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Abstract
Active, passive and resting state paradigms using functional MRI (fMRI) or EEG may
reveal consciousness in the vegetative (VS) and the minimal conscious state (MCS).
A meta-analysis was performed to assess the prevalence of preserved consciousness
in VS and MCS as revealed by fMRI and EEG, including command following (active paradigms),
cortical functional connectivity elicited by external stimuli (passive paradigms)
and default mode networks (resting state). Studies were selected from multiple indexing
databases until February 2015 and evaluated using the Quality Assessment of Diagnostic
Accuracy Studies-2. 37 studies were identified, including 1041 patients (mean age
43 years, range 16-89; male/female 2.1:1; 39.5% traumatic brain injuries). MCS patients
were more likely than VS patients to follow commands during active paradigms (32%
vs 14%; OR 2.85 (95% CI 1.90 to 4.27; p<0.0001)) and to show preserved functional
cortical connectivity during passive paradigms (55% vs 26%; OR 3.53 (95% CI 2.49 to
4.99; p<0.0001)). Passive paradigms suggested preserved consciousness more often than
active paradigms (38% vs 24%; OR 1.98 (95% CI 1.54 to 2.54; p<0.0001)). Data on resting
state paradigms were insufficient for statistical evaluation. In conclusion, active
paradigms may underestimate the degree of consciousness as compared to passive paradigms.
While MCS patients show signs of preserved consciousness more frequently in both paradigms,
roughly 15% of patients with a clinical diagnosis of VS are able to follow commands
by modifying their brain activity. However, there remain important limitations at
the single-subject level; for example, patients from both categories may show command
following despite negative passive paradigms.
Systematic reviews and meta-analyses are essential to summarise evidence relating to efficacy and safety of healthcare interventions accurately and reliably. The clarity and transparency of these reports, however, are not optimal. Poor reporting of systematic reviews diminishes their value to clinicians, policy makers, and other users. Since the development of the QUOROM (quality of reporting of meta-analysis) statement—a reporting guideline published in 1999—there have been several conceptual, methodological, and practical advances regarding the conduct and reporting of systematic reviews and meta-analyses. Also, reviews of published systematic reviews have found that key information about these studies is often poorly reported. Realising these issues, an international group that included experienced authors and methodologists developed PRISMA (preferred reporting items for systematic reviews and meta-analyses) as an evolution of the original QUOROM guideline for systematic reviews and meta-analyses of evaluations of health care interventions. The PRISMA statement consists of a 27-item checklist and a four-phase flow diagram. The checklist includes items deemed essential for transparent reporting of a systematic review. In this explanation and elaboration document, we explain the meaning and rationale for each checklist item. For each item, we include an example of good reporting and, where possible, references to relevant empirical studies and methodological literature. The PRISMA statement, this document, and the associated website (www.prisma-statement.org/) should be helpful resources to improve reporting of systematic reviews and meta-analyses.
In 2003, the QUADAS tool for systematic reviews of diagnostic accuracy studies was developed. Experience, anecdotal reports, and feedback suggested areas for improvement; therefore, QUADAS-2 was developed. This tool comprises 4 domains: patient selection, index test, reference standard, and flow and timing. Each domain is assessed in terms of risk of bias, and the first 3 domains are also assessed in terms of concerns regarding applicability. Signalling questions are included to help judge risk of bias. The QUADAS-2 tool is applied in 4 phases: summarize the review question, tailor the tool and produce review-specific guidance, construct a flow diagram for the primary study, and judge bias and applicability. This tool will allow for more transparent rating of bias and applicability of primary diagnostic accuracy studies.
Thirty years of brain imaging research has converged to define the brain's default network-a novel and only recently appreciated brain system that participates in internal modes of cognition. Here we synthesize past observations to provide strong evidence that the default network is a specific, anatomically defined brain system preferentially active when individuals are not focused on the external environment. Analysis of connectional anatomy in the monkey supports the presence of an interconnected brain system. Providing insight into function, the default network is active when individuals are engaged in internally focused tasks including autobiographical memory retrieval, envisioning the future, and conceiving the perspectives of others. Probing the functional anatomy of the network in detail reveals that it is best understood as multiple interacting subsystems. The medial temporal lobe subsystem provides information from prior experiences in the form of memories and associations that are the building blocks of mental simulation. The medial prefrontal subsystem facilitates the flexible use of this information during the construction of self-relevant mental simulations. These two subsystems converge on important nodes of integration including the posterior cingulate cortex. The implications of these functional and anatomical observations are discussed in relation to possible adaptive roles of the default network for using past experiences to plan for the future, navigate social interactions, and maximize the utility of moments when we are not otherwise engaged by the external world. We conclude by discussing the relevance of the default network for understanding mental disorders including autism, schizophrenia, and Alzheimer's disease.
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