title: How the heart speaks to the brain: neural activity during cardiorespiratory interoceptive stimulation.
abstract: Prominent theories emphasize key roles for the insular cortex in the central representation of interoceptive sensations, but how this brain region responds dynamically to changes in interoceptive state remains incompletely understood. Here, we systematically modulated cardiorespiratory sensations in humans using bolus infusions of isoproterenol, a rapidly acting peripheral beta-adrenergic agonist similar to adrenaline. To identify central neural processes underlying these parametrically modulated interoceptive states, we used pharmacological functional magnetic resonance imaging (phMRI) to simultaneously measure blood-oxygenation-level dependent (BOLD) and arterial spin labelling (ASL) signals in healthy participants. Isoproterenol infusions induced dose-dependent increases in heart rate and cardiorespiratory interoception, with all participants endorsing increased sensations at the highest dose. These reports were accompanied by increased BOLD and ASL activation of the right insular cortex at the highest dose. Different responses across insula subregions were also observed. During anticipation, insula activation increased in more anterior regions. During stimulation, activation increased in the mid-dorsal and posterior insula on the right, but decreased in the same regions on the left. This study demonstrates the feasibility of phMRI for assessing brain activation during adrenergic interoceptive stimulation, and provides further evidence supporting a dynamic role for the insula in representing changes in cardiorespiratory states.This article is part of the themed issue 'Interoception beyond homeostasis: affect, cognition and mental health'.
authors.affiliation: Laureate Institute for Brain Research, Tulsa, OK 74136, USA.
authors.forename: Mahlega S
authors.identifier: 0000-0002-0410-577X
authors.initials: MS
authors.lastname: Hassanpour
authors.affiliation: Laboratory of FMRI Technology (LOFT), Mark & Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California (USC), Los Angeles, CA 90032, USA.
authors.forename: Lirong
authors.initials: L
authors.lastname: Yan
authors.affiliation: Laboratory of FMRI Technology (LOFT), Mark & Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California (USC), Los Angeles, CA 90032, USA.
authors.forename: Danny J J
authors.initials: DJ
authors.lastname: Wang
authors.affiliation: Oxley College of Health Sciences, University of Tulsa, Tulsa, OK 74136, USA.
authors.forename: Rachel C
authors.initials: RC
authors.lastname: Lapidus
authors.affiliation: Department of Psychiatry, Semel Institute for Neuroscience and Human Behavior UCLA, Los Angeles, CA 90095, USA.
authors.forename: Armen C
authors.initials: AC
authors.lastname: Arevian
authors.affiliation: Laureate Institute for Brain Research, Tulsa, OK 74136, USA.|Oxley College of Health Sciences, University of Tulsa, Tulsa, OK 74136, USA.
authors.forename: W Kyle
authors.initials: WK
authors.lastname: Simmons
authors.affiliation: Department of Psychiatry, Semel Institute for Neuroscience and Human Behavior UCLA, Los Angeles, CA 90095, USA.
authors.forename: Jamie D
authors.initials: JD
authors.lastname: Feusner
authors.affiliation: Laureate Institute for Brain Research, Tulsa, OK 74136, USA skhalsa@laureateinstitute.org.|Oxley College of Health Sciences, University of Tulsa, Tulsa, OK 74136, USA.
authors.forename: Sahib S
authors.initials: SS
authors.lastname: Khalsa
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000328:Adult; D002540:Cerebral Cortex / Q000502:physiology; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D065812:Interoception / Q000187:drug effects*; D007545:Isoproterenol / Q000494:pharmacology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010100:Oxygen / Q000097:blood; D056152:Respiratory Rate / Q000187:drug effects*; D055815:Young Adult
chemical_list: D000318:Adrenergic beta-Agonists; D007545:Isoproterenol; D010100:Oxygen
keywords: cardiac; emotion; insula; interoception; pharmacological functional magnetic resonance imaging; respiration