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      Developing Brain Vital Signs: Initial Framework for Monitoring Brain Function Changes Over Time

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          Abstract

          Clinical assessment of brain function relies heavily on indirect behavior-based tests. Unfortunately, behavior-based assessments are subjective and therefore susceptible to several confounding factors. Event-related brain potentials (ERPs), derived from electroencephalography (EEG), are often used to provide objective, physiological measures of brain function. Historically, ERPs have been characterized extensively within research settings, with limited but growing clinical applications. Over the past 20 years, we have developed clinical ERP applications for the evaluation of functional status following serious injury and/or disease. This work has identified an important gap: the need for a clinically accessible framework to evaluate ERP measures. Crucially, this enables baseline measures before brain dysfunction occurs, and might enable the routine collection of brain function metrics in the future much like blood pressure measures today. Here, we propose such a framework for extracting specific ERPs as potential “brain vital signs.” This framework enabled the translation/transformation of complex ERP data into accessible metrics of brain function for wider clinical utilization. To formalize the framework, three essential ERPs were selected as initial indicators: (1) the auditory N100 (Auditory sensation); (2) the auditory oddball P300 (Basic attention); and (3) the auditory speech processing N400 (Cognitive processing). First step validation was conducted on healthy younger and older adults (age range: 22–82 years). Results confirmed specific ERPs at the individual level (86.81–98.96%), verified predictable age-related differences (P300 latency delays in older adults, p < 0.05), and demonstrated successful linear transformation into the proposed brain vital sign (BVS) framework (basic attention latency sub-component of BVS framework reflects delays in older adults, p < 0.05). The findings represent an initial critical step in developing, extracting, and characterizing ERPs as vital signs, critical for subsequent evaluation of dysfunction in conditions like concussion and/or dementia.

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          Most cited references25

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          Reading senseless sentences: brain potentials reflect semantic incongruity.

          In a sentence reading task, words that occurred out of context were associated with specific types of event-related brain potentials. Words that were physically aberrant (larger than normal) elecited a late positive series of potentials, whereas semantically inappropriate words elicited a late negative wave (N400). The N400 wave may be an electrophysiological sign of the "reprocessing" of semantically anomalous information.
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            Diagnostic accuracy of the vegetative and minimally conscious state: Clinical consensus versus standardized neurobehavioral assessment

            Background Previously published studies have reported that up to 43% of patients with disorders of consciousness are erroneously assigned a diagnosis of vegetative state (VS). However, no recent studies have investigated the accuracy of this grave clinical diagnosis. In this study, we compared consensus-based diagnoses of VS and MCS to those based on a well-established standardized neurobehavioral rating scale, the JFK Coma Recovery Scale-Revised (CRS-R). Methods We prospectively followed 103 patients (55 ± 19 years) with mixed etiologies and compared the clinical consensus diagnosis provided by the physician on the basis of the medical staff's daily observations to diagnoses derived from CRS-R assessments performed by research staff. All patients were assigned a diagnosis of 'VS', 'MCS' or 'uncertain diagnosis.' Results Of the 44 patients diagnosed with VS based on the clinical consensus of the medical team, 18 (41%) were found to be in MCS following standardized assessment with the CRS-R. In the 41 patients with a consensus diagnosis of MCS, 4 (10%) had emerged from MCS, according to the CRS-R. We also found that the majority of patients assigned an uncertain diagnosis by clinical consensus (89%) were in MCS based on CRS-R findings. Conclusion Despite the importance of diagnostic accuracy, the rate of misdiagnosis of VS has not substantially changed in the past 15 years. Standardized neurobehavioral assessment is a more sensitive means of establishing differential diagnosis in patients with disorders of consciousness when compared to diagnoses determined by clinical consensus.
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              Event-related potentials in clinical research: guidelines for eliciting, recording, and quantifying mismatch negativity, P300, and N400.

              This paper describes recommended methods for the use of event-related brain potentials (ERPs) in clinical research and reviews applications to a variety of psychiatric and neurological disorders. Techniques are presented for eliciting, recording, and quantifying three major cognitive components with confirmed clinical utility: mismatch negativity (MMN), P300, and N400. Also highlighted are applications of each of the components as methods of investigating central nervous system pathology. The guidelines are intended to assist investigators who use ERPs in clinical research, in an effort to provide clear and concise recommendations and thereby to standardize methodology and facilitate comparability of data across laboratories.
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                Author and article information

                Contributors
                Journal
                Front Neurosci
                Front Neurosci
                Front. Neurosci.
                Frontiers in Neuroscience
                Frontiers Media S.A.
                1662-4548
                1662-453X
                12 May 2016
                2016
                : 10
                : 211
                Affiliations
                [1] 1Faculty of Applied Science, School of Engineering Science, Simon Fraser University Burnaby, BC, Canada
                [2] 2NeuroTech Lab, Simon Fraser University and Fraser Health Authority Surrey, BC, Canada
                [3] 3Health Sciences and Innovation, Surrey Memorial Hospital, Fraser Health Authority Surrey, BC, Canada
                [4] 4Biomedical Physiology and Kinesiology, Faculty of Science, Simon Fraser University Burnaby, BC, Canada
                [5] 5Sports Medicine Center, Mayo Clinic Rochester, MN, USA
                [6] 6Department of Psychiatry, Icahn School of Medicine at Mount Sinai New York, NY, USA
                [7] 7Joseph Sagol Neuroscience Centre, Sheeba Medical Centre Ramat Gan, Israel
                [8] 8HealthTech Connex Inc. Surrey, BC, Canada
                Author notes

                Edited by: Xi-Nian Zuo, Chinese Academy of Sciences, China

                Reviewed by: Delia Cabrera DeBuc, University of Miami, USA; Olivier David, Université Joseph Fourier-Grenoble, France

                *Correspondence: Ryan C. N. D'Arcy rdarcy@ 123456sfu.ca

                This article was submitted to Brain Imaging Methods, a section of the journal Frontiers in Neuroscience

                Article
                10.3389/fnins.2016.00211
                4867677
                27242415
                cc16b210-fce4-430e-b94f-7474d16d9553
                Copyright © 2016 Ghosh Hajra, Liu, Song, Fickling, Liu, Pawlowski, Jorgensen, Smith, Schnaider-Beeri, Van Den Broek, Rizzotti, Fisher and D'Arcy.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 09 March 2016
                : 26 April 2016
                Page count
                Figures: 6, Tables: 6, Equations: 2, References: 34, Pages: 10, Words: 7108
                Funding
                Funded by: Mitacs 10.13039/501100004489
                Award ID: IT03240
                Funded by: Canadian Institutes of Health Research 10.13039/501100000024
                Funded by: Natural Sciences and Engineering Research Council of Canada 10.13039/501100000038
                Categories
                Neuroscience
                Original Research

                Neurosciences
                clinical neuroscience,erps,evoked potentials,vital signs,neurology
                Neurosciences
                clinical neuroscience, erps, evoked potentials, vital signs, neurology

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