Thought translation, tennis and Turing tests in the vegetative state
In: Phenomenology and the cognitive sciences, Band 8, Heft 3, S. 361-370
ISSN: 1572-8676
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In: Phenomenology and the cognitive sciences, Band 8, Heft 3, S. 361-370
ISSN: 1572-8676
The locked-in syndrome (LIS) describes patients who are awake and conscious but severely deefferented leaving the patient in a state of almost complete immobility and loss of verbal communication. The etiology ranges from acute (e.g., brainstem stroke, which is the most frequent cause of LIS) to chronic causes (e.g., amyotrophic lateral sclerosis; ALS). In this article we review and present new data on the psychosocial adjustment to LIS. We refer to quality of life (QoL) and the degree of depressive symptoms as a measure of psychosocial adjustment. Various studies suggest that despite their extreme motor impairment, a significant number of LIS patients maintain a good QoL that seems unrelated to their state of physical functioning. Likewise, depression is not predicted by the physical state of the patients. A successful psychological adjustment to the disease was shown to be related to problem-oriented coping strategies, like seeking for information, and emotional coping strategies like denial--the latter may, nevertheless, vary with disease stage. Perceived social support seems to be the strongest predictor of psychosocial adjustment. QoL in LIS patients is often in the same range as in age-matched healthy individuals. Interestingly, there is evidence that significant others, like primary caregivers or spouses, rate LIS patients' QoL significantly lower than the patients themselves. With regard to depressed mood, ALS patients without symptoms focus significantly more often on internal factors that can be retained in the course of the disease contrary to patients with depressive symptoms who preferably name external factors as very important, such as health, which will degrade in the course of the disease. Typically, ALS patients with a higher degree of depressive symptoms experience significantly less "very pleasant" situations. The herein presented data strongly question the assumption among doctors, health-care workers, lay persons, and politicians that severe motor disability necessarily is intolerable and leads to end-of-life decisions or euthanasia. Existing evidence supports that biased clinicians provide less-aggressive medical treatment in LIS patients. Thus, psychological treatment for depression, effective strategies for coping with the disease, and support concerning the maintenance of the social network are needed to cope with the disease. Novel communication devices and assistive technology now offers an increasing number of LIS patients to resume a meaningful life and an active role in society. ; Peer reviewed
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Detection and interpretation of signs of "covert command following" in patients with disorders of consciousness (DOC) remains a challenge for clinicians. In this study, we used a tactile P3-based BCI in 12 patients without behavioral command following, attempting to establish "covert command following." These results were then confronted to cerebral metabolism preservation as measured with glucose PET (FDG-PET). One patient showed "covert command following" (i.e., above-threshold BCI performance) during the active tactile paradigm. This patient also showed a higher cerebral glucose metabolism within the language network (presumably required for command following) when compared with the other patients without "covert command-following" but having a cerebral glucose metabolism indicative of minimally conscious state. Our results suggest that the P3-based BCI might probe "covert command following" in patients without behavioral response to command and therefore could be a valuable addition in the clinical assessment of patients with DOC. ; The study was supported by the University and University Hospital of Liège, the French Speaking Community Concerted Research Action (ARC 12-17/01), the Belgian National Funds for Scientific Research (FRS-FNRS), Human Brain Project (EU-H2020-fetflagship-hbp-sga1-ga720270), Luminous project (EU-H2020-fetopen-ga686764), the James McDonnell Foundation, Mind Science Foundation, IAP research network P7/06 of the Belgian Government (Belgian Science Policy), the European Commission, the Public Utility Foundation Université Européenne du Travail, Fondazione Europea di Ricerca Biomedica, the Bial Foundation, Belgian National Plan Cancer (139), ECH2020 project ComaWare. CC is a Marie Sklodowska-Curie fellow (H2020-MSCA-IF-2016-ADOC-752686).
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One of the worst outcomes of acquired brain injury is the vegetative state, recently renamed 'unresponsive wakefulness syndrome' (VS/UWS). A patient in VS/UWS shows reflexive behaviour such as spontaneous eye opening and breathing, but no signs of awareness of the self or the environment. We performed a systematic review of VS/UWS prevalence studies and assessed their reliability. Medline, Embase, the Cochrane Library, CINAHL and PsycINFO were searched in April 2013 for cross-sectional point or period prevalence studies explicitly stating the prevalence of VS/UWS due to acute causes within the general population. We additionally checked bibliographies and consulted experts in the field to obtain 'grey data' like government reports. Relevant publications underwent quality assessment and data-extraction. We retrieved 1032 papers out of which 14 met the inclusion criteria. Prevalence figures varied from 0.2 to 6.1 VS/UWS patients per 100 000 members of the population. However, the publications' methodological quality differed substantially, in particular with regards to inclusion criteria and diagnosis verification. The reliability of VS/UWS prevalence figures is poor. Methodological flaws in available prevalence studies, the fact that 5/14 of the studies predate the identification of the minimally conscious state (MCS) as a distinct entity in 2002, and insufficient verification of included cases may lead to both overestimation and underestimation of the actual number of patients in VS/UWS. ; Peer reviewed
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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). ; Peer reviewed
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Low-level states of consciousness are characterized by disruptions of brain activity that sustain arousal and awareness. Yet, how structural, dynamical, local and network brain properties interplay in the different levels of consciousness is unknown. Here, we study fMRI brain dynamics from patients that suffered brain injuries leading to a disorder of consciousness and from healthy subjects undergoing propofol-induced sedation. We show that pathological and pharmacological low-level states of consciousness display less recurrent, less connected and more segregated synchronization patterns than conscious state. We use whole-brain models built upon healthy and injured structural connectivity to interpret these dynamical effects. We found that low-level states of consciousness were associated with reduced network interactions, together with more homogeneous and more structurally constrained local dynamics. Notably, these changes lead the structural hub regions to lose their stability during low-level states of consciousness, thus attenuating the differences between hubs and non-hubs brain dynamics. ; A.L.G. and G.D. were supported by Swiss National Science Foundation Sinergia grant no. 170873. A.P.A. and G.D. received funding from the FLAG-ERA JTC (PCI2018- 092891). G.D., S.L. and G.Z.L. received funding from the European Union's Horizon 2020 Framework Programme for Research and Innovation under the Specific Grant Agreement No. 785907 (Human Brain Project SGA2) and No. 945539 (Human Brain Project SGA3). G.D. acknowledges the Spanish Ministry Project PSI2016-75688-P (AEI/ FEDER), the Catalan Research Group Support 2017 SGR 1545, and AWAKENING (PID2019-105772GB-I00, AEI FEDER EU) funded by the Spanish Ministry of Science, Innovation and Universities (MCIU), State Research Agency (AEI) and European Regional Development Funds (FEDER). The study was further supported by the University and University Hospital of Liège, the Belgian National Funds for Scientific Research (FRS-FNRS), the European Space Agency (ESA) and the ...
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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). 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. 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). ; Belgian National Funds for Scientific Research
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Funding Information: This work was supported by the Institute for Information and Communications Technology Planning and Evaluation (IITP) funded by the Korean government (Nos. 2017-0-00451; 2017-0-01779; 2019-0-00079; 2019-0-01371; and 2021-0-02068), the University and University Hospital of Liège, Belgian National Fund for Scientific Research (F.R.S-FNRS), the Italian Ministry of Health, GR-2016–02361494 (to S.C.), the Canadian Institute for Advanced Research (CIFAR) (to M.M.), European Union's Horizon 2020 Framework Program for Research and Innovation under the Specific Grant Agreement (No. 945539, Human Brain Project SGA3) (to M.M. and S.L.), BIAL Foundation, AstraZeneca Foundation, Fund Generate, King Baudouin Foundation, DOCMA project [EU-H2020-MSCA-RISE-–778234], James McDonnell Foundation, Mind Science Foundation, Fondazione Europea di Ricerca Biomedica, National Institutes of Health (No. R01MH064498), Academy of Finland (Nos. 265680 and 294625), Tiny Blue Dot Foundation (to M.M.), and grant EraPerMed JTC 2019 "PerBrain" (to M.R.). L.R.D.S. and R.P. are PhD fellows, O.G. and A. T. are research associates, and S.L. is research director at the F.R.S.–FNRS. We thank S. Lapuschkin for sharing the code; further, we thank all the healthy participants, patients, and their families who participated in this study. Publisher Copyright: © 2022, The Author(s). ; Consciousness can be defined by two components: arousal (wakefulness) and awareness (subjective experience). However, neurophysiological consciousness metrics able to disentangle between these components have not been reported. Here, we propose an explainable consciousness indicator (ECI) using deep learning to disentangle the components of consciousness. We employ electroencephalographic (EEG) responses to transcranial magnetic stimulation under various conditions, including sleep (n = 6), general anesthesia (n = 16), and severe brain injury (n = 34). We also test our framework using resting-state EEG under general anesthesia (n = 15) and severe brain injury (n = 34). ECI simultaneously quantifies arousal and awareness under physiological, pharmacological, and pathological conditions. Particularly, ketamine-induced anesthesia and rapid eye movement sleep with low arousal and high awareness are clearly distinguished from other states. In addition, parietal regions appear most relevant for quantifying arousal and awareness. This indicator provides insights into the neural correlates of altered states of consciousness. ; Peer reviewed
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ObjectiveValidating objective, brain-based indices of consciousness in behaviorally unresponsive patients represents a challenge due to the impossibility of obtaining independent evidence through subjective reports. Here we address this problem by first validating a promising metric of consciousnessthe Perturbational Complexity Index (PCI)in a benchmark population who could confirm the presence or absence of consciousness through subjective reports, and then applying the same index to patients with disorders of consciousness (DOCs). MethodsThe benchmark population encompassed 150 healthy controls and communicative brain-injured subjects in various states of conscious wakefulness, disconnected consciousness, and unconsciousness. Receiver operating characteristic curve analysis was performed to define an optimal cutoff for discriminating between the conscious and unconscious conditions. This cutoff was then applied to a cohort of noncommunicative DOC patients (38 in a minimally conscious state [MCS] and 43 in a vegetative state [VS]). ResultsWe found an empirical cutoff that discriminated with 100% sensitivity and specificity between the conscious and the unconscious conditions in the benchmark population. This cutoff resulted in a sensitivity of 94.7% in detecting MCS and allowed the identification of a number of unresponsive VS patients (9 of 43) with high values of PCI, overlapping with the distribution of the benchmark conscious condition. InterpretationGiven its high sensitivity and specificity in the benchmark and MCS population, PCI offers a reliable, independently validated stratification of unresponsive patients that has important physiopathological and therapeutic implications. In particular, the high-PCI subgroup of VS patients may retain a capacity for consciousness that is not expressed in behavior. Ann Neurol 2016;80:718-729 ; Prin "Connage" (Italian Government) ; European Union (EU) ; James S. McDonnell Foundation Scholar Award ; Belgian National Fund for Scientific Research ; Templeton World Charity Foundation ; McDonnell Foundation ; Distinguished Chair in Consciousness Science at the University of Wisconsin ; Univ Milan, Dept Biomed & Clin Sci L Sacco, Via GB Grassi 74, I-20157 Milan, Italy ; Fdn Europea Ric Biomed, Milan, Italy ; Univ Milano Bicocca, Sch Med & Surg, Dept Hlth Sci, Monza, Italy ; Univ Fed Sao Paulo, Inst Sci & Technol, Sao Jose Dos Campos, Brazil ; Fdn Don Gnocchi Onlus, Ist Ricovero & Cura Carattere Sci, Milan, Italy ; Univ Wisconsin, Dept Psychiat, Madison, WI 53706 USA ; Univ Wisconsin, Dept Neurol, Madison, WI 53706 USA ; Univ Liege, Coma Sci Grp, GIGA, Liege, Belgium ; Univ Liege, Dept Neurol, Liege, Belgium ; Univ Hosp Liege, Liege, Belgium ; Grande Osped Metropolitano Niguarda Ca Granda, Neurocrit Care Unit, Azienda Sociosanit Terr, Dept Neurosci, Milan, Italy ; Institute of Science and Technology, Universidade Federal de São Paulo (UNIFESP), São José dos Campos, Brazil ; EU: 600806 ; EU: 686764 ; EU: 720270 ; Web of Science
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Background: The European Union (EU) aims to optimize patient protection and efficiency of health-care research by harmonizing procedures across Member States. Nonetheless, further improvements are required to increase multicenter research efficiency. We investigated IRB procedures in a large prospective European multicenter study on traumatic brain injury (TBI), aiming to inform and stimulate initiatives to improve efficiency. Methods: We reviewed relevant documents regarding IRB submission and IRB approval from European neurotrauma centers participating in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI). Documents included detailed information on IRB procedures and the duration from IRB submission until approval(s). They were translated and analyzed to determine the level of harmonization of IRB procedures within Europe. Results: From 18 countries, 66 centers provided the requested documents. The primary IRB review was conducted centrally (N = 11, 61%) or locally (N = 7, 39%) and primary IRB approval was obtained after one (N = 8, 44%), two (N = 6, 33%) or three (N = 4, 23%) review rounds with a median duration of respectively 50 and 98 days until primary IRB approval. Additional IRB approval was required in 55% of countries and could increase duration to 535 days. Total duration from submission until required IRB approval was obtained was 114 days (IQR 75-224) and appeared to be shorter after submission to local IRBs compared to central IRBs (50 vs. 138 days, p = 0.0074). Conclusion: We found variation in IRB procedures between and within European countries. There were differences in submission and approval requirements, number of review rounds and total duration. Research collaborations could benefit from the implementation of more uniform legislation and regulation while acknowledging local cultural habits and moral values between countries. ; Peer reviewed
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Purpose: Enrolling traumatic brain injury (TBI) patients with an inability to provide informed consent in research is challenging. Alternatives to patient consent are not sufficiently embedded in European and national legislation, which allows procedural variation and bias. We aimed to quantify variations in informed consent policy and practice. Methods: Variation was explored in the CENTER-TBI study. Policies were reported by using a questionnaire and national legislation. Data on used informed consent procedures were available for 4498 patients from 57 centres across 17 European countries. Results: Variation in the use of informed consent procedures was found between and within EU member states. Proxy informed consent (N = 1377;64%) was the most frequently used type of consent in the ICU, followed by patient informed consent (N = 426;20%) and deferred consent (N = 334;16%). Deferred consent was only actively used in 15 centres (26%), although it was considered valid in 47 centres (82%). Conclusions: Alternatives to patient consent are essential for TBI research. While there seems to be concordance amongst national legislations, there is regional variability in institutional practices with respect to the use of different informed consent procedures. Variation could be caused by several reasons, including inconsistencies in clear legislation or knowledge of such legislation amongst researchers. ; Peer reviewed
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Abstract: Background: The European Union (EU) aims to optimize patient protection and efficiency of health-care research by harmonizing procedures across Member States. Nonetheless, further improvements are required to increase multicenter research efficiency. We investigated IRB procedures in a large prospective European multicenter study on traumatic brain injury (TBI), aiming to inform and stimulate initiatives to improve efficiency. Methods: We reviewed relevant documents regarding IRB submission and IRB approval from European neurotrauma centers participating in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI). Documents included detailed information on IRB procedures and the duration from IRB submission until approval(s). They were translated and analyzed to determine the level of harmonization of IRB procedures within Europe. Results: From 18 countries, 66 centers provided the requested documents. The primary IRB review was conducted centrally (N = 11, 61%) or locally (N = 7, 39%) and primary IRB approval was obtained after one (N = 8, 44%), two (N = 6, 33%) or three (N = 4, 23%) review rounds with a median duration of respectively 50 and 98 days until primary IRB approval. Additional IRB approval was required in 55% of countries and could increase duration to 535 days. Total duration from submission until required IRB approval was obtained was 114 days (IQR 75–224) and appeared to be shorter after submission to local IRBs compared to central IRBs (50 vs. 138 days, p = 0.0074). Conclusion: We found variation in IRB procedures between and within European countries. There were differences in submission and approval requirements, number of review rounds and total duration. Research collaborations could benefit from the implementation of more uniform legislation and regulation while acknowledging local cultural habits and moral values between countries.
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