Rizwan Kalani, MD

Mikell CB, Banks GP, Frey HP, Youngerman BE, Nelp TB, Karas PJ, et al. Frontal Networks Associated With Command Following After Hemorrhagic Stroke. Stroke. 2014

We often assess level of arousal by a patient’s ability to follow commands. In this study, Mikell et al evaluated which brain structures are necessary to follow commands in the setting of acute intracerebral hemorrhage (ICH) or subarachnoid hemorrhage (SAH) using a multimodality approach – a combination of structural and functional MRI (fMRI) as well as continuous EEG monitoring.

Data from 25 patients with spontaneous ICH or SAH that completed all components of the multi-modality testing were analyzed from a prospective, single-center database. 9 patients (36%) were unresponsive (unable to follow simple, 1-step commands) and 16 were awake at time of testing. Structural injury to the pons, midbrain, and thalamus was initially evaluated (by lesion volume quantification) using structural MRI. Resting state fMRI was then used to identify which brain networks were disrupted in the unresponsive patients compared to those who were awake. The relationship between the default mode network (DMN – the brain regions active when a person is awake and at rest) and the task-positive network (TPN – areas responding to attention-demanding tasks) were evaluated. Lastly, continuous EEG was used to confirm changes in functional connectivity seen.

There was no significant difference between the hemorrhage sizes of the unresponsive and awake patients. 6 functional networks were impaired in unresponsive patients by fMRI – these were located in the premotor, dorsal anterior cingulate, and supplementary motor areas. Connectivity between the DMN and right orbitofrontal cortex was decreased in unresponsive patients. Interestingly, new connections between the TPN and DMN were seen in unresponsive patients that were not seen in those who were awake. These findings were supported by EEG coherence data.

This manuscript suggests that disruption of frontal network connectivity (instead of the actual structural injury) accounts for unresponsiveness in the setting of ICH/SAH. It supports the idea that altered connectivity to (rather than within) the DMN is lost in an unresponsive state. Future studies will need to evaluate the mechanisms by which these network connectivity changes occur and how each individual network involved affects consciousness. The principal limitations of this study are the small number of patients included and inability to evaluate the effect of intracranial pressure on the findings.