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A Possible Biomarker for Vegetative State Patients who Retain Awareness




The thalamus (green) and primary motor cortex (blue). Image courtesy of University of Birmingham/Dr. Davinia Fernández-Espejo.


Researchers have identified a possible biomarker for patients in a vegetative state who retain some level of conscious awareness, despite being unable to move or speak.


The findings, published online October 19 in JAMA Neurology, suggest that structural damage to the fibers connecting the thalamus and the primary motor cortex impede the translation of thought into action.


For years, physicians assumed that all patients in a vegetative state — unable to move or speak — were alike. But more recent research has shown that some patients in a vegetative state retain some level of awareness, showing signs of neural activity on neuroimaging in response to certain commands (being asked to imagine hitting a tennis ball, for example) despite remaining behaviorally unresponsive.


The investigators said that damage to the pathways that physically connect the thalamus — “one of the hubs of consciousness,” said study author Davinia Fernández-Espejo, PhD, in a news release — and the motor cortex may explain why a patient who retains so-called “covert awareness” remains incapable of intentional movement.


In the current study, the researchers identified one such patient — Patient 1 — who fulfilled all the clinical criteria for a vegetative state but consistently showed evidence of covert awareness on multiple MRI and EEG assessments. The patient had sustained a severe traumatic brain injury (TBI) and had been in a vegetative state for more than 12 years.


This patient was compared with a second TBI patient — Patient 2 — with similar clinical variables, but who was able to produce some intentional movements (moving her right upper limb to reach for different objects, for example). The study also enrolled 15 healthy volunteers as controls.


The researchers used functional magnetic resonance imaging (fMRI) to compare brain regions involved in voluntary motor imagery (imagining a movement) to motor execution (carrying out a movement). They asked the control participants to either imagine hitting a tennis ball or to actually hit a tennis ball, then looked at the brain regions that became activated in each task.


They discovered that excitatory outputs from the thalamus to the primary motor cortex were activated when the participants performed the action, but not when they only thought about doing it, suggesting that this circuit played a critical role in producing voluntary movements.


Based on these findings, the researchers then used diffusion tensor imaging (DTI) tractography to evaluate the structural integrity of the fibers connecting the thalamus and the primary motor cortex in the two TBI patients. They discovered that these fibers were damaged in Patient 1 (fractional anistrophy, 0.294; p=0.047), but not in Patient 2 (fractional anistrophy, 0.413; p=0.35).


“To our knowledge, this study provides the first direct neural correlate for the absence of intentional movement in a covertly aware, but clinically vegetative, patient,” the study authors wrote.


“The ultimate aim is to use this information in targeted therapies that can drastically improve the quality of life of patients,” Dr. Fernández-Espejo said. “For example, with the advances being made in assistive technology, if we can help a patient to regain even limited movement in one finger, it opens up so many possibilities for communication and control of their environment.”


For more articles on research in vegetative state patients, browse our archives here.