title: Altered hypothalamic functional connectivity in cluster headache: a longitudinal resting-state functional MRI study.
abstract: BACKGROUND
  Neuroimaging studies implicate hypothalamic dysfunction in the pathogenesis of cluster headache (CH). Disruptions in non-traditional pain processing areas, including the cerebellum and visual cortex, have also been reported in CH. It is unknown whether the hypothalamus interacts significantly with these areas, and whether any such interactions vary between the 'in-bout' and 'out-of-bout' periods in CH. This study aimed to investigate the resting-state functional connectivity (FC) of the hypothalamus of patients with CH.
  
  
  METHODS
  Using 3-T functional MRI, we conducted a seed-based resting-state intrinsic FC analysis of the hypothalamus in 18 episodic CH patients during in-bout and out-of-bout periods, and in 19 healthy controls. Correlations between hypothalamic FC and clinical variables were also assessed.
  
  
  RESULTS
  Compared to controls, CH patients showed hypothalamic FC changes with the medial frontal gyrus and occipital cuneus during in-bout and out-of-bout periods. Compared to out-of-bout scans, in-bout scans revealed decreased hypothalamic FC with the medial frontal gyrus, precuneus, and cerebellar areas (tonsil, declive and culmen). Additionally, the annual bout frequency correlated significantly with the hypothalamic FC in the cerebellar culmen (r=-0.576, p=0.02) and cerebellar declive (r=-0.522, p=0.038).
  
  
  CONCLUSIONS
  Our findings suggest that in CH, FC differences between the hypothalamus and its regional distribution extends beyond traditional pain processing areas, primarily to the cerebellar, frontal and occipital areas. These changes may be important and associated with CH pathophysiology.
authors.affiliation: Institute of Brain Science, National Yang-Ming University, Taipei, Taiwan Department of Neurology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Fu-Chi
authors.initials: FC
authors.lastname: Yang
authors.affiliation: Institute of Neuroscience, National Yang-Ming University, Taipei, Taiwan Brain Research Center, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Kun-Hsien
authors.initials: KH
authors.lastname: Chou
authors.affiliation: Department of Neurology, National Yang-Ming University, Taipei, Taiwan Department of Neurology, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Jong-Ling
authors.initials: JL
authors.lastname: Fuh
authors.affiliation: Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Pei-Lin
authors.initials: PL
authors.lastname: Lee
authors.affiliation: Department of Radiology, National Yang-Ming University, Taipei, Taiwan Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Jiing-Feng
authors.initials: JF
authors.lastname: Lirng
authors.affiliation: Institute of Brain Science, National Yang-Ming University, Taipei, Taiwan Brain Research Center, National Yang-Ming University, Taipei, Taiwan Department of Neurology, National Yang-Ming University, Taipei, Taiwan Department of Neurology, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Yung-Yang
authors.initials: YY
authors.lastname: Lin
authors.affiliation: Institute of Brain Science, National Yang-Ming University, Taipei, Taiwan Institute of Neuroscience, National Yang-Ming University, Taipei, Taiwan Brain Research Center, National Yang-Ming University, Taipei, Taiwan Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Ching-Po
authors.initials: CP
authors.lastname: Lin
authors.affiliation: Institute of Brain Science, National Yang-Ming University, Taipei, Taiwan Brain Research Center, National Yang-Ming University, Taipei, Taiwan Department of Neurology, National Yang-Ming University, Taipei, Taiwan Department of Neurology, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Shuu-Jiun
authors.initials: SJ
authors.lastname: Wang
mesh_terms: D000328:Adult; D002531:Cerebellum / Q000473:pathology; D002540:Cerebral Cortex / Q000473:pathology; D003027:Cluster Headache / Q000473:pathology*; D005260:Female; D006801:Humans; D007031:Hypothalamus / Q000473:pathology*; D007091:Image Processing, Computer-Assisted; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009434:Neural Pathways / Q000473:pathology*; D012146:Rest; D055815:Young Adult
keywords: HEADACHE; MRI; PAIN