Closed-Loop Deep Brain Stimulation Is Superior in Ameliorating Parkinsonism

Rosin, Boris; Slovik, Maya; Mitelman, Rea; Rivlin‐Etzion, Michal; Haber, Suzanne N.; Israel, Zvi; Vaadia, Eilon; Bergman, Hagai

doi:10.1016/j.neuron.2011.08.023

Cited by 708 publications

(573 citation statements)

References 76 publications

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“…The most pressing scientific and engineering issue in this effort is that reliable biomarkers for disease severity need to be found, and that the implanted device(s) must be able to detect them and adjust their output accordingly. In encouraging studies in parkinsonian primates it was shown that STN DBS triggered by the firing patterns of MC cortical neurons treated parkinsonism more effectively than conventional DBS [335], and subsequent studies in humans showed that STN DBS can be controlled by recorded LFP signals in the STN [336]. Major issues remain unsolved, including further optimization of the detection and extraction of the control signals, demonstration of the stability of the relationship between these signals and the disease signs and symptoms, and the obvious need to minimize battery consumption of the added sensing circuitry in the new devices.…”

Section: Technical Developments and Future Of Neuromodulationmentioning

confidence: 99%

Deep Brain Stimulation for Movement Disorders of Basal Ganglia Origin: Restoring Function or Functionality?

2016

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Deep brain stimulation (DBS) is highly effective for both hypo-and hyperkinetic movement disorders of basal ganglia origin. The clinical use of DBS is, in part, empiric, based on the experience with prior surgical ablative therapies for these disorders, and, in part, driven by scientific discoveries made decades ago. In this review, we consider anatomical and functional concepts of the basal ganglia relevant to our understanding of DBS mechanisms, as well as our current understanding of the pathophysiology of two of the most commonly DBS-treated conditions, Parkinson's disease and dystonia. Finally, we discuss the proposed mechanism(s) of action of DBS in restoring function in patients with movement disorders. The signs and symptoms of the various disorders appear to result from signature disordered activity in the basal ganglia output, which disrupts the activity in thalamocortical and brainstem networks. The available evidence suggests that the effects of DBS are strongly dependent on targeting sensorimotor portions of specific nodes of the basal gangliathalamocortical motor circuit, that is, the subthalamic nucleus and the internal segment of the globus pallidus. There is little evidence to suggest that DBS in patients with movement disorders restores normal basal ganglia functions (e.g., their role in movement or reinforcement learning). Instead, it appears that high-frequency DBS replaces the abnormal basal ganglia output with a more tolerable pattern, which helps to restore the functionality of downstream networks.

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Section: Technical Developments and Future Of Neuromodulationmentioning

confidence: 99%

Deep Brain Stimulation for Movement Disorders of Basal Ganglia Origin: Restoring Function or Functionality?

2016

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“…Proof of principle of aDBS has now been demonstrated in a non -human primate model of PD 13 . This used a single cortical motor neuron to control stimulation with firing of the neuron triggering DBS stimulation after a fixed delay.…”

Section: Introductionmentioning

confidence: 99%

Controlling Parkinson's Disease With Adaptive Deep Brain Stimulation

Little

Pogosyan

Neal³

et al. 2014

JoVE

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Adaptive deep brain stimulation (aDBS) has the potential to improve the treatment of Parkinson's disease by optimizing stimulation in real time according to fluctuating disease and medication state. In the present realization of adaptive DBS we record and stimulate from the DBS electrodes implanted in the subthalamic nucleus of patients with Parkinson's disease in the early post-operative period. Local field potentials are analogue filtered between 3 and 47 Hz before being passed to a data acquisition unit where they are digitally filtered again around the patient specific beta peak, rectified and smoothed to give an online reading of the beta amplitude. A threshold for beta amplitude is set heuristically, which, if crossed, passes a trigger signal to the stimulator. The stimulator then ramps up stimulation to a pre-determined clinically effective voltage over 250 msec and continues to stimulate until the beta amplitude again falls down below threshold. Stimulation continues in this manner with brief episodes of ramped DBS during periods of heightened beta power.Clinical efficacy is assessed after a minimum period of stabilization (5 min) through the unblinded and blinded video assessment of motor function using a selection of scores from the Unified Parkinson's Rating Scale (UPDRS). Recent work has demonstrated a reduction in power consumption with aDBS as well as an improvement in clinical scores compared to conventional DBS. Chronic aDBS could now be trialed in Parkinsonism.

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“…In contrast to open-loop control, closed-loop control can by design deal with all these situations. For this reason there is a growing interest in investigating feedback-control both experimentally [2,[22][23][24] and theoretically [39]. The goal of the experimental work has been to demonstrate that closed-loop control is indeed effective, whereas the theoretical studies aimed at providing a deeper understanding of the underlying conditions and mechanisms.…”

Section: Discussionmentioning

confidence: 99%

“…Importantly, the method is not restricted to stimulation of deep structures, but could be applied non-invasively to modulate activity in cortical layers as well [21]. Finally, the theoretical insights we provide into the mechanisms of feedback control in SNNs could also explain the recent success of event-driven stimulation schemes [22][23][24].…”

Section: Introductionmentioning

confidence: 87%

Recovery of dynamics and function in spiking neural networks by closed-loop control

Vlachos

Taşkın

Aertsen

et al. 2015

Preprint

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There is a growing interest in developing novel brain stimulation methods to control disease--related aberrant neural activity and to address basic neuroscience questions. Conventional methods for manipulating brain activity rely on open-loop approaches that usually lead to excessive stimulation and, crucially, do not restore the original computations performed by the network. Thus, they are often accompanied by undesired side-effects. Here, we introduce delayed feedback control (DFC), a conceptually simple but effective method, to control pathological oscillations in spiking neural networks (SNNs). Using mathematical analysis and numerical simulations we show that DFC can restore a wide range of aberrant network dynamics either by suppressing or enhancing synchronous irregular activity. Importantly, DFC, besides steering the system back to a healthy state, also recovers the computations performed by the underlying network. Finally, using our theory we identify the role of single neuron and synapse properties in determining the stability of the closed-loop system. Author SummaryBrain stimulation is being used to ease symptoms in several neurological disorders in cases where pharmacological treatment is not effective (anymore). The most common way for stimulation so far has been to apply a fixed, predetermined stimulus irrespective of the actual state of the brain or the condition of the patient. Recently, alternative strategies such as event-triggered stimulation protocols have attracted the interest of researchers. In these protocols the state of the affected brain area is continuously monitored, but the stimulus is only applied if certain criteria are met. Here we go one step further and present a truly closed-loop stimulation protocol. That is, a stimulus is being continuously provided and the magnitude of the stimulus depends, at any point in time, on the ongoing neural activity dynamics of the affected brain area. This results not only in suppression of the pathological activity, but also in a partial recovery of the transfer function of the activity dynamics. Thus, the ability of the lesioned brain area to carry out relevant computations is restored up to a point as well. PLOS Computational Biology |

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Closed-Loop Deep Brain Stimulation Is Superior in Ameliorating Parkinsonism

Cited by 708 publications

References 76 publications

Deep Brain Stimulation for Movement Disorders of Basal Ganglia Origin: Restoring Function or Functionality?

Deep Brain Stimulation for Movement Disorders of Basal Ganglia Origin: Restoring Function or Functionality?

Controlling Parkinson's Disease With Adaptive Deep Brain Stimulation

Recovery of dynamics and function in spiking neural networks by closed-loop control

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