Biomarkers for closed-loop deep brain stimulation in Parkinson disease and beyond

Bouthour, Walid; Mégevand, Pierre; Donoghue, John P.; Lüscher, Christian; Birbaumer, Niels; Krack, Paul

doi:10.1038/s41582-019-0166-4

Cited by 170 publications

(136 citation statements)

References 138 publications

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“…In vivo electrochemical techniques have been used for decades to detect subsecond and submillimeter resolution changes in extracellular concentrations of neurochemicals, such as dopamine, serotonin, glutamate, and adenosine, in animal models. Further, abnormal neurochemical and electrophysiological activity has been implicated in a host of psychiatric and other neurological disorders, with relevant biomarkers for Parkinson's disease (PD), 7 essential tremor (ET), 8 epilepsy, 9 Tourette syndrome (TS), 10 obsessive-compulsive disorder (OCD), 11 and depression. 12…”

Section: Fig 1 Depiction Of Open-and Closed-loop Neurostimulation Amentioning

confidence: 99%

“…The therapeutic effects of DBS in PD are associated with the modulation of cortical and subcortical beta and gamma oscillations. 7,13 Electrophysiological measurements in basal ganglia structures, as well as oscillatory activities of local field potentials (LFPs) in the dorsolateral motor region of the STN during functional neurosurgery, have provided critical insights into the pathophysiology of PD. Accordingly, closed-loop DBS systems, such as the Activa PC+S (Medtronic), 14 have focused on beta and gamma power as potential biomarkers for adaptive modulation of stimulation amplitude and frequency.…”

Section: Parkinson's Diseasementioning

confidence: 99%

“…Ideal biomarker candidates should have high disease specificity and a high signal-to-noise ratio, should be unaffected by external conditions, and should be readily measurable over a long period across multiple disease states. 7,71 Several biomarkers have been proposed for augmenting stimulation parameters, such as action potentials, LFPs, massed potentials, electrocorticographic activity, and neurotransmitter signaling. However, no single biomarker is sufficient to monitor progression of neurological disease symptomology or applications of DBS; further research is needed to isolate biomarkers and relate them to disease states and individualized pathophysiologies.…”

Section: Innovations and Challenges Of Closed-loop Dbs Systemsmentioning

confidence: 99%

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Clinical applications of neurochemical and electrophysiological measurements for closed-loop neurostimulation

Price¹,

Rusheen

Barath³

et al. 2020

Neurosurgical Focus

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The development of closed-loop deep brain stimulation (DBS) systems represents a significant opportunity for innovation in the clinical application of neurostimulation therapies. Despite the highly dynamic nature of neurological diseases, open-loop DBS applications are incapable of modifying parameters in real time to react to fluctuations in disease states. Thus, current practice for the designation of stimulation parameters, such as duration, amplitude, and pulse frequency, is an algorithmic process. Ideal stimulation parameters are highly individualized and must reflect both the specific disease presentation and the unique pathophysiology presented by the individual. Stimulation parameters currently require a lengthy trial-and-error process to achieve the maximal therapeutic effect and can only be modified during clinical visits. The major impediment to the development of automated, adaptive closed-loop systems involves the selection of highly specific disease-related biomarkers to provide feedback for the stimulation platform. This review explores the disease relevance of neurochemical and electrophysiological biomarkers for the development of closed-loop neurostimulation technologies. Electrophysiological biomarkers, such as local field potentials, have been used to monitor disease states. Real-time measurement of neurochemical substances may be similarly useful for disease characterization. Thus, the introduction of measurable neurochemical analytes has significantly expanded biomarker options for feedback-sensitive neuromodulation systems. The potential use of biomarker monitoring to advance neurostimulation approaches for treatment of Parkinson’s disease, essential tremor, epilepsy, Tourette syndrome, obsessive-compulsive disorder, chronic pain, and depression is examined. Further, challenges and advances in the development of closed-loop neurostimulation technology are reviewed, as well as opportunities for next-generation closed-loop platforms.

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Section: Fig 1 Depiction Of Open-and Closed-loop Neurostimulation Amentioning

confidence: 99%

Section: Parkinson's Diseasementioning

confidence: 99%

Section: Innovations and Challenges Of Closed-loop Dbs Systemsmentioning

confidence: 99%

See 1 more Smart Citation

Clinical applications of neurochemical and electrophysiological measurements for closed-loop neurostimulation

Price¹,

Rusheen

Barath³

et al. 2020

Neurosurgical Focus

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“…It seems likely that the field of brainmachine interfaces will evolve quickly, especially given the promise for a multitude of medical applications. At the same time, ethical concerns arise, especially regarding invasive devices that do not just read out but also stimulate neural activity, such as treatments for Parkinson's disease and epilepsy patients 4 . Such neural manipulation can affect a patient's autonomy and sense of personhood 5 , and it is a challenging task to weigh complex neuroethical concerns against medical benefits.…”

Section: Return Of Cyberneticsmentioning

confidence: 99%

Return of cybernetics

2019

Nat Mach Intell

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“…However, from a control theory perspective, open-loop methods are generally inferior to closed-loop control that incorporates feedback based on the real-time state of the system (Shanechi, 2019). Thus, neuromodulation therapies may be more effective if controlled by ongoing electrophysiological measurements (Bouthour et al, 2019, Cagnan et al, 2019, for example to enhance beneficial oscillations or to destabilise pathological brain states such as epileptic seizures. Unfortunately, many potential applications of closed-loop neurostimulation are hampered by large artefacts associated with electrical stimulation, particularly when monitoring and modulating the same local population of neurons.…”

mentioning

confidence: 99%

Closed-loop optogenetic control of normal and pathological network dynamics

Zaaimi¹,

Turnbull²,

Hazra³

et al. 2020

Preprint

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Electrical neurostimulation is effective in treating neurological disorders, but associated recording artefacts generally limit applications to ‘open-loop’ stimuli. Since light does not prevent concurrent electrical recordings, optogenetics enables real-time, continuous ‘closed-loop’ control of brain activity. Here we show that closed-loop optogenetic stimulation with excitatory opsins (CLOSe) affords precise manipulation of neural dynamics, both in vitro, in brain slices from transgenic mice, and in vivo, with anesthetised monkeys. We demonstrate the generation of oscillations in quiescent tissue, enhancement or suppression of endogenous patterns in active tissue, and modulation of seizure-like bursts elicited by 4-aminopyridine. New network properties, emergent under CLOSe, depended on the phase-shift imposed between neural activity and optical stimulation, and could be modelled with a nonlinear dynamical system. In particular, CLOSe could stabilise or destabilise limit cycles associated with seizure oscillations, evident from systematic changes in the variability and entropy of seizure trajectories that correlated with their altered duration and intensity. Furthermore, CLOSe was achieved using intracortical optrodes incorporating light-emitting diodes, paving the way for translation of closed-loop optogenetics towards therapeutic applications in humans.

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Biomarkers for closed-loop deep brain stimulation in Parkinson disease and beyond

Cited by 170 publications

References 138 publications

Clinical applications of neurochemical and electrophysiological measurements for closed-loop neurostimulation

Clinical applications of neurochemical and electrophysiological measurements for closed-loop neurostimulation

Return of cybernetics

Closed-loop optogenetic control of normal and pathological network dynamics

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