Defective functional connectivity between posterior hypothalamus and regions of the diencephalic-mesencephalic junction in chronic cluster headache

Stefania Ferraro, Anna Nigri, Maria Grazia Bruzzone, Luca Brivio, Alberto Proietti Cecchini, Mattia Verri, Luisa Chiapparini, Massimo Leone

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Objective: We tested the hypothesis of a defective functional connectivity between the posterior hypothalamus and diencephalic-mesencephalic regions in chronic cluster headache based on: a) clinical and neuro-endocrinological findings in cluster headache patients; b) neuroimaging findings during cluster headache attacks; c) neuroimaging findings in drug-refractory chronic cluster headache patients improved after successful deep brain stimulation. Methods: Resting state functional magnetic resonance imaging, associated with a seed-based approach, was employed to investigate the functional connectivity of the posterior hypothalamus in chronic cluster headache patients (n = 17) compared to age and sex-matched healthy subjects (n = 16). Random-effect analyses were performed to study differences between patients and controls in ipsilateral and contralateral-to-the-pain posterior hypothalamus functional connectivity. Results: Cluster headache patients showed an increased functional connectivity between the ipsilateral posterior hypothalamus and a number of diencephalic-mesencephalic structures, comprising ventral tegmental area, dorsal nuclei of raphe, and bilateral substantia nigra, sub-thalamic nucleus, and red nucleus (p < 0.005 FDR-corrected vs. control group). No difference between patients and controls was found comparing the contralateral hypothalami. Conclusions: The observed deranged functional connectivity between the posterior ipsilateral hypothalamus and diencephalic-mesencephalic regions in chronic cluster headache patients mainly involves structures that are part of (i.e. ventral tegmental area, substantia nigra) or modulate (dorsal nuclei of raphe, sub-thalamic nucleus) the midbrain dopaminergic systems. The midbrain dopaminergic systems could play a role in cluster headache pathophysiology and in particular in the chronicization process. Future studies are needed to better clarify if this finding is specific to cluster headache or if it represents an unspecific response to chronic pain.

Original languageEnglish
Pages (from-to)1910-1918
Number of pages9
JournalCephalalgia
Volume38
Issue number13
DOIs
Publication statusPublished - Nov 1 2018

Fingerprint

Posterior Hypothalamus
Cluster Headache
Thalamic Nuclei
Ventral Tegmental Area
Substantia Nigra
Mesencephalon
Neuroimaging
Red Nucleus
Deep Brain Stimulation
Chronic Pain
Hypothalamus
Seeds
Healthy Volunteers
Magnetic Resonance Imaging
Pain

Keywords

  • Chronic cluster headache
  • hypothalamus
  • midbrain dopaminergic systems
  • RS-fMRI

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Defective functional connectivity between posterior hypothalamus and regions of the diencephalic-mesencephalic junction in chronic cluster headache. / Ferraro, Stefania; Nigri, Anna; Bruzzone, Maria Grazia; Brivio, Luca; Proietti Cecchini, Alberto; Verri, Mattia; Chiapparini, Luisa; Leone, Massimo.

In: Cephalalgia, Vol. 38, No. 13, 01.11.2018, p. 1910-1918.

Research output: Contribution to journalArticle

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AU - Proietti Cecchini, Alberto

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AU - Chiapparini, Luisa

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N2 - Objective: We tested the hypothesis of a defective functional connectivity between the posterior hypothalamus and diencephalic-mesencephalic regions in chronic cluster headache based on: a) clinical and neuro-endocrinological findings in cluster headache patients; b) neuroimaging findings during cluster headache attacks; c) neuroimaging findings in drug-refractory chronic cluster headache patients improved after successful deep brain stimulation. Methods: Resting state functional magnetic resonance imaging, associated with a seed-based approach, was employed to investigate the functional connectivity of the posterior hypothalamus in chronic cluster headache patients (n = 17) compared to age and sex-matched healthy subjects (n = 16). Random-effect analyses were performed to study differences between patients and controls in ipsilateral and contralateral-to-the-pain posterior hypothalamus functional connectivity. Results: Cluster headache patients showed an increased functional connectivity between the ipsilateral posterior hypothalamus and a number of diencephalic-mesencephalic structures, comprising ventral tegmental area, dorsal nuclei of raphe, and bilateral substantia nigra, sub-thalamic nucleus, and red nucleus (p < 0.005 FDR-corrected vs. control group). No difference between patients and controls was found comparing the contralateral hypothalami. Conclusions: The observed deranged functional connectivity between the posterior ipsilateral hypothalamus and diencephalic-mesencephalic regions in chronic cluster headache patients mainly involves structures that are part of (i.e. ventral tegmental area, substantia nigra) or modulate (dorsal nuclei of raphe, sub-thalamic nucleus) the midbrain dopaminergic systems. The midbrain dopaminergic systems could play a role in cluster headache pathophysiology and in particular in the chronicization process. Future studies are needed to better clarify if this finding is specific to cluster headache or if it represents an unspecific response to chronic pain.

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