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Review
. 2014 Feb 1;86:10-8.
doi: 10.1016/j.neuroimage.2013.04.042. Epub 2013 Apr 22.

GABA in the Insula - A Predictor of the Neural Response to Interoceptive Awareness

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Free PMC article
Review

GABA in the Insula - A Predictor of the Neural Response to Interoceptive Awareness

Christine Wiebking et al. Neuroimage. .
Free PMC article

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.

Keywords: Depressed affect; GABA; Insula; Interoception; MRS; fMRI.

Figures

Figure 1
Figure 1
A) Whole brain contrast [IA > EA] (voxel P FDR ≤ 0.02) and placement of the left insula MRS voxel (green). B) Extracted signal changes from the insula MRS voxel. Bars show BOLD responses (mean ± SEM, n = 15 participants) for IA (red) and EA (yellow) (see also Suppl. table 1B). Paired t-tests (two-tailed) show significant differences between the conditions (** P ≤ 0.001). C) The region of the insula MRS voxel was applied to an independent data sample (n = 30 healthy participants) that used the same fMRI paradigm (see also Suppl. table 1B). Paired t-tests (two-tailed) between IA (red) and EA (yellow) confirm results seen in B (** P ≤ 0.001). D) The scatter plot shows residuals for the BOLD responses of IA in the MRS insula voxel (r = 0.58, * P ≤ 0.05) as well as GABA/NAA following grey matter correction (see also Table 1A). Signal changes for EA show no association to GABA/NAA. E) Voxel-wise regressions within the MRS voxel (red, cluster P FWE ≤ 0.01) (see also Suppl. table 2A) identify the anatomical region within the MRS voxel showing a positive relationship between IA and GABA/NAA. The amount of grey matter in the MRS voxel was included as regressor of no interest.
Figure 2
Figure 2
A) The left scatter plot (in purple) shows a negative relationship between residuals for BHS and GABA/NAA in the left insula (r = -0.62, * P ≤ 0.05, n = 15) (see also Table 1A), controlling for grey matter volume. B) The right scatter plot (in red) shows residuals for the BOLD responses of IA in the MRS insula voxel correlated with BHS (r = 0.58, * P ≤ 0.05) (see also Table 1A). Signal changes for EA show no association to BHS. C) Voxel-wise regressions show in cyan the positive regression IA × GABA/NAA (as in Figure 1E, cluster P FWE ≤ 0.01), in purple the negative regression IA × BHS (cluster P FWE ≤ 0.001) (Suppl. table 2A), and in white the overlap between these. All regressions included the amount of grey matter as control variable.
Figure 3
Figure 3
Overview showing the inter-relationship between the neurochemical level by GABA/NAA concentration, the neural level by signal changes for interoception, and the behavioral level of depression as assessed by the Beck Hopelessness Scale.

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