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      Toward Improving Diagnostic Strategies in Chronic Disorders of Consciousness: An Overview on the (Re-)Emergent Role of Neurophysiology

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          Abstract

          The differential diagnosis of patients with Disorder of Consciousness (DoC), in particular in the chronic phase, is significantly difficult. Actually, about 40% of patients with unresponsive wakefulness syndrome (UWS) and the minimally conscious state (MCS) are misdiagnosed. Indeed, only advanced paraclinical approaches, including advanced EEG analyses, can allow achieving a more reliable diagnosis, that is, discovering residual traces of awareness in patients with UWS (namely, functional Locked-In Syndrome (fLIS)). These approaches aim at capturing the residual brain network models, at rest or that may be activated in response to relevant stimuli, which may be appropriate for awareness to emerge (despite their insufficiency to generate purposeful motor behaviors). For this, different brain network models have been studied in patients with DoC by using sensory stimuli (i.e., passive tasks), probing response to commands (i.e., active tasks), and during resting-state. Since it can be difficult for patients with DoC to perform even simple active tasks, this scoping review aims at summarizing the current, innovative neurophysiological examination methods in resting state/passive modality to differentiate and prognosticate patients with DoC. We conclude that the electrophysiologically-based diagnostic procedures represent an important resource for diagnosis, prognosis, and, therefore, management of patients with DoC, using advance passive and resting state paradigm analyses for the patients who lie in the “greyzones” between MCS, UWS, and fLIS.

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          Willful modulation of brain activity in disorders of consciousness.

          The differential diagnosis of disorders of consciousness is challenging. The rate of misdiagnosis is approximately 40%, and new methods are required to complement bedside testing, particularly if the patient's capacity to show behavioral signs of awareness is diminished. At two major referral centers in Cambridge, United Kingdom, and Liege, Belgium, we performed a study involving 54 patients with disorders of consciousness. We used functional magnetic resonance imaging (MRI) to assess each patient's ability to generate willful, neuroanatomically specific, blood-oxygenation-level-dependent responses during two established mental-imagery tasks. A technique was then developed to determine whether such tasks could be used to communicate yes-or-no answers to simple questions. Of the 54 patients enrolled in the study, 5 were able to willfully modulate their brain activity. In three of these patients, additional bedside testing revealed some sign of awareness, but in the other two patients, no voluntary behavior could be detected by means of clinical assessment. One patient was able to use our technique to answer yes or no to questions during functional MRI; however, it remained impossible to establish any form of communication at the bedside. These results show that a small proportion of patients in a vegetative or minimally conscious state have brain activation reflecting some awareness and cognition. Careful clinical examination will result in reclassification of the state of consciousness in some of these patients. This technique may be useful in establishing basic communication with patients who appear to be unresponsive. 2010 Massachusetts Medical Society
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            Unresponsive wakefulness syndrome: a new name for the vegetative state or apallic syndrome

            Background Some patients awaken from coma (that is, open the eyes) but remain unresponsive (that is, only showing reflex movements without response to command). This syndrome has been coined vegetative state. We here present a new name for this challenging neurological condition: unresponsive wakefulness syndrome (abbreviated UWS). Discussion Many clinicians feel uncomfortable when referring to patients as vegetative. Indeed, to most of the lay public and media vegetative state has a pejorative connotation and seems inappropriately to refer to these patients as being vegetable-like. Some political and religious groups have hence felt the need to emphasize these vulnerable patients' rights as human beings. Moreover, since its first description over 35 years ago, an increasing number of functional neuroimaging and cognitive evoked potential studies have shown that physicians should be cautious to make strong claims about awareness in some patients without behavioral responses to command. Given these concerns regarding the negative associations intrinsic to the term vegetative state as well as the diagnostic errors and their potential effect on the treatment and care for these patients (who sometimes never recover behavioral signs of consciousness but often recover to what was recently coined a minimally conscious state) we here propose to replace the name. Conclusion Since after 35 years the medical community has been unsuccessful in changing the pejorative image associated with the words vegetative state, we think it would be better to change the term itself. We here offer physicians the possibility to refer to this condition as unresponsive wakefulness syndrome or UWS. As this neutral descriptive term indicates, it refers to patients showing a number of clinical signs (hence syndrome) of unresponsiveness (that is, without response to commands) in the presence of wakefulness (that is, eye opening).
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              An information integration theory of consciousness

              Background Consciousness poses two main problems. The first is understanding the conditions that determine to what extent a system has conscious experience. For instance, why is our consciousness generated by certain parts of our brain, such as the thalamocortical system, and not by other parts, such as the cerebellum? And why are we conscious during wakefulness and much less so during dreamless sleep? The second problem is understanding the conditions that determine what kind of consciousness a system has. For example, why do specific parts of the brain contribute specific qualities to our conscious experience, such as vision and audition? Presentation of the hypothesis This paper presents a theory about what consciousness is and how it can be measured. According to the theory, consciousness corresponds to the capacity of a system to integrate information. This claim is motivated by two key phenomenological properties of consciousness: differentiation – the availability of a very large number of conscious experiences; and integration – the unity of each such experience. The theory states that the quantity of consciousness available to a system can be measured as the Φ value of a complex of elements. Φ is the amount of causally effective information that can be integrated across the informational weakest link of a subset of elements. A complex is a subset of elements with Φ>0 that is not part of a subset of higher Φ. The theory also claims that the quality of consciousness is determined by the informational relationships among the elements of a complex, which are specified by the values of effective information among them. Finally, each particular conscious experience is specified by the value, at any given time, of the variables mediating informational interactions among the elements of a complex. Testing the hypothesis The information integration theory accounts, in a principled manner, for several neurobiological observations concerning consciousness. As shown here, these include the association of consciousness with certain neural systems rather than with others; the fact that neural processes underlying consciousness can influence or be influenced by neural processes that remain unconscious; the reduction of consciousness during dreamless sleep and generalized seizures; and the time requirements on neural interactions that support consciousness. Implications of the hypothesis The theory entails that consciousness is a fundamental quantity, that it is graded, that it is present in infants and animals, and that it should be possible to build conscious artifacts.
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                Author and article information

                Journal
                Brain Sci
                Brain Sci
                brainsci
                Brain Sciences
                MDPI
                2076-3425
                10 January 2020
                January 2020
                : 10
                : 1
                : 42
                Affiliations
                [1 ]IRCCS Centro Neurolesi Bonino Pulejo, 98124 Messina, Italy; luana.billeri@ 123456irccsme.it (L.B.); simona.portaro@ 123456irccsme.it (S.P.); g.naro11@ 123456alice.it (A.N.)
                [2 ]Padre Pio Foundation and Rehabilitation Centers, San Giovanni Rotondo, 71013 Foggia, Italy; uo.tecnologica@ 123456fondazionepadrepio-onlus.it
                [3 ]Stomatodental Center, 98100 Messina, Italy; david.militi@ 123456alice.it
                Author notes
                [* ]Correspondence: serena.diba@ 123456gmail.com (S.F.); salbro77@ 123456tiscali.it (R.S.C.); Tel.: +39-090-6012-8166 (R.S.C.)
                [†]

                These authors contributed equally to this work.

                Author information
                https://orcid.org/0000-0002-8566-3166
                Article
                brainsci-10-00042
                10.3390/brainsci10010042
                7016627
                31936844
                5a16ac71-abfd-4361-91cd-67f054337703
                © 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
                : 18 November 2019
                : 08 January 2020
                Categories
                Perspective

                disorder of consciousness (doc),unresponsive wakefulness syndrome (uws),minimally conscious state (mcs),functional locked-in syndrome (flis),resting state,passive paradigms,neurophysiology

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