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Parkinson Disease: HELP
Articles by Peter Brown
Based on 114 articles published since 2010
(Why 114 articles?)
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Between 2010 and 2020, P. Brown wrote the following 114 articles about Parkinson Disease.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4 · 5
1 Editorial Making use of pathological synchrony in Parkinson's disease. 2013

Brown, Peter. · ·Clin Neurophysiol · Pubmed #23177455.

ABSTRACT: -- No abstract --

2 Review Adaptive Deep Brain Stimulation for Movement Disorders: The Long Road to Clinical Therapy. 2017

Meidahl, Anders Christian / Tinkhauser, Gerd / Herz, Damian Marc / Cagnan, Hayriye / Debarros, Jean / Brown, Peter. ·Medical Research Council Brain Network Dynamics Unit at the University of Oxford, Oxford, UK. · Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, Oxford, UK. · Department of Neurology, Bern University Hospital and University of Bern, Bern, Switzerland. · Institute of Neurology, University College London, London, UK. ·Mov Disord · Pubmed #28597557.

ABSTRACT: Continuous high-frequency DBS is an established treatment for essential tremor and Parkinson's disease. Current developments focus on trying to widen the therapeutic window of DBS. Adaptive DBS (aDBS), where stimulation is dynamically controlled by feedback from biomarkers of pathological brain circuit activity, is one such development. Relevant biomarkers may be central, such as local field potential activity, or peripheral, such as inertial tremor data. Moreover, stimulation may be directed by the amplitude or the phase (timing) of the biomarker signal. In this review, we evaluate existing aDBS studies as proof-of-principle, discuss their limitations, most of which stem from their acute nature, and propose what is needed to take aDBS into a chronic setting. © 2017 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

3 Review Pedunculopontine Nucleus Region Deep Brain Stimulation in Parkinson Disease: Surgical Techniques, Side Effects, and Postoperative Imaging. 2016

Hamani, Clement / Lozano, Andres M / Mazzone, Paolo A M / Moro, Elena / Hutchison, William / Silburn, Peter A / Zrinzo, Ludvic / Alam, Mesbah / Goetz, Laurent / Pereira, Erlick / Rughani, Anand / Thevathasan, Wesley / Aziz, Tipu / Bloem, Bastiaan R / Brown, Peter / Chabardes, Stephan / Coyne, Terry / Foote, Kelly / Garcia-Rill, Edgar / Hirsch, Etienne C / Okun, Michael S / Krauss, Joachim K. ·Division of Neurosurgery, Toronto Western Hospital, University of Toronto, Toronto, Ont., Canada. ·Stereotact Funct Neurosurg · Pubmed #27728909.

ABSTRACT: The pedunculopontine nucleus (PPN) region has received considerable attention in clinical studies as a target for deep brain stimulation (DBS) in Parkinson disease. These studies have yielded variable results with an overall impression of improvement in falls and freezing in many but not all patients treated. We evaluated the available data on the surgical anatomy and terminology of the PPN region in a companion paper. Here we focus on issues concerning surgical technique, imaging, and early side effects of surgery. The aim of this paper was to gain more insight into the reasoning for choosing specific techniques and to discuss shortcomings of available studies. Our data demonstrate the wide range in almost all fields which were investigated. There are a number of important challenges to be resolved, such as identification of the optimal target, the choice of the surgical approach to optimize electrode placement, the impact on the outcome of specific surgical techniques, the reliability of intraoperative confirmation of the target, and methodological differences in postoperative validation of the electrode position. There is considerable variability both within and across groups, the overall experience with PPN DBS is still limited, and there is a lack of controlled trials. Despite these challenges, the procedure seems to provide benefit to selected patients and appears to be relatively safe. One important limitation in comparing studies from different centers and analyzing outcomes is the great variability in targeting and surgical techniques, as shown in our paper. The challenges we identified will be of relevance when designing future studies to better address several controversial issues. We hope that the data we accumulated may facilitate the development of surgical protocols for PPN DBS.

4 Review Pedunculopontine Nucleus Region Deep Brain Stimulation in Parkinson Disease: Surgical Anatomy and Terminology. 2016

Hamani, Clement / Aziz, Tipu / Bloem, Bastiaan R / Brown, Peter / Chabardes, Stephan / Coyne, Terry / Foote, Kelly / Garcia-Rill, Edgar / Hirsch, Etienne C / Lozano, Andres M / Mazzone, Paolo A M / Okun, Michael S / Hutchison, William / Silburn, Peter / Zrinzo, Ludvic / Alam, Mesbah / Goetz, Laurent / Pereira, Erlick / Rughani, Anand / Thevathasan, Wesley / Moro, Elena / Krauss, Joachim K. ·Division of Neurosurgery, Toronto Western Hospital, University of Toronto, Toronto, Ont., Canada. ·Stereotact Funct Neurosurg · Pubmed #27723662.

ABSTRACT: Several lines of evidence over the last few years have been important in ascertaining that the pedunculopontine nucleus (PPN) region could be considered as a potential target for deep brain stimulation (DBS) to treat freezing and other problems as part of a spectrum of gait disorders in Parkinson disease and other akinetic movement disorders. Since the introduction of PPN DBS, a variety of clinical studies have been published. Most indicate improvements in freezing and falls in patients who are severely affected by these problems. The results across patients, however, have been variable, perhaps reflecting patient selection, heterogeneity in target selection and differences in surgical methodology and stimulation settings. Here we outline both the accumulated knowledge and the domains of uncertainty in surgical anatomy and terminology. Specific topics were assigned to groups of experts, and this work was accumulated and reviewed by the executive committee of the working group. Areas of disagreement were discussed and modified accordingly until a consensus could be reached. We demonstrate that both the anatomy and the functional role of the PPN region need further study. The borders of the PPN and of adjacent nuclei differ when different brainstem atlases and atlas slices are compared. It is difficult to delineate precisely the PPN pars dissipata from the nucleus cuneiformis, as these structures partially overlap. This lack of clarity contributes to the difficulty in targeting and determining the exact localization of the electrodes implanted in patients with akinetic gait disorders. Future clinical studies need to consider these issues.

5 Review Adaptive deep brain stimulation in Parkinson's disease. 2016

Beudel, M / Brown, P. ·Department of Neurology, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands. · Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, OX3 9DU, UK; The Medical Research Council Brain Network Dynamics Unit at the University of Oxford, OX1 3TH, UK. Electronic address: peter.brown@ndcn.ox.ac.uk. ·Parkinsonism Relat Disord · Pubmed #26411502.

ABSTRACT: Although Deep Brain Stimulation (DBS) is an established treatment for Parkinson's disease (PD), there are still limitations in terms of effectivity, side-effects and battery consumption. One of the reasons for this may be that not only pathological but also physiological neural activity can be suppressed whilst stimulating. For this reason, adaptive DBS (aDBS), where stimulation is applied according to the level of pathological activity, might be advantageous. Initial studies of aDBS demonstrate effectiveness in PD, but there are still many questions to be answered before aDBS can be applied clinically. Here we discuss the feedback signals and stimulation algorithms involved in adaptive stimulation in PD and sketch a potential road-map towards clinical application.

6 Review The subthalamic nucleus, oscillations, and conflict. 2015

Zavala, Baltazar / Zaghloul, Kareem / Brown, Peter. ·Experimental Neurology Group, Nuffield Department of Clinical Neurology, University of Oxford John Radcliffe Hospital, Oxford, UK; Surgical Neurology Branch, National Institutes of Health, Bethesda, MD, USA. ·Mov Disord · Pubmed #25688872.

ABSTRACT: The subthalamic nucleus (STN), which is currently the most common target for deep brain stimulation (DBS) for Parkinson's disease (PD), has received increased attention over the past few years for the roles it may play in functions beyond simple motor control. In this article, we highlight several of the theoretical, interventional, and electrophysiological studies that have implicated the STN in response inhibition. Most influential among this evidence has been the reported effect of STN DBS in increasing impulsive responses in the laboratory setting. Yet, how this relates to pathological impulsivity in patients' everyday lives remains uncertain.

7 Review Focusing brain therapeutic interventions in space and time for Parkinson's disease. 2014

Little, S / Brown, P. ·Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, OX3 9DU, UK. · Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, OX3 9DU, UK. Electronic address: peter.brown@ndcn.ox.ac.uk. ·Curr Biol · Pubmed #25247369.

ABSTRACT: The last decade has seen major progress at all levels of neuroscience, from genes and molecules up to integrated systems-level models of brain function. In particular, there have been advances in the understanding of cell-type-specific contributions to function, together with a clearer account of how these contributions are coordinated from moment to moment to organise behavior. A major current endeavor is to leverage this knowledge to develop new therapeutic approaches. In Parkinson's disease, there are a number of promising emerging treatments. Here, we will highlight three ambitious novel therapeutic approaches for this condition, each robustly driven by primary neuroscience. Pharmacogenetics genetically re-engineers neurons to produce neurotrophins that are neuroprotective to vulnerable dopaminergic cells or to directly replace dopamine through enzyme transduction. Deep brain stimulation (DBS) is undergoing a transformation, with adaptive DBS controlled by neural signals resulting in better motor outcomes and significant reductions in overall stimulation that could reduce side effects. Finally, optogenetics presents the opportunity to achieve cell-type-specific control with a high temporal specification on a large enough scale to effectively repair network-level dysfunction.

8 Review The highs and lows of beta activity in cortico-basal ganglia loops. 2014

Brittain, John-Stuart / Sharott, Andrew / Brown, Peter. ·Experimental Neurology Group, Nuffield Department of Clinical Neuroscience, University of Oxford, Oxford, OX3 9DU, UK. ·Eur J Neurosci · Pubmed #24890470.

ABSTRACT: Oscillatory activity in the beta (13-30 Hz) frequency band is widespread in cortico-basal ganglia circuits, and becomes prominent in Parkinson's disease (PD). Here we develop the hypothesis that the degree of synchronization in this frequency band is a critical factor in gating computation across a population of neurons, with increases in beta band synchrony entailing a loss of information-coding space and hence computational capacity. Task and context drive this dynamic gating, so that for each state there will be an optimal level of network synchrony, and levels lower or higher than this will impair behavioural performance. Thus, both the pathological exaggeration of synchrony, as observed in PD, and the ability of interventions like deep brain stimulation (DBS) to excessively suppress synchrony can potentially lead to impairments in behavioural performance. Indeed, under physiological conditions, the manipulation of computational capacity by beta activity may itself present a mechanism of action selection and maintenance.

9 Review The functional role of beta oscillations in Parkinson's disease. 2014

Little, Simon / Brown, Peter. ·Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford. OX3 9DU, UK. ·Parkinsonism Relat Disord · Pubmed #24262186.

ABSTRACT: Modulations of beta oscillations (13-30 Hz) during normal motor control suggest that they may act to promote current motor set at the expense of new movements. These oscillations are greatly enhanced in Parkinson's disease (PD) and there is strong correlative evidence linking beta activity at rest and beta changes in response to treatment with bradykinesia and rigidity. Some evidence that this link may be mechanistically important or causal comes from studies in which either cortical or subcortical sites have been stimulated in the beta frequency range causing modest but significant slowing of movements. However, recent trials in which high frequency deep brain stimulation (DBS) has only been delivered during periods of elevated beta activity have demonstrated major clinical effects that even exceed those of standard continuous high frequency DBS. These studies suggest that beta activity may be both causally and quantitatively important in the motor impairment of PD, and demonstrate how improvements in the understanding of the pathophysiology of PD can lead to enhanced therapeutic interventions in this condition.

10 Review Oscillations and the basal ganglia: motor control and beyond. 2014

Brittain, John-Stuart / Brown, Peter. ·Experimental Neurology Group, Charles Wolfson Clinical Research Facility, Nuffield Department of Clinical Neuroscience, University of Oxford, Oxford OX3 9DU, UK. ·Neuroimage · Pubmed #23711535.

ABSTRACT: Oscillations form a ubiquitous feature of the central nervous system. Evidence is accruing from cortical and sub-cortical recordings that these rhythms may be functionally important, although the precise details of their roles remain unclear. The basal ganglia share this predilection for rhythmic activity which, as we see in Parkinson's disease, becomes further enhanced in the dopamine depleted state. While certain cortical rhythms appear to penetrate the basal ganglia, others are transformed or blocked. Here, we discuss the functional association of oscillations in the basal ganglia and their relationship with cortical activity. We further explore the neural underpinnings of such oscillatory activity, including the important balance to be struck between facilitating information transmission and limiting information coding capacity. Finally, we introduce the notion that synchronised oscillatory activity can be broadly categorised as immutability promoting rhythms that reinforce incumbent processes, and mutability promoting rhythms that favour novel processing.

11 Review Synchronized neural oscillations and the pathophysiology of Parkinson's disease. 2013

Oswal, Ashwini / Brown, Peter / Litvak, Vladimir. ·aDepartment of Clinical Neurology, John Radcliffe Hospital, Oxford bWellcome Trust Centre for Neuroimaging, Institute of Neurology, London, UK. ·Curr Opin Neurol · Pubmed #24150222.

ABSTRACT: PURPOSE OF THE REVIEW: Developments in functional neurosurgery for movement disorders and recent advances in electrophysiological techniques have allowed important insights into the role of oscillations in corticobasal ganglia circuits, both in health and in neurological disease states. Here we review recent developments in our understanding of how abnormally synchronized oscillatory activity within the corticobasal ganglia loop may play a key role in the pathophysiology of cognitive and motor phenotypes in Parkinson's disease. RECENT FINDINGS: Recent developments highlight the motor and non-motor roles of α, β and γ oscillations in the context of Parkinson's disease. They also emphasize the importance of oscillatory coupling between basal ganglia and cortex and draw attention to the importance of interactions between different frequency bands. SUMMARY: Oscillatory activities across multiple frequency bands and their cross-frequency interactions within spatially segregated loops of the basal ganglia-thalamo-cortical system may relate to distinct components of clinical impairment, both motor and non-motor. It is hoped that this characterization will lead to improved interventions like deep brain stimulation, tailored to specific components of clinical impairment and their associated spatial and spectral signatures.

12 Review γ oscillations in the human basal ganglia. 2013

Jenkinson, Ned / Kühn, Andrea A / Brown, Peter. ·Functional Neurosurgery and Experimental Neurology Group, University of Oxford, University Offices, Level 6, West Wing John Radcliffe Hospital, Oxford, OX3 9DU, UK. ned.jenkinson@dpag.ox.ac.uk ·Exp Neurol · Pubmed #22841500.

ABSTRACT: Interest in beta activity in the basal ganglia has mushroomed since it was first identified in the subthalamic nucleus of patients with Parkinson's disease in Jonathan Dostrovsky's landmark paper (Levy et al., 2000). Here we consider a less explored phenomenon; namely gamma frequency synchronisation of neurons in the basal ganglia. Gamma oscillations have been reported in a distributed network involving the basal ganglia, thalamus and motor cortex, and have been described in a wide range of diseases as well as during increased arousal and voluntary movement. In Parkinson's disease, gamma activity is promoted by dopaminergic therapy. These features suggest that its elevation may be involved in the production of movement and this hypothesis is supported by the correlation between the amplitude of gamma activity and limb kinematics. Here we review these data, discuss the functional anatomy of gamma activity in basal ganglia and question how closely it relates to the coding of movement parameters.

13 Clinical Trial Intact Acquisition and Short-Term Retention of Non-Motor Procedural Learning in Parkinson's Disease. 2016

Panouillères, Muriel T N / Tofaris, George K / Brown, Peter / Jenkinson, Ned. ·Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom. · School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Birmingham, United Kingdom. ·PLoS One · Pubmed #26906905.

ABSTRACT: Procedural learning is a form of memory where people implicitly acquire a skill through repeated practice. People with Parkinson's disease (PD) have been found to acquire motor adaptation, a form of motor procedural learning, similarly to healthy older adults but they have deficits in long-term retention. A similar pattern of normal learning on initial exposure with a deficit in retention seen on subsequent days has also been seen in mirror-reading, a form of non-motor procedural learning. It is a well-studied fact that disrupting sleep will impair the consolidation of procedural memories. Given the prevalence of sleep disturbances in PD, the lack of retention on following days seen in these studies could simply be a side effect of this well-known symptom of PD. Because of this, we wondered whether people with PD would present with deficits in the short-term retention of a non-motor procedural learning task, when the test of retention was done the same day as the initial exposure. The aim of the present study was then to investigate acquisition and retention in the immediate short term of cognitive procedural learning using the mirror-reading task in people with PD. This task involved two conditions: one where triads of mirror-inverted words were always new that allowed assessing the learning of mirror-reading skill and another one where some of the triads were presented repeatedly during the experiment that allowed assessing the word-specific learning. People with PD both ON and OFF their normal medication were compared to healthy older adults and young adults. Participants were re-tested 50 minutes break after initial exposure to probe for short-term retention. The results of this study show that all groups of participants acquired and retained the two skills (mirror-reading and word-specific) similarly. These results suggest that neither healthy ageing nor the degeneration within the basal ganglia that occurs in PD does affect the mechanisms that underpin the acquisition of these new non-motor procedural learning skills and their short-term memories.

14 Clinical Trial A spatiotemporal analysis of gait freezing and the impact of pedunculopontine nucleus stimulation. 2012

Thevathasan, Wesley / Cole, Michael H / Graepel, Cara L / Hyam, Jonathan A / Jenkinson, Ned / Brittain, John-Stuart / Coyne, Terry J / Silburn, Peter A / Aziz, Tipu Z / Kerr, Graham / Brown, Peter. ·Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK. wesley.thevathasan@nds.ox.ac.uk ·Brain · Pubmed #22396391.

ABSTRACT: Gait freezing is an episodic arrest of locomotion due to an inability to take normal steps. Pedunculopontine nucleus stimulation is an emerging therapy proposed to improve gait freezing, even where refractory to medication. However, the efficacy and precise effects of pedunculopontine nucleus stimulation on Parkinsonian gait disturbance are not established. The clinical application of this new therapy is controversial and it is unknown if bilateral stimulation is more effective than unilateral. Here, in a double-blinded study using objective spatiotemporal gait analysis, we assessed the impact of unilateral and bilateral pedunculopontine nucleus stimulation on triggered episodes of gait freezing and on background deficits of unconstrained gait in Parkinson's disease. Under experimental conditions, while OFF medication, Parkinsonian patients with severe gait freezing implanted with pedunculopontine nucleus stimulators below the pontomesencephalic junction were assessed during three conditions; off stimulation, unilateral stimulation and bilateral stimulation. Results were compared to Parkinsonian patients without gait freezing matched for disease severity and healthy controls. Pedunculopontine nucleus stimulation improved objective measures of gait freezing, with bilateral stimulation more effective than unilateral. During unconstrained walking, Parkinsonian patients who experience gait freezing had reduced step length and increased step length variability compared to patients without gait freezing; however, these deficits were unchanged by pedunculopontine nucleus stimulation. Chronic pedunculopontine nucleus stimulation improved Freezing of Gait Questionnaire scores, reflecting a reduction of the freezing encountered in patients' usual environments and medication states. This study provides objective, double-blinded evidence that in a specific subgroup of Parkinsonian patients, stimulation of a caudal pedunculopontine nucleus region selectively improves gait freezing but not background deficits in step length. Bilateral stimulation was more effective than unilateral.

15 Clinical Trial A block to pre-prepared movement in gait freezing, relieved by pedunculopontine nucleus stimulation. 2011

Thevathasan, Wesley / Pogosyan, Alek / Hyam, Jonathan A / Jenkinson, Ned / Bogdanovic, Marko / Coyne, Terry J / Silburn, Peter A / Aziz, Tipu Z / Brown, Peter. ·Department of Clinical Neurology, University of Oxford, UK. ·Brain · Pubmed #21705424.

ABSTRACT: Gait freezing and postural instability are disabling features of Parkinsonian disorders, treatable with pedunculopontine nucleus stimulation. Both features are considered deficits of proximal and axial musculature, innervated predominantly by reticulospinal pathways and tend to manifest when gait and posture require adjustment. Adjustments to gait and posture are amenable to pre-preparation and rapid triggered release. Experimentally, such accelerated release can be elicited by loud auditory stimuli--a phenomenon known as 'StartReact'. We observed StartReact in healthy and Parkinsonian controls. However, StartReact was absent in Parkinsonian patients with severe gait freezing and postural instability. Pedunculopontine nucleus stimulation restored StartReact proximally and proximal reaction times to loud stimuli correlated with gait and postural disturbance. These findings suggest a relative block to triggered, pre-prepared movement in gait freezing and postural instability, relieved by pedunculopontine nucleus stimulation.

16 Clinical Trial Deep brain stimulation can suppress pathological synchronisation in parkinsonian patients. 2011

Eusebio, A / Thevathasan, W / Doyle Gaynor, L / Pogosyan, A / Bye, E / Foltynie, T / Zrinzo, L / Ashkan, K / Aziz, T / Brown, P. ·Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, London, UK. ·J Neurol Neurosurg Psychiatry · Pubmed #20935326.

ABSTRACT: BACKGROUND: Although deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a highly effective therapeutic intervention in severe Parkinson's disease, its mechanism of action remains unclear. One possibility is that DBS suppresses local pathologically synchronised oscillatory activity. METHODS: To explore this, the authors recorded from DBS electrodes implanted in the STN of 16 patients with Parkinson's disease during simultaneous stimulation (pulse width 60 μs; frequency 130 Hz) of the same target using a specially designed amplifier. The authors analysed data from 25 sides. RESULTS: The authors found that DBS progressively suppressed peaks in local field potential activity at frequencies between 11 and 30 Hz as voltage was increased beyond a stimulation threshold of 1.5 V. Median peak power had fallen to 54% of baseline values by a stimulation intensity of 3.0 V. CONCLUSION: The findings suggest that DBS can suppress pathological 11-30 Hz activity in the vicinity of stimulation in patients with Parkinson's disease. This suppression occurs at stimulation voltages that are clinically effective.

17 Article The Effect of Unilateral Subthalamic Nucleus Deep Brain Stimulation on Contralateral Subthalamic Nucleus Local Field Potentials. 2020

Hasegawa, Harutomo / Fischer, Petra / Tan, Huiling / Pogosyan, Alek / Samuel, Michael / Brown, Peter / Ashkan, Keyoumars. ·Department of Neurosurgery, King's College Hospital, London, UK. · Department of Neurology, King's College Hospital, London, UK. · Medical Research Council Brain Network Dynamics Unit at the University of Oxford, Oxford, UK. · Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, Oxford, UK. ·Neuromodulation · Pubmed #32281215.

ABSTRACT: OBJECTIVES: Unilateral subthalamic nucleus (STN) deep brain stimulation (DBS) for Parkinson's disease (PD) improves ipsilateral symptoms, but how this occurs is not well understood. We investigated whether unilateral STN DBS suppresses contralateral STN beta activity in the local field potential (LFP), since previous research has shown that activity in the beta band can correlate with the severity of contralateral clinical symptoms and is modulated by DBS. MATERIALS AND METHODS: We recorded STN LFPs from 14 patients who underwent bilateral STN DBS for PD. Following a baseline recording, unilateral STN stimulation was delivered at therapeutic parameters while LFPs were recorded from the contralateral (unstimulated) STN. RESULTS: Unilateral STN DBS suppressed contralateral beta power (p = 0.039, relative suppression = -5.7% ± [SD] 16% when averaging across the highest beta peak channels; p = 0.033, relative suppression = -5.2% ± 13% when averaging across all channels). Unilateral STN DBS produced a 17% ipsilateral (p = 0.016) and 29% contralateral (p = 0.002) improvement in upper limb hemi-body bradykinesia-rigidity (UPDRS-III, items 3.3-3.6). The ipsilateral clinical improvement and the change in contralateral beta power were not significantly correlated. CONCLUSIONS: Unilateral STN DBS suppresses contralateral STN beta LFP. This indicates that unilateral STN DBS modulates bilateral basal ganglia networks. It remains unclear whether this mechanism accounts for the ipsilateral motor improvements.

18 Article Movement-related coupling of human subthalamic nucleus spikes to cortical gamma. 2020

Fischer, Petra / Lipski, Witold J / Neumann, Wolf-Julian / Turner, Robert S / Fries, Pascal / Brown, Peter / Richardson, R Mark. ·Medical Research Council Brain Network Dynamics Unit, University of Oxford, Oxford, United Kingdom. · Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom. · Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, United States. · Department of Neurology, Campus Mitte, Charite - Universitaetsmedizin Berlin, Berlin, Germany. · Department of Neurobiology, University of Pittsburgh, Pittsburgh, United States. · Center for the Neural Basis of Cognition, University of Pittsburgh, Pittsburgh, United States. · Ernst Strüngmann Institute (ESI) for Neuroscience in Cooperation with Max Planck Society, Frankfurt, Germany. · Donders Institute for Brain, Cognition and Behaviour, Nijmegen, Netherlands. · Department of Neurosurgery, Massachusetts General Hospital, Boston, United States. · Harvard Medical School, Boston, United States. ·Elife · Pubmed #32159515.

ABSTRACT: Cortico-basal ganglia interactions continuously shape the way we move. Ideas about how this circuit works are based largely on models those consider only firing rate as the mechanism of information transfer. A distinct feature of neural activity accompanying movement, however, is increased motor cortical and basal ganglia gamma synchrony. To investigate the relationship between neuronal firing in the basal ganglia and cortical gamma activity during movement, we analysed human ECoG and subthalamic nucleus (STN) unit activity during hand gripping. We found that fast reaction times were preceded by enhanced STN spike-to-cortical gamma phase coupling, indicating a role in motor preparation. Importantly, increased gamma phase coupling occurred independent of changes in mean STN firing rates, and the relative timing of STN spikes was offset by half a gamma cycle for ipsilateral vs. contralateral movements, indicating that relative spike timing is as relevant as firing rate for understanding cortico-basal ganglia information transfer.

19 Article Subthalamic nucleus activity dynamics and limb movement prediction in Parkinson's disease. 2020

Khawaldeh, Saed / Tinkhauser, Gerd / Shah, Syed Ahmar / Peterman, Katrin / Debove, Ines / Nguyen, T A Khoa / Nowacki, Andreas / Lachenmayer, M Lenard / Schuepbach, Michael / Pollo, Claudio / Krack, Paul / Woolrich, Mark / Brown, Peter. ·MRC Brain Network Dynamics Unit, University of Oxford, UK. · Nuffield Department of Clinical Neurosciences, University of Oxford, UK. · Oxford Centre for Human Brain Activity, Wellcome Centre for Integrative Neuroimaging, University of Oxford, UK. · Department of Neurology, Bern University Hospital and University of Bern, Switzerland. · Usher Institute of Population Health Sciences and Informatics, Edinburgh Medical School, The University of Edinburgh, Edinburgh, UK. · Department of Neurosurgery, Bern University Hospital and University of Bern, Switzerland. ·Brain · Pubmed #32040563.

ABSTRACT: Whilst exaggerated bursts of beta frequency band oscillatory synchronization in the subthalamic nucleus have been associated with motor impairment in Parkinson's disease, a plausible mechanism linking the two phenomena has been lacking. Here we test the hypothesis that increased synchronization denoted by beta bursting might compromise information coding capacity in basal ganglia networks. To this end we recorded local field potential activity in the subthalamic nucleus of 18 patients with Parkinson's disease as they executed cued upper and lower limb movements. We used the accuracy of local field potential-based classification of the limb to be moved on each trial as an index of the information held by the system with respect to intended action. Machine learning using the naïve Bayes conditional probability model was used for classification. Local field potential dynamics allowed accurate prediction of intended movements well ahead of their execution, with an area under the receiver operator characteristic curve of 0.80 ± 0.04 before imperative cues when the demanded action was known ahead of time. The presence of bursts of local field potential activity in the alpha, and even more so, in the beta frequency band significantly compromised the prediction of the limb to be moved. We conclude that low frequency bursts, particularly those in the beta band, restrict the capacity of the basal ganglia system to encode physiologically relevant information about intended actions. The current findings are also important as they suggest that local subthalamic activity may potentially be decoded to enable effector selection, in addition to force control in restorative brain-machine interface applications.

20 Article The Cumulative Effect of Transient Synchrony States on Motor Performance in Parkinson's Disease. 2020

Tinkhauser, Gerd / Torrecillos, Flavie / Pogosyan, Alek / Mostofi, Abteen / Bange, Manuel / Fischer, Petra / Tan, Huiling / Hasegawa, Harutomo / Glaser, Martin / Muthuraman, Muthuraman / Groppa, Sergiu / Ashkan, Keyoumars / Pereira, Erlick A / Brown, Peter. ·Medical Research Council Brain Network Dynamics Unit at the University of Oxford, OX1 3TH Oxford, United Kingdom. · Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DU, United Kingdom. · Department of Neurology, Bern University Hospital and University of Bern, 3010 Bern, Switzerland. · Neurosciences Research Centre, Molecular and Clinical Sciences Research Institute, St George's, University of London, London SW17 0RE, United Kingdom. · Movement Disorders and Neurostimulation, Department of Neurology, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany. · Department of Neurosurgery,King's College Hospital, King's College London, SE59RS, United Kingdom, and. · Department of Neurosurgery, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany. · Medical Research Council Brain Network Dynamics Unit at the University of Oxford, OX1 3TH Oxford, United Kingdom, peter.brown@ndcn.ox.ac.uk. ·J Neurosci · Pubmed #31919131.

ABSTRACT: Bursts of beta frequency band activity in the basal ganglia of patients with Parkinson's disease (PD) are associated with impaired motor performance. Here we test in human adults whether small variations in the timing of movement relative to beta bursts have a critical effect on movement velocity and whether the cumulative effects of multiple beta bursts, both locally and across networks, matter. We recorded local field potentials from the subthalamic nucleus (STN) in 15 PD patients of both genders OFF-medication, during temporary lead externalization after deep brain stimulation surgery. Beta bursts were defined as periods exceeding the 75th percentile amplitude threshold. Subjects performed a visual cued joystick reaching task, with the visual cue being triggered in real time with different temporal relationships to bursts of STN beta activity. The velocity of actions made in response to cues prospectively triggered by STN beta bursts was slower than when responses were not time-locked to recent beta bursts. Importantly, slow movements were those that followed multiple bursts close to each other within a trial. In contrast, small differences in the delay between the last burst and movement onset had no significant impact on velocity. Moreover, when the overlap of bursts between the two STN was high, slowing was more pronounced. Our findings suggest that the cumulative, but recent, history of beta bursting, both locally and across basal ganglia networks, may impact on motor performance.

21 Article Improved detection of Parkinsonian resting tremor with feature engineering and Kalman filtering. 2020

Yao, Lin / Brown, Peter / Shoaran, Mahsa. ·ECE Department, Cornell University, Ithaca, NY, USA. Electronic address: ly329@cornell.edu. · Medical Research Council Brain Network Dynamics Unit, University of Oxford, Oxford, UK; Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, Oxford, UK. · ECE Department, Cornell University, Ithaca, NY, USA. ·Clin Neurophysiol · Pubmed #31744673.

ABSTRACT: OBJECTIVE: Accurate and reliable detection of tremor onset in Parkinson's disease (PD) is critical to the success of adaptive deep brain stimulation (aDBS) therapy. Here, we investigated the potential use of feature engineering and machine learning methods for more accurate detection of rest tremor in PD. METHODS: We analyzed the local field potential (LFP) recordings from the subthalamic nucleus region in 12 patients with PD (16 recordings). To explore the optimal biomarkers and the best performing classifier, the performance of state-of-the-art machine learning (ML) algorithms and various features of the subthalamic LFPs were compared. We further used a Kalman filtering technique in feature domain to reduce the false positive rate. RESULTS: The Hjorth complexity showed a higher correlation with tremor, compared to other features in our study. In addition, by optimal selection of a maximum of five features with a sequential feature selection method and using the gradient boosted decision trees as the classifier, the system could achieve an average F1 score of up to 88.7% and a detection lead of 0.52 s. The use of Kalman filtering in feature space significantly improved the specificity by 17.0% (p = 0.002), thereby potentially reducing the unnecessary power dissipation of the conventional DBS system. CONCLUSION: The use of relevant features combined with Kalman filtering and machine learning improves the accuracy of tremor detection during rest. SIGNIFICANCE: The proposed method offers a potential solution for efficient on-demand stimulation for PD tremor.

22 Article Beta Oscillation-Targeted Neurofeedback Training Based on Subthalamic LFPs in Parkinsonian Patients. 2019

He, Shenghong / Syed, Emilie / Torrecillos, Flavie / Tinkhauser, Gerd / Fischer, Petra / Pogosyan, Alek / Pereira, Erlick / Ashkan, Keyoumars / Hasegawa, Harutomo / Brown, Peter / Tan, Huiling. ·MRC Brain Network Dynamics Unit and Nuffield Department of Clinical Neurosciences in University of Oxford, United Kingdom. · Neurosurgery and Consultant Neurosurgeon St George's University Hospital, London, United Kingdom. · Department of Neurosurgery, King's College Hospital NHS Foundation Trust, King's Health Partners, London, United Kingdom. ·Int IEEE EMBS Conf Neural Eng · Pubmed #31768227.

ABSTRACT: Increased oscillatory activities in the beta frequency band (13-30 Hz) in the subthalamic nucleus (STN), and in particular prolonged episodes of increased synchrony in this frequency band, have been associated with motor symptoms such as bradykinesia and rigidity in Parkinson's disease (PD). Numerous studies have investigated sensorimotor cortical beta oscillations either as a control signal for Brain Computer Interfaces (BCI) or as target signal for neurofeedback training (NFB). However, it still remains unknown whether patients with PD can gain control of the pathological oscillations recorded from a subcortical site - the STN - with neurofeedback training. We tried to address this question in the current study. Specifically, we designed a simple basketball game, in which the position of a basketball changes based on the occurrence of events of temporally increased beta power quantified in real-time. Participants practised in the game to control the position of the basketball, which requires modulation of the beta oscillations recorded from STN local field potentials (LFPs). Our results suggest that it is possible to use neurofeedback training for PD patients to downregulate pathological beta oscillations in STN LFPs, and that this can lead to a reduction of beta oscillations in the cortical-STN motor network.

23 Article Subthalamic nucleus oscillations correlate with vulnerability to freezing of gait in patients with Parkinson's disease. 2019

Chen, Chiung-Chu / Yeh, Chien-Hung / Chan, Hsiao-Lung / Chang, Ya-Ju / Tu, Po-Hsun / Yeh, Chih-Hua / Lu, Chin-Song / Fischer, Petra / Tinkhauser, Gerd / Tan, Huiling / Brown, Peter. ·Division of Movement Disorders, Department of Neurology, Chang Gung Memorial Hospital, Linkou, Taiwan; Neuroscience Research Center, Chang Gung Memorial Hospital, Linkou, Taiwan; School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan. Electronic address: neurozoe@gmail.com. · Division of Movement Disorders, Department of Neurology, Chang Gung Memorial Hospital, Linkou, Taiwan; Medical Research Council Brain Network Dynamics Unit at the University of Oxford, OX1 3TH Oxford, United Kingdom; Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, OX3 9DU Oxford, United Kingdom. · Neuroscience Research Center, Chang Gung Memorial Hospital, Linkou, Taiwan; Department of Electrical Engineering, College of Engineering, Chang Gung University, Taoyuan, Taiwan. · Neuroscience Research Center, Chang Gung Memorial Hospital, Linkou, Taiwan; School of Physical Therapy and Graduate Institute of Rehabilitation Science, College of Medicine, Healthy Aging Research Center, Chang Gung University, Taoyuan, Taiwan. · School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Department of Neurosurgery, Chang Gung Memorial Hospital, Linkou, Taiwan. · School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Department of Neuroradiology, Chang Gung Memorial Hospital, Linkou, Taiwan. · Division of Movement Disorders, Department of Neurology, Chang Gung Memorial Hospital, Linkou, Taiwan; Neuroscience Research Center, Chang Gung Memorial Hospital, Linkou, Taiwan; Professor Lu Neurological Clinic, Taoyuan, Taiwan. · Medical Research Council Brain Network Dynamics Unit at the University of Oxford, OX1 3TH Oxford, United Kingdom; Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, OX3 9DU Oxford, United Kingdom. · Medical Research Council Brain Network Dynamics Unit at the University of Oxford, OX1 3TH Oxford, United Kingdom; Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, OX3 9DU Oxford, United Kingdom; Department of Neurology, Bern University Hospital and University of Bern, Bern, Switzerland. ·Neurobiol Dis · Pubmed #31494286.

ABSTRACT: Freezing of gait (FOG) is a disabling clinical phenomenon often found in patients with advanced Parkinson's disease (PD). FOG impairs motor function, causes falls and leads to loss of independence. Whereas dual tasking that distracts patients' attention precipitates FOG, auditory or visual cues ameliorate this phenomenon. The pathophysiology of FOG remains unclear. Previous studies suggest that the basal ganglia are involved in the generation of FOG. Investigation of the modulation of neuronal activities within basal ganglia structures during walking is warranted. To this end, we recorded local field potentials (LFP) from the subthalamic nucleus (STN) while PD patients performed single-task gait (ST) or walked while dual-tasking (DT). An index of FOG (iFOG) derived from trunk accelerometry was used as an objective measure to differentiate FOG-vulnerable gait from normal gait. Two spectral activities recorded from the STN region were associated with vulnerability to freezing. Greater LFP power in the low beta (15-21 Hz) and theta (5-8 Hz) bands were noted during periods of vulnerable gait in both ST and DT states. Whereas the elevation of low beta activities was distributed across STN, the increase in theta activity was focal and found in ventral STN and/or substantia nigra (SNr) in ST. The results demonstrate that low beta and theta band oscillations within the STN area occur during gait susceptible to freezing in PD. They also add to the evidence that narrow band ~18 Hz activity may be linked to FOG.

24 Article Predicting the effects of deep brain stimulation using a reduced coupled oscillator model. 2019

Weerasinghe, Gihan / Duchet, Benoit / Cagnan, Hayriye / Brown, Peter / Bick, Christian / Bogacz, Rafal. ·MRC Brain Network Dynamics Unit, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom. · Oxford Centre for Industrial and Applied Mathematics, Mathematical Institute, University of Oxford, Oxford, United Kingdom. · Centre for Systems, Dynamics and Control and Department of Mathematics, University of Exeter, Exeter, United Kingdom. · EPSRC Centre for Predictive Modelling in Healthcare, University of Exeter, Exeter, United Kingdom. ·PLoS Comput Biol · Pubmed #31393880.

ABSTRACT: Deep brain stimulation (DBS) is known to be an effective treatment for a variety of neurological disorders, including Parkinson's disease and essential tremor (ET). At present, it involves administering a train of pulses with constant frequency via electrodes implanted into the brain. New 'closed-loop' approaches involve delivering stimulation according to the ongoing symptoms or brain activity and have the potential to provide improvements in terms of efficiency, efficacy and reduction of side effects. The success of closed-loop DBS depends on being able to devise a stimulation strategy that minimizes oscillations in neural activity associated with symptoms of motor disorders. A useful stepping stone towards this is to construct a mathematical model, which can describe how the brain oscillations should change when stimulation is applied at a particular state of the system. Our work focuses on the use of coupled oscillators to represent neurons in areas generating pathological oscillations. Using a reduced form of the Kuramoto model, we analyse how a patient should respond to stimulation when neural oscillations have a given phase and amplitude, provided a number of conditions are satisfied. For such patients, we predict that the best stimulation strategy should be phase specific but also that stimulation should have a greater effect if applied when the amplitude of brain oscillations is lower. We compare this surprising prediction with data obtained from ET patients. In light of our predictions, we also propose a new hybrid strategy which effectively combines two of the closed-loop strategies found in the literature, namely phase-locked and adaptive DBS.

25 Article Temporal evolution of beta bursts in the parkinsonian cortical and basal ganglia network. 2019

Cagnan, Hayriye / Mallet, Nicolas / Moll, Christian K E / Gulberti, Alessandro / Holt, Abbey B / Westphal, Manfred / Gerloff, Christian / Engel, Andreas K / Hamel, Wolfgang / Magill, Peter J / Brown, Peter / Sharott, Andrew. ·Medical Research Council Brain Network Dynamics Unit, Department of Pharmacology, University of Oxford, OX1 3TH Oxford, United Kingdom; hayriye.cagnan@ndcn.ox.ac.uk andrew.sharott@pharm.ox.ac.uk. · Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DU, United Kingdom. · Institut des Maladies Neurodégénératives, Universite de Bordeaux, 33076 Bordeaux, France. · CNRS UMR 5293, Institut des Maladies Neurodégénératives, 33076 Bordeaux, France. · Department of Neurophysiology and Pathophysiology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany. · Medical Research Council Brain Network Dynamics Unit, Department of Pharmacology, University of Oxford, OX1 3TH Oxford, United Kingdom. · Department of Neurosurgery, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany. · Department of Neurology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany. · Oxford Parkinson's Disease Centre, University of Oxford, OX1 3QX Oxford, United Kingdom. ·Proc Natl Acad Sci U S A · Pubmed #31341079.

ABSTRACT: Beta frequency oscillations (15 to 35 Hz) in cortical and basal ganglia circuits become abnormally synchronized in Parkinson's disease (PD). How excessive beta oscillations emerge in these circuits is unclear. We addressed this issue by defining the firing properties of basal ganglia neurons around the emergence of cortical beta bursts (β bursts), transient (50 to 350 ms) increases in the beta amplitude of cortical signals. In PD patients, the phase locking of background spiking activity in the subthalamic nucleus (STN) to frontal electroencephalograms preceded the onset and followed the temporal profile of cortical β bursts, with conditions of synchronization consistent within and across bursts. Neuronal ensemble recordings in multiple basal ganglia structures of parkinsonian rats revealed that these dynamics were recapitulated in STN, but also in external globus pallidus and striatum. The onset of consistent phase-locking conditions was preceded by abrupt phase slips between cortical and basal ganglia ensemble signals. Single-unit recordings demonstrated that ensemble-level properties of synchronization were not underlain by changes in firing rate but, rather, by the timing of action potentials in relation to cortical oscillation phase. Notably, the preferred angle of phase-locked action potential firing in each basal ganglia structure was shifted during burst initiation, then maintained stable phase relations during the burst. Subthalamic, pallidal, and striatal neurons engaged and disengaged with cortical β bursts to different extents and timings. The temporal evolution of cortical and basal ganglia synchronization is cell type-selective, which could be key for the generation/ maintenance of excessive beta oscillations in parkinsonism.

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