging, 18(1), 32–42.

    Article  CAS  Google Scholar 

  • Dauvilliers, Y., Arnulf, I., & Mignot, E. (2007). Narcolepsy with cataplexy. Lancet, 369(9560), 499–511. https://doi.org/10.1016/S0140-6736(07)60237-2.

    Article  PubMed  Google Scholar 

  • Davatzikos, C. (2004). Why voxel-based morphometric analysis should be used with great caution when characterizing group differences. Neuroimage, 23(1), 17–20.

    Article  Google Scholar 

  • Groppe, D. M., Urbach, T. P., & Kutas, M. (2011). Mass univariate analysis of event-related brain potentials/fields I: A critical tutorial review. Psychophysiology, 48(12), 1711–1725. https://doi.org/10.1111/j.1469-8986.2011.01273.x.

    Article  PubMed  PubMed Central  Google Scholar 

  • Jeon, S., Cho, J. W., Kim, H., Evans, A. C., Hong, S. B., & Joo, E. Y. (2018). A five-year longitudinal study reveals progressive cortical thinning in narcolepsy and faster cortical thinning in relation to early-onset. Brain Imaging and Behavior. https://doi.org/10.1007/s11682-018-9981-2.

  • Joo, E. Y. (2013). Morphological changes in narcolepsy. Journal Korean Sleep Research Society, 10(2), 35–38. https://doi.org/10.13078/jksrs.13007.

    Article  Google Scholar 

  • Joo, E. Y., Tae, W. S., Kim, S. T., & Hong, S. B. (2009). Gray matter concentration abnormality in brains of narcolepsy patients. Korean Journal of Radiology, 10(6), 552–558. https://doi.org/10.3348/kjr.2009.10.6.552.

    Article  PubMed  PubMed Central  Google Scholar 

  • Joo, E. Y., Jeon, S., Lee, M., Kim, S. T., Yoon, U., Koo, D. L., Lee, J. M., & Hong, S. B. (2011). Analysis of cortical thickness in narcolepsy patients with cataplexy. Sleep, 34(10), 1357–1364. https://doi.org/10.5665/sleep.1278.

    Article  PubMed  PubMed Central  Google Scholar 

  • Joo, E. Y., Kim, S. H., Kim, S. T., & Hong, S. B. (2012). Hippocampal volume and memory in narcoleptics with cataplexy. Sleep Medicine, 13(4), 396–401. https://doi.org/10.1016/j.sleep.2011.09.017.

    Article  PubMed  Google Scholar 

  • Jung, N. Y., Han, C. E., Kim, H. J., Yoo, S. W., Kim, H. J., Kim, E. J., Na, D. L., Lockhart, S. N., Jagust, W. J., Seong, J. K., & Seo, S. W. (2016). Tract-specific correlates of neuropsychological deficits in patients with subcortical vascular cognitive impairment. Journal of Alzheimer's Disease, 50(4), 1125–1135. https://doi.org/10.3233/jad-150841.

    Article  CAS  PubMed  Google Scholar 

  • Kim, H., Suh, S., Joo, E. Y., & Hong, S. B. (2016). Morphological alterations in amygdalo-hippocampal substructures in narcolepsy patients with cataplexy. Brain Imaging and Behavior, 10(4), 984–994. https://doi.org/10.1007/s11682-015-9450-0.

    Article  PubMed  Google Scholar 

  • Martino, J., Brogna, C., Robles, S. G., Vergani, F., & Duffau, H. (2010). Anatomic dissection of the inferior fronto-occipital fasciculus revisited in the lights of brain stimulation data. cortex, 46(5), 691–699.

    Article  Google Scholar 

  • Menzler, K., Belke, M., Unger, M. M., Ohletz, T., Keil, B., Heverhagen, J. T., Rosenow, F., Mayer, G., Oertel, W. H., Möller, J. C., & Knake, S. (2012). DTI reveals hypothalamic and brainstem white matter lesions in patients with idiopathic narcolepsy. Sleep Medicine, 13(6), 736–742. https://doi.org/10.1016/j.sleep.2012.02.013.

    Article  CAS  PubMed  Google Scholar 

  • 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(2), 265–269.

    Article  CAS  Google Scholar 

  • Moseley, M. E., Wendland, M. F., & Kucharczyk, J. (1991). Magnetic resonance imaging of diffusion and perfusion. Topics in Magnetic Resonance Imaging, 3(3), 50-67.

    PubMed  Google Scholar 

  • Nakamura, M., Nishida, S., Hayashida, K., Ueki, Y., Dauvilliers, Y., & Inoue, Y. (2013). Differences in brain morphological findings between narcolepsy with and without cataplexy. PLoS One, 8(11), e81059.

    Article  Google Scholar 

  • Naumann, A., Bellebaum, C., & Daum, I. (2006). Cognitive deficits in narcolepsy. Journal of Sleep Research, 15(3), 329–338. https://doi.org/10.1111/j.1365-2869.2006.00533.x.

    Article  CAS  PubMed  Google Scholar 

  • O'Donnell, L. J., Westin, C. F., & Golby, A. J. (2009). Tract-based morphometry for white matter group analysis. Neuroimage, 45(3), 832–844. https://doi.org/10.1016/j.neuroimage.2008.12.023.

  • Park, Y. K., Kwon, O. H., Joo, E. Y., Kim, J. H., Lee, J. M., Kim, S. T., & Hong, S. B. (2016). White matter alterations in narcolepsy patients with cataplexy: Tract-based spatial statistics. Journal of Sleep Research, 25(2), 181–189.

    Article  Google Scholar 

  • Roth, T., Dauvilliers, Y., Mignot, E., Montplaisir, J., Paul, J., Swick, T., et al. (2013). Disrupted nighttime sleep in narcolepsy. Journal of Clinical Sleep Medicine, 9(09), 955–965.

    Article  Google Scholar 

  • Sarubbo, S., De Benedictis, A., Maldonado, I. L., Basso, G., & Duffau, H. (2013). Frontal terminations for the inferior fronto-occipital fascicle: Anatomical dissection, DTI study and functional considerations on a multi-component bundle. Brain Structure and Function, 218(1), 21–37.

    Article  Google Scholar 

  • Sateia, M. J. (2014). International classification of sleep disorders. Chest, 146(5), 1387–1394.

    Article  Google Scholar 

  • Scherfler, C., Frauscher, B., Schocke, M., Nocker, M., Gschliesser, V., Ehrmann, L., Niederreiter, M., Esterhammer, R., Seppi, K., Brandauer, E., Poewe, W., & Högl, B. (2012). White and gray matter abnormalities in narcolepsy with cataplexy. Sleep, 35(3), 345–351.

    Article  Google Scholar 

  • Singh, S., Singh, K., Trivedi, R., Goyal, S., Kaur, P., Singh, N., Bhatia, T., Deshpande, S. N., & Khushu, S. (2016). Microstructural abnormalities of uncinate fasciculus as a function of impaired cognition in schizophrenia: A DTI study. Journal of Biosciences, 41(3), 419–426.

    Article  CAS  Google Scholar 

  • Yasmin, H., Nakata, Y., Aoki, S., Abe, O., Sato, N., Nemoto, K., Arima, K., Furuta, N., Uno, M., Hirai, S., Masutani, Y., & Ohtomo, K. (2008). Diffusion abnormalities of the uncinate fasciculus in Alzheimer's disease: Diffusion tensor tract-specific analysis using a new method to measure the core of the tract. Neuroradiology, 50(4), 293–299. https://doi.org/10.1007/s00234-007-0353-7.

    Article  PubMed  Google Scholar 

  • 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), ARTN e49790. https://doi.org/10.1371/journal.pone.0049790.

    Article  CAS  Google Scholar 

  • Yoo, S. W., Guevara, P., Jeong, Y., Yoo, K., Shin, J. S., Mangin, J. F., & Seong, J. K. (2015). An example-based multi-atlas approach to automatic labeling of white matter tracts. PLoS One, 10(7), e0133337. https://doi.org/10.1371/journal.pone.0133337.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zamarian, L., Hogl, B., Delazer, M., Hingerl, K., Gabelia, D., Mitterling, T., et al. (2015). Subjective deficits of attention, cognition and depression in patients with narcolepsy. Sleep Medicine, 16(1), 45–51. https://doi.org/10.1016/j.sleep.2014.07.025.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by Samsung Medical Center Grant (OTC1190671), by Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Science, ICT & Future Planning, Republic of Korea (2017R1A2B4003120), by Samsung Biomedical Research Institute grant (SMX1170571), by the National Research Foundation of Korea(NRF) grant funded by the Korea government(MSIP) (No.2016R1A2B4014398), and the National Research Council of Science & Technology (NST)grant by the Korea government (MSIT) (No. CAP-18-01-KIST).

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Joon-Kyung Seong or Eun Yeon Joo.

Ethics declarations

Conflict of interest

This was not an industry supported study. The authors have no commercial, financial, or otherrelationship related to the subject of this paper that could constitute or suggest a conflict ofinterest.

Ethical approval

All procedures performed in studies involving human participants were in accordance withthe ethical standards of the Institutional Review Board of the Samsung Medical Center.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

ESM 1

(DOCX 14 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Park, H.R., Kim, H.R., Seong, JK. et al. Localizing deficits in white matter tracts of patients with narcolepsy with cataplexy: tract-specific statistical analysis. Brain Imaging and Behavior 14, 1674–1681 (2020). https://doi.org/10.1007/s11682-019-00100-z

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11682-019-00100-z

Keywords

Navigation