title: Stimulating at the right time: phase-specific deep brain stimulation.
abstract: SEE MOLL AND ENGEL DOI101093/AWW308 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Brain regions dynamically engage and disengage with one another to execute everyday actions from movement to decision making. Pathologies such as Parkinson's disease and tremor emerge when brain regions controlling movement cannot readily decouple, compromising motor function. Here, we propose a novel stimulation strategy that selectively regulates neural synchrony through phase-specific stimulation. We demonstrate for the first time the therapeutic potential of such a stimulation strategy for the treatment of patients with pathological tremor. Symptom suppression is achieved by delivering stimulation to the ventrolateral thalamus, timed according to the patient's tremor rhythm. Sustained locking of deep brain stimulation to a particular phase of tremor afforded clinically significant tremor relief (up to 87% tremor suppression) in selected patients with essential tremor despite delivering less than half the energy of conventional high frequency stimulation. Phase-specific stimulation efficacy depended on the resonant characteristics of the underlying tremor network. Selective regulation of neural synchrony through phase-locked stimulation has the potential to both increase the efficiency of therapy and to minimize stimulation-induced side effects.
authors.affiliation: 1 Institute of Neurology, University College London, London, UK h.cagnan@ucl.ac.uk.|2 Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.|3 Medical Research Council Brain Network Dynamics Unit, University of Oxford, Oxford, UK.
authors.forename: Hayriye
authors.initials: H
authors.lastname: Cagnan
authors.affiliation: 2 Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.|3 Medical Research Council Brain Network Dynamics Unit, University of Oxford, Oxford, UK.
authors.forename: David
authors.initials: D
authors.lastname: Pedrosa
authors.affiliation: 1 Institute of Neurology, University College London, London, UK.
authors.forename: Simon
authors.initials: S
authors.lastname: Little
authors.affiliation: 2 Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.|3 Medical Research Council Brain Network Dynamics Unit, University of Oxford, Oxford, UK.
authors.forename: Alek
authors.initials: A
authors.lastname: Pogosyan
authors.affiliation: 2 Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
authors.forename: Binith
authors.initials: B
authors.lastname: Cheeran
authors.affiliation: 2 Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
authors.forename: Tipu
authors.initials: T
authors.lastname: Aziz
authors.affiliation: 2 Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
authors.forename: Alexander
authors.initials: A
authors.lastname: Green
authors.affiliation: 2 Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
authors.forename: James
authors.initials: J
authors.lastname: Fitzgerald
authors.affiliation: 1 Institute of Neurology, University College London, London, UK.
authors.forename: Thomas
authors.initials: T
authors.lastname: Foltynie
authors.affiliation: 1 Institute of Neurology, University College London, London, UK.
authors.forename: Patricia
authors.initials: P
authors.lastname: Limousin
authors.affiliation: 1 Institute of Neurology, University College London, London, UK.
authors.forename: Ludvic
authors.initials: L
authors.lastname: Zrinzo
authors.affiliation: 1 Institute of Neurology, University College London, London, UK.
authors.forename: Marwan
authors.initials: M
authors.lastname: Hariz
authors.affiliation: 1 Institute of Neurology, University College London, London, UK.
authors.forename: Karl J
authors.initials: KJ
authors.lastname: Friston
authors.affiliation: 4 Medtronic Neuromodulation, Minneapolis, USA.
authors.forename: Timothy
authors.initials: T
authors.lastname: Denison
authors.affiliation: 2 Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.|3 Medical Research Council Brain Network Dynamics Unit, University of Oxford, Oxford, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Brown
mesh_terms: D061725:Accelerometry; D046690:Deep Brain Stimulation / Q000379:methods*; D004421:Dystonia / Q000150:complications*; D020329:Essential Tremor / Q000503:physiopathology / Q000628:therapy*; D006801:Humans; D013788:Thalamus; D014202:Tremor / Q000209:etiology / Q000503:physiopathology / Q000628:therapy*
keywords: closed-loop stimulation; dystonic tremor; essential tremor; synchrony; ventrolateral thalamus