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      Detecting the Potential for Consciousness in Unresponsive Patients Using the Perturbational Complexity Index

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          Abstract

          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.

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          Most cited references31

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          The JFK Coma Recovery Scale-Revised: measurement characteristics and diagnostic utility.

          To determine the measurement properties and diagnostic utility of the JFK Coma Recovery Scale-Revised (CRS-R). Analysis of interrater and test-retest reliability, internal consistency, concurrent validity, and diagnostic accuracy. Acute inpatient brain injury rehabilitation hospital. Convenience sample of 80 patients with severe acquired brain injury admitted to an inpatient Coma Intervention Program with a diagnosis of either vegetative state (VS) or minimally conscious state (MCS). Not applicable. The CRS-R, the JFK Coma Recovery Scale (CRS), and the Disability Rating Scale (DRS). Interrater and test-retest reliability were high for CRS-R total scores. Subscale analysis showed moderate to high interrater and test-retest agreement although systematic differences in scoring were noted on the visual and oromotor/verbal subscales. CRS-R total scores correlated significantly with total scores on the CRS and DRS indicating acceptable concurrent validity. The CRS-R was able to distinguish 10 patients in an MCS who were otherwise misclassified as in a VS by the DRS. The CRS-R can be administered reliably by trained examiners and repeated measurements yield stable estimates of patient status. CRS-R subscale scores demonstrated good agreement across raters and ratings but should be used cautiously because some scores were underrepresented in the current study. The CRS-R appears capable of differentiating patients in an MCS from those in a VS.
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            A theoretically based index of consciousness independent of sensory processing and behavior.

            One challenging aspect of the clinical assessment of brain-injured, unresponsive patients is the lack of an objective measure of consciousness that is independent of the subject's ability to interact with the external environment. Theoretical considerations suggest that consciousness depends on the brain's ability to support complex activity patterns that are, at once, distributed among interacting cortical areas (integrated) and differentiated in space and time (information-rich). We introduce and test a theory-driven index of the level of consciousness called the perturbational complexity index (PCI). PCI is calculated by (i) perturbing the cortex with transcranial magnetic stimulation (TMS) to engage distributed interactions in the brain (integration) and (ii) compressing the spatiotemporal pattern of these electrocortical responses to measure their algorithmic complexity (information). We test PCI on a large data set of TMS-evoked potentials recorded in healthy subjects during wakefulness, dreaming, nonrapid eye movement sleep, and different levels of sedation induced by anesthetic agents (midazolam, xenon, and propofol), as well as in patients who had emerged from coma (vegetative state, minimally conscious state, and locked-in syndrome). PCI reliably discriminated the level of consciousness in single individuals during wakefulness, sleep, and anesthesia, as well as in patients who had emerged from coma and recovered a minimal level of consciousness. PCI can potentially be used for objective determination of the level of consciousness at the bedside.
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              European Academy of Neurology guideline on the diagnosis of coma and other disorders of consciousness

              Patients with acquired brain injury and acute or prolonged disorders of consciousness (DoC) are challenging. Evidence to support diagnostic decisions on coma and other DoC is limited but accumulating. This guideline provides the state-of-the-art evidence regarding the diagnosis of DoC, summarizing data from bedside examination techniques, functional neuroimaging and electroencephalography (EEG).
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                Author and article information

                Journal
                Brain Sci
                Brain Sci
                brainsci
                Brain Sciences
                MDPI
                2076-3425
                27 November 2020
                December 2020
                : 10
                : 12
                : 917
                Affiliations
                [1 ]Research Center of Neurology, Volokolamskoe Shosse, 80, Moscow 125367, Russia; alexandra.poydasheva@ 123456gmail.com (A.G.P.); bakulinilya@ 123456gmail.com (I.S.B.); milalegostaeva@ 123456gmail.com (L.A.L.); lizaveta.mochalova@ 123456gmail.com (E.G.I.); dmsergeev@ 123456yandex.ru (D.V.S.); lavrentevan@ 123456mail.ru (A.N.S.); Moomin10j@ 123456mail.ru (E.I.K.); kulikovasn@ 123456gmail.com (S.N.M.); dmitrylagoda.doc@ 123456gmail.com (D.Y.L.); Ryabinkina11@ 123456mail.ru (Y.V.R.); nasu2709@ 123456mail.ru (N.A.S.); mpi711@ 123456gmail.com (M.A.P.)
                [2 ]Department of Biomedical and Clinical Sciences “L. Sacco”, University of Milan, 20157 Milan, Italy; silvia.casarotto@ 123456unimi.it
                [3 ]IRCCS Fondazione Don Carlo Gnocchi ONLUS, 20148 Milan, Italy; acomanducci@ 123456dongnocchi.it
                Author notes
                [* ]Correspondence: d_sinitsyn@ 123456mail.ru
                Author information
                https://orcid.org/0000-0001-9951-9803
                https://orcid.org/0000-0003-1841-1177
                https://orcid.org/0000-0003-0716-3737
                https://orcid.org/0000-0001-7778-6687
                https://orcid.org/0000-0003-0382-7719
                https://orcid.org/0000-0002-9130-1292
                https://orcid.org/0000-0001-9396-6063
                https://orcid.org/0000-0002-9093-344X
                Article
                brainsci-10-00917
                10.3390/brainsci10120917
                7760168
                33260944
                a1466ef6-acf5-4b74-b475-bc762594e5a0
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 28 September 2020
                : 24 November 2020
                Categories
                Article

                disorders of consciousness,unresponsive wakefulness syndrome,minimally conscious state,diagnosis,perturbational complexity index,electroencephalography,transcranial magnetic stimulation,reliability

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