Toward a common clinical lexicon of consciousness.
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ABSTRACT:
SUBMITTER: Bacchi S
PROVIDER: S-EPMC10504159 | biostudies-literature | 2023 Sep
REPOSITORIES: biostudies-literature
Publications
Toward a common clinical lexicon of consciousness.
Bacchi Stephen S Tan Sheryn S Slee Mark M
Internal and emergency medicine 20230708 6
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Project description:In Being No One, Metzinger (2004[2003]) introduces an approach to the scientific study of consciousness that draws on theories and results from different disciplines, targeted at multiple levels of analysis. Descriptions and assumptions formulated at, for instance, the phenomenological, representationalist, and neurobiological levels of analysis provide different perspectives on the same phenomenon, which can ultimately yield necessary and sufficient conditions for applying the concept of phenomenal representation. In this way, the "method of interdisciplinary constraint satisfaction (MICS)" (as it has been called by Weisberg, 2005) promotes our understanding of consciousness. However, even more than a decade after the first publication of Being No One, we still lack a mature science of consciousness. This paper makes the following meta-theoretical contribution: It analyzes the hurdles an approach such as MICS has yet to overcome and discusses to what extent existing approaches solve the problems left open by MICS. Furthermore, it argues that a unifying theory of different features of consciousness is required to reach a mature science of consciousness.
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Project description:To encourage the process of harmonization, the biobank community should support and use a common terminology. Relevant terms may be found in general thesauri for medicine, legal instruments or specific glossaries for biobanking. A comparison of the use of these sources has so far not been conducted and would be a useful instrument to further promote harmonization and data sharing. Thus, the purpose of the present study was to investigate the preference of definitions important for sharing biological samples and data. Definitions for 10 terms -[human] biobank, sample/specimen, sample collection, study, aliquot, coded, identifying information, anonymised, personal data and informed consent-were collected from several sources. A web-based questionnaire was sent to 560 European individuals working with biobanks asking to select their preferred definition for the terms. A total of 123 people participated in the survey, giving a response rate of 23%. The result was evaluated from four aspects: scope of definitions, potential regional differences, differences in semantics and definitions in the context of ontologies, guided by comments from responders. Indicative from the survey is the risk of focusing only on the research aspect of biobanking in definitions. Hence, it is recommended that important terms should be formulated in such a way that all areas of biobanking are covered to improve the bridges between research and clinical application. Since several of the terms investigated here within can also be found in a legal context, which may differ between countries, establishing what is a proper definition on how it adheres to law is also crucial.
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Project description:Clinical research into consciousness has long focused on cortical macroscopic networks and their disruption in pathological or pharmacological consciousness perturbation. Despite demonstrating diagnostic utility in disorders of consciousness (DoC) and monitoring anesthetic depth, these cortico-centric approaches have been unable to characterize which neurochemical systems may underpin consciousness alterations. Instead, preclinical experiments have long implicated the dopaminergic ventral tegmental area (VTA) in the brainstem. Despite dopaminergic agonist efficacy in DoC patients equally pointing to dopamine, the VTA has not been studied in human perturbed consciousness. To bridge this translational gap between preclinical subcortical and clinical cortico-centric perspectives, we assessed functional connectivity changes of a histologically characterized VTA using functional MRI recordings of pharmacologically (propofol sedation) and pathologically perturbed consciousness (DoC patients). Both cohorts demonstrated VTA disconnection from the precuneus and posterior cingulate (PCu/PCC), a main default mode network node widely implicated in consciousness. Strikingly, the stronger VTA-PCu/PCC connectivity was, the more the PCu/PCC functional connectome resembled its awake configuration, suggesting a possible neuromodulatory relationship. VTA-PCu/PCC connectivity increased toward healthy control levels only in DoC patients who behaviorally improved at follow-up assessment. To test whether VTA-PCu/PCC connectivity can be affected by a dopaminergic agonist, we demonstrated in a separate set of traumatic brain injury patients without DoC that methylphenidate significantly increased this connectivity. Together, our results characterize an in vivo dopaminergic connectivity deficit common to reversible and chronic consciousness perturbation. This noninvasive assessment of the dopaminergic system bridges preclinical and clinical work, associating dopaminergic VTA function with macroscopic network alterations, thereby elucidating a critical aspect of brainstem-cortical interplay for consciousness.
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Project description:As the clinical trial landscape for patients with disorders of consciousness (DoC) expands, consideration of associated ethical challenges and opportunities is of ever-increasing importance. Responsible conduct of research in the vulnerable population of persons with DoC, including those with coma, vegetative state/unresponsive wakefulness syndrome (VS/UWS), minimally conscious state (MCS), covert cortical processing (CCP), and cognitive motor dissociation (CMD), demands proactive deliberation of unique ethical issues that may arise and the adoption of robust protections to safeguard patients, surrogates, and other key stakeholders. Here we identify and critically evaluate four central categories of ethical considerations in clinical trials involving participants with DoC: (1) autonomy, respect for persons and informed consent of individuals with liminal consciousness; (2) balancing unknown benefits and risks, especially considering the epistemological gap between behavior and consciousness that complicates ordinary ascription of subjective states; (3) disclosure to surrogates and clinical teams of investigational results pertaining to consciousness; and (4) justice considerations, including equitable access to clinical trial enrollment across communities and geographies. We outline guiding principles and research opportunities for clinicians, neuroethicists, and researchers engaged in DoC clinical trials to advance ethical study design and deployment in this complex yet crucial area of investigation.
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Project description:Teaching and learning of clinical reasoning are core principles of medical education. However, little guidance exists for faculty leaders to navigate curricular transitions between pre-clerkship and clerkship curricular phases. This study compares how educational leaders in these two phases understand clinical reasoning instruction. Previously reported cross-sectional surveys of pre-clerkship clinical skills course directors, and clerkship leaders were compared. Comparisons focused on perceived importance of a number of core clinical reasoning concepts, barriers to clinical reasoning instruction, level of familiarity across the undergraduate medical curriculum, and inclusion of clinical reasoning instruction in each area of the curriculum. Analyses were performed using the Mann Whitney U test. Both sets of leaders rated lack of curricular time as the largest barrier to teaching clinical reasoning. Clerkship leaders also noted a lack of faculty with skills to teach clinical reasoning concepts as a significant barrier (p < 0.02), while pre-clerkship leaders were more likely to perceive that these concepts were too advanced for their students (p < 0.001). Pre-clerkship leaders reported a higher level of familiarity with the clerkship curriculum than clerkship leaders reported of the pre-clerkship curriculum (p < 0.001). As faculty transition students from the pre-clerkship to the clerkship phase, a shared understanding of what is taught and when, accompanied by successful faculty development, may aid the development of longitudinal, milestone-based clinical reasoning instruction.
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Project description:Background: Innate lymphoid cells (ILCs) comprise cytotoxic NK cells and “helper” ILCs (hILCs). Human hILC development is less characterized as compared to NK cells, although all ILCs are developmentally related. It has been reported that the immunosuppressive drugs glucocorticoids (GCs) regulate ILCs function, but whether they control ILCs differentiation from hematopoietic stem cells (HSCs) is unknown. Objective: We sought to analyze the effect of GCs on ILC development from HSCs. Methods: We exploited an in vitro system to generate and expand from peripheral blood (PB) HSCs a multipotent CD56+ ILC precursor able to differentiate into NK cells, ILC1s and ILC3s. We also analyzed ex vivo, at different time points, the PB of allogeneic HSC transplantation (HSCT) recipients who were or were not treated with GCs and compared ILC subset reconstitution. Results: We show that, in vitro, GCs favor the generation of NK cells from myeloid precursors, while they strongly impair lymphoid development. In support to these data, HSCT recipients who had been treated with GCs display a lower number of circulating hILCs, including the ILCP previously identified as a systemic substrate for tissue ILC differentiation. Conclusions: GCs impair the development of the CD117+ ILCP from CD34+ HSCs, while they do not affect the further steps of ILCP differentiation towards NK cells and hILC subsets. This reflects an association of GC treatment with a marked reduction of circulating hILCs in the recipients of HSCT.
2021-11-05 | GSE186950 | GEO