Neural substrates of interoceptive sensibility: An integrated study in normal and pathological functioning Author: Maddalena Boccia1, Alice Teghil2, Simona Raimo3, Antonella Di Vita4, Dario Grossi5, Cecilia Guariglia2, Liana Palermo6 Affiliation: <sup>1</sup> Department of Psychology, Sapienza University of Rome, Italy; Cognitive and Motor Rehabilitation and Neuroimaging Unit, IRCCS Santa Lucia, Italy. Electronic address: maddalena.boccia@uniroma1.it. <sup>2</sup> Department of Psychology, Sapienza University of Rome, Italy; Cognitive and Motor Rehabilitation and Neuroimaging Unit, IRCCS Santa Lucia, Italy. <sup>3</sup> Department of Medical and Surgical Science, Magna Graecia University of Catanzaro, Italy. <sup>4</sup> Department of Human Neuroscience, Sapienza University of Rome, Italy. <sup>5</sup> Department of Psychology, University of Campania Luigi Vanvitelli, Italy. <sup>6</sup> Department of Medical and Surgical Science, Magna Graecia University of Catanzaro, Italy; Cognitive and Motor Rehabilitation and Neuroimaging Unit, IRCCS Santa Lucia, Italy. Conference/Journal: Neuropsychologia Date published: 2023 Feb 4 Other: Special Notes: doi: 10.1016/j.neuropsychologia.2023.108504. , Word Count: 262 In early studies interoception strictly referred to the awareness of visceral sensation, but recent theories have expanded this concept to denote the ongoing status of the body, including somatosensory feelings. Here, we integrated data from normal and pathological functioning to disclose neural underpinnings of interoceptive sensibility, taking into account the crucial distinction between visceral and somatosensory feelings. Twenty-seven healthy young individuals underwent structural MRI (including T1w images and DTI). Voxel-wise analyses of the gyrification index (GI) and fractional anisotropy (FA) data were performed to assess the relation between interoceptive sensibility and surface morphometry and anatomical connectivity. Thirty-three unilateral brain-damaged patients took part in this study for Voxel-Based Lesion-Symptom Mapping (VLSM) and track-wise hodological lesion-deficit analysis (TWH). All participants completed the Self-Awareness Questionnaire (SAQ), a self-report tool assessing interoceptive sensibility of visceral (F1) and somatosensory feelings (F2). TBSS showed that F2 was positively associated with FA in the bilateral anterior thalamic radiation, corticospinal tract, cingulum, forceps, inferior longitudinal, fronto-occipital, superior longitudinal, and uncinate fasciculi; no significant association was detected for F1. However, F1 was positively associated with GI in the left anterior cingulate cortex. VLSM showed that F1 mainly relies on the right posterior insula, whereas F2 is related mostly to subcortical nuclei and surrounding white matter in the right hemisphere. Accordingly, patients with disconnection of the anterior thalamic projection, corticospinal tract, inferior fronto-occipital, inferior longitudinal, uncinate and superior longitudinal fasciculus III showed lower scores on F2. Overall, results support the dissociation between interoceptive sensibility of visceral and somatosensory feelings. Keywords: Hodological; Interoception; Somatosensorial sensations; VLSM; Visceral sensations. PMID: 36746344 DOI: 10.1016/j.neuropsychologia.2023.108504