Multimodal Characterization of the Semantic N400 Response within a Rapid Evaluation Brain Vital Sign Framework

Background: For nearly four decades, the N400 has been an important brainwave marker of semantic processing. It can be recorded non-invasively from the scalp using electrical and/or magnetic sensors, but largely within the restricted domain of research laboratories specialized to run specifc N400 experiments. However, there is increasing evidence of signifcant clinical utility for the N400 in neurological evaluation, particularly at the individual level. To enable clinical applications, we recently reported a rapid evaluation framework known as “brain vital signs” that successfully incorporated the N400 response as one of the core components for cognitive function evaluation. The current study characterized the rapidly evoked N400 response to demonstrate that it shares consistent features with traditional N400 responses acquired in research laboratory settings—thereby enabling its translation into brain vital signs applications.Methods: Data were collected from 17 healthy individuals using magnetoencephalography (MEG) and electroencephalography (EEG), with analysis of sensor-level efects as well as evaluation of brain sources. Individual-level N400 responses were classifed using machine learning to determine the percentage of participants in whom the response was successfully detected.Results: The N400 response was observed in both M/EEG modalities showing signifcant diferences to incongruent versus congruent condition in the expected time range (p<0.05). Also as expected, N400-related brain activity was observed in the temporal and inferior frontal cortical regions, with typical left-hemispheric asymmetry. Classifcation robustly confrmed the N400 efect at the individual level with high accuracy (89%), sensitivity (0.88) and specifcity (0.90).Conclusion: The brain vital sign N400 characteristics were highly consistent with features of the previously reported N400 responses acquired using traditional laboratory-based experiments. These results provide important evidence supporting clinical translation of the rapidly acquired N400 response as a potential tool for assessments of higher cognitive functions.