Deep brain stimulation for Parkinson's disease modulates high-frequency evoked and spontaneous neural activity

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dc.contributor.authorSinclair, Nicholas
dc.contributor.authorMcDermott, Hugh
dc.contributor.authorFallon, James
dc.contributor.authorPerera, Thushara
dc.contributor.authorBrown, Peter
dc.contributor.authorBulluss, Kristian
dc.contributor.authorThevathasan, Wesley
dc.date.accessioned2019-08-27T04:25:54Z
dc.date.available2019-08-27T04:25:54Z
dc.date.issued2019-07
dc.description.abstractDeep brain stimulation is an established therapy for Parkinson's disease; however, its effectiveness is hindered by limited understanding of therapeutic mechanisms and the lack of a robust feedback signal for tailoring stimulation. We recently reported that subthalamic nucleus deep brain stimulation evokes a neural response resembling a decaying high-frequency (200-500Hz) oscillation that typically has a duration of at least 10ms and is localizable to the dorsal sub-region. As the morphology of this response suggests a propensity for the underlying neural circuitry to oscillate at a particular frequency, we have named it evoked resonant neural activity. Here, we determine whether this evoked activity is modulated by therapeutic stimulation - a critical attribute of a feedback signal. Furthermore, we investigated whether any related changes occurred in spontaneous local field potentials. Evoked and spontaneous neural activity was intraoperatively recorded from 19 subthalamic nuclei in patients with Parkinson's disease. Recordings were obtained before therapeutic stimulation and during 130Hz stimulation at increasing amplitudes (0.67-3.38mA), 'washout' of therapeutic effects, and non-therapeutic 20Hz stimulation. Therapeutic efficacy was assessed using clinical bradykinesia and rigidity scores. The frequency and amplitude of evoked resonant neural activity varied with the level of 130Hz stimulation (p<.001). This modulation coincided with improvement in bradykinesia and rigidity (p<.001), and correlated with spontaneous beta band suppression (p<.001). Evoked neural activity occupied a similar frequency band to spontaneous high-frequency oscillations (200-400Hz), both of which decreased to around twice the 130Hz stimulation rate. Non-therapeutic stimulation at 20Hz evoked, but did not modulate, resonant activity. These results indicate that therapeutic deep brain stimulation alters the frequency of evoked and spontaneous oscillations recorded in the subthalamic nucleus that are likely generated by loops within the cortico-basal ganglia-thalamo-cortical network. Evoked resonant neural activity therefore has potential as a tool for providing insight into brain network function and has key attributes of a dynamic feedback signal for optimizing therapy.en_US
dc.description.sponsorshipThis work was supported by the Colonial Foundation, St Vincent's Hospital Research Endowment Fund, and the National Health and Medical Research Council [project grant #1103238]. The Bionics Institute acknowledges the support it receives from the Victorian Government through its operational infrastructure program. N.C.S. is supported through an Australian Government Research Training Program Scholarship. P.B. is supported by the Medical Research Council of Great Britain. W.T is supported by Lions International and the National Health and Medical Research Council.en_US
dc.identifier.citationSinclair, N. C., H. J. McDermott, J. B. Fallon, T. Perera, P. Brown, K. J. Bulluss, and W. Thevathasan. 2019. Deep brain stimulation for Parkinson's disease modulates high-frequency evoked and spontaneous neural activity. Neurobiology of disease. 130: 104522.en_US
dc.identifier.issn0969-9961
dc.identifier.urihttp://repository.bionicsinstitute.org:8080/handle/123456789/363
dc.language.isoenen_US
dc.publisherElsevier, Inc.en_US
dc.subjectDeep brain stimulationen_US
dc.subjectParkinson's diseaseen_US
dc.subjectEvoked resonant neural activityen_US
dc.subjectLocal field potentialsen_US
dc.subjectHigh frequency oscillationsen_US
dc.subjectSubthalamic nucleusen_US
dc.titleDeep brain stimulation for Parkinson's disease modulates high-frequency evoked and spontaneous neural activityen_US
dc.typeArticleen_US
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