Role of the posterior insular cortex in cardiorespiratory interoception during fear

Weiand, Caroline (2026): Role of the posterior insular cortex in cardiorespiratory interoception during fear. Dissertation, LMU München: Medizinische Fakultät

Abstract

Interoception refers to the sensing, processing, regulation and prediction of internal signals. During fear, baseline, homeostatic interoceptive processes are disrupted in favor of changes, which are required to avoid danger and harm. However, when fear becomes pathological, these processes are altered. A growing body of literature suggests important interactions between different interoceptive measures and emotion regulation. Most prominently, cardiac and respiratory interoception have been implicated in fear and anxiety. An additional cardiac measure commonly used to reflect internal arousal state is heart rate variability which has been implicated to reflect trait anxiety. Furthermore, imaging studies have revealed the insular cortex as an important interoceptive hub. Importantly, the insular cortex has shown to not only be crucial in normal interoceptive processing but to also display a markedly altered activity in patients with anxiety disorders. Interestingly, anxiety disorders are associated with disruptions of brain-body communication. Bodily signals are transmitted via cranial nerves and processed in the brainstem, before reaching cortical levels. The most important components of this lower order processing are the vagus nerve and the nucleus of the solitary tract (NTS). On the cortical level, the posterior insular cortex (pInsCtx), also called the visceral cortex, receives, processes, and influences these internal as well as external cues. This ability, along with its inter-connection properties, makes it a central cortical region that is heavily involved in interoception. Additionally, the pInsCtx has been shown to play a crucial part in the processing of aversive emotions. As such, it has been identified to play an important role in fear and extinction learning. Moreover, studies implicated pInsCtx in the perception and regulation of cardiac signals by suggesting a tight coupling during fear. This study aims to advance current knowledge of body-brain interactions during fear by characterizing pInsCtx interactions with cardiac and respiratory measures during fear and anxiety. Wireless telemetry in freely moving mice was utilized to measure cardiac signals via electrocardiogram (ECG) recordings as well as respiration via measurements of changes in intrapleural pressure. The ECG signals further allowed for calculation of the heart rate variability. Additionally, bulk calcium recordings via fiber photometry were employed to measure neuronal pInsCtx activity. To obtain a comprehensive picture of pInsCtx-body interactions, measurements were taken during undisturbed settings in the home cage, during conditioned fear learning and fear extinction, and innate fear paradigms. Further-more, to explore differences between signaling in the brainstem versus the pInsCtx, additional fiber photometry recordings from the NTS were obtained in a subset of animals. Lastly, brain-body interactions were probed for directionality and utility in predictive analyses. My results indicate that activity in the pInsCtx reflects different interoceptive computations compared to the brainstem. They further suggest that pInsCtx and body relationship is not only cue- and behaviour- dependent, but also changes depending on internal fear state. I found a significant positive interaction between the pInsCtx and heart rate variability during fear learning, highlighting the potential of the pInsCtx to reflect arousal rather than purely autonomic signaling. Intriguingly, my findings provide evidence for the emergence of a lateralization in the pInsCtx during fear learning. Moreover, directionality analyses reveal fear-state dependent changes in pInsCtx-body interactions. Finally, my data indicates an important role of the interaction between pInsCtx and respiration as a feature of successful fear extinction. Overall, this study corroborates the role of pInsCtx in fear and processing of bodily signals, adding insights into bidirectional cardiorespiratory influences and emotional lateralization.

• Dokumententyp: Dissertationen (Dissertation, LMU München)
• Keywords: circuit neuroscience, interoception, insular cortex, cardiac signals, respiration, fear, anxiety, medical research, translational research
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften ; 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• Fakultäten: Medizinische Fakultät
• Sprache der Hochschulschrift: Englisch
• Datum der mündlichen Prüfung: 15. Januar 2026
• 1. Bericht­erstatter:in: Binder, Elisabeth