Exploring interoceptive adaptations and connectivity following SAINT: Insights from insula
Poster No:
622
Submission Type:
Abstract Submission
Authors:
John Coetzee1, Ella Teuscher2, Clive Veerapal1, Irakli Kaloiani1, Andrew Geoly1, Martin Tik3, Nolan Williams4
Institutions:
1Stanford, Palo Alto, CA, 2Medical University of Vienna, Vienna, Vienna, 3Medical University of Vienna, Wien, Vienna, 4Stanford University, Stanford, CA
First Author:
Co-Author(s):
Introduction:
Interoceptive ability is often reduced in clinically depressed patients - this state has further been described as a "locked-in" brain according to Barrett et al. (2016). Previous research has highlighted the critical role of the anterior insula in integrating interoceptive signals from both the body and brain, positioning it as a central hub in the brain's interoceptive network (Fermin et al., 2023). Furthermore, TMS administered to the DLPFC has produced a direct change in entrainment of the heart interbeat interval - this finding has been proposed to involve the frontal-vagal network as well as interoceptive network (Dijkstra et al 2023). In this exploratory study, we tested whether an insula-centered interoceptive network overlaps with the subgenual anterior cingulate cortex (sgACC)-centered depression network targeted by Stanford Neuromodulation Therapy (SNT). We also investigated whether enhanced connectivity from the anterior insula to SNT-relevant regions, including DLPFC and sgACC, correlates with changes in subscales of clinical measures associated with interoception following SNT.
Methods:
Twenty-nine patients with treatment resistant depression (TRD) underwent SNT in a randomized double-blinded clinical trial as described in Cole et al. (2022). At baseline and at 1-week post SNT, resting state scans were acquired and the Montgomery Asberg Depression Rating Scale (MADRS) questionnaire was administered. Imaging was performed on a 3TGE Discovery MR750. Patients were instructed to let their minds wander during 8-min EPI scans (TR = 2000 ms, TE = 30 ms, flip angle = 77°, slice acceleration factor = 3, FOV = 230 × 230 mm, matrix = 128 × 128 voxels, 1.8 × 1.8 mm). After QC a small number of participants were excluded for either MRI artifacts or missing behavioral data. After preprocessing (as in Mitra et al. 2023), seed-voxel correlation was performed using a spherical ROI around the peak region of a Neurosynth meta-analysis using the term "interoceptive", i.e. anterior insula (36,22,2 MNI [x,y,z], radius=10mm (Yarkoni et al., 2011). Functional connectivity (FC) maps were averaged to compare with the sgACC anticorrelated network (see Fig. 1) and participant-wise differences between 1-week and baseline were calculated. Contrast FC maps were regressed across participants (second level) as implemented in SPM12 against the change in the average of following interoception-related measures from MADRS: inner tension, reduced appetite, inability to feel.
Results:
The SNT targeted sgACC network generally overlaps with interoceptive circuits see Figure 1. Increased interoception on self-rated MADRS items 1-week post SAINT, compared to baseline, was associated with increased connectivity from insula to DLPFC [25.70, 61.58, 33.1], p(unc.) = .003, f2 = 0.60, see Figure 2a, and to orbitofrontal cortex (OFC) [43.67, 50.79, -11.9], p(unc.) = .002, f2 = 0.62, see Figure 2c. Moreover, increased interoception on self-rated MADRS items 1-week post SAINT, compared to baseline, was associated with decreased connectivity from insula to sgACC [-1.26, 32.82, -17.3], but this was insignificant, p(unc.) = .735, f2 = 1.24, see Figure 2b. None of the p-values in this exploratory analysis remained significant after applying the False Discovery Rate (FDR) correction.
·The SNT target network generally overlaps with interoceptive circuits: the anterior insula (left panel) and the sgACC (right panel) resting state FC maps are similar.
·Functional connectivity in the interoceptive network.
Conclusions:
The sgACC-centered network targeted by SNT broadly overlaps with an anterior insula-centered network derived from Neurosynth. Changes in subscales of clinical measures associated with interoception following SNT were associated with increased connectivity between insula and DLPFC as well as OFC, and decreased connectivity between insula and sgACC, although the latter was insignificant. This provides support for the idea that interoceptive ability may be affected during depression. This provides support for the predictive-coding theory of emotion as put forward by Barrett et al. (2016) in which the experience of emotion is derived from interoceptive experiences.
Brain Stimulation:
TMS
Disorders of the Nervous System:
Psychiatric (eg. Depression, Anxiety, Schizophrenia)
Emotion, Motivation and Social Neuroscience:
Emotional Perception 1
Novel Imaging Acquisition Methods:
BOLD fMRI
Perception, Attention and Motor Behavior:
Perception and Attention Other 2
Keywords:
Affective Disorders
Cognition
Emotions
FUNCTIONAL MRI
Limbic Systems
Perception
Psychiatric Disorders
Transcranial Magnetic Stimulation (TMS)
1|2Indicates the priority used for review
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Provide references using APA citation style.
Cole, E. J., Phillips, A. L., Bentzley, B. S., Stimpson, K. H., Nejad, R., Barmak, F., ... & Williams, N. R. (2022). Stanford neuromodulation therapy (SNT): a double-blind randomized controlled trial. American Journal of Psychiatry, 179(2), 132-141.
Dijkstra, E., van Dijk, H., Vila-Rodriguez, F., Zwienenberg, L., Rouwhorst, R., Coetzee, J. P., ... & Arns, M. (2023). Transcranial magnetic stimulation–induced heart-brain coupling: Implications for site selection and frontal thresholding—Preliminary findings. Biological Psychiatry Global Open Science, 3(4), 939-947.
Dijkstra, E. S., Frandsen, S. B., van Dijk, H., Duecker, F., Taylor, J. J., Sack, A. T., ... & Siddiqi, S. H. (2024). Probing prefrontal-sgACC connectivity using TMS-induced heart–brain coupling. Nature Mental Health, 1-9.
Fermin, A. S., Sasaoka, T., Maekawa, T., Chan, H. L., Machizawa, M. G., Okada, G., ... & Yamawaki, S. (2023). Insula neuroanatomical networks predict interoceptive awareness. Heliyon, 9(8).
Mitra, A., Raichle, M. E., Geoly, A. D., Kratter, I. H., & Williams, N. R. (2023). Targeted neurostimulation reverses a spatiotemporal biomarker of treatment-resistant depression. Proceedings of the National Academy of Sciences, 120(21), e2218958120.
Yarkoni, T., Poldrack, R. A., Nichols, T. E., Van Essen, D. C., & Wager, T. D. (2011). Large-scale automated synthesis of human functional neuroimaging data. Nature methods, 8(8), 665-670.