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.
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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.
Bookstein, F. L. (2001). “Voxel-based morphometry” should not be used with imperfectly registered images. Neuroimage, 14(6), 1454–1462.
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.
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.
Davatzikos, C. (2004). Why voxel-based morphometric analysis should be used with great caution when characterizing group differences. Neuroimage, 23(1), 17–20.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Sateia, M. J. (2014). International classification of sleep disorders. Chest, 146(5), 1387–1394.
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.
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.
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.
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.
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.
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.
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).
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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
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DOI: https://doi.org/10.1007/s11682-019-00100-z