Morphological alterations in amygdalo-hippocampal substructures in narcolepsy patients with cataplexy
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Although the role of hypocretin-mediated amygdalo-hippocampal dysfunction is hypothesized to be linked with narcolepsy, there have been no human MRI studies investigating the relationship between their regional volume and key symptoms of narcolepsy. To investigate the morphological changes of amygdalo-hippocampus and its relationship with clinical features in patients with narcolepsy, point-wise morphometry that allowed for measuring the regional volumes of amygdalo-hippocampus on T1-weighted MRI was applied. Participants were 33 drug-naïve patients and 35 age-/gender-matched controls (mean ± SD: 27 ± 6 years). We compared hippocampal and amygdalar subfields volumes between patients and controls and correlated between volume and clinical and neuropsychological features in patients. Bilateral hippocampal atrophy (183 vertices) was identified mainly located within the CA1 subfield (FDR < 0.05). Significant amygdalar volume reduction was found in the areas of the centromedial (102 vertices) and laterobasal nuclear groups (LB, 35 vertices). There was no volume increase in patients relative to controls (FDR >0.2). After controlling depressive mood, sleep quality, age, and gender, hippocampal CA1 atrophy and amygdalar centromedial atrophy were associated with longer duration of daytime sleepiness and shorter mean REM sleep latency (|r| >0.44, p < 0.01). The amygdalar centromedial atrophy was associated with longer duration of cataplexy (|r| >0.47, p < 0.005). Subfields atrophy of amygdalo-hippocampus in untreated patients with narcolepsy that was found relative to controls suggests that CA1 of the hippocampus and centromedial area of amygdala are closely related to the severity of narcolepsy and play a crucial role in the circuitry of cataplexy.
KeywordsNarcolepsy Amygdale Hippocampus Surface analysis MRI volumetry
This study was funded by Basic Science Research Program through the National Research Foundation of Korea of the Ministry of Science, ICT & Future Planning, Republic of Korea (No. 2014R1A1A3049510) and by Samsung Biomedical Research Institute grant (#OTX0002111).
Conflict of interest
All authors (Kim H, Suh S, Joo EY, and Hong SB) declare that they have no conflict of interest.
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.
Informed consent was obtained from all individual participants included in the study.
- Amunts, K., Kedo, O., Kindler, M., Pieperhoff, P., Mohlberg, H., Shah, N. J., et al. (2005). Cytoarchitectonic mapping of the human amygdala, hippocampal region and entorhinal cortex: intersubject variability and probability maps. Anatomy and Embryology, 210(5–6), 343–352.CrossRefPubMedGoogle Scholar
- Benjamini, Y., & Hochberg, Y. (1995). Controlling the false discovery rate: a practical and powerful approach to multiple testing. Journal of the Royal Statistical Society: Series B Methodological, 57(1), 289–300.Google Scholar
- Beyer, M. K., Bronnick, K. S., Hwang, K. S., Bergsland, N., Tysnes, O. B., Larsen, J. P., et al. (2013). Verbal memory is associated with structural hippocampal changes in newly diagnosed Parkinson’s disease. Journal of Neurology, Neurosurgery, and Psychiatry, 84(1), 23–28.CrossRefPubMedGoogle Scholar
- Doherty, D. G., Penzotti, J. E., Koelle, D. M., Kwok, W. W., Lybrand, T. P., Masewicz, S., et al. (1998). Structural basis of specificity and degeneracy of T cell recognition: pluriallelic restriction of T cell responses to a peptide antigen involves both specific and promiscuous interactions between the T cell receptor, peptide, and HLA-DR. Journal of Immunology (Baltimore, Md. : 1950), 161(7), 3527–3535.Google Scholar
- Duvernoy, H. M. (2005). The human hippocampus: An atlas of applied anatomy (3rd ed.). New York: Springer Verlag.Google Scholar
- Gerig, G., Styner, M., Jones, D., Weinberger, D., & Lieberman, J. (2001). Shape analysis of brain ventricles using SPHARM. Mathematical Methods in Biomedical Image Analysis. IEEE Workshop on Kauai, HI (pp. 171–178).Google Scholar
- Kim, H., Besson, P., Colliot, O., Bernasconi, A., & Bernasconi, N. (2008). Surface-based vector analysis using heat equation interpolation: a new approach to quantify local hippocampal volume changes. Medical Image Computing and Computer-Assisted Intervention, 11(Pt 1), 1008–1015.PubMedGoogle Scholar
- Mizumori, S. J., McNaughton, B. L., Barnes, C. A., & Fox, K. B. (1989). Preserved spatial coding in hippocampal CA1 pyramidal cells during reversible suppression of CA3c output: evidence for pattern completion in hippocampus. The Journal of Neuroscience : The Official Journal of the Society for Neuroscience, 9(11), 3915–3928.Google Scholar
- Selbach, O., Bohla, C., Barbara, A., Doreulee, N., Eriksson, K. S., Sergeeva, O. A., et al. (2010). Orexins/hypocretins control bistability of hippocampal long-term synaptic plasticity through co-activation of multiple kinases. Acta Physiologica (Oxford, England), 198(3), 277–285.CrossRefGoogle Scholar
- Styner, M., Oguz, I., Xu, S., Brechbuhler, C., Pantazis, D., & Gerig, G. (2006a). Statistical shape analysis of brain structures using SPHARM-PDM. The Insight Journal, 2006, 1–7.Google Scholar
- Styner, M., Oguz, I., Xu, S., Brechbuhler, C., Pantazis, D., Levitt, J. J., et al. (2006b). Framework for the statistical shape analysis of brain structures using SPHARM-PDM. The Insight Journal, 2006, 242–250.Google Scholar
- Wu, M., Zhang, Z., Leranth, C., Xu, C., van den Pol, A. N., & Alreja, M. (2002). Hypocretin increases impulse flow in the septohippocampal GABAergic pathway: implications for arousal via a mechanism of hippocampal disinhibition. The Journal of Neuroscience : The Official Journal of the Society for Neuroscience, 22(17), 7754–7765.Google Scholar