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      Effect of transcranial pulsed electromagnetic fields (T-PEMF) on functional rate of force development and movement speed in persons with Parkinson’s disease: A randomized clinical trial

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          Abstract

          Background

          Parkinson’s disease is caused by dopaminergic neurodegeneration resulting in motor impairments as slow movement speed and impaired balance and coordination. Pulsed electromagnetic fields are suggested to have neuroprotective effects, and could alleviate symptoms.

          Objective

          To study 1) effects of 8-week daily transcranial pulsed electromagnetic field treatment on functional rate of force development and movement speed during two motor tasks with different levels of complexity, 2) if treatment effects depend on motor performance at baseline.

          Methods

          Ninety-seven persons with Parkinson’s disease were randomized to active transcranial pulsed electromagnetic field (squared bipolar 3 ms pulses, 50 Hz) or placebo treatment with homebased treatment 30 min/day for 8 weeks. Functional rate of force development and completion time of a sit-to-stand and a dynamic postural balance task were assessed pre and post intervention. Participants were sub-grouped in high- and low-performers according to their baseline motor performance level. Repeated measure ANOVAs were used.

          Results

          Active treatment tended to improve rate of force development during chair rise more than placebo (P = 0.064). High-performers receiving active treatment improved rate of force development during chair rise more than high-performers receiving placebo treatment (P = 0.049, active/placebo: 11.9±1.1 to 12.5±1.9 BW/s ≈ 5% / 12.4±1.3 to 12.2±1.3 BW/s, no change). No other between-treatment-group or between-treatment-subgroup differences were found. Data on rate of force development of the dynamic balance task and completion times of both motor tasks improved but did not allow for between-treatment differentiation.

          Conclusion

          Treatment with transcranial pulsed electromagnetic fields was superior to placebo regarding functional rate of force development during chair rise among high-performers. Active treatment tended to increase functional rate of force development while placebo did not. Our results suggest that mildly affected persons with Parkinson’s disease have a larger potential for neural rehabilitation than more severely affected persons and indicate that early treatment initiation may be beneficial.

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          Most cited references35

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          A comprehensive review of the effects of rTMS on motor cortical excitability and inhibition.

          Repetitive transcranial magnetic stimulation (rTMS) procedures are being widely applied in therapeutic and investigative studies. Numerous studies have investigated the effects of rTMS on cortical excitability and inhibition, yielding somewhat contradictory results. The purpose of this study was to comprehensively review this literature to guide the selection of methodology in therapeutic studies. We conducted a comprehensive review of all identified studies that investigated effects of low and/or high frequency rTMS on motor cortical excitability or inhibition. Low frequency rTMS appears to produce a transient reduction in cortical excitability as assessed by motor evoked potential (MEP) size and produces no substantial effect on cortical inhibition. High frequency rTMS appears to produce a persistent increase in MEP size and a reduction in cortical inhibition measured with paired pulse methods although few studies have investigated frequencies greater than 5Hz. A number of novel stimulation paradigms have significant potential for altering cortical excitability but require further investigation. Although commonly applied forms of rTMS have effects on cortical excitability, more substantial effects may be obtained through the use of novel stimulation paradigms or innovative approaches to the stimulation of areas connected to a potential target site. Further research is required, however, before these paradigms can be more widely adopted.
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            Human capacity for explosive force production: neural and contractile determinants.

            This study assessed the integrative neural and contractile determinants of human knee extension explosive force production. Forty untrained participants performed voluntary and involuntary (supramaximally evoked twitches and octets - eight pulses at 300 Hz that elicit the maximum possible rate of force development) explosive isometric contractions of the knee extensors. Explosive force (F0-150 ms) and sequential rate of force development (RFD, 50-ms epochs) were measured. Surface electromyography (EMG) amplitude was recorded (superficial quadriceps and hamstrings, 50-ms epochs) and normalized (quadriceps to Mmax, hamstrings to EMGmax). Maximum voluntary force (MVF) was also assessed. Multiple linear regressions assessed the significant neural and contractile determinants of absolute and relative (%MVF) explosive force and sequential RFD. Explosive force production exhibited substantial interindividual variability, particularly during the early phase of contraction [F50, 13-fold (absolute); 7.5-fold (relative)]. Multiple regression explained 59-93% (absolute) and 35-60% (relative) of the variance in explosive force production. The primary determinants of explosive force changed during the contraction (F0-50, quadriceps EMG and Twitch F; RFD50-100, Octet RFD0-50; F100-150, MVF). In conclusion, explosive force production was largely explained by predictor neural and contractile variables, but the specific determinants changed during the phase of contraction.
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              Exposure to extremely low-frequency (50 Hz) electromagnetic fields enhances adult hippocampal neurogenesis in C57BL/6 mice.

              Throughout life, new neurons are continuously generated in the hippocampus, which is therefore a major site of structural plasticity in the adult brain. We recently demonstrated that extremely low-frequency electromagnetic fields (ELFEFs) promote the neuronal differentiation of neural stem cells in vitro by up-regulating Ca(v)1-channel activity. The aim of the present study was to determine whether 50-Hz/1 mT ELFEF stimulation also affects adult hippocampal neurogenesis in vivo, and if so, to identify the molecular mechanisms underlying this action and its functional impact on synaptic plasticity. ELFEF exposure (1 to 7 h/day for 7 days) significantly enhanced neurogenesis in the dentate gyrus (DG) of adult mice, as documented by increased numbers of cells double-labeled for 5-bromo-deoxyuridine (BrdU) and doublecortin. Quantitative RT-PCR analysis of hippocampal extracts revealed significant ELFEF exposure-induced increases in the transcription of pro-neuronal genes (Mash1, NeuroD2, Hes1) and genes encoding Ca(v)1.2 channel α(1C) subunits. Increased expression of NeuroD1, NeuroD2 and Ca(v)1 channels was also documented by Western blot analysis. Immunofluorescence experiments showed that, 30 days after ELFEF stimulation, roughly half of the newly generated immature neurons had survived and become mature dentate granule cells (as shown by their immunoreactivity for both BrdU and NeuN) and were integrated into the granule cell layer of the DG. Electrophysiological experiments demonstrated that the new mature neurons influenced hippocampal synaptic plasticity, as reflected by increased long-term potentiation. Our findings show that ELFEF exposure can be an effective tool for increasing in vivo neurogenesis, and they could lead to the development of novel therapeutic approaches in regenerative medicine. Copyright © 2010 Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: SoftwareRole: VisualizationRole: Writing – original draft
                Role: ConceptualizationRole: Data curationRole: Funding acquisitionRole: InvestigationRole: Project administrationRole: ResourcesRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: Project administrationRole: ResourcesRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: ResourcesRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: Funding acquisitionRole: MethodologyRole: SupervisionRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                25 September 2018
                2018
                : 13
                : 9
                : e0204478
                Affiliations
                [1 ] Department of Neurology, Odense University Hospital, University of Southern Denmark, Odense, Denmark
                [2 ] Department of Clinical Research, University of Southern Denmark, Odense, Denmark
                [3 ] The Danish Rehabilitation Centre for Neuromuscular Diseases, Taastrup, Denmark
                [4 ] Psychiatric Research Unit, Psychiatric Centre North Zealand, University of Copenhagen, Hillerød, Denmark
                University of Toronto, CANADA
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0002-9267-9334
                Article
                PONE-D-18-02765
                10.1371/journal.pone.0204478
                6155540
                30252895
                00e22503-0a6f-4a88-b1a6-cdfb30b06d59
                © 2018 Malling et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 30 January 2018
                : 6 September 2018
                Page count
                Figures: 4, Tables: 1, Pages: 16
                Funding
                Funded by: Den A. P. Møllerske Støttefond
                Award ID: 10415
                Award Recipient : Lene Wermut
                Funded by: Grosserer L F Foghts Fond
                Award ID: 20825
                Award Recipient :
                This work was supported by Den A. P. Møllerske Støttefond, Copenhagen, Denmark (grant# 10415, https://www.apmollerfonde.dk/ansoegning/stoettefonden, received by Lene Wermuth) and Grosserer L. F. Foghts Fond, Charlottenlund, Denmark (grant# 20825, http://foghtsfond.dk, received by Ole Gredal). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Medicine and Health Sciences
                Neurology
                Neurodegenerative Diseases
                Movement Disorders
                Parkinson Disease
                Physical Sciences
                Physics
                Electromagnetism
                Electromagnetic Fields
                Biology and Life Sciences
                Anatomy
                Musculoskeletal System
                Medicine and Health Sciences
                Anatomy
                Musculoskeletal System
                Biology and Life Sciences
                Neuroscience
                Cognitive Science
                Cognitive Neuroscience
                Motor Reactions
                Postural Control
                Biology and Life Sciences
                Neuroscience
                Cognitive Neuroscience
                Motor Reactions
                Postural Control
                Medicine and Health Sciences
                Surgical and Invasive Medical Procedures
                Functional Electrical Stimulation
                Physical Sciences
                Physics
                Classical Mechanics
                Motion
                Torque
                Biology and Life Sciences
                Biochemistry
                Neurochemistry
                Neurochemicals
                Dopaminergics
                Biology and Life Sciences
                Neuroscience
                Neurochemistry
                Neurochemicals
                Dopaminergics
                Biology and Life Sciences
                Neuroscience
                Neurotransmission
                Custom metadata
                All relevant data are within the paper and its Supporting Information files.

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