title: Brain activity following esophageal acid infusion using positron emission tomography.
abstract: OBJECTIVE
  To investigate symptoms and brain activity following esophageal acid infusion.
  
  
  METHODS
  Fifteen healthy volunteers were recruited for the study. Hydrochloric acid (pH 1 and 2) and distilled water (pH 7) were randomly and repeatedly infused into the esophagus. The brain activity was evaluated by positron emission tomography. The severity of heartburn elicited by the infusion was rated on an auditory analog scale of 0-10.
  
  
  RESULTS
  The severity of heartburn following each infusion showed a step-wise increase with increasing acidity of the perfusate. The heartburn scores were significantly higher in the second pH 1 infusion compared with the first infusion. Acid and distilled water infusion induced activation of various brain areas such as the anterior insula, temporal gyrus, and anterior/posterior cingulate cortex. At pH 1 or 2, in particular, activation was observed in some emotion-related brain areas such as the more anterior part of the anterior cingulate cortex, parahippocampal gyrus, or the temporal pole. Strong activation of the orbitofrontal cortex was found by subtraction analysis of the two second pH 1 infusions, with a significant increase of heartburn symptoms.
  
  
  CONCLUSIONS
  Emotion-related brain areas were activated by esophageal acid stimulation. The orbitofrontal area might be involved in symptom processing, with esophageal sensitization induced by repeated acid stimulation.
authors.affiliation: Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8574, Japan.
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Abe
authors.forename: Manabu
authors.initials: M
authors.lastname: Tashiro
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Koike
authors.forename: Katsunori
authors.initials: K
authors.lastname: Iijima
authors.forename: Akira
authors.initials: A
authors.lastname: Imatani
authors.forename: Shuichi
authors.initials: S
authors.lastname: Ohara
authors.forename: Satoshi
authors.initials: S
authors.lastname: Watanabe
authors.forename: Shin
authors.initials: S
authors.lastname: Fukudo
authors.forename: Tooru
authors.initials: T
authors.lastname: Shimosegawa
mesh_terms: D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging* / Q000502:physiology*; D006179:Gyrus Cinguli / Q000000981:diagnostic imaging / Q000502:physiology; D006356:Heartburn / Q000139:chemically induced* / Q000453:epidemiology / Q000503:physiopathology; D006801:Humans; D006851:Hydrochloric Acid / Q000009:adverse effects*; D006863:Hydrogen-Ion Concentration; D015994:Incidence; D008297:Male; D020534:Parahippocampal Gyrus / Q000000981:diagnostic imaging / Q000502:physiology; D049268:Positron-Emission Tomography; D012720:Severity of Illness Index
chemical_list: D006851:Hydrochloric Acid