In this recent paper Morlet and others detected traces of consciousness in 21% of a cohort of comatose, vegetative, and minimally-conscious using an auditory-oddball–based ERP task. The assumption in this retrospective case series was that responses to the auditory-oddbal paradigm would be similar in brain-injured people with disorders of consciousness (DoC) and normal controls if the former had the ability to mentally follow directions and respond to the environment.

Reading this reminded me of a paper by Owen et al. from 2006, one of the first papers I read as a medical student newly interested in neurology, and which was followed-up a few years later by another and another from the same lab.

I didn’t know I was going to be a neurophysiologist at the time. I knew I was a little put off of patient-facing medicine but I had found that in the neurologic exam there was enough geekiness and subtlety to keep my interest. Nevertheless the implication of the paper exploded my novel conceptions of the worth of a neurological examination. Here was a person who looked, according to expert opinion, to have no awareness of the outside world—but whose responsiveness to the selfsame world was demonstrably modulable.

A note on terminology: the term unresponsive wakefulness syndrome (UWS) was coined in 2010 as a replacement for the semantically troublesome vegetative state (VS) and appears to still have some currency based on Google Scholar but nonetheless is less well-known than VS. I will use VS. The minimally conscious state will be abbreviated MCS; in several of the papers the Coma Recovery Scale—Revised nomenclature of MCS+ and MCS- is used.

The 2007 paper tried to show residual consciousness in a patient with clinical VS by demonstrating BOLD signal changes “indistinguishable” from those of healthy, awake volunteers to two imagery tasks: imagining playing tennis and imagining moving from room to room in the patient’s house. An interesting finding, if present in only one person. The follow-up in 2011 studied more patients and used an electroencephalographic marker of altered μ frequency power to a task of imagined limb movement. They published again in 2012 on a task and measure of “sensorimotor β activity” which they felt was an easier and more consistent test of preserved awareness.

It’s all well and good to be tantalizing but what does it mean to say that a person who clinically looks like VS has features consistent with consciousness? It’s an assertion (and in one patient!) without much effect. Naturally, if true, it’s to great subjective effect to the person who is an analogous position as one who is locked-in. So it’s papers subsequent to the early work of Owen and their lab that show the trajectories of people with DoC that are the more authoritative.

So in the most recent paper by Morlet et alii there are two important points. One is that they included both coma and post-coma patients. Two is that they tracked the evolution of the subjects’ DOC over time. (I might say, interestingly, that the third important point is that there are facilities in the world that are regularly doing this kind of protocol in a clinical context, which blows me away.) Almost all of their responders, which included people who had not yet emerged from clinical coma, progressed to the state of exit-MCS within half a year. That said, the majority of non-responders—65%—also evolved to exit-MCS. The true positive rate (SEN) is therefore low. But the true negative rate (SPC) and PPV are quite high. Therefore one can say that if a patient shows a positive effect on the test they are likely to awake but if they don’t there’s still some nontrivial chance that they will awake. In this cohort 71% evolved to exit-MCS regardless.

What is a positive test? Either the appearance of an attention-modulated appearance of P3 or N2 or a P3 in the focused attention task. Which amounts to showing that new ERP components show up when hearing deviant tones in the oddball task when the patient was asked to count the number of deviant stimuli.

Now don’t take this post as authoritative—there’s actually a ton more literature about neurophysiology in DoC. For more reading go read a Chinese review of resting-state EEG or IFCN expert opinion on the subject.