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      Multimodal Evaluation of TMS - Induced Somatosensory Plasticity and Behavioral Recovery in Rats With Contusion Spinal Cord Injury

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          Abstract

          Introduction: Spinal cord injury (SCI) causes partial or complete damage to sensory and motor pathways and induces immediate changes in cortical function. Current rehabilitative strategies do not address this early alteration, therefore impacting the degree of neuroplasticity and subsequent recovery. The following study aims to test if a non-invasive brain stimulation technique such as repetitive transcranial magnetic stimulation (rTMS) is effective in promoting plasticity and rehabilitation, and can be used as an early intervention strategy in a rat model of SCI.

          Methods: A contusion SCI was induced at segment T9 in adult rats. An rTMS coil was positioned over the brain to deliver high frequency stimulation. Behavior, motor and sensory functions were tested in three groups: SCI rats that received high-frequency (20 Hz) rTMS within 10 min post-injury (acute-TMS; n = 7); SCI rats that received TMS starting 2 weeks post-injury (chronic-TMS; n = 5), and SCI rats that received sham TMS (no-TMS, n = 5). Locomotion was evaluated by the Basso, Beattie, and Bresnahan (BBB) and gridwalk tests. Motor evoked potentials (MEP) were recorded from the forepaw across all groups to measure integrity of motor pathways. Functional MRI (fMRI) responses to contralateral tactile hindlimb stimulation were measured in an 11.7T horizontal bore small-animal scanner.

          Results: The acute-TMS group demonstrated the fastest improvements in locomotor performance in both the BBB and gridwalk tests compared to chronic and no-TMS groups. MEP responses from forepaw showed significantly greater difference in the inter-peak latency between acute-TMS and no-TMS groups, suggesting increases in motor function. Finally, the acute-TMS group showed increased fMRI-evoked responses to hindlimb stimulation over the right and left hindlimb (LHL) primary somatosensory representations (S1), respectively; the chronic-TMS group showed moderate sensory responses in comparison, and the no-TMS group exhibited the lowest sensory responses to both hindlimbs.

          Conclusion: The results suggest that rTMS therapy beginning in the acute phase after SCI promotes neuroplasticity and is an effective rehabilitative approach in a rat model of SCI.

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          Efficacy and safety of transcranial magnetic stimulation in the acute treatment of major depression: a multisite randomized controlled trial.

          We tested whether transcranial magnetic stimulation (TMS) over the left dorsolateral prefrontal cortex (DLPFC) is effective and safe in the acute treatment of major depression. In a double-blind, multisite study, 301 medication-free patients with major depression who had not benefited from prior treatment were randomized to active (n = 155) or sham TMS (n = 146) conditions. Sessions were conducted five times per week with TMS at 10 pulses/sec, 120% of motor threshold, 3000 pulses/session, for 4-6 weeks. Primary outcome was the symptom score change as assessed at week 4 with the Montgomery-Asberg Depression Rating Scale (MADRS). Secondary outcomes included changes on the 17- and 24-item Hamilton Depression Rating Scale (HAMD) and response and remission rates with the MADRS and HAMD. Active TMS was significantly superior to sham TMS on the MADRS at week 4 (with a post hoc correction for inequality in symptom severity between groups at baseline), as well as on the HAMD17 and HAMD24 scales at weeks 4 and 6. Response rates were significantly higher with active TMS on all three scales at weeks 4 and 6. Remission rates were approximately twofold higher with active TMS at week 6 and significant on the MADRS and HAMD24 scales (but not the HAMD17 scale). Active TMS was well tolerated with a low dropout rate for adverse events (4.5%) that were generally mild and limited to transient scalp discomfort or pain. Transcranial magnetic stimulation was effective in treating major depression with minimal side effects reported. It offers clinicians a novel alternative for the treatment of this disorder.
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            Global prevalence and incidence of traumatic spinal cord injury

            Background Spinal cord injury (SCI) is a traumatic event that impacts a patient’s physical, psychological, and social well-being and places substantial financial burden on health care systems. To determine the true impact of SCI, this systematic review aims to summarize literature reporting on either the incidence or prevalence of SCI. Methods A systematic search was conducted using PubMed, MEDLINE, MEDLINE in process, EMBASE, Cochrane Controlled Trial Register, and Cochrane Database of Systematic Reviews to identify relevant literature published through June 2013. We sought studies that provided regional, provincial/state, or national data on the incidence of SCI or reported estimates of disease prevalence. The level of evidence of each study was rated using a scale that evaluated study design, methodology, sampling bias, and precision of estimates. Results The initial search yielded 5,874 articles, 48 of which met the inclusion criteria. Forty-four studies estimated the incidence of SCI and nine reported the prevalence, with five discussing both. Of the incidence studies, 14 provided figures at a regional, ten at a state or provincial level and 21 at a national level. The prevalence of SCI was highest in the United States of America (906 per million) and lowest in the Rhone-Alpes region, France (250 per million) and Helsinki, Finland (280 per million). With respect to states and provinces in North America, the crude annual incidence of SCI was highest in Alaska (83 per million) and Mississippi (77 per million) and lowest in Alabama (29.4 per million), despite a large percentage of violence injuries (21.2%). Annual incidences were above 50 per million in the Hualien County in Taiwan (56.1 per million), the central Portugal region (58 per million), and Olmsted County in Minnesota (54.8 per million) and were lower than 20 per million in Taipei, Taiwan (14.6 per million), the Rhone-Alpes region in France (12.7 per million), Aragon, Spain (12.1 per million), Southeast Turkey (16.9 per million), and Stockholm, Sweden (19.5 per million). The highest national incidence was 49.1 per million in New Zealand, and the lowest incidences were in Fiji (10.0 per million) and Spain (8.0 per million). The majority of studies showed a high male-to-female ratio and an age of peak incidence of younger than 30 years old. Traffic accidents were typically the most common cause of SCI, followed by falls in the elderly population. Conclusion This review demonstrates that the incidence, prevalence, and causation of SCI differs between developing and developed countries and suggests that management and preventative strategies need to be tailored to regional trends. The rising aging population in westernized countries also indicates that traumatic SCI secondary to falls may become an increasing public health challenge and that incidence among the elderly may rise with increasing life expectancy.
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              Experimental modeling of spinal cord injury: characterization of a force-defined injury device.

              We examined the ability of a novel spinal cord injury (SCI) device to produce graded morphological and behavioral changes in the adult rat following an injury at thoracic level 10 (T10). The injury device uses force applied to the tissue as the control variable rather than tissue displacement. This has the advantage of eliminating errors that may arise from tissue movement prior to injury. Three different injury severities, defined by the amount of force applied to the exposed spinal cord at T10 (100, 150, and 200 kdyn), were evaluated at two different survival times (7 and 42 d). Unbiased stereology was employed to evaluate morphological differences following the injury. Quantitative behavioral assessment employed the Basso, Beattie, and Bresnahan locomotive rating scale. There was a significant force-related decline in locomotive ability following the injury. Animals subjected to a 200-kdyn injury performed significantly worse than animals subjected to a 100- and 150-kdyn injury. The locomotor ability at different days post injury significantly correlated with the amount of force applied to the spinal cord. Statistical analysis revealed several significant force-related morphological differences following the injury. The greatest loss of white and gray matter occurred at the site of injury impact and extended in both a rostral and caudal direction. Animals subjected to the greatest force (200 kdyn) displayed the least amount of spared tissue at both survival times indicative of the most severe injury. The amount of spared tissue significantly correlated with the locomotor ability. This novel rodent model of SCI provides a significant improvement over existing devices for SCI by reducing variability with a constant preset force to define the injury.
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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
                24 April 2019
                2019
                : 13
                : 387
                Affiliations
                [1] 1Department of Biomedical Engineering, Michigan State University , East Lansing, MI, United States
                [2] 2The Institute for Quantitative Health Science and Engineering, Michigan State University , East Lansing, MI, United States
                [3] 3F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute , Baltimore, MD, United States
                [4] 4Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine , Baltimore, MD, United States
                [5] 5Department of Neurology and Pathology, Johns Hopkins University School of Medicine , Baltimore, MD, United States
                [6] 6International Center for Spinal Cord Injury, Kennedy Krieger Institute , Baltimore, MD, United States
                [7] 7Department of Physical Medicine and Rehabilitation, Johns Hopkins University School of Medicine , Baltimore, MD, United States
                [8] 8Department of Radiology, Michigan State University , East Lansing, MI, United States
                Author notes

                Edited by: Laura Ballerini, Scuola Internazionale Superiore di Studi Avanzati (SISSA), Italy

                Reviewed by: Andrea Nistri, Scuola Internazionale Superiore di Studi Avanzati (SISSA), Italy; Maria Concepcion Serrano, Spanish National Research Council (CSIC), Spain

                *Correspondence: Galit Pelled, pelledga@ 123456msu.edu

                This article was submitted to Neural Technology, a section of the journal Frontiers in Neuroscience

                Article
                10.3389/fnins.2019.00387
                6491761
                31068784
                7f36ff47-3f52-417d-b301-01dbefc6b349
                Copyright © 2019 Krishnan, Shin, Belegu, Celnik, Reimers, Smith and Pelled.

                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) and the copyright owner(s) 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
                : 15 January 2019
                : 04 April 2019
                Page count
                Figures: 4, Tables: 0, Equations: 0, References: 59, Pages: 9, Words: 0
                Funding
                Funded by: National Institutes of Health 10.13039/100000002
                Award ID: R01NS072171
                Award ID: R01NS079288
                Categories
                Neuroscience
                Original Research

                Neurosciences
                transcranial magnetic stimulation,spinal cord injury,plasticity,behavior,functional magnetic resonance imaging

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