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      Does suppression of oscillatory synchronisation mediate some of the therapeutic effects of DBS in patients with Parkinson's disease?

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          Abstract

          There is growing evidence for exaggerated oscillatory neuronal synchronisation in patients with Parkinson's disease (PD). In particular, oscillations at around 20 Hz, in the so-called beta frequency band, relate to the cardinal symptoms of bradykinesia and rigidity. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) can significantly improve these motor impairments. Recent evidence has demonstrated reduction of beta oscillations concurrent with alleviation of PD motor symptoms, raising the possibility that suppression of aberrant activity may mediate the effects of DBS. Here we review the evidence supporting suppression of pathological oscillations during stimulation and discuss how this might underlie the efficacy of DBS. We also consider how beta activity may provide a feedback signal suitable for next generation closed-loop and intelligent stimulators.

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          Most cited references79

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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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            Long-term suppression of tremor by chronic stimulation of the ventral intermediate thalamic nucleus.

            The usefulness of high-frequency stimulation of the ventral intermediate nucleus (Vim) as the first neurosurgical procedure in disabling tremor was assessed in 26 patients with Parkinson's disease and 6 with essential tremor. 7 of these patients had already undergone thalamotomy contralateral to the stimulated side, and 11 others had bilateral Vim stimulation at the same time. Chronic stimulating electrodes connected to a pulse generator were implanted in the Vim. Tremor amplitude at rest, during posture holding, and during action and intention manoeuvres was assessed by means of accelerometry. Of the 43 thalami stimulated, 27 showed complete relief from tremor and 11 major improvement (88%). The improvement was maintained for up to 29 months (mean follow-up 13 [SD 9] months). Adverse effects were mild and could be eradicated by reduction or cessation of stimulation. This reversibility and adaptability, allowing control of side-effects, make thalamic stimulation preferable to thalamotomy, especially when treatment of both sides of the brain is needed.
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              Dopaminergic modulation of neuronal excitability in the striatum and nucleus accumbens.

              The striatum and its ventral extension, the nucleus accumbens, are involved in behaviors as diverse as motor planning, drug seeking, and learning. Invariably, these striatally mediated behaviors depend on intact dopaminergic innervation. However, the mechanisms by which dopamine modulates neuronal function in the striatum and nucleus accumbens have been difficult to elucidate. Recent electrophysiological studies have revealed that dopamine alters both voltage-dependent conductances and synaptic transmission, resulting in state-dependent modulation of target cells. These studies make clear predictions about how dopamine, particularly via D1 receptor activation, should alter the responsiveness of striatal neurons to extrinsic excitatory synaptic activity.
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                Author and article information

                Journal
                Front Integr Neurosci
                Front Integr Neurosci
                Front. Integr. Neurosci.
                Frontiers in Integrative Neuroscience
                Frontiers Media S.A.
                1662-5145
                16 April 2012
                10 July 2012
                2012
                : 6
                : 47
                Affiliations
                [1] 1Department of Neurology and Movement Disorders, Assistance Publique - Hôpitaux de Marseille, Timone University Hospital Marseille, France
                [2] 2Institut de Neurosciences de la Timone – UMR 7289, Aix Marseille Université – CNRS Marseille, France
                [3] 3Department of Clinical Neurology, John Radcliffe Hospital Oxford, UK
                Author notes

                Edited by: Sridevi V. Sarma, Johns Hopkins University, USA

                Reviewed by: Antonio Pereira, Federal University of Rio Grande do Norte, Brazil; Pierfilippo De Sanctis, Albert Einstein College of Medicine, USA

                *Correspondence: Alexandre Eusebio, Department of Neurology and Movement Disorders, Timone University Hospital, 264 rue Saint-Pierre, 13385 Marseille Cedex 05, France. e-mail: alexandre.eusebio@ 123456ap-hm.fr
                Article
                10.3389/fnint.2012.00047
                3392592
                22787444
                1c6b6406-664b-4cd1-8a71-3fc19769ddc0
                Copyright © 2012 Eusebio, Cagnan and Brown.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.

                History
                : 21 February 2012
                : 25 June 2012
                Page count
                Figures: 1, Tables: 0, Equations: 0, References: 118, Pages: 9, Words: 8886
                Categories
                Neuroscience
                Review Article

                Neurosciences
                oscillations,parkinson's disease,basal ganglia,deep brain stimulation,neurophysiology

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