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These gaps could be partially elucidated by structural and functional advanced neuroimaging investigations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Although we are aware that substantial achievements have come from preclinical, neurophysiological, and biochemical experiments, the present narrative review aims to summarize the most significant findings from structural, microstructural, and functional neuroimaging investigations, as well as the consequent progresses in understanding CH pathophysiological mechanisms, to achieve a comprehensive and unifying model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Advanced neuroimaging techniques have contributed to overcoming the peripheral hypothesis that CH is of cavernous sinus pathology, in transitioning from the pure vascular hypothesis to a more comprehensive trigeminovascular model, and, above all, in clarifying the role of the hypothalamus and its connections in the genesis of CH.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Altogether, neuroimaging findings strongly suggest that, beyond the theoretical model of the \u201cpain matrix,\u201d the model of the \u201cneurolimbic pain network\u201d that is accepted in migraine research could also be extended to CH. Indeed, although the hypothalamus\u2019 role is undeniable, the genesis of CH attacks is complex and seems to not be just the result of a single \u201cgenerator.\u201d Cortical\u2010hypothalamic\u2010brainstem functional interconnections that can switch between out\u2010of\u2010bout and in\u2010bout periods, igniting the trigeminovascular system (probably by means of top\u2010down mechanisms) and the consensual trigeminal autonomic reflexes, may represent the \u201cneuronal background\u201d of CH.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/head.14279","type":"journal-article","created":{"date-parts":[[2022,3,22]],"date-time":"2022-03-22T00:25:49Z","timestamp":1647908749000},"page":"436-452","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Cluster headache pathophysiology: What we have learned from advanced 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