The reliability of the N400 in single subjects: Implications for patients with disorders of consciousness

Abstract

Functional neuroimaging assessments of residual cognitive capacities, including those that support language, can improve diagnostic and prognostic accuracy in patients with disorders of consciousness. Due to the portability and relative inexpensiveness of electroencephalography, the N400 event-related potential component has been proposed as a clinically valid means to identify preserved linguistic function in non-communicative patients. Across three experiments, we show that changes in both stimuli and task demands significantly influence the probability of detecting statistically significant N400 effects — that is, the difference in N400 amplitudes caused by the experimental manipulation. In terms of task demands, passively heard linguistic stimuli were significantly less likely to elicit N400 effects than task-relevant stimuli. Due to the inability of the majority of patients with disorders of consciousness to follow task commands, the insensitivity of passive listening would impede the identification of residual language abilities even when such abilities exist. In terms of stimuli, passively heard normatively associated word pairs produced the highest detection rate of N400 effects (50% of the participants), compared with semantically-similar word pairs (0%) and high-cloze sentences (17%). This result is consistent with a prediction error account of N400 magnitude, with highly predictable targets leading to smaller N400 waves, and therefore larger N400 effects. Overall, our data indicate that non-repeating normatively associated word pairs provide the highest probability of detecting single-subject N400s during passive listening, and may thereby provide a clinically viable means of assessing residual linguistic function. We also show that more liberal analyses may further increase the detection-rate, but at the potential cost of increased false alarms.

Divergent neural responses to narrative speech in disorders of consciousness

“…We used the inexact augmented Lagrange multiplier method for computing rPCA37 and applied the method on the combined set of subjects.”16 This was done because the rPCA method allows for the substitution of outlier samples with interpolated data, ensuring the temporal continuity of the signal, which is essential to our analysis.…”

“…While such EEG measures appear to index cognitive processes, it is not clear that ERPs capture the type of auditory attention required to comprehend speech in everyday environments. Importantly, previous attempts to probe semantic verbal processing in DOC patients using EEG with short speech segments (mostly the N400 ERP component)14, 15 have generally failed to make diagnostic predictions for individual patients 16. In contrast, EEG responses to longer speech segments have shown promise in quantifying consciousness in acute traumatic brain injury 17…”

Probing ERP correlates of verbal semantic processing in patients with impaired consciousness

“…In order to boost the N400 and LPC, we could use active tasks focused on semantic attributes of word pairs, rather than instructing subjects to simply attend to the stimuli without engaging in any specific task. Indeed, (Cruse et al, 2014) designed three experiments in normal controls, and showed that while N400 could be detected at the single-subject level in a semantically related word-pair paradigm using an active response task in 75% (9/12) of subjects, this proportion dropped to 58% (7/12) when subjects were instructed to simply pay attention to the semantic relation covertly, and to 0% when they were asked to passively listen to the material. Then in a second experiment, they showed that the use of word-pair stimuli generated from normative associations -as done in our work -increased the detection of N400 in the passive condition in 50% of subjects.…”

Somatosensory attention identifies both overt and covert awareness in disorders of consciousness

“…Data from the mental imagery paradigm were preprocessed using SPM8 (http://www.fil. 42,44 In the first step, data were compared at each time point using a t test. 13 For the selective attention paradigm, preprocessing was performed with AA software.…”

“…43 This technique has been described in detail previously. 42,44 In the first step, data were compared at each time point using a t test. In the second step, t values of adjacent spatiotemporal points with p < 0.05 were clustered together by summating their t values.…”