title: Down-regulation of insular cortex responses to dyspnea and pain in asthma.
abstract: BACKGROUND
  Dyspnea is the impairing cardinal symptom of asthma but its accurate perception is also crucial for timely initiation of treatment. However, the underlying brain mechanisms of perceived dyspnea in patients with asthma are unknown.
  
  
  OBJECTIVE
  To study brain mechanisms of dyspnea in asthma.
  
  
  METHODS
  By using functional magnetic resonance imaging we compared the neuronal responses to experimentally induced dyspnea in patients with asthma and healthy controls. These brain activations were compared with neuronal responses evoked by pain to study neuronal generalization processes to another, similarly unpleasant, physiological sensation.
  
  
  RESULTS
  While lying in the scanner, fourteen patients with mild-to-moderate asthma and fourteen matched healthy controls repeatedly underwent conditions of mild dyspnea, severe dyspnea, mild pain and severe pain. Dyspnea was induced by resistive loaded breathing. Heat pain of similar intensity was induced by a contact thermode. Whereas the sensory intensity of both sensations was rated similar by patients and controls, ratings of the affective unpleasantness of dyspnea and pain were reduced in patients. This perceptual difference was mirrored by reduced insular cortex activity, but increased activity in the periaqueductal gray (PAG) in patients during both increased dyspnea and pain. Connectivity analyses showed that asthma-specific down-regulation of the insular cortex during dyspnea and pain was moderated by increased PAG activity.
  
  
  CONCLUSIONS
  The results suggest a down-regulation of affect-related insular cortex activity by the PAG during perceived dyspnea and pain in patients with asthma. This might represent a neuronal habituation mechanism reducing the affective unpleasantness of dyspnea in asthma, which generalizes to other unpleasant physiological sensations such as pain.
authors.affiliation: Department of Psychology, University of Hamburg, 20146 Hamburg, Germany. andreas.vonleupoldt@uni-hamburg.de
authors.forename: Andreas
authors.initials: A
authors.lastname: von Leupoldt
authors.forename: Tobias
authors.initials: T
authors.lastname: Sommer
authors.forename: Sarah
authors.initials: S
authors.lastname: Kegat
authors.forename: Falk
authors.initials: F
authors.lastname: Eippert
authors.forename: Hans Jörg
authors.initials: HJ
authors.lastname: Baumann
authors.forename: Hans
authors.initials: H
authors.lastname: Klose
authors.forename: Bernhard
authors.initials: B
authors.lastname: Dahme
authors.forename: Christian
authors.initials: C
authors.lastname: Büchel
mesh_terms: D000328:Adult; D001249:Asthma / Q000150:complications / Q000503:physiopathology*; D002540:Cerebral Cortex / Q000473:pathology / Q000503:physiopathology*; D004417:Dyspnea / Q000150:complications / Q000503:physiopathology*; D005073:Evoked Potentials, Somatosensory / Q000502:physiology; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D010146:Pain / Q000150:complications / Q000503:physiopathology*; D012684:Sensory Thresholds / Q000502:physiology; D012720:Severity of Illness Index