One in Four Brain Injury Patients Who Appear Unresponsive Respond Covertly

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Functional MRI and EEG detect awareness in coma or vegetative states

by
Judy George,

Deputy Managing Editor, MedPage Today,


August 14, 2024

Cognitive-motor dissociation — a phenomenon that occurs when patients who appear unresponsive perform cognitive tasks that can be detected on functional MRI (fMRI) or electroencephalography (EEG) — occurred in one in four people with severe brain injury, a prospective cohort study found.

The study evaluated 241 unresponsive patients with brain injury who were given verbal commands — to imagine playing tennis, or to imagine opening and closing their hand, for example.

Of these, 60 patients (25%) repeatedly showed brain activation on fMRI or EEG indicating they were covertly following instructions, reported Nicholas Schiff, MD, of Weill Cornell Medicine in New York City, and co-authors in the New England Journal of Medicine.

Cognitive-motor dissociation was associated with younger age, longer time since injury, and brain trauma as an etiologic factor. In total, 11 patients with cognitive-motor dissociation were assessed with fMRI only, 13 were assessed with EEG only, and 36 with both techniques.

“This research shows that a substantial fraction of apparently unresponsive, severely brain-injured persons are aware and can engage in sustained cognitive activity,” Schiff told MedPage Today. “These findings importantly point to the need to establish infrastructure to evaluate patients and to begin efforts to test possible therapies to help them.”

Persons with cognitive-motor dissociation have cognitive abilities that exceed their motor abilities, Schiff noted. “They show a sharp dissociation with a high level of retained cognitive ability and limited or no motor responses,” he said.

Earlier work reported that cognitive-motor dissociation occurred in 15% to 20% of brain-injured patients who seemed unresponsive. One study suggested that detecting it soon after injury may predict recovery.

“The percentage of participants with cognitive motor dissociation is 5 to 10 percentage points higher in our study than in previous studies,” Schiff and co-authors pointed out.

“This finding may be due to our multimodal approach, which classified the participants who underwent assessment with both techniques on the basis of responses on either fMRI or EEG,” they wrote. “The percentage of participants with cognitive motor dissociation may have been even higher if all the participants had been assessed with both imaging techniques.”

Schiff and colleagues evaluated 353 adults with disorders of consciousness at six sites from 2006 to 2023. Some sites recruited participants from intensive care units soon after severe brain injury trauma, stroke, or cardiac arrest; others included participants who had brain injury years ago.

The researchers conducted behavioral assessments using the Coma Recovery Scale-Revised (CRS-R). They divided participants into two groups based on whether responses to verbal commands or intelligible speech were observed during CRS-R evaluations.

Participants had a median age of about 38. The median time between brain injury and CRS-R assessment was 7.9 months; 25% of participants had a CRS-R evaluation within 28 days after injury. Brain trauma was an etiologic factor in 50% of cases.

Overall, 241 patients had a behavioral diagnosis of coma, vegetative state, or minimally conscious state-minus (i.e., they showed signs of awareness but not responses to commands or intelligible verbal output). The other 112 patients had observable responses to verbal commands.

In the group with observable response to verbal commands, fMRI or EEG detected covert responses in only 43 of 112 patients (38%).

“The paradigms used in studies of task-based fMRI and EEG may require more cognitive resources (e.g., short-term memory, selective attention, and mental persistence) than in typical command-following trials performed at the bedside,” Schiff and co-authors suggested. “Although this hypothesis has not been proven, it is supported by our finding that responses on fMRI and EEG were detected in only 38% of the participants with an observable response to commands at the bedside.”

American Academy of Neurology guidelines note that the natural history of disorders of consciousness is not well-defined and prognosis can be challenging. Recently, a propensity score analysis led by co-author Yelena Bodien, PhD, of Mass General Brigham in Boston, suggested that some patients with severe traumatic brain injury who had life support withdrawn may have survived and achieved at least partial independence.

“Our team’s recent studies suggest there is a benefit to waiting before decisions are made to withdraw life support, because some patients may be more conscious than they appear, and patients with even the most severe injuries may recover and regain independence,” Bodien told MedPage Today. “Our papers highlight the need for improved access to advanced testing, like with fMRI, long-term monitoring of recovery, and evidence-based medical guidelines so doctors do not have to rely on their past experiences to establish prognosis.”

Survival bias may have influenced outcomes in this study, Schiff and colleagues said. Participating sites used heterogeneous strategies to acquire, analyze, and interpret fMRI and EEG data, they acknowledged.

“Our findings may therefore not be generalizable across all centers,” the researchers wrote. “Large-scale validation studies are needed to improve data acquisition and analysis for clinical translation.”