International study detects consciousness in unconscious patients with severe brain injuries

New research co-led by experts at Mass General Brigham has found that brain scans can detect consciousness in some unresponsive brain-injured patients.

In the study, 241 participants with severe brain injuries who failed to respond to a simple instruction were assessed using functional MRI (fMRI), electroencephalography (EEG), or both tests.

During these tests, participants heard instructions such as “imagine opening and closing your hand,” followed 15 to 30 seconds later by “stop imagining opening and closing your hand.” Brain responses to fMRI and EEG showed that 60 (25%) of the participants followed this instruction repeatedly and covertly for several minutes.

According to the authors of the study, published on August 15 in the New England Journal of MedicinePatients who exhibit this phenomenon, called motor cognitive dissociation, understand language, remember instructions, and can maintain attention, even when they appear unresponsive. In these patients, cognitive (i.e., thinking) abilities exceed motor abilities and are therefore dissociated from them.

“Some patients with severe brain injuries do not appear to understand their external world. However, when they are assessed using advanced techniques such as fMRI and EEG, we can detect brain activity that suggests otherwise,” said the study’s lead author, Yelena Bodien, Ph.D., an investigator with the Spaulding-Harvard Traumatic Brain Injury Model Systems and Massachusetts General Hospital’s Center for Neurotechnology and Neurorecovery.

“These results raise crucial ethical, clinical and scientific questions, such as: How can we harness this invisible cognitive ability to establish a communication system and promote subsequent healing?”

After a significant brain injury, people may experience a disturbance of consciousness, which can include coma, a vegetative state, or a minimally conscious state. Since the first study demonstrating motor-cognitive dissociation in people with disturbance of consciousness was published nearly two decades ago, centers around the world have found that this condition occurs in approximately 15 to 20 percent of unconscious patients.

However, the current study suggests that this condition may be present in 25% of patients, or even more. Cognitive-motor dissociation was more common in participants assessed by fMRI and EEG, suggesting that multiple tests, using different approaches, may be needed to ensure that awareness is not missed.

This study involved data collected over a period of approximately 15 years from participants at six different sites across the United States, the United Kingdom, and Europe. Each site developed and rigorously tested its methods for detecting cognitive motor dissociation to minimize the possibility of a positive result being obtained by mistake.

Some sites recruited participants from the intensive care unit just days after they suffered a severe brain injury, often following trauma such as a car accident, stroke, or cardiac arrest. Other sites recruited participants who had been living in nursing homes or at home for months or years after their injury or illness.

In addition to studying the 241 participants who did not respond to simple instructions, the study included 112 participants who responded to simple instructions given at the bedside. This latter group was expected to perform well on fMRI and EEG tests, but in 62% of these participants, the researchers did not detect brain responses suggesting that they were following instructions covertly.

The authors note that this result may reflect the complexity of fMRI and EEG tasks and highlights the high level of thinking skills required to perform them.

Just knowing that someone is cognitively aware and more capable than they first appear can dramatically change their clinical care.

“Families have told us that once a positive test result revealing cognitive-motor dissociation is shared with the patients’ clinical team, it can change how the team interacts with their loved one,” Bodien said.

“Suddenly, the team is paying more attention to subtle behavioral signs that might be under voluntary control, or talking to the patient, or playing music in the room. On the other hand, missing motor cognitive dissociation can have serious consequences, including premature withdrawal of resuscitation care, loss of signs of consciousness, and lack of access to intensive rehabilitation.”

“We’re seeing that this kind of clear dissociation of preserved cognitive abilities and the lack of behavioral evidence of it is not uncommon. I think we now have an ethical obligation to engage with these patients, to try to help them connect to the world,” said the study’s senior author, Dr. Nicholas Schiff, the Jerold B. Katz Professor of Neurology and Neuroscience at the Feil Family Brain and Mind Research Institute at Weill Cornell Medicine and the consortium’s administrative lead.

“What we need here is what we in our consortium have been trying to put in place for twenty years: a sustained effort to help patients with disorders of consciousness through systematic medical research, technological development and better clinical infrastructure.

One limitation of the study is that the tests were not standardized. Each study site tested patients in its own way, creating variability in the data. Additionally, many participants were recruited because family members heard about the study and contacted the researchers.

This recruitment approach limits the ability of researchers to determine the global prevalence of motor cognitive dissociation. There are no professional guidelines stipulating how motor cognitive dissociation should be assessed and most centers are unable to provide these tests; clinical translation will need to be a focus of future research.

“To continue our progress in this area, we need to validate our tools and develop approaches to systematically and pragmatically assess non-reactive patients so that testing is more accessible,” Bodien said.

“The Mass General Hospital Emergent Consciousness Program offers these clinical assessments. However, elsewhere, a patient may have to enroll in a research study to be tested. We know that cognitive motor dissociation is not uncommon, but resources and infrastructure are needed to optimize detection of this condition and provide adequate support to patients and their families.”

The researchers added that these findings could spur research into specific interventions aimed at promoting effective communication, including brain-computer interfaces.

A separate team of researchers at Mass General Brigham is studying brain-computer interfaces (BCIs) as a potential intervention that could one day have applications for many types of patients who are unable to communicate effectively.

Another study published in the same issue of New England Journal of Medicine Co-author Leigh Hochberg, MD, PhD, of the Department of Neurology and the Center for Neurotechnology and Neurorecovery at Mass General Hospital, reported that a man with ALS and severe speech impairment used an experimental BCI implant to convert his attempted speech into text on a screen.