In vivo structural connectome of arousal and motor brainstem nuclei by 7 Tesla and 3 Tesla MRI

Abstract

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.

Integrating brainstem and cortical functional architectures

“…Likewise, we demonstrate that cortical regions follow an anterior-posterior gradient with respect to their functional connectivity strength to the brainstem, with the largest cortex-to-brainstem hubs existing in anterior cingulate cortex. Previous studies have reported greater diffusion-weighted MRI-derived structural connectivity from anterior cortex to brainstem [44,106]. Similarly, transcriptomic analysis of human von Economo neurons, whose cell bodies are restricted to layer V of the anterior cortex, have shown that these bipolar neurons express transcriptional factors associated with long-range projections to the brainstem [30,58].…”

Integrating brainstem and cortical functional architectures

“…Likewise, we demonstrate that cortical regions follow an anterior-posterior gradient with respect to their functional connectivity strength to the brainstem, with the largest cortex-to-brainstem hubs existing in anterior cingulate cortex. Previous studies have reported greater diffusion-weighted MRI-derived structural connectivity from anterior cortex to brainstem [44, 105]. Similarly, transcriptomic analysis of human von Economo neurons, whose cell bodies are restricted to layer V of the anterior cortex, have shown that these bipolar neurons express transcriptional factors associated with long-range projections to the brainstem [30, 57].…”

“…Brainstem functional connectivity may also facilitate the development of better computational models of ongoing dynamics [70, 124]. While the present work extends the study of in vivo human cortical function to the brainstem, it is increasingly possible to integrate not only brainstem function, but the structure and function of the cerebellum, subcortex, and spinal cord, into a single wiring diagram of the complete human central nervous system [44, 49, 53, 105].…”

Generators of the frequency-following response in the subthalamic nucleus: implications for non-invasive deep brain stimulation

“…To date, there is little to suggest direct connections between the STN and IC or other brainstem auditory nuclei. However, there are several lower brainstem motor centres that both directly synapse with the STN and auditory nuclei, including the mesencephalic locomotor region (MLR), caudal pontine reticular nucleus, trigeminal nucleus and nucleus solitaris 48,[50][51][52] . This possible link between the auditory, lower brainstem motor systems and the STN requires further assessment, as it may have possible therapeutic implications.…”