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Abstract
Background
Despite hypothalamus has long being considered to be involved in the pathophysiology of cluster headache, the inconsistencies of previous neuroimaging studies and a limited understanding of the hypothalamic areas involved, impede a comprehensive interpretation of its involvement in this condition.
Methods
We used an automated algorithm to extract hypothalamic subunit volumes from 105 cluster headache patients (57 chronic and 48 episodic) and 59 healthy individuals; after correcting the measures for the respective intracranial volumes, we performed the relevant comparisons employing logist regression models.
Only for subunits that emerged as abnormal, we calculated their correlation with the years of illness and the number of headache attacks per day, and the effects of lithium treatment. As a post-hoc approach, using the 7 T resting-state fMRI dataset from the Human Connectome Project, we investigated whether the observed abnormal subunit, comprising the paraventricular nucleus and preoptic area, shows robust functional connectivity with the mesocorticolimbic system, which is known to be modulated by oxytocin neurons in the paraventricular nucleus and that is is abnormal in chronic cluster headache patients.
Results
Patients with chronic (but not episodic) cluster headache, compared to control participants, present an increased volume of the anterior–superior hypothalamic subunit ipsilateral to the pain, which, remarkably, also correlates significantly with the number of daily attacks. The post-hoc approach showed that this hypothalamic area presents robust functional connectivity with the mesocorticolimbic system under physiological conditions. No evidence of the effects of lithium treatment on this abnormal subunit was found.
Conclusions
We identified the ipsilateral-to-the-pain antero-superior subunit, where the paraventricular nucleus and preoptic area are located, as the key hypothalamic region of the pathophysiology of chronic cluster headache. The significant correlation between the volume of this area and the number of daily attacks crucially reinforces this interpretation. The well-known roles of the paraventricular nucleus in coordinating autonomic and neuroendocrine flow in stress adaptation and modulation of trigeminovascular mechanisms offer important insights into the understanding of the pathophysiology of cluster headache.
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Details
1 University of Electronic Science and Technology of China, School of Life Science and Technology, MOE Key Laboratory for Neuroinformation, Chengdu, China (GRID:grid.54549.39) (ISNI:0000 0004 0369 4060); Sichuan Provincial Center for Mental Health, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Center of Psychosomatic Medicine, Chengdu, China (GRID:grid.54549.39); Fondazione IRCCS Istituto Neurologico Carlo Besta, Department of Neuroradiology, Milan, Italy (GRID:grid.417894.7) (ISNI:0000 0001 0707 5492)
2 Fondazione IRCCS Istituto Neurologico Carlo Besta, Department of Neuroradiology, Milan, Italy (GRID:grid.417894.7) (ISNI:0000 0001 0707 5492)
3 Fondazione IRCCS Istituto Neurologico Carlo Besta, Department of Neuroradiology, Milan, Italy (GRID:grid.417894.7) (ISNI:0000 0001 0707 5492); Fodazione IRCCS Policlinico San Matteo, Radiology Unit, Pavia, Italy (GRID:grid.419425.f) (ISNI:0000 0004 1760 3027)
4 Fondazione IRCCS Istituto Neurologico Carlo Besta, Department of Neuroradiology, Milan, Italy (GRID:grid.417894.7) (ISNI:0000 0001 0707 5492); University of Parma, Department of Medicine and Surgery, Parma, Italy (GRID:grid.10383.39) (ISNI:0000 0004 1758 0937)
5 Sichuan Provincial Center for Mental Health, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Center of Psychosomatic Medicine, Chengdu, China (GRID:grid.10383.39); University of Pinar del Río “Hermanos Saiz Montes de Oca”, Faculty of Technical Sciences, Pinar del Río, Cuba (GRID:grid.441390.b) (ISNI:0000 0004 0401 9913)
6 Fondazione IRCCS Istituto Neurologico Carlo Besta, Department of Neuroalgology, Milan, Italy (GRID:grid.417894.7) (ISNI:0000 0001 0707 5492)
7 Fondazione Maugeri, IRCCS, Department of Neurology, Milan, Italy (GRID:grid.414603.4)
8 University of Electronic Science and Technology of China, School of Life Science and Technology, MOE Key Laboratory for Neuroinformation, Chengdu, China (GRID:grid.54549.39) (ISNI:0000 0004 0369 4060); Sichuan Provincial Center for Mental Health, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Center of Psychosomatic Medicine, Chengdu, China (GRID:grid.54549.39); The University of Hong Kong, State Key Laboratory of Brain and Cognitive Sciences, Hong Kong, China (GRID:grid.194645.b) (ISNI:0000 0001 2174 2757); The University of Hong Kong, Department of Psychology, Hong Kong, China (GRID:grid.194645.b) (ISNI:0000 0001 2174 2757)