A human brain network derived from coma-causing brainstem lesions

Abstract

Objective: To characterize a brainstem location specific to coma-causing lesions, and its functional connectivity network. Methods: We compared 12 coma-causing brainstem lesions to 24 control brainstem lesions using voxel-based lesion-symptom mapping in a case-control design to identify a site significantly associated with coma. We next used resting-state functional connectivity from a healthy cohort to identify a network of regions functionally connected to this brainstem site. We further investigated the cortical regions of this network by comparing their spatial topography to that of known networks and by evaluating their functional connectivity in patients with disorders of consciousness. Results: A small region in the rostral dorsolateral pontine tegmentum was significantly associated with coma-causing lesions. In healthy adults, this brainstem site was functionally connected to the ventral anterior insula (AI) and pregenual anterior cingulate cortex (pACC). These cortical areas aligned poorly with previously defined resting-state networks, better matching the distribution of von Economo neurons. Finally, connectivity between the AI and pACC was disrupted in patients with disorders of consciousness, and to a greater degree than other brain networks. Conclusions: Injury to a small region in the pontine tegmentum is significantly associated with coma. This brainstem site is functionally connected to 2 cortical regions, the AI and pACC, which become disconnected in disorders of consciousness. This network of brain regions may have a role in the maintenance of human consciousness.

Cortical lesions causing loss of consciousness are anticorrelated with the dorsal brainstem

“…We next used a large database of rs‐fcMRI from healthy participants ( N = 1,000) to identify brain areas functionally connected to each lesion location (Yeo et al, ), as depicted schematically in Figure . Functional connectivity between lesion location and our previously defined coma‐specific area of the brainstem tegmentum (Fischer et al, ) was significantly associated with LOC ( B = 1.2 [per −.01 change in F z], p = .004, Figure ). This connectivity remained a significant and independent predictor when lesion volume ( B = 1.2, p = .01) or lesion volume and hemisphere ( B = 1.2, p = .002) were included as covariates.…”

Toward an electrophysiological “sweet spot” for deep brain stimulation in the subthalamic nucleus

“…Diffusion spectrum datasets used here were acquired on special MRI hardware allowing for b‐values up to 10,000 s/mm 2 , leading to connectivity estimates that are much more robust than those acquired in individual patients. Such normative connectome data has proven valuable in predicting stroke symptoms from patient‐specific lesions [Boes et al, , Darby et al, , Fischer et al, , Laganiere et al, ] and has been applied to the context of DBS before, as well [Bonmassar et al, , Horn et al, , Fox et al, ]. Despite these advantages, normative connectome data does not include patient‐specific anatomical features.…”

Thalamic strokes that severely impair arousal extend into the brainstem

“…9 An alternative explanation for our findings would be that lesions must damage both the thalamus and brainstem to severely impair arousal, but this is not consistent with past evidence that ischemic strokes and other lesions limited to the brainstem cause coma. 1,4 …”