title: Uncertainty in anticipation of uncomfortable rectal distension is modulated by the autonomic nervous system--a fMRI study in healthy volunteers.
abstract: The human brain responds both before and during the application of aversive stimuli. Anticipation allows the organism to prepare its nociceptive system to respond adequately to the subsequent stimulus. The context in which an uncomfortable stimulus is experienced may also influence neural processing. Uncertainty of occurrence, timing and intensity of an aversive event may lead to increased anticipatory anxiety, fear, physiological arousal and sensory perception. We aimed to identify, in healthy volunteers, the effects of uncertainty in the anticipation of uncomfortable rectal distension, and the impact of the autonomic nervous system (ANS) activity and anxiety-related psychological variables on neural mechanisms of anticipation of rectal distension using fMRI. Barostat-controlled uncomfortable rectal distensions were preceded by cued uncertain or certain anticipation in 15 healthy volunteers in a fMRI protocol at 3T. Electrocardiographic data were concurrently registered by MR scanner. The low frequency (LF)-component of the heart rate variability (HRV) time-series was extracted and inserted as a regressor in the fMRI model ('LF-HRV model'). The impact of ANS activity was analyzed by comparing the fMRI signal in the 'standard model' and in the 'LF-HRV model' across the different anticipation and distension conditions. The scores of the psychological questionnaires and the rating of perceived anticipatory anxiety were included as covariates in the fMRI data analysis. Our experiments led to the following key findings: 1) the subgenual anterior cingulate cortex (sgACC) is the only activation site that relates to uncertainty in healthy volunteers and is directly correlated to individual questionnaire score for pain-related anxiety; 2) uncertain anticipation of rectal distension involved several relevant brain regions, namely activation of sgACC and medial prefrontal cortex and deactivation of amygdala, insula, thalamus, secondary somatosensory cortex, supplementary motor area and cerebellum; 3) most of the brain activity during anticipation, but not distension, is associated with activity of the central autonomic network. This approach could be applied to study the ANS impact on brain activity in various pathological conditions, namely in patients with chronic digestive conditions characterized by visceral discomfort and ANS imbalance such as irritable bowel syndrome or inflammatory bowel diseases.
authors.affiliation: INSERM, U836, F-38000 Grenoble, France; Univ. Grenoble Alpes, GIN, F-38000 Grenoble, France; CHU de Grenoble, Clinique Universitaire de Pédiatrie, F-38000 Grenoble, France. Electronic address: arubio@chu-grenoble.fr.
authors.forename: Amandine
authors.initials: A
authors.lastname: Rubio
authors.affiliation: University Psychiatric Centre, Liaison Psychiatry, University Hospital Gasthuisberg, B-3000 Leuven, Belgium; Department of Clinical and Experimental Medicine, Translational Research Center for Gastrointestinal Diseases, University of Leuven, B-3000 Leuven, Belgium.
authors.forename: Lukas
authors.initials: L
authors.lastname: Van Oudenhove
authors.affiliation: INSERM, U836, F-38000 Grenoble, France; Univ. Grenoble Alpes, GIN, F-38000 Grenoble, France; Univ. Savoie, F-73000 Chambery, France.
authors.forename: Sonia
authors.initials: S
authors.lastname: Pellissier
authors.affiliation: Department of Clinical and Experimental Medicine, Translational Research Center for Gastrointestinal Diseases, University of Leuven, B-3000 Leuven, Belgium.
authors.forename: Huynh Giao
authors.initials: HG
authors.lastname: Ly
authors.affiliation: University Psychiatric Centre, Liaison Psychiatry, University Hospital Gasthuisberg, B-3000 Leuven, Belgium; Laboratory for Cognitive Neurology, KU Leuven, B-3000 Leuven, Belgium; Medical Imaging Research Centre, KU Leuven, B-3000 Leuven, Belgium.
authors.forename: Patrick
authors.initials: P
authors.lastname: Dupont
authors.affiliation: INSERM, U836, F-38000 Grenoble, France; Univ. Grenoble Alpes, GIN, F-38000 Grenoble, France.
authors.forename: Hugo
authors.initials: H
authors.lastname: Lafaye de Micheaux
authors.affiliation: Department of Clinical and Experimental Medicine, Translational Research Center for Gastrointestinal Diseases, University of Leuven, B-3000 Leuven, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: Tack
authors.affiliation: Univ. Savoie, F-73000 Chambery, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Dantzer
authors.affiliation: INSERM, U836, F-38000 Grenoble, France; Univ. Grenoble Alpes, GIN, F-38000 Grenoble, France.
authors.forename: Chantal
authors.initials: C
authors.lastname: Delon-Martin
authors.affiliation: INSERM, U836, F-38000 Grenoble, France; Univ. Grenoble Alpes, GIN, F-38000 Grenoble, France; Clinique Universitaire d'Hépato-Gastroentérologie, CHU de Grenoble, Hôpital Albert Michallon, F-38000 Grenoble, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Bonaz
mesh_terms: D000328:Adult; D059031:Anticipation, Psychological / Q000502:physiology*; D001007:Anxiety / Q000523:psychology; D001341:Autonomic Nervous System / Q000502:physiology*; D001921:Brain / Q000502:physiology; D003463:Cues; D004562:Electrocardiography; D005260:Female; D006179:Gyrus Cinguli / Q000502:physiology; D064368:Healthy Volunteers; D006339:Heart Rate / Q000502:physiology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009415:Nerve Net / Q000502:physiology; D059225:Nociception / Q000502:physiology; D010146:Pain / Q000503:physiopathology; D010812:Physical Stimulation; D012007:Rectum / Q000294:innervation / Q000502:physiology*; D035501:Uncertainty; D055815:Young Adult
keywords: Anterior cingulate cortex; Anticipation; Anxiety; Autonomic nervous system; Discomfort; HRV; Rectal distension; fMRI