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

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.

当前，昏迷预后评估通常结合行为学、反射学及潜在的神经影像学检查结果，由主治医师进行解读。脑电图（electroencephalography, EEG），尤其是事件相关脑电位（event-related brain potentials, ERP），因多项研究证实特定ERP成分——包括失配负波（mismatch negativity, MMN）与P3a成分——对昏迷苏醒具有阳性预测价值，而受到学界广泛关注。本研究设计了一系列ERP实验范式，旨在对应并反映递增的认知加工层级，同时额外探究每种范式的语境强度对其诱发出ERP能力的影响。随后，本研究在未向被试明确指示需关注刺激的前提下使用这些范式，以甄别哪些范式具备足够的语境强度，可在被试未主动参与的情况下诱发出ERP——这一情境在脑损伤患者中十分常见。本研究在年轻与年长两组成人被试中对这些范式进行了验证，并在另一组年轻成人被试中验证了主动参与带来的反应差异。研究结果显示，具备更强刺激语境特征的范式表现优于语境较弱的范式；且与年轻成人相比，年长成人的ERP反应普遍显著减弱且潜伏期延长。基于上述结果，本研究推荐采用包含新奇刺激的听觉Oddball范式以诱发出失配负波与P300，同时采用语义违背语句以诱发出N400成分。本研究结果同时佐证了一项操作流程：无论患者的诊断结果或意识状态如何，均应向被试告知实验方案的要求，以帮助具备注意力能力的被试呈现出最为显著的ERP反应。