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      Transcranial Direct Current Stimulation in Patients with Prolonged Disorders of Consciousness: Combined Behavioral and Event-Related Potential Evidence

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          Abstract

          Background

          The electrophysiological evidence supporting the therapeutic efficacy of multiple transcranial direct current stimulation (tDCS) sessions on consciousness improvement in patients with prolonged disorders of consciousness (DOCs) has not been firmly established.

          Objectives

          To assess the effects of repeated tDCS in patients with prolonged DOCs by Coma Recovery Scale-Revised (CRS-R) score and event-related potential (ERP).

          Method

          Using a sham-controlled randomized double-blind design, 26 patients were randomly assigned to either a real [five vegetative state (VS) and eight minimally conscious state (MCS) patients] or sham (six VS and seven MCS patients) stimulation group. The patients in the real stimulation group underwent 20 anodal tDCS sessions of the left dorsolateral prefrontal cortex (DLPFC) over 10 consecutive working days. The CRS-R score and P300 amplitude and latency in a hierarchical cognitive assessment were recorded to evaluate the consciousness level before tDCS and immediately after the 20 sessions.

          Results

          The intra-group CRS-R analysis revealed a clinically significant improvement in the MCS patients in the real stimulation group. The inter-group CRS-R analysis showed a significant difference in CRS-R between VS and MCS patients at baseline in both the real and sham stimulation groups. The intra-group ERP analysis revealed a significant increase in P300 amplitude after tDCS in the MCS patients in the real stimulation group, but no significant differences in P300 latency. For the inter-group ERP analysis, we observed significant differences regarding the presence of P300 at baseline between the VS and MCS patients in both groups.

          Conclusion

          The repeated anodal tDCS of the left DLPFC could produce clinically significant improvements in MCS patients. The observed tDCS-related consciousness improvements might be related to improvements in attention resource allocation (reflected by the P300 amplitude). The findings support the use of tDCS in clinical practice and ERP might serve as an efficient electrophysiological assessment tool in patients with DOCs.

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          Most cited references35

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          Medical aspects of the persistent vegetative state (1). The Multi-Society Task Force on PVS.

          This consensus statement of the Multi-Society Task Force summarizes current knowledge of the medical aspects of the persistent vegetative state in adults and children. The vegetative state is a clinical condition of complete unawareness of the self and the environment, accompanied by sleep-wake cycles, with either complete or partial preservation of hypothalamic and brain-stem autonomic functions. In addition, patients in a vegetative state show no evidence of sustained, reproducible, purposeful, or voluntary behavioral responses to visual, auditory, tactile, or noxious stimuli; show no evidence of language comprehension or expression; have bowel and bladder incontinence; and have variably preserved cranial-nerve and spinal reflexes. We define persistent vegetative state as a vegetative state present one month after acute traumatic or nontraumatic brain injury or lasting for at least one month in patients with degenerative or metabolic disorders or developmental malformations. The clinical course and outcome of a persistent vegetative state depend on its cause. Three categories of disorder can cause such a state: acute traumatic and non-traumatic brain injuries; degenerative and metabolic brain disorders, and severe congenital malformations of the nervous system. Recovery of consciousness from a posttraumatic persistent vegetative state is unlikely after 12 months in adults and children. Recovery from a nontraumatic persistent vegetative state after three months is exceedingly rare in both adults and children. Patients with degenerative or metabolic disorders or congenital malformations who remain in a persistent vegetative state for several months are unlikely to recover consciousness. The life span of adults and children in such a state is substantially reduced. For most such patients, life expectancy ranges from 2 to 5 years; survival beyond 10 years is unusual.
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            tDCS-enhanced motor and cognitive function in neurological diseases.

            Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation tool that is now being widely used in neuroscientific and clinical research in humans. While initial studies focused on modulation of cortical excitability, the technique quickly progressed to studies on motor and cognitive functions in healthy humans and in patients with neurological diseases. In the present review we will first provide the reader with a brief background on the basic principles of tDCS. In the main part, we will outline recent studies with tDCS that aimed at enhancing behavioral outcome or disease-specific symptoms in patients suffering from mild cognitive impairment, Alzheimer's disease, movement disorders, and epilepsy, or persistent deficits after stroke. The review will close with a summary statement on the present use of tDCS in the treatment of neurological disorders, and an outlook to further developments in this realm. tDCS may be an ideal tool to be administered in parallel to intensive cognitive or motor training in neurological disease, but efficacy for the areas of activities and participation still needs to be established in controlled randomized trials. Its use in reducing disease-specific symptoms like dystonia or epileptic seizures is still unclear. Copyright © 2013 Elsevier Inc. All rights reserved.
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              Is There “One” DLPFC in Cognitive Action Control? Evidence for Heterogeneity From Co-Activation-Based Parcellation

              The dorsolateral prefrontal cortex (DLPFC) has consistently been implicated in cognitive control of motor behavior. There is, however, considerable variability in the exact location and extension of these activations across functional magnetic resonance imaging (fMRI) experiments. This poses the question of whether this variability reflects sampling error and spatial uncertainty in fMRI experiments or structural and functional heterogeneity of this region. This study shows that the right DLPFC as observed in 4 different experiments tapping executive action control may be subdivided into 2 distinct subregions-an anterior-ventral and a posterior-dorsal one -based on their whole-brain co-activation patterns across neuroimaging studies. Investigation of task-dependent and task-independent connectivity revealed both clusters to be involved in distinct neural networks. The posterior subregion showed increased connectivity with bilateral intraparietal sulci, whereas the anterior subregion showed increased connectivity with the anterior cingulate cortex. Functional characterization with quantitative forward and reverse inferences revealed the anterior network to be more strongly associated with attention and action inhibition processes, whereas the posterior network was more strongly related to action execution and working memory. The present data provide evidence that cognitive action control in the right DLPFC may rely on differentiable neural networks and cognitive functions.
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                Author and article information

                Contributors
                Journal
                Front Neurol
                Front Neurol
                Front. Neurol.
                Frontiers in Neurology
                Frontiers Media S.A.
                1664-2295
                21 November 2017
                2017
                : 8
                : 620
                Affiliations
                [1] 1Department of Rehabilitation Medicine, Xuan Wu Hospital, Capital Medical University , Beijing, China
                Author notes

                Edited by: Bryan G. Young, London Health Sciences Centre, Canada

                Reviewed by: Aldo Ragazzoni, Fondazione PAS, Italy; Davinia Fernández-Espejo, University of Birmingham, United Kingdom; Teneille Emma Gofton, University of Western Ontario, Canada

                *Correspondence: Weiqun Song, songwq66@ 123456126.com

                Specialty section: This article was submitted to Neurocritical and Neurohospitalist Care, a section of the journal Frontiers in Neurology

                Article
                10.3389/fneur.2017.00620
                5702306
                29209270
                d84e2576-6ec3-4fb2-8888-8ed7d32c0589
                Copyright © 2017 Zhang, Song, Du, Huo, Shan and Li.

                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
                : 21 August 2017
                : 06 November 2017
                Page count
                Figures: 3, Tables: 5, Equations: 0, References: 43, Pages: 10, Words: 7656
                Funding
                Funded by: National Natural Science Foundation of China 10.13039/501100001809
                Award ID: 81371194
                Categories
                Neuroscience
                Original Research

                Neurology
                transcranial direct current stimulation,coma recovery scale-revised,event-related potentials,p300,disorders of consciousness

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