Toward an In Vivo Neuroimaging Template of Human Brainstem Nuclei of the Ascending Arousal, Autonomic, and Motor Systems

Abstract

Brainstem nuclei (Bn) in humans play a crucial role in vital functions, such as arousal, autonomic homeostasis, sensory and motor relay, nociception, sleep, and cranial nerve function, and they have been implicated in a vast array of brain pathologies. However, an in vivo delineation of most human Bn has been elusive because of limited sensitivity and contrast for detecting these small regions using standard neuroimaging methods. To precisely identify several human Bn in vivo, we employed a 7 Tesla scanner equipped with multi-channel receive-coil array, which provided high magnetic resonance imaging sensitivity, and a multi-contrast (diffusion fractional anisotropy and T2-weighted) echo-planar-imaging approach, which provided complementary contrasts for Bn anatomy with matched geometric distortions and resolution. Through a combined examination of 1.3 mm 3 multi-contrast anatomical images acquired in healthy human adults, we semi-automatically generated in vivo probabilistic Bn labels of the ascending arousal (median and dorsal raphe), autonomic (raphe magnus, periaqueductal gray), and motor (inferior olivary nuclei, two subregions of the substantia nigra compatible with pars compacta and pars reticulata, two subregions of the red nucleus, and, in the diencephalon, two subregions of the subthalamic nucleus) systems. These labels constitute a first step toward the development of an in vivo neuroimaging template of Bn in standard space to facilitate future clinical and research investigations of human brainstem function and pathology. Proof-of-concept clinical use of this template is demonstrated in a minimally conscious patient with traumatic brainstem hemorrhages precisely localized to the raphe Bn involved in arousal.

The Structural Connectome of the Human Central Homeostatic Network

“…Nevertheless, in recognition of the inherent challenges associated with precise localization of brainstem nuclei, we are distributing to the academic community the Harvard Ascending Arousal Network Atlas (www.martinos.org/resources/aanatlas)-a resource that we hope will enable replication of these connectivity results and facilitate the ongoing development of automated algorithms for segmentation of homeostatic brainstem nuclei (Bianciardi et al, 2015).…”

In vivo functional connectome of human brainstem nuclei of the ascending arousal, autonomic, and motor systems by high spatial resolution 7-Tesla fMRI

“…: 28 ± 1 years, age range = [20 36]) healthy subjects (the same subjects participating in [11]) underwent 7 Tesla MRI (Siemens Healthcare, Erlangen, Germany), after giving written informed consent. The human subject protocol was approved by the Institutional Review Board of the Massachusetts General Hospital.…”

“…To achieve whole-brain coverage, high spatial resolution, non-prohibitively long repetition time (TR) and high fMRI sensitivity required to delineate an in vivo brainstem-brain functional connectome, we took advantage of ultra-high field fMRI for brainstem imaging and recent advances in the MRI acquisition speed. First, we focused on the specific Bn of the ascending arousal, autonomic and motor systems which we have recently delineated by the use of multi-contrast distortion- and resolution-matched echo-planar images (EPI) at 7 Tesla [11]. Specifically, we used this original template of Bn labels in standard (Montreal Neurological Institute, MNI) space [11] to define the location of seed regions for hypothesis-driven (i.e.…”

“…First, we focused on the specific Bn of the ascending arousal, autonomic and motor systems which we have recently delineated by the use of multi-contrast distortion- and resolution-matched echo-planar images (EPI) at 7 Tesla [11]. Specifically, we used this original template of Bn labels in standard (Montreal Neurological Institute, MNI) space [11] to define the location of seed regions for hypothesis-driven (i.e. based on the anatomical location of Bn) brainstem-brain fMRI connectivity analysis.…”

Reduced functional connectivity between ventromedial prefrontal cortex and insula relates to longer corrected QT interval in HIV+ and HIV− individuals

“…The association found here between decreased CD4 count and weaker rsFC requires confirmation by larger studies, which may also reveal effects of other HIV-related factors. Future work may employ stronger magnetic fields and higher voxel resolution to examine brainstem nuclei involved in cardio-autonomic regulation (Bianciardi et al, 2015). It will be important for such research to address the multisymptomatic nature of HIV-CVD comorbidity and to detail the contributions of primary cardio-metabolic dysfunction and immunosuppression, and of secondary factors such as anti-retroviral regimen, to HIV-related autonomic dysfunction (Chow et al, 2006, 2011) and ventricular arrhythmias (Girgis et al, 1997).…”