Functional connectome of brainstem nuclei involved in autonomic, limbic, pain and sensory processing in living humans from 7 Tesla resting state fMRI

Despite remarkable advances in mapping the functional connectivity of the cortex, the functional connectivity of subcortical regions is understudied in living humans. This is the case for brainstem nuclei that control vital processes, such as autonomic, limbic, nociceptive and sensory functions. This is because of the lack of precise brainstem nuclei localization, of adequate sensitivity and resolution in the deepest brain regions, as well as of optimized processing for the brainstem. To close the gap between the cortex and the brainstem, on 20 healthy subjects, we computed a correlation-based functional connectome of 15 brainstem nuclei involved in autonomic, limbic, nociceptive, and sensory function (superior and inferior colliculi, ventral tegmental area-parabrachial pigmented nucleus complex, microcellular tegmental nucleus-prabigeminal nucleus complex, lateral and medial parabrachial nuclei, vestibular and superior olivary complex, superior and inferior medullary reticular formation, viscerosensory motor nucleus, raphe magnus, pallidus, and obscurus, and parvicellular reticular nucleus – alpha part) with the rest of the brain. Specifically, we exploited 1.1mm isotropic resolution 7 Tesla resting-state fMRI, ad-hoc coregistration and physiological noise correction strategies, and a recently developed probabilistic template of brainstem nuclei. Further, we used 2.5mm isotropic resolution resting-state fMRI data acquired on a 3 Tesla scanner to assess the translatability of our results to conventional datasets. We report highly consistent correlation coefficients across subjects, confirming available literature on autonomic, limbic, nociceptive and sensory pathways, as well as high interconnectivity within the central autonomic network and the vestibular network. Interestingly, our results showed evidence of vestibulo-autonomic interactions in line with previous work. Comparison of 7 Tesla and 3 Tesla findings showed high translatability of results to conventional settings for brainstem-cortical connectivity and good yet weaker translatability for brainstem-brainstem connectivity. The brainstem functional connectome might bring new insight in the understanding of autonomic, limbic, nociceptive and sensory function in health and disease. ### Competing Interest Statement The authors have declared no competing interest. * PTg : Pedunculopontine Tegmental Nucleus LDTg-CGPn : Laterodorsal Tegmental Nucleus and Central Gray of the Rhombencephalon PnO-PnC : Pontine Reticular Nucleus, Oral Part and Pontine Reticular Nucleus, Caudal Part LC : Locus Coeruleus SubC : Subcoeruleus ION : Inferior Olivary Complex CLi-RLi : Caudal Linear Raphe and Rostral Linear Raphe SC : Superior Colliculus IC : Inferior Colliculus VTA-PBP : Ventral Tegmental Area and Parabrachial Pigmented Nucleus MiTg-PBG : Microcellular Tegmental Nucleus LPB : Lateral Parabrachial MPB : Medial Parabrachial Ve : Vestibular nucleus SOC : Superior Olivary Complex sMRt : Superior Medullary Reticular Formation iMRt : Inferior Medullary Reticular Formation VSM : Viscerosensory Motor Nucleus RMg : Raphe Magnus ROb : Raphe Obscurus RPa : Raphe Pallidus PCRtA : Parvicellular Reticular Nucleus, Alpha Part