title: GABA in the insula - a predictor of the neural response to interoceptive awareness.
abstract: The insula has been identified as a key region involved in interoceptive awareness. Whilst imaging studies have investigated the neural activation patterns in this region involved in intero- and exteroceptive awareness, the underlying biochemical mechanisms still remain unclear. In order to investigate these, a well-established fMRI task targeting interoceptive awareness (heartbeat counting) and exteroceptive awareness (tone counting) was combined with magnetic resonance spectroscopy (MRS). Controlling for physiological noise, neural activity in the insula during intero- and exteroceptive awareness was confirmed in an independent data sample using the same fMRI design. Focussing on MRS values from the left insula and combining them with neural activity during intero- and exteroceptive awareness in the same healthy individuals, we demonstrated that GABA concentration in a region highly involved in interoceptive processing is correlated with neural responses to interoceptive stimuli, as opposed to exteroceptive stimuli. In addition, both GABA and interoceptive signal changes in the insula predicted the degree of depressed affect, as measured by the Beck Hopelessness Scale. On the one hand, the association between GABA concentration and neural activity during interoceptive awareness provides novel insight into the biochemical underpinnings of insula function and interoception. On the other, through the additional association of both GABA and neural activity during interoception with depressed affect, these data also bear potentially important implications for psychiatric disorders like depression and anxiety, where GABAergic deficits, altered insula function and abnormal affect coincide.
authors.affiliation: Department of Biology, Freie Universität Berlin, Germany; Institute of Mental Health Research, Ottawa, Canada. Electronic address: christine.wiebking@gmx.com.
authors.forename: Christine
authors.initials: C
authors.lastname: Wiebking
authors.affiliation: Institute of Mental Health Research, Ottawa, Canada.
authors.forename: Niall W
authors.initials: NW
authors.lastname: Duncan
authors.affiliation: Functional Neuroimaging Unit and Department of Psychology, University of Montréal, Canada.
authors.forename: Brice
authors.initials: B
authors.lastname: Tiret
authors.affiliation: Institute of Mental Health Research, Ottawa, Canada.
authors.forename: Dave J
authors.initials: DJ
authors.lastname: Hayes
authors.affiliation: Center for Magnetic Resonance Research and Department of Radiology, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Marjaǹska
authors.affiliation: Functional Neuroimaging Unit and Department of Psychology, University of Montréal, Canada.
authors.forename: Julien
authors.initials: J
authors.lastname: Doyon
authors.affiliation: Cluster of Excellence "Languages of Emotion" and Dahlem Institute for Neuroimaging of Emotion (D.I.N.E.), Freie Universität Berlin, Germany.
authors.forename: Malek
authors.initials: M
authors.lastname: Bajbouj
authors.affiliation: Institute of Mental Health Research, Ottawa, Canada.
authors.forename: Georg
authors.initials: G
authors.lastname: Northoff
mesh_terms: D000293:Adolescent; D000328:Adult; D001364:Awareness / Q000502:physiology*; D015415:Biomarkers / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D018377:Neurotransmitter Agents / Q000378:metabolism; D012016:Reference Values; D012677:Sensation / Q000502:physiology*; D014018:Tissue Distribution; D055815:Young Adult; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D018377:Neurotransmitter Agents; D005680:gamma-Aminobutyric Acid
keywords: Depressed affect; GABA; Insula; Interoception; MRS; fMRI