Brain Connectivity May Predict Coma Recovery

Pauline Anderson

November 12, 2015

New research is shining a light on the importance to human consciousness of a brain region that traditionally gets little attention from neurologists — the posteromedial cortex (PMC).

The study suggests that coma resulting from traumatic or anoxic brain injury was related to disruption in the large-scale network that connects the PMC with the medial prefrontal cortex (mPFC) and that the greater the loss of connectivity, the poorer the outcome, said lead author, Stein Silva, MD, PhD, associate professor, critical care unit, University Teaching Hospital, INSERM, Toulouse, France.

The researchers were able to predict, on the basis of the amount of connectivity, which comatose patients did better. "The patients who have lost almost all this connection (between the PMC and mPFC) have the worst outcome, and the people who keep this connection were able to recover," Dr Silva told Medscape Medical News.

Dr Stein Silva

The study is published online November 11 in Neurology.

The analysis included 27 comatose patients with severe brain injury (Glasgow Coma Scale score <8) from four intensive care units affiliated with the University Teaching Hospital. Clinically, these patients look alike, said Dr Silva. "They're in bed; they have a tube in their mouth; their eyes are closed."

Of these, 14 had a traumatic brain injury and 13 an anoxic injury, such as cardiac arrest. The study also included 14 age-matched healthy persons.

Using resting state functional MRI, Dr Silva and his colleagues explored the neural communication or functional connectivity of the PMC, which is known to play a key role in changes of consciousness, for example, during sleep or general anesthesia.

This brain area is also involved in dementia, with amyloid plaques having been detected here in patients with Alzheimer's disease, Dr Silva noted.

The focus of interest for the current study was two subregions of the PMC: the precuneus and posterior cingulate cortex (PCC).

The researchers found that compared to healthy volunteers, the patients who continued to be comatose had a loss or breakdown of communication between the PMC and mPFC areas.

Disruption Pattern

They identified a two-fold connectivity disruption pattern. First, a midline decoupling of PCC and mPFC suggested network sensitivity to changes in level of consciousness. This is in line with the hypothesis of a dysfunctional mesocircuit, which posits that the anterior forebrain function is markedly downregulated in all severe brain injuries.

Second, there was a deficit of the normal correlation over time between PCC and lateral parietal cortices (mainly the supramarginal gyrus) that have been associated with external awareness.

"We suggest that our data could depict breakdown of the dynamic reciprocal interaction between internal and external awareness systems during coma and highlight the pivotal role of PCC for 'tuning' the whole-brain meta-stable status," he said.

What was interesting, Dr Silva added, was that not all communication from the PMC was lost in the comatose patients. The researchers noted that the precuneus was still working. "Not every network at rest disappears during coma," he said.

What was surprising to the researchers was that the patients with traumatic brain injury were similar to those who survived cardiac arrest in terms of brain connectivity.

"I expected to see more of a difference because the mechanism (of coma) was really different," he said. On the one hand, there is a global lack of oxygen possibly causing neuronal damage, and on the other, diffuse axonal injury and possibly blood in the brain.

"This is an important result because it means that probably what we are finding is related to consciousness itself and not the etiology."

At 3 months, researchers assessed outcome using the Coma Recovery Scale-Revised. At this point, four of the patients in a coma had recovered consciousness, while the others remained in a minimally conscious state or in a vegetative state.

Recovery Prediction

"It's really challenging to predict that now using standard of care because all we have is motor response. Every day, you ask the patient, 'Are you able to open your eyes?' and 'Are you able to move?' That's clearly not enough."

He's got some thoughts about how to retain connectivity in the brain region responsible for consciousness. "My idea is to use what has been done over the last few years in other fields like stroke," where neurologists are various interventions to "mobilize brain plasticity."

One intervention could be stimulating this brain region, possibly through transcranial magnetic stimulation, said Dr Silva.

He would like to collaborate with others to try to replicate the findings of the current study in a larger cohort. Another of his projects is to learn what's happening structurally when comatose patients lose connections between brain regions involved in consciousness.

Medscape Medical News invited James L. Bernat, MD, professor, neuroscience, and professor, neurology and medicine, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, and a member of the American Academy of Neurology, to comment on this study.

He described it as "one piece of a very large picture puzzle in terms so how the brain maps conscious awareness."

Although the study is "interesting" and may prove important, "it doesn't answer everything" and is "not front page news," said Dr Bernat.

He agreed that some type of electric stimulation to "jump start" some of these brain areas is a "plausible hypothesis." He cited the case reported about 8 years ago of deep brain stimulation in a patient who was in a stable minimally conscious state.

"They put deep brain stimulation electrodes in the intralaminar nuclei of the thalamus — these are medial thalamic nuclei that have to do with consciousness — and when these stimuli were put through the electrodes, the patient began to talk more and was much more interactive and alert."

Dr Bernat found it interesting that traumatic brain–injured and cardiac arrest patients in the study were so similar in terms of brain connectivity. "These are two separate pathologies and they have different prognoses, so the fact that both groups had this finding to me is significant."

The study was supported by the French Association of Craniofacial Trauma, Institute for Brain Sciences of Toulouse, and INSERM. The authors have disclosed no relevant financial relationships.

Neurology. Published online November 11, 2015. Abstract


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