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      An update on adaptive deep brain stimulation in Parkinson's disease

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          ABSTRACT

          Advancing conventional open‐loop DBS as a therapy for PD is crucial for overcoming important issues such as the delicate balance between beneficial and adverse effects and limited battery longevity that are currently associated with treatment. Closed‐loop or adaptive DBS aims to overcome these limitations by real‐time adjustment of stimulation parameters based on continuous feedback input signals that are representative of the patient's clinical state. The focus of this update is to discuss the most recent developments regarding potential input signals and possible stimulation parameter modulation for adaptive DBS in PD. Potential input signals for adaptive DBS include basal ganglia local field potentials, cortical recordings (electrocorticography), wearable sensors, and eHealth and mHealth devices. Furthermore, adaptive DBS can be applied with different approaches of stimulation parameter modulation, the feasibility of which can be adapted depending on specific PD phenotypes. Implementation of technological developments like machine learning show potential in the design of such approaches; however, energy consumption deserves further attention. Furthermore, we discuss future considerations regarding the clinical implementation of adaptive DBS in PD. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

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          Most cited references65

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          Effect of parkinsonian signs and symptoms of bilateral subthalamic nucleus stimulation.

          In monkeys rendered parkinsonian, lesions and electrical stimulation of the subthalamic nucleus reduce all major motor disturbances. The effect of electrical stimulation of the subthalamic nucleus was assessed in three patients with disabling akinetic-rigid Parkinson's disease and severe motor fluctuations. Quadripolar electrodes connected to a pulse generator were implanted in the subthalamic nuclei on both sides. Patients were evaluated with the unified Parkinson's disease rating scale and timed motor tests. 3 months after surgery, activities of daily living scores had improved by 58-88% and motor scores by 42-84%. This improvement was maintained for up to 8 months in the first patient operated upon. One patient was confused for 2 weeks after surgery, and another developed neuropsychological impairment related to a thalamic infarction which improved over 3 months. In one patient, stimulation could induce ballism that was stopped by reduction of stimulation. This is the first demonstration in human beings of the part played by the subthalamic nuclei in the pathophysiology of Parkinson's disease.
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            Adaptive deep brain stimulation for Parkinson’s disease using motor cortex sensing

            Objective Contemporary deep brain stimulation for Parkinson’s disease is delivered continuously, and adjustments based on patient’s changing symptoms must be made manually by a trained clinician. Patients may be subjected to energy intensive settings at times when they are not needed, possibly resulting in stimulation-induced adverse effects, such as dyskinesia. One solution is “adaptive” DBS, in which stimulation is modified in real time based on neural signals that co-vary with the severity of motor signs or of stimulation-induced adverse effects. Here we show the feasibility of adaptive DBS using a fully implanted neural prosthesis. Approach We demonstrate adaptive deep brain stimulation in two patients with Parkinson’s disease using a fully implanted neural prosthesis that is enabled to utilize brain sensing to control stimulation amplitude (Activa PC+S). We used a cortical narrowband gamma (60-90 Hz) oscillation related to dyskinesia to decrease stimulation voltage when gamma oscillatory activity is high (indicating dyskinesia) and increase stimulation voltage when it is low. Main Results We demonstrate the feasibility of “adaptive deep brain stimulation” in two patients with Parkinson’s disease. In short term in-clinic testing, energy savings were substantial (38-45%), and therapeutic efficacy was maintained. Significance This is the first demonstration of adaptive DBS in Parkinson’s disease using a fully implanted device and neural sensing. Our approach is distinct from other strategies utilizing basal ganglia signals for feedback control.
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              Gamma Oscillations in the Hyperkinetic State Detected with Chronic Human Brain Recordings in Parkinson's Disease.

              Hyperkinetic states are common in human movement disorders, but their neural basis remains uncertain. One such condition is dyskinesia, a serious adverse effect of medical and surgical treatment for Parkinson's disease (PD). To study this, we used a novel, totally implanted, bidirectional neural interface to obtain multisite long-term recordings. We focus our analysis on two patients with PD who experienced frequent dyskinesia and studied them both at rest and during voluntary movement. We show that dyskinesia is associated with a narrowband gamma oscillation in motor cortex between 60 and 90 Hz, a similar, though weaker, oscillation in subthalamic nucleus, and strong phase coherence between the two. Dyskinesia-related oscillations are minimally affected by voluntary movement. When dyskinesia persists during therapeutic deep brain stimulation (DBS), the peak frequency of this signal shifts to half the stimulation frequency. These findings suggest a circuit-level mechanism for the generation of dyskinesia as well as a promising control signal for closed-loop DBS.
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                Author and article information

                Contributors
                p.kubben@mumc.nl
                Journal
                Mov Disord
                Mov. Disord
                10.1002/(ISSN)1531-8257
                MDS
                Movement Disorders
                John Wiley and Sons Inc. (Hoboken )
                0885-3185
                1531-8257
                24 October 2018
                December 2018
                : 33
                : 12 ( doiID: 10.1002/mds.v33.12 )
                : 1834-1843
                Affiliations
                [ 1 ] Departments of Neurosurgery Maastricht University Medical Center Maastricht The Netherlands
                [ 2 ] Department of Neurology Maastricht University Medical Center Maastricht The Netherlands
                [ 3 ] Department of Clinical Neurophysiology Maastricht University Medical Center Maastricht The Netherlands
                [ 4 ] School of Mental Health and Neuroscience Maastricht University Medical Center Maastricht The Netherlands
                Author notes
                [*] [* ] Correspondence to: Dr. Pieter Kubben, Department of Neurosurgery, Maastricht University Medical Center, P. Debyelaan 25, 6229 HX Maastricht, The Netherlands. E‐mail: p.kubben@ 123456mumc.nl
                [†]

                J.H. and M.H. are co‐first authors.

                Article
                MDS115
                10.1002/mds.115
                6587997
                30357911
                f3c0c7ab-ffdd-42f6-82b4-152055d3ff2c
                © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 29 March 2018
                : 26 June 2018
                : 08 July 2018
                Page count
                Figures: 4, Tables: 0, Pages: 10, Words: 8059
                Categories
                Review
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                Custom metadata
                2.0
                mds115
                December 2018
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.6.4 mode:remove_FC converted:21.06.2019

                Medicine
                adaptive,closed‐loop,deep brain stimulation,parkinson's disease,stimulation paradigms
                Medicine
                adaptive, closed‐loop, deep brain stimulation, parkinson's disease, stimulation paradigms

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