The difficulties of behavioral evaluation of prolonged disorders of consciousness (DOC) motivate the development of brain-based diagnostic approaches. The perturbational complexity index (PCI), which measures the complexity of electroencephalographic (EEG) responses to transcranial magnetic stimulation (TMS), showed a remarkable sensitivity in detecting minimal signs of consciousness in previous studies. Here, we tested the reliability of PCI in an independently collected sample of 24 severely brain-injured patients, including 11 unresponsive wakefulness syndrome (UWS), 12 minimally conscious state (MCS) patients, and 1 emergence from MCS patient. We found that the individual maximum PCI value across stimulation sites fell within the consciousness range (i.e., was higher than PCI*, which is an empirical cutoff previously validated on a benchmark population) in 11 MCS patients, yielding a sensitivity of 92% that surpassed qualitative evaluation of resting EEG. Most UWS patients (n = 7, 64%) showed a slow and stereotypical TMS-EEG response, associated with low-complexity PCI values (i.e., ≤PCI*). Four UWS patients (36%) provided high-complexity PCI values, which might suggest a covert capacity for consciousness. In conclusion, this study successfully replicated the performance of PCI in discriminating between UWS and MCS patients, further motivating the application of TMS-EEG in the workflow of DOC evaluation.

Background: Navigated repetitive transcranial magnetic stimulation (rTMS) is a promising tool for neuromodulation. In previous studies it has been shown that the activity of the default mode network (DMN) areas, particularly of its key region—the angular gyrus—is positively correlated with the level of consciousness. Our study aimed to explore the effect of rTMS of the angular gyrus as a new approach for disorders of consciousness (DOC) treatment; Methods: A 10-session 2-week high-frequency rTMS protocol was delivered over the left angular gyrus in 38 DOC patients with repeated neurobehavioral assessments obtained at baseline and in 2 days after the stimulation course was complete; Results: 20 Hz-rTMS over left angular gyrus improved the coma recovery scale revised (CRS-R) total score in minimally conscious state (MCS) patients. We observed no effects in vegetative state (VS) patients; and Conclusions: The left angular gyrus is likely to be effective target for rTMS in patients with present signs of consciousness.

Differential diagnosis of unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS) is one of the most challenging problems for specialists who deal with chronic disorders of consciousness (DOC). The aim of the current study was to develop a conventional MRI-based scale and to evaluate its role in distinguishing chronic disorders of consciousness (Disorders of Consciousness MRI-based Distinguishing Scale, DOC-MRIDS). Data were acquired from 30 patients with clinically diagnosed chronic disorders of consciousness. All patients underwent conventional MRI using a Siemens Verio 3.0 T scanner, which included T2 and T1 sequences for patient assessment. Diffuse cortical atrophy, ventricular enlargement, sulcal widening, leukoaraiosis, brainstem and/or thalamus degeneration, corpus callosum degeneration, and corpus callosum lesions were assessed according to DOC-MRIDS criteria, with a total score calculation. The ROC-analysis showed that a reasonable threshold DOC-MRIDS total score was 5.5, that is, patients with DOC-MRIDS total score of 6 and above were classified as UWS and 5 and below as MCS, with sensitivity of 82.4% and specificity of 92.3%. The novel structural MRI-based scale for the assessment of typical brain lesions in patients with chronic DOC is relatively easy to apply, and provides good specificity and sensitivity values for discrimination between UWS and MCS.

It has been proposed that the effectiveness of non-invasive brain stimulation (NIBS) as a cognitive enhancement technique may be enhanced by combining the stimulation with concurrent cognitive activity. However, the benefits of such a combination in comparison to protocols without ongoing cognitive activity have not yet been studied. In the present study, we investigate the effects of fMRI-guided high-frequency repetitive transcranial magnetic stimulation (HF rTMS) over the left dorsolateral prefrontal cortex (DLPFC) on working memory (WM) in healthy volunteers, using an n-back task with spatial and verbal stimuli and a spatial span task. In two combined protocols (TMS + WM + (maintenance) and TMS + WM + (rest)) trains of stimuli were applied in the maintenance and rest periods of the modified Sternberg task, respectively. We compared them to HF rTMS without a cognitive load (TMS + WM −) and control stimulation (TMS − WM + (maintenance)). No serious adverse effects appeared in this study. Among all protocols, significant effects on WM were shown only for the TMS + WM − with oppositely directed influences of this protocol on storage and manipulation in spatial WM. Moreover, there was a significant difference between the effects of TMS + WM − and TMS + WM + (maintenance), suggesting that simultaneous cognitive activity does not necessarily lead to an increase in TMS effects.