How far can we go in chronic disorders of consciousness differential diagnosis? The use of neuromodulation in detecting internal and external awareness

Awareness generation and modulation may depend on a balanced information integration and differentiation across default mode network (DMN) and external awareness networks (EAN). Neuromodulation approaches, capable of shaping information processing, may highlight residual network activities supporting awareness, which are not detectable through active paradigms, thus allowing to differentiate chronic disorders of consciousness (DoC). We studied aftereffects of repetitive transcranial magnetic stimulation (rTMS) by applying graph theory within canonical frequency bands to compare the markers of these networks in the electroencephalographic data from 20 patients with DoC. We found that patients' high-frequency networks suffered from a large-scale connectivity breakdown, paralleled by a local hyperconnectivity, whereas low-frequency networks showed a preserved but dysfunctional large-scale connectivity. There was a correlation between metrics and the behavioral awareness. Interestingly, two persons with UWS showed a residual rTMS-induced modulation of the functional correlations between the DMN and the EAN, as observed in patients with MCS. Hence, we may hypothesize that the patients with UWS who demonstrate evidence of residual DMN-EAN functional correlation may be misdiagnosed, given that such residual network correlations could support covert consciousness.