Cortico-Limbic and Sensorimotor Network Connectivity Link Brain Function to Atherosclerosis in Chronic Stress: Beyond Amygdala-PFC

Chronic stress is a recognized risk factor for atherosclerotic cardiovascular disease (CVD), yet the underlying biological mechanisms remain incompletely understood. Dysregulation of cortico-limbic brain circuits, leading to heightened systemic inflammation and accelerated progression of CVD risk factors, has been proposed as a central pathway. Prior research has primarily focused on altered connectivity between the amygdala and the prefrontal cortex (PFC); however, the contributions of additional cortical and subcortical regions have not been fully delineated. In this study, we utilized a multimodal imaging approach, integrating brain magnetic resonance imaging (MRI) and vascular imaging, to assess both functional and structural connectivity between the amygdala and broader brain networks. Consistent with previous findings demonstrating increased inflammation, greater atherosclerotic burden, and impaired amygdala- PFC connectivity in chronically stressed individuals, we show that task-based functional and structural connectivity measures independently distinguish participants with higher versus lower atherosclerotic burden. Importantly, while limbic and prefrontal regions remain critical, our findings also highlight brain regions involved in sensorimotor and autonomic processes, including the sensorimotor cortices and cerebellum, in the stress-atherosclerosis pathway. By expanding the scope beyond the amygdala-PFC axis, these results offer a more comprehensive framework for understanding the neural mechanisms linking chronic stress to CVD and may guide the development of novel therapeutic strategies aimed at neuroimmune modulation.