Charting the Unpredictable: Using fMRI patterns to determine outcome in acutely comatose patients

Every year in Canada around 50,000 people suffer brain injuries, with those experiencing severe traumas often becoming comatose for days or weeks post-incident. While there exists a battery of physiological prognostic indicators, such as pupillary light reflex (or lack thereof), and patterns of EEG activity, there remains a significant subset of patients who retain an indeterminate prognosis even after their completion. The use of sophisticated imaging techniques like fMRI has provided a modern way of mapping residual cognitive function in newly comatose patients. Currently, three fMRI studies have looked at the preservation of neural connectivity of two brain networks as potential markers of outcome. While all these studies found a (modest) positive correlation between the BOLD signal strength of the intact network and better patient outcome, significant further work is required before the technique could become clinically useful.

Dr. Charles Weijer of Western University, stresses, however, that this imminent research raises several ethical concerns: patients do not have decisional capacity, time restraints may not permit the proper procurement of surrogate informed consent, critically ill patients are clearly a vulnerable population, and it is not clear how the fMRI study results would impact patient prognosis and treatment decisions. As well, there exist practical concerns including the intra-hospital transport of patients to the fMRI machine, and the time needed outside of the ICU to perform the scans.

As a recent graduate in neuroscience another particular concern struck me – why had the researchers of the previous fMRI studies only considered two networks? The first mapped the preservation of activity in S1 after a stimulus to the hand, while the following two studies assessed the resting state connectivity of the default mode network. These are just two of several networks that have been mapped and are reliably found in healthy patients. I would be curious to see if there is prognostic contribution by analyzing other connectivity, like the auditory or executive resting state networks. Exploring the integrity of several neural networks as potential prognostic indices may allow future research to hone in on a target rather than just testing on a ‘one by one’ basis.

An analogous issue has emerged at STREAM regarding the trajectory of research in the field of cancer biomarkers and the proper method of exploring a new study space. Similar to the intended use of fMRI in previous situation, the biomarkers are being evaluated as predictive markers of outcome to specific cancer therapies. We have noticed that early studies in this field apply a very narrow set of research techniques to try and validate a biomarker. These methods are often suboptimal and it is only much later down the road that researchers branch out into other more successful methods. A notable example of this is can be seen in our evaluation of the research trajectory of one potential biomarker in lung cancer – ERCC1. A non-specific antibody had been routinely used to detect the presence of the marker, and it wasn’t until years later that basic research into a more appropriate antibody was initiated. This is likely part of the reason for the notably sluggish progress in the field. We propose that ideally, novel research programs would start with studies looking at a broad set of potential targets and then taper these down over time, as the accumulating evidence would warrant. Acutely comatose patients are a new and important population for fMRI studies, and to me it seems like this research program might benefit by encouraging future studies to evaluate and compare the predictive use of multiple networks so that they most rigorously map the study space.

Context: On January 12^th, Charles Weijer, visiting from the Rotman Institute of Philosophy at Western University, gave the first talk in the new STREAM speaker series. He spoke on the ethical considerations involved in performing fMRI studies on acutely comatose patients in the ICU.

2015 February 6 | Leave a comment

@Manual{stream2015-683,
    title = {Charting the Unpredictable: Using fMRI patterns to determine outcome in acutely comatose patients},
    journal = {STREAM research},
    author = {Brianna Barsanti-Innes},
    address = {Montreal, Canada},
    date = 2015,
    month = feb,
    day = 6,
    url = {https://www.translationalethics.com/2015/02/06/charting-the-unpredictable-using-fmri-patterns-to-determine-outcome-in-acutely-comatose-patients/}
}