Despite extensive neuroimaging research of primary sensory cortices involved in auditory and visual functions, subcortical structures within these domains, such as the inferior and superior colliculi, the medial and lateral geniculate nuclei and the superior olivary complex, are currently understudied with magnetic resonance imaging (MRI) in living humans. This is because a precise localization of these nuclei is hampered by the limited contrast and sensitivity of conventional neuroimaging methods for deep brain nuclei. In this work, we used 7 Tesla multi-modal (T₂-weighted and diffusion fractional anisotropy) 1.1 mm isotropic resolution MRI to achieve high sensitivity and contrast for single-subject brainstem and thalamic nuclei delineation. After precise coregistration to stereotactic space, we generated an in vivo human probabilistic atlas of auditory (medial geniculate nucleus, inferior colliculus, and superior olivary complex) and visual (lateral geniculate nucleus and superior colliculus) subcortical nuclei. We foresee the use of this atlas as a tool to precisely identify the location and shape of auditory/visual deep nuclei in research as well as clinical human studies.

Autonomic, pain, limbic, and sensory processes are mainly governed by the central nervous system, with brainstem nuclei as relay centers for these crucial functions. Yet, the structural connectivity of brainstem nuclei in living humans remains understudied. These tiny structures are difficult to locate using conventional in vivo MRI, and ex vivo brainstem nuclei atlases lack precise and automatic transformability to in vivo images. To fill this gap, we mapped our recently developed probabilistic brainstem nuclei atlas developed in living humans to high‐spatial resolution (1.7 mm isotropic) and diffusion weighted imaging (DWI) at 7 Tesla in 20 healthy participants. To demonstrate clinical translatability, we also acquired 3 Tesla DWI with conventional resolution (2.5 mm isotropic) in the same participants. Results showed the structural connectome of 15 autonomic, pain, limbic, and sensory (including vestibular) brainstem nuclei/nuclei complex (superior/inferior colliculi, ventral tegmental area‐parabrachial pigmented, microcellular tegmental–parabigeminal, lateral/medial parabrachial, vestibular, superior olivary, superior/inferior medullary reticular formation, viscerosensory motor, raphe magnus/pallidus/obscurus, parvicellular reticular nucleus‐alpha part), derived from probabilistic tractography computation. Through graph measure analysis, we identified network hubs and demonstrated high intercommunity communication in these nuclei. We found good (r = .5) translational capability of the 7 Tesla connectome to clinical (i.e., 3 Tesla) datasets. Furthermore, we validated the structural connectome by building diagrams of autonomic/pain/limbic connectivity, vestibular connectivity, and their interactions, and by inspecting the presence of specific links based on human and animal literature. These findings offer a baseline for studies of these brainstem nuclei and their functions in health and disease, including autonomic dysfunction, chronic pain, psychiatric, and vestibular disorders.

Brainstem nuclei are key participants in the generation and maintenance of arousal, which is a basic function that modulates wakefulness/sleep, autonomic responses, affect, attention, and consciousness. Their mechanism is based on diffuse pathways ascending from the brainstem to the thalamus, hypothalamus, basal forebrain and cortex. Several arousal brainstem nuclei also participate in motor functions that allow humans to respond and interact with the surrounding through a multipathway motor network. Yet, little is known about the structural connectivity of arousal and motor brainstem nuclei in living humans. This is due to the lack of appropriate tools able to accurately visualize brainstem nuclei in conventional imaging. Using a recently developed in vivo probabilistic brainstem nuclei atlas and 7 Tesla diffusion‐weighted images (DWI), we built the structural connectome of 18 arousal and motor brainstem nuclei in living humans (n = 19). Furthermore, to investigate the translatability of our findings to standard clinical MRI, we acquired 3 Tesla DWI on the same subjects, and measured the association of the connectome across scanners. For both arousal and motor circuits, our results showed high connectivity within brainstem nuclei, and with expected subcortical and cortical structures based on animal studies. The association between 3 Tesla and 7 Tesla connectivity values was good, especially within the brainstem. The resulting structural connectome might be used as a baseline to better understand arousal and motor functions in health and disease in humans.

The brainstem is a fundamental component of the central nervous system yet it is typically excluded from in vivo human brain mapping efforts, precluding a complete understanding of how the brainstem influences cortical function. Here we use high-resolution 7 Tesla fMRI to derive a functional connectome encompassing cortex as well as 58 brainstem nuclei spanning the midbrain, pons and medulla. We identify a compact set of integrative hubs in the brainstem with widespread connectivity with cerebral cortex. Patterns of connectivity between brainstem and cerebral cortex manifest as multiple emergent phenomena including neurophysiological oscillatory rhythms, patterns of cognitive functional specialization, and the unimodal-transmodal functional hierarchy. This persistent alignment between cortical functional topographies and brainstem nuclei is shaped by the spatial arrangement of multiple neurotransmitter receptors and transporters. We replicate all findings using 3 Tesla data from the same participants. Collectively, we find that multiple organizational features of cortical activity can be traced back to the brainstem.