Neuroanatomy of catecholaminergic circuits in the brainstem and hypothalamus using T1-weighted and diffusion magnetic resonance imaging in humans: implications for brain-immune interactions, cardiovascular disease, neuropsychiatric disorders, stress response, and COVID-19

Neuroimaging allows the study of brain structures that previously were undetectable due to their small size and location. Herein we focused on the core catecholaminergic circuitries in the human brain, involving the coerulean noradrenergic (or norepi-nephrine, NE) and dopaminergic (DA) systems. Using T1-weighted MRI morphometry and dMRI tractography, this study was carried out in one post-mortem human ultra-high-resolution dataset of the brainstem and diencephalon and in healthy human datasets from the Human Connectome Project repository. We investigated 26 connections of brainstem origin (13 in the left side and 13 in the right side) associated with the NE and DA circuitries. We delineated the coerulean NE and DA core central catechol-aminergic circuitries of the brainstem and hypothalamus in the post-mortem dataset, including all targeted fiber connections. Importantly, this was also achieved in the HCP datasets. These results emphasize the importance of multispectral neuroimaging in the study of chemical neuroanatomical circuitries and its application in clinical conditions such as cardiovascular disease, major depression, schizophrenia, and other disorders associated with chronic stress and brain-immune interactions such as COVID-19.