Deep brain stimulation for Parkinson's disease modulates high-frequency evoked and spontaneous neural activity
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Date
2019-07
Journal Title
Journal ISSN
Volume Title
Publisher
Elsevier, Inc.
Abstract
Deep 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.
Description
Keywords
Deep brain stimulation, Parkinson's disease, Evoked resonant neural activity, Local field potentials, High frequency oscillations, Subthalamic nucleus
Citation
Sinclair, 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.