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      Neurophysiological Correlates of Gait in the Human Basal Ganglia and the PPN Region in Parkinson’s Disease


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          This study aimed to characterize the neurophysiological correlates of gait in the human pedunculopontine nucleus (PPN) region and the globus pallidus internus (GPi) in Parkinson’s disease (PD) cohort. Though much is known about the PPN region through animal studies, there are limited physiological recordings from ambulatory humans. The PPN has recently garnered interest as a potential deep brain stimulation (DBS) target for improving gait and freezing of gait (FoG) in PD. We used bidirectional neurostimulators to record from the human PPN region and GPi in a small cohort of severely affected PD subjects with FoG despite optimized dopaminergic medications. Five subjects, with confirmed on-dopaminergic medication FoG, were implanted with bilateral GPi and bilateral PPN region DBS electrodes. Electrophysiological recordings were obtained during various gait tasks for 5 months postoperatively in both the off- and on-medication conditions (obtained during the no stimulation condition). The results revealed suppression of low beta power in the GPi and a 1–8 Hz modulation in the PPN region which correlated with human gait. The PPN feature correlated with walking speed. GPi beta desynchronization and PPN low-frequency synchronization were observed as subjects progressed from rest to ambulatory tasks. Our findings add to our understanding of the neurophysiology underpinning gait and will likely contribute to the development of novel therapies for abnormal gait in PD.

          Clinical Trial Registration: Clinicaltrials.gov identifier; NCT02318927.

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          BCI2000: a general-purpose brain-computer interface (BCI) system.

          Many laboratories have begun to develop brain-computer interface (BCI) systems that provide communication and control capabilities to people with severe motor disabilities. Further progress and realization of practical applications depends on systematic evaluations and comparisons of different brain signals, recording methods, processing algorithms, output formats, and operating protocols. However, the typical BCI system is designed specifically for one particular BCI method and is, therefore, not suited to the systematic studies that are essential for continued progress. In response to this problem, we have developed a documented general-purpose BCI research and development platform called BCI2000. BCI2000 can incorporate alone or in combination any brain signals, signal processing methods, output devices, and operating protocols. This report is intended to describe to investigators, biomedical engineers, and computer scientists the concepts that the BC12000 system is based upon and gives examples of successful BCI implementations using this system. To date, we have used BCI2000 to create BCI systems for a variety of brain signals, processing methods, and applications. The data show that these systems function well in online operation and that BCI2000 satisfies the stringent real-time requirements of BCI systems. By substantially reducing labor and cost, BCI2000 facilitates the implementation of different BCI systems and other psychophysiological experiments. It is available with full documentation and free of charge for research or educational purposes and is currently being used in a variety of studies by many research groups.
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            Bilateral deep brain stimulation of the pedunculopontine and subthalamic nuclei in severe Parkinson's disease.

            Gait disturbances and akinesia are extremely disabling in advanced Parkinson's disease. It has been suggested that modulation of the activity of the pedunculopontine nucleus (PPN) may be beneficial in the treatment of these symptoms. We report the clinical affects of deep brain stimulation (DBS) in the PPN and subthalamic nucleus (STN). Six patients with unsatisfactory pharmacological control of axial signs such as gait and postural stability underwent bilateral implantation of DBS electrodes in the STN and PPN. Clinical effects were evaluated 2-6 months after surgery in the OFF- and ON-medication state, with both STN and PPN stimulation ON or OFF, or with only one target being stimulated. Bilateral PPN-DBS at 25 Hz in OFF-medication produced an immediate 45% amelioration of the motor Unified Parkinson's Disease Rating Scale (UPDRS) subscale score, followed by a decline to give a final improvement of 32% in the score after 3-6 months. In contrast, bilateral STN-DBS at 130-185 Hz led to about 54% improvement. PPN-DBS was particularly effective on gait and postural items. In ON-medication state, the association of STN and PPN-DBS provided a significant further improvement when compared to the specific benefit mediated by the activation of either single target. Moreover, the combined DBS of both targets promoted a substantial amelioration in the performance of daily living activities. These findings indicate that, in patients with advanced Parkinson's disease, PPN-DBS associated with standard STN-DBS may be useful in improving gait and in optimizing the dopamine-mediated ON-state, particularly in those whose response to STN only DBS has deteriorated over time. This combination of targets may also prove useful in extra-pyramidal disorders, such as progressive supranuclear palsy, for which treatments are currently elusive.
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              PDQ-39: a review of the development, validation and application of a Parkinson's disease quality of life questionnaire and its associated measures.

              Parkinson's disease is a common degenerative neurological condition. A number of general instruments exist to measure quality of life, but these were not designed to address areas salient to a specific disease. This contribution reviews the development and validation of the PDQ-39, a short 39-item quality of life questionnaire for Parkinson's disease. PDQ-39 data can be presented either in profile form or as a single index. This report also reviews the development and validation of a briefer measure (PDQ-8) derived from the PDQ-39, and of two summary indices (PDQ-39SI and PDQ-8SI.

                Author and article information

                Front Hum Neurosci
                Front Hum Neurosci
                Front. Hum. Neurosci.
                Frontiers in Human Neuroscience
                Frontiers Media S.A.
                04 June 2020
                : 14
                [1] 1Department of Electrical and Computer Engineering, University of Florida , Gainesville, FL, United States
                [2] 2Norman Fixel Institute for Neurological Diseases and the Program for Movement Disorders and Neurorestoration, University of Florida , Gainesville, FL, United States
                [3] 3Department of Applied Physiology and Kinesiology, University of Florida , Gainesville, FL, United States
                [4] 4J. Crayton Pruitt Department of Biomedical Engineering, University of Florida , Gainesville, FL, United States
                [5] 5School of Kinesiology, Auburn University , Auburn, AL, United States
                [6] 6Tecnológico de Monterrey, Escuela de Medicina y Ciencias de la Salud , Monterrey, Mexico
                [7] 7Department of Neurology , University of Florida, Gainesville, FL, United States
                [8] 8Department of Neurosurgery , University of Florida, Gainesville, FL, United States
                Author notes

                Edited by: Vladimir Litvak, University College London, United Kingdom

                Reviewed by: Chiung-Chu Chen, Linkou Chang Gung Memorial Hospital, Taiwan; Petra Fischer, University of Oxford, United Kingdom

                *Correspondence: Aysegul Gunduz agunduz@ 123456ufl.edu

                These authors share first authorship

                These authors share senior authorship

                Specialty section: This article was submitted to Brain Imaging and Stimulation, a section of the journal Frontiers in Human Neuroscience

                Copyright © 2020 Molina, Hass, Sowalsky, Schmitt, Opri, Roper, Martinez-Ramirez, Hess, Foote, Okun and Gunduz.

                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.

                Page count
                Figures: 4, Tables: 1, Equations: 0, References: 55, Pages: 10, Words: 7342
                Funded by: Michael J. Fox Foundation for Parkinson’s Research 10.13039/100000864
                Funded by: National Institutes of Health 10.13039/100000002
                Human Neuroscience
                Brief Research Report

                parkinson’s disease (pd),brainstem,deep brain stimulation (dbs),gait,dbs,deep brain stimulation


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