Cortical circuits linking peripheral inflammation to affective states.
- 1Department of Neuroscience, Kavli Institute for Neuroscience, Yale University School of Medicine, New Haven, CT, United States.
- 2Wu Tsai Institute, Yale University, New Haven, CT, United States.
Abstract
Affective disorders, such as anxiety and depression, are more prevalent in individuals with inflammatory diseases than in the general population. This comorbidity suggests biological links between immune activation and affective dysregulation. Indeed, there is extensive literature on the impact of inflammation on brain function. Peripheral immune challenges activate subcortical and brainstem regions that regulate emotions and physiological homeostasis. However, cortical regions are also engaged during peripheral inflammation, and cortical dysfunction is a central feature of affective pathology. Drawing primarily on mechanistic work in rodents, we review how peripheral inflammation reaches the cortical circuits that govern emotion and how it is translated into affective changes. This communication begins with two complementary routes by which immune signals reach the brain: neural and humoral pathways. In the neural pathway, cytokine-selective vagal afferents preserve the anatomical origin of inflammation and relay it to the brainstem and downstream regions. In the humoral pathway, circulating mediators act on circumventricular organs and across the blood-brain barrier. Cortical regions, such as the prefrontal cortex, insular cortex, and primary somatosensory cortex, transform these signals into altered behavior. This occurs through shifts in excitatory/inhibitory balance, top-down control of the amygdala, and interoceptive predictions of bodily state. We integrate these studies into a circuit-level model in which inflammation biases cortical processing toward threat, driving the transition from adaptive responses to maladaptive affective dysregulation. Defining which immune signals engage which circuits, and with what specificity, remains a central open question and a promising route toward targeting the affective consequences of inflammatory disease.
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BibTeX
@article{jun2026cortical,
title = {{Cortical circuits linking peripheral inflammation to affective states.}},
author = {Dahae J Jun and Shi Tang and Emilia Favuzzi},
journal = {Frontiers in cellular neuroscience},
year = {2026},
month = oct,
doi = {10.3389/fncel.2026.1951226},
url = {https://europepmc.org/article/MED/42924168},
note = {CC BY},
}
RIS
TY - JOUR
TI - Cortical circuits linking peripheral inflammation to affective states.
AU - Dahae J Jun
AU - Shi Tang
AU - Emilia Favuzzi
PY - 2026
DA - 2026/10/08
JO - Frontiers in cellular neuroscience
DO - 10.3389/fncel.2026.1951226
UR - https://europepmc.org/article/MED/42924168
AB - Affective disorders, such as anxiety and depression, are more prevalent in individuals with inflammatory diseases than in the general population. This comorbidity suggests biological links between immune activation and affective dysregulation. Indeed, there is extensive literature on the impact of inflammation on brain function. Peripheral immune challenges activate subcortical and brainstem regions that regulate emotions and physiological homeostasis. However, cortical regions are also engaged during peripheral inflammation, and cortical dysfunction is a central feature of affective pathology. Drawing primarily on mechanistic work in rodents, we review how peripheral inflammation reaches the cortical circuits that govern emotion and how it is translated into affective changes. This communication begins with two complementary routes by which immune signals reach the brain: neural and humoral pathways. In the neural pathway, cytokine-selective vagal afferents preserve the anatomical origin of inflammation and relay it to the brainstem and downstream regions. In the humoral pathway, circulating mediators act on circumventricular organs and across the blood-brain barrier. Cortical regions, such as the prefrontal cortex, insular cortex, and primary somatosensory cortex, transform these signals into altered behavior. This occurs through shifts in excitatory/inhibitory balance, top-down control of the amygdala, and interoceptive predictions of bodily state. We integrate these studies into a circuit-level model in which inflammation biases cortical processing toward threat, driving the transition from adaptive responses to maladaptive affective dysregulation. Defining which immune signals engage which circuits, and with what specificity, remains a central open question and a promising route toward targeting the affective consequences of inflammatory disease.
SN - 1662-5102
ER -