A framework for the extended monitoring of levels of cognitive function in unresponsive patients

Abstract

Generally, prognostication of coma outcome currently combines behavioral, reflex, and possibly neuroimaging tests that are interpreted by an attending physician. Electroencephalography, particularly, event-related brain potentials (ERP) have received attention due to evidence demonstrating the positive predictive value of certain ERP including the mismatch negativity (MMN) and the P3a, for coma emergence. We describe a set of ERP paradigms designed to require and reflect increasing levels of cognitive processing with the added objective of determining the influence of each paradigm's context strength on its ability to elicit ERPs. These paradigms were then used without explicit instructions to participants to attend to the stimuli to determine which paradigms possessed sufficient context "strength" to elicit ERPs in the absence of active participation on the part of the subject; a circumstance often encountered in brain injury patients. These paradigms were then validated on two groups of adults-younger and older, and the difference due to active participation was validated on another group of younger adults. Results show that paradigms with stronger stimulus context features performed better than those with weaker contexts, and that older adults generally had significantly attenuated and delayed responses compared to younger adults. Based on these findings, it is recommended the use of the auditory oddball paradigm that includes novel stimuli to elicit the mismatch negativity and P300, and semantic violation sentences to elicit the N400. These findings also reinforce the procedure of instructing participants about the requirements of a protocol-regardless of the patient's diagnosis or apparent state-in order to help those who are able to attend to show the most robust responses possible.

Fig 1. Graphical representation electrode members of the Regions of Interest (ROIs).

Mid Frontal (red, 4 electrodes): F1, F2, Fz, AFz. Mid Central (green, 6 electrodes): C1, C2, Cz, FC1, FC2, FCz. Mid Parietal (blue, 6 electrodes): P1, P2, Pz, CP1, CP2, CPz.

Fig 2. Grand average difference waveforms in the Mid Central ROI of the oddball mismatch MMN and corresponding peak topographic maps.

The mean difference response for the younger adult (blue) and older adult (orange) groups are plotted. Dashed colored lines indicate the mean group latency from individually scored MMN peak latencies. Scalp topography maps show voltage distributions at mean group peak latencies.

Fig 3. Grand average waveforms at Mid Central ROI to the familiar and unfamiliar novels and corresponding peak topographic maps within the oddball mismatch.

The mean responses to the familiar novel (FN) for younger adults (blue) and older adults (green), and the unfamiliar novel (UFN) for younger adults (orange) and older adults (red) groups are plotted. Dashed colored lines indicate the mean group latency from individually scored P300 peak latencies. Scalp topography maps show voltage distributions at mean group peak latencies.

Fig 4. The amplitude Group x Condition x ROI interaction to the P300 response within the oddball mismatch.

The mean values of each combination of group, condition, and ROI are plotted. Younger adults are represented with red circles, and older adults with blue triangles. Error bars represent ±0.5 SEM.

Fig 5. Grand average difference waveforms in the Mid Frontal ROI of the pattern violation mismatch MMN to the first and second deviants and corresponding peak topographic maps.

The mean difference response to the first and second deviants for the younger adult and older adult groups are plotted. Young adult first deviant (blue), younger adult second deviant (orange), older adult first deviant (green), and older adult second deviant (red). Dashed colored lines indicate the mean group latency from individually scored MMN peak latencies. Scalp topography maps show voltage distributions at mean group peak latencies.

Fig 6. Grand average waveforms to a list of Common First Names, the Subject’s Own Name, and a list of Non-salient Other Words and their corresponding peak topographic maps within the Subject’s Own Name paradigm.

A: The younger adult group’s average responses in the Mid Parietal ROI to the Common First Names (blue), Subject’s Own Name (orange), and the list of Non-salient Other Words (green) are plotted. B: The older adult group’s average responses in the Mid Frontal ROI to the Common First Names (blue), Subject’s Own Name (orange), and the list of Non-salient Other Words (green) are plotted.

Fig 7. Grand average waveforms to Congruent, Incongruent, Low Probability, and Phonological Foil terminal words and their corresponding peak topographic maps within the semantic violation sentences paradigm.

A: The younger adult group’s average responses in the Mid Central ROI to the list of Congruent (blue), Low Probability (orange), Incongruent (green) and Phonological Foil (red) terminal words are plotted. B: The older adult group’s average responses in the Mid Parietal ROI to the list of Congruent (blue), Low Probability (orange), Incongruent (green) and Phonological Foil (red) terminal words are plotted. Dashed colored lines indicate the mean group latency from individually scored N400 peak latencies. Scalp topography maps show voltage distributions at mean group peak latencies.

Fig 8. The latency Group x Condition x ROI interaction to the N400 response for the semantic violation sentences paradigm.

The mean values of each combination of group, condition, and ROI are plotted. Younger adults are represented with red circles, and older adults with blue triangles. Error bars represent ±0.5 SEM.

Fig 9. Grand average waveforms to Congruent, Incongruent, Nonword, and Pseudoword target words and their corresponding peak topographic maps within the word-word priming paradigm.

A: The younger adult group’s average responses in the Mid Central ROI to the list of Congruent (blue), Incongruent (orange), Nonword (green) and Pseudoword (red) target words are plotted. B: The older adult group’s average responses in the Mid Parietal ROI to the list of Congruent (blue), Incongruent (orange), Nonword (green) and Pseudoword (red) target words are plotted. Dashed colored lines indicate the mean group latency from individually scored N400 peak latencies. Scalp topography maps show voltage distributions at mean group peak latencies.

Fig 10. The latency Group x Condition x ROI interaction to the N400 response for the word-word priming paradigm.

The mean values of each combination of group, condition, and ROI are plotted. Younger adults are represented with red circles, and older adults with blue triangles. Error bars represent ±0.5 SEM.

Fig 11. Grand average waveforms at Cz to a list of Common First Names, the Subject’s Own Name, and a list of Non-salient Other Words and their corresponding peak topographic maps within the Subject’s Own Name paradigm with the behavioral manipulation.

A: The average responses to the Common First Names (blue), Subject’s Own Name (orange), and the list of Non-salient Other Words (green) in the Passive condition are plotted. B: The average responses to the Common First Names (blue), Subject’s Own Name (orange), and the list of Non-salient Other Words (green) in the Active condition are plotted. Dashed colored lines indicate the mean group latency from individually scored P300 peak latencies. Scalp topography maps show voltage distributions at mean group peak latencies.

Fig 12. The amplitude Behavioural Condition x Task Condition x ROI interaction to the P3 response for the Subject’s Own Name paradigm.

The mean values of each combination of behavioural condition, task condition, and ROI are plotted. The passive task condition is represented with red circles, and the active task condition with blue triangles. Error bars represent ±0.5 SEM.

Fig 13. Grand average waveforms at Cz to Congruent, Incongruent, Low Probability, and Phonological Foil terminal words and their corresponding peak topographic maps within the semantic violation sentences paradigm with the behavioral manipulation.

A: The average responses to the list of Congruent (blue), Low Probability (orange), Incongruent (green) and Phonological Foil (red) terminal words in the Passive condition are plotted. B: The average responses to the list of Congruent (blue), Low Probability (orange), Incongruent (green) and Phonological Foil (red) terminal words in the Active condition are plotted. Dashed colored lines indicate the mean group latency from individually scored N400 peak latencies. Scalp topography maps show voltage distributions at mean group peak latencies.

Fig 14. Grand average waveforms at Cz to Congruent, Incongruent, Nonword, and Pseudoword target words and their corresponding peak topographic maps within the word-word priming paradigm with the behavioral manipulation.

A: The average responses to the list of Congruent (blue), Incongruent (orange), Nonword (green) and Pseudoword (red) target words in the Passive condition are plotted. B: The average responses to the list of Congruent (blue), Incongruent (orange), Nonword (green) and Pseudoword (red) target words in the Active condition are plotted. Dashed colored lines indicate the mean group latency from individually scored N400 peak latencies. Scalp topography maps show voltage distributions at mean group peak latencies.