title: Subthalamic beta oscillations are attenuated after withdrawal of chronic high frequency neurostimulation in Parkinson's disease.
abstract: Subthalamic nucleus (STN) local field potential (LFP) recordings demonstrate beta (13-30Hz) band oscillations in Parkinson's disease (PD) defined as elevations of spectral power. The amount of attenuation of beta band power on therapeutic levels of high frequency (HF) deep brain stimulation (DBS) and/or dopaminergic medication has been correlated with the degree of improvement in bradykinesia and rigidity from the therapy, which has led to the suggestion that elevated beta band power is a marker of PD motor disability. A fundamental question has not been answered: whether there is a prolonged attenuation of beta band power after withdrawal of chronic HF DBS and whether this is related to a lack of progression or even improvement in the underlying motor disability. Until now, in human PD subjects, STN LFP recordings were only attainable in the peri-operative period and after short periods of stimulation. For the first time, using an investigational, implanted sensing neurostimulator (Activa® PC+S, Medtronic, Inc.), STN LFPs and motor disability were recorded/assessed after withdrawal of chronic (6 and 12month) HF DBS in freely moving PD subjects. Beta band power was similar within 14s and 60min after stimulation was withdrawn, suggesting that "off therapy" experiments can be conducted almost immediately after stimulation is turned off. After withdrawal of 6 and 12months of STN DBS, beta band power was significantly lower (P<0.05 at 6 and 12months) and off therapy UPDRS scores were better (P<0.05 at 12months) compared to before DBS was started. The attenuation in beta band power was correlated with improvement in motor disability scores (P<0.05). These findings were supported by evidence of a gradual increase in beta band power in two unstimulated STNs after 24months and could not be explained by changes in lead impedance. This suggests that chronic HF DBS exerts long-term plasticity in the sensorimotor network, which may contribute to a lack of progression in underlying motor disability in PD.
authors.affiliation: Stanford University Department of Neurology and Neurological Sciences, Rm H3136, SUMC, 300 Pasteur Drive, Stanford, CA 94305, USA.
authors.forename: Megan H
authors.initials: MH
authors.lastname: Trager
authors.affiliation: Stanford University Department of Neurology and Neurological Sciences, Rm H3136, SUMC, 300 Pasteur Drive, Stanford, CA 94305, USA.
authors.forename: Mandy Miller
authors.initials: MM
authors.lastname: Koop
authors.affiliation: Stanford University Department of Neurology and Neurological Sciences, Rm H3136, SUMC, 300 Pasteur Drive, Stanford, CA 94305, USA.
authors.forename: Anca
authors.initials: A
authors.lastname: Velisar
authors.affiliation: Stanford University Department of Neurology and Neurological Sciences, Rm H3136, SUMC, 300 Pasteur Drive, Stanford, CA 94305, USA.
authors.forename: Zack
authors.initials: Z
authors.lastname: Blumenfeld
authors.affiliation: Stanford University Department of Neurology and Neurological Sciences, Rm H3136, SUMC, 300 Pasteur Drive, Stanford, CA 94305, USA.
authors.forename: Judy Syrkin
authors.initials: JS
authors.lastname: Nikolau
authors.affiliation: Stanford University Department of Neurology and Neurological Sciences, Rm H3136, SUMC, 300 Pasteur Drive, Stanford, CA 94305, USA.
authors.forename: Emma J
authors.initials: EJ
authors.lastname: Quinn
authors.affiliation: Stanford University Department of Neurology and Neurological Sciences, Rm H3136, SUMC, 300 Pasteur Drive, Stanford, CA 94305, USA.
authors.forename: Talora
authors.initials: T
authors.lastname: Martin
authors.affiliation: Stanford University Department of Neurology and Neurological Sciences, Rm H3136, SUMC, 300 Pasteur Drive, Stanford, CA 94305, USA; Stanford University Department of Neurosurgery, 300 Pasteur Drive, Stanford, CA 94305, USA.
authors.forename: Helen
authors.initials: H
authors.lastname: Bronte-Stewart
mesh_terms: D000328:Adult; D000368:Aged; D001611:Beta Rhythm / Q000502:physiology*; D046690:Deep Brain Stimulation; D015259:Dopamine Agents / Q000627:therapeutic use; D005260:Female; D006801:Humans; D058542:Implantable Neurostimulators; D007980:Levodopa / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000150:complications / Q000188:drug therapy / Q000628:therapy*; D013057:Spectrum Analysis; D020531:Subthalamic Nucleus / Q000502:physiology*; D013997:Time Factors
chemical_list: D015259:Dopamine Agents; D007980:Levodopa
keywords: Beta band oscillations; Deep brain stimulation; Parkinson's disease; Subthalamic nucleus; Unified Parkinson's disease rating scale