Localization and Network of Coma-Causing Brainstem Lesions: Evidence for a Human Consciousness Network

Abstract

Focal brainstem lesions can disrupt arousal and cause coma, yet the exact location of the brainstem region critical to arousal and its associated network are unknown. First, we compare brainstem lesions between 12 patients with coma and 24 patients without coma to identify a region specific to coma-causing lesions. Second, we determine the network connectivity of this brainstem region and each individual coma-causing lesion using resting state functional connectivity MRI data acquired from 98 healthy subjects. Third, we evaluate the functional connectivity of this network in patients with disorders of consciousness (51 patients versus 21 controls). These analyses reveal a small, coma-specific region in the left pontine tegmentum, near the medial parabrachial nucleus. This brainstem region, and each individual coma-causing lesion, is functionally connected to the left agranular, anterior insula (AI), and pregenual anterior cingulate cortex (pACC). These cortical sites align poorly with previously defined functional networks but match the distribution of von Economo neurons (VENs). Finally, functional connectivity between AI and pACC is disrupted in patients with impaired awareness. These results show that coma-causing lesions overlap a specific brainstem location that is functionally connected to specific cortical areas, defining a unique human brain network. The brainstem node, if lesioned, disrupts arousal while the VEN-containing cortical nodes exhibit abnormalities in patients with disrupted awareness. We propose that this network may represent a neuroanatomical substrate linking arousal and awareness, the two principal components of human consciousness.