title: In medication-overuse headache, fMRI shows long-lasting dysfunction in midbrain areas.
abstract: OBJECTIVE
  The primary aim of our study was to evaluate if a group of medication-overuse headache (MOH) patients present dysfunctions in the mesocorticolimbic dopamine circuit. The secondary aim was to disentangle the role of the medication overuse and of the acute/chronic headache in determining these alterations and to investigate their persistence.
  
  
  BACKGROUND
  Several researches have suggested that MOH may belong to the spectrum of addictive behavior. Preclinical models and neuroimaging studies have consistently demonstrated that in addiction, critical long-lasting alterations occur in the mesocorticolimbic dopamine circuit. If MOH shares some neurophysiological features with addiction, long-lasting functional alterations of the mesocorticolimbic dopamine system related to medication overuse should be present.
  
  
  METHODS
  We collected functional magnetic resonance imaging data during the execution of a decision-making under risk paradigm in 8 MOH patients immediately after beginning medication withdrawal, in 8 detoxified MOH patients at 6 months after beginning medication withdrawal, in 8 chronic migraine patients, and in 8 control subjects.
  
  
  RESULTS
  Our results revealed that MOH patients present: (1) reduced task-related activity in the substantia nigra/ventral tegmental area complex and increased activity in the ventromedial prefrontal cortex, when compared with controls; (2) reduced activity in the substantia nigra/ventral tegmental area complex, when compared with chronic migraine patients; (3) increased activity in the ventromedial prefrontal cortex, when compared with detoxified MOH patients.
  
  
  CONCLUSIONS
  Our study showed that MOH patients present dysfunctions in the mesocorticolimbic dopamine circuit, in particular in the ventromedial prefrontal cortex and in the substantia nigra/ventral tegmental area complex. The ventromedial prefrontal cortex dysfunctions seem to be reversible and attributable to the acute/chronic headache, whereas the substantia nigra/ventral tegmental area complex dysfunctions are persistent and possibly related to medication overuse. These dysfunctions might be the expression of long-lasting neuroadaptations related to the overuse of medications and/or a pre-existing neurophysiological condition leading to vulnerability to medication overuse. The observed persistent dysfunctions in the midbrain dopamine suggest that MOH may share some neurophysiological features with addiction.
authors.affiliation: Neuroradiology Department, Foundation IRCCS Neurological Institute Carlo Besta, Milan, Italy. stefania.ferraro@istituto-besta.it
authors.forename: Stefania
authors.initials: S
authors.lastname: Ferraro
authors.forename: Licia
authors.initials: L
authors.lastname: Grazzi
authors.forename: Riccardo
authors.initials: R
authors.lastname: Muffatti
authors.forename: Simone
authors.initials: S
authors.lastname: Nava
authors.forename: Francesco
authors.initials: F
authors.lastname: Ghielmetti
authors.forename: Nicola
authors.initials: N
authors.lastname: Bertolino
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Mandelli
authors.forename: Eleonora
authors.initials: E
authors.lastname: Visintin
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Bruzzone
authors.forename: Anna
authors.initials: A
authors.lastname: Nigri
authors.forename: Francesca
authors.initials: F
authors.lastname: Epifani
authors.forename: Gennaro
authors.initials: G
authors.lastname: Bussone
authors.forename: Luisa
authors.initials: L
authors.lastname: Chiapparini
mesh_terms: D000328:Adult; D005260:Female; D051271:Headache Disorders, Secondary / Q000175:diagnosis* / Q000503:physiopathology*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000639:trends*; D008636:Mesencephalon / Q000503:physiopathology*; D008875:Middle Aged; D013997:Time Factors
keywords: addiction; decision-making under risk; functional magnetic resonance imaging; medication-overuse headache; mesocorticolimbic dopamine circuit