title: A 'complex' of brain metabolites distinguish altered chemistry in the cingulate cortex of episodic migraine patients.
abstract: Despite the prevalence of migraine, the pathophysiology of the disease remains unclear. Current understanding of migraine has alluded to the possibility of a hyperexcitable brain. The aim of the current study is to investigate human brain metabolite differences in the anterior cingulate cortex (ACC) during the interictal phase in migraine patients. We hypothesized that there may be differences in levels of excitatory neurotransmitters and/or their derivatives in the migraine cohort in support of the theory of hyperexcitability in migraine. 2D J-resolved proton magnetic resonance spectroscopy ((1)H-MRS) data were acquired on a 3 Tesla (3 T) MRI from a voxel placed over the ACC of 32 migraine patients (MP; 23 females, 9 males, age 33 ± 9.6 years) and 33 healthy controls (HC; 25 females, 8 males, age 32 ± 9.6 years). Amplitude correlation matrices were constructed for each subject to evaluate metabolite discriminability. ProFit-estimated metabolite peak areas were normalized to a water reference signal to assess subject differences. The initial analysis of variance (ANOVA) was performed to test for group differences for all metabolites/creatine (Cre) ratios between healthy controls and migraineurs but showed no statistically significant differences. In addition, we used a multivariate approach to distinguish migraineurs from healthy subjects based on the metabolite/Cre ratio. A quadratic discriminant analysis (QDA) model was used to identify 3 metabolite ratios sufficient to minimize minimum classification error (MCE). The 3 selected metabolite ratios were aspartate (Asp)/Cre, N-acetyl aspartate (NAA)/Cre, and glutamine (Gln)/Cre. These findings are in support of a 'complex' of metabolite alterations, which may underlie changes in neuronal chemistry in the migraine brain. Furthermore, the parallel changes in the three-metabolite 'complex' may confer more subtle but biological processes that are ongoing. The data also support the current theory that the migraine brain is hyperexcitable even in the interictal state.
authors.affiliation: Pain/Analgesia Imaging Neuroscience (P.A.I.N.) Group, Department of Anesthesia Critical Care and Pain Medicine, Boston Children's Hospital, Center for Pain and the Brain, Harvard Medical School, Waltham, MA, USA; Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, USA; Departments of Psychiatry and Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02114, USA.
authors.forename: L
authors.initials: L
authors.lastname: Becerra
authors.affiliation: Pain/Analgesia Imaging Neuroscience (P.A.I.N.) Group, Department of Anesthesia Critical Care and Pain Medicine, Boston Children's Hospital, Center for Pain and the Brain, Harvard Medical School, Waltham, MA, USA; Brain Imaging Center, McLean Hospital, Harvard Medical School, Belmont, MA, USA.
authors.forename: R
authors.initials: R
authors.lastname: Veggeberg
authors.affiliation: Department of Radiology, University of Utah, School of Medicine, Salt Lake City, UT, USA; VISN 19 MIRECC, Salt Lake City, UT, USA.
authors.forename: A
authors.initials: A
authors.lastname: Prescot
authors.affiliation: Brain Imaging Center, McLean Hospital, Harvard Medical School, Belmont, MA, USA.
authors.forename: J E
authors.initials: JE
authors.lastname: Jensen
authors.affiliation: Department of Psychiatry, University of Utah, Salt Lake City, UT, USA; VISN 19 MIRECC, Salt Lake City, UT, USA.
authors.forename: P
authors.initials: P
authors.lastname: Renshaw
authors.affiliation: Department of Oral and Maxillofacial Surgery, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Scrivani
authors.affiliation: Department of Neurology, Tufts Medical Center, Boston, MA, USA.
authors.forename: E L H
authors.initials: ELH
authors.lastname: Spierings
authors.affiliation: Anesthesia and Critical Care, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors.forename: R
authors.initials: R
authors.lastname: Burstein
authors.affiliation: Pain/Analgesia Imaging Neuroscience (P.A.I.N.) Group, Department of Anesthesia Critical Care and Pain Medicine, Boston Children's Hospital, Center for Pain and the Brain, Harvard Medical School, Waltham, MA, USA; Departments of Psychiatry and Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02114, USA; Brain Imaging Center, McLean Hospital, Harvard Medical School, Belmont, MA, USA. Electronic address: david.borsook@childrens.harvard.edu.
authors.forename: D
authors.initials: D
authors.lastname: Borsook
mesh_terms: D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D015331:Cohort Studies; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism*; D006179:Gyrus Cinguli / Q000000981:diagnostic imaging / Q000378:metabolism*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D008881:Migraine Disorders / Q000000981:diagnostic imaging / Q000473:pathology*; D066244:Proton Magnetic Resonance Spectroscopy; D055815:Young Adult
chemical_list: D005973:Glutamine; D001224:Aspartic Acid; D018698:Glutamic Acid; C000179:N-acetylaspartate
keywords: 2D J-resolved; Anterior cingulate cortex (ACC); Central sensitization; Excitatory neurotransmitters; Interictal migraine; Magnetic resonance spectroscopy (MRS)