Stoffel, Natascha (2025). The Role of Oxytocin and Interoception in Functional Neurological Disorders. (Thesis). Universität Bern, Bern
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25stoffel_n.pdf - Thesis Available under License Creative Commons: Attribution (CC-BY 4.0). Download (17MB) | Preview |
Abstract
Functional Neurological Disorder (FND) is characterized by symptoms such as motor or sensory dysfunction or functional/dissociative seizures. Unfortunately, the mechanisms behind the disorder are still incompletely understood, leading to a lack of specific treatment. Interoception, the processing of internal bodily signals, has been considered a potential site where the processing of sensory signals might deviate. However, empirical findings on interoceptive functions in FND remain inconsistent, largely due to methodological variability and the lack of comprehensive, multimodal assessments. The present dissertation addresses these limitations by comprehensively investigating interoception across multiple domains in a large and mixed cohort of FND patients. Furthermore, the project explores the oxytocinergic system as a potential biological vulnerability factor, given its role in modulating stress responses - a key risk factor for FND - and assigning salience to interoceptive inputs. Interoceptive functioning was assessed across trait, behavioral, physiological, and neural levels, comparing a mixed symptom cohort of patients with FND to a sex-aged matched healthy controls (HC). Self-reported interoception was measured using both the Multidimensional Assessment of Interoceptive Awareness (MAIA) and the Interoceptive Accuracy Scale (IAS). Interoceptive accuracy was evaluated using the Heartbeat Counting Task (HCT) both in its traditional form and in a novel aroused condition induced via breath-hold instruction. Respiratory interoceptive sensitivity and metacognition were measured using the Respiratory Resistance Sensitivity Task (RRST), introducing breath as a newly studied interoceptive modality in FND. Neural processing of cardiac signals was assessed via Heartbeat-Evoked Potentials (HEPs), focusing specifically on attentional modulation. Finally, the oxytocinergic system was examined through salivary oxytocin (OXT) levels, genotyping of the OXT receptor OXTR, and its methylation rates, and linked to resting-state functional connectivity to explore neurobiological correlates of the biological vulnerability candidate. FND patients self-reported being significantly less interoceptive using both questionnaires, compared to the HCs. No group differences emerged in cardiac accuracy using the HCT; however, we identified reduced respiratory sensitivity in patients. Metacognition in FND was intact, while both sensitivity and metacognition correlated with self-reported somatoform dissociation symptoms. Further, EEG data revealed lower HEP responses in patients, and interactions of brain network activation with group and attentional focus conditions. Finally, the presence of the A allele at the OXTR was associated with FND, and with increased OXTR methylation, which was then positively associated with salivary OXT uniquely for patients with FND. Salivary OXT also correlated with altered functional connectivity of the amygdala with other regions in patients. This work presents compelling evidence that there is an interoceptive and oxytocinergic dysregulation in FND. Having measured interoception comprehensively across various dimensions and different modalities, the interoceptive system should be considered both a clinical marker and a therapeutic target. Electrophysiological and neuroimaging markers, such as lower HEPs and resting-state connectivity, point to potential neural signatures of the disorder. Meanwhile, impairments in interoceptive self-report and attention, along with their association with somatoform dissociation, suggest mechanisms through which symptoms may arise or persist. The observed alterations in the proposed vulnerability system of OXT suggest a neuroendocrine contribution. The group-specific differences of the various levels possibly reflect a gene–environment interactions or compensatory processes. Given oxytocin's role in modulating limbic circuits and sensory integration, such disruptions may underlie maladaptive salience attribution in FND. Together, these findings offer a deeper understanding of FND pathophysiology and point toward integrated intervention strategies targeting both interoceptive and neuroendocrine systems.
| Item Type: | Thesis |
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| Dissertation Type: | Cumulative |
| Date of Defense: | 29 September 2025 |
| Subjects: | 600 Technology > 610 Medicine & health |
| Institute / Center: | 07 Faculty of Human Sciences > Institute of Psychology |
| Depositing User: | Hammer Igor |
| Date Deposited: | 16 Oct 2025 12:13 |
| Last Modified: | 16 Oct 2025 12:13 |
| URI: | https://boristheses.unibe.ch/id/eprint/6800 |
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