The N400 and disorders of consciousness [New paper]

When I interviewed for a post-doc to study disorders of consciousness with EEG in 2009, I talked about the N400 effect and how it would surely be a good way to identify speech comprehension in non-communicative patients. After many years of trying, now I'm not so convinced.

The N400 is a negative-going event-related potential (ERP) that peaks around 400ms after the onset of meaningful stimuli and is primarily sensitive to the context in which the stimulus is presented. For example, chair elicits a larger N400 when heard after the word potato (an unrelated prime) than after the word table (a related prime). The specific cognitive process reflected in the N400 effect is still a matter of debate. However, it is clearly sensitive to the meaning of speech, and so could provide a marker of semantic access in non-communicative patients, such as disorders of consciousness.

However, as we described in an earlier paper, the chances of detecting an N400 effect are quite small unless the patient is able to follow instructions to complete a top-down semantic judgment task. Clearly this would rule out (the presumably majority of) those patients who can process the meaning of the speech but who are unable to concentrate on a cognitive task for 20-mins or so.

In our new paper, published in Neuroimage: Clinical, we describe an EEG adaptation of a previously published hierarchical fMRI paradigm for assessment of auditory processing (Coleman et al., 2009, Brain). The paper included data from London, Ontario, and Cambridge, England, collected over several years. The highest level of our hierarchy - semantic processing - was indexed by the N400 effect. However, this effect was evident in the EEG of only 1 of the 16 patients with a prolonged disorder of consciousness. This result did not survive correction for multiple comparisons, nor did we identify semantic processing in any patients whose behaviour clearly indicated an ability to understand speech (i.e. they could follow commands).

In summary, the utility of the N400 semantic priming effect in disorders of consciousness is unclear. That doesn't mean that studying speech and semantics in disorders of consciousness is not a worthwhile endeavour. However, perhaps we need paradigms and analyses that are more robust to the challenges of limited data collection in patients with limited cognitive capacity.

Reference:

Beukema, S., Gonzalez-Lara, L. E., Finoia, P., Kamau, E., Allanson, J., Chennu, S., Gibson, R. M., Pickard, J. D., Owen, A. M., & Cruse, D. (2016). A hierarchy of event-related potential markers of auditory processing in disorders of consciousness. Neuroimage: Clinical, In Press. dx.doi.org/10.1016/j.nicl.2016.08.003

Figure: ERP effect topographies and source estimates for two levels of our hierarchy.