Signal Processing in the Vagus Nerve: Hypotheses Based on New Genetic and Anatomical Evidence Author: Clare Shaffer1, Lisa Feldman Barrett2, Karen S Quigley3 Affiliation: <sup>1</sup> Department of Psychology, College of Science, Northeastern University, Boston, MA. Electronic address: shaffer.c@northeastern.edu. <sup>2</sup> Department of Psychology, College of Science, Northeastern University, Boston, MA; Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA. <sup>3</sup> Department of Psychology, College of Science, Northeastern University, Boston, MA. Electronic address: k.quigley@northeastern.edu. Conference/Journal: Biol Psychol Date published: 2023 Jul 5 Other: Special Notes: doi: 10.1016/j.biopsycho.2023.108626. , Word Count: 210 Each organism must regulate its internal state in a metabolically efficient way as it interacts in space and time with an ever-changing and only partly predictable world. Success in this endeavor is largely determined by the ongoing communication between brain and body, and the vagus nerve is a crucial structure in that dialogue. In this review, we introduce the novel hypothesis that the afferent vagus nerve is engaged in signal processing rather than just signal relay. New genetic and structural evidence of vagal afferent fiber anatomy motivates two hypotheses: (1) that sensory signals informing on the physiological state of the body compute both spatial and temporal viscerosensory features as they ascend the vagus nerve, following patterns found in other sensory architectures, such as the visual and olfactory systems; and (2) that ascending and descending signals modulate one another, calling into question the strict segregation of sensory and motor signals, respectively. Finally, we discuss several implications of our two hypotheses for understanding the role of viscerosensory signal processing in predictive energy regulation (i.e., allostasis) as well as the role of metabolic signals in memory and in disorders of prediction (e.g., mood disorders). Keywords: allostasis; depression; fascicles; interoception; memory; molecular gradients; mood; multisensory integration; sensorimotor integration; viscerotopic mapping. PMID: 37419401 DOI: 10.1016/j.biopsycho.2023.108626