Consciousness beyond unresponsiveness
After admission at the IRU for a multifocal brain injury of vascular origin, the patient remained unresponsive for five weeks during which repeated CRS-R examinations resulted in a VS/UWS diagnosis. According to recent recommendations (Giacino et al. , 2018; Comanducci et al. , 2020; Kondziella et al. , 2020), the patient underwent a series of paraclinical exams, including visual and quantitative assessment of the resting EEG background, multimodal EP and EMG to explore sensory and motor pathways as well as ERP to investigate residual cognitive functions. Finding a preserved EEG background or evidence of late cognitive ERP, such as the late P3, would have provided a specific indication of a condition of clinical-paraclinical dissociation, such as those previously described as covert awareness (Owen et al. , 2006), cognitive-motor dissociations (CMD) (Schiff, 2015), functional LIS (Giacino et al. , 2009), MCS* (Gosserieset al. , 2014), covert cortical processing (Edlow et al. , 2021). However, this possibility was apparently inconsistent with the finding of a severely disorganized EEG background and the absence of a P3. The novelty of the present report is that these negative results were followed by a deeper level of investigation, involving TMS-EEG and eventually by a fMRI active paradigm. As described in a recent expert review (Comanducci et al. , 2020), the rationale for such a hierarchical evaluation is that while EEG and ERP can provide a specific indication of preserved consciousness when they are positive, they are inconclusive in case of a negative result due to their low sensitivity. Indeed, a direct assessment of the complexity of causal interactions within the thalamocortical system, revealed a preserved capacity for consciousness according to published norms, i.e. complexity values that are only found in conscious subjects (Casali et al. , 2013; Sarasso et al. , 2015; Casarotto et al. , 2016; Sinitsynet al. , 2020). In the absence of behavioral responsiveness and lack of communication, the question of what it means for a particular patient to have high brain complexity is hard to resolve. In general, inferring an actual instance of preserved experience is based on the evidence that control subjects who show PCImax>0.31 during unresponsiveness in sleep or under ketamine anesthesia regularly report dream experiences upon awakening. In the present case, two additional elements strongly support this conclusion. The first element is the fMRI evidence that the patient was able to engage in volitional activity in response to verbal commands during periods of unresponsiveness. The second element is the convergent evidence (bilateral mesial-frontal lesional pattern, abnormal EEG frontal slowing, altered EEG frontal response to TMS, MEP and EMG showing a severe disconnection along the central and peripheral motor pathway) that unresponsiveness could be explained by a fundamental impairment of executive/motor circuits and pathways, rather than by unconsciousness.