Inconsistent Subthalamic Beta Expression in the Local Field Potential amid In- and Anti-Phasic Neuronal Bursts.

Abstract

BackgroundElevated beta (12-32 Hz) activity in the local field potential (LFP) of the subthalamic nucleus (STN) is a hallmark of Parkinsons disease and closely tied to synchronized spiking. Albeit the biomarkers prevalence has not been independently and reliably assessed, it is employed to guide deep brain stimulation (DBS) lead implantation. Likewise, beta is under investigation to inform DBS programming and adaptive DBS. This study assesses the applicability of these efforts by quantifying the biomarkers prevalence and investigating its relationship to synchronized beta-bursting neurons. MethodsSTN LFP and spiking activity of n = 156 patients with Parkinsons disease from six DBS centers recorded via microelectrodes was examined. Spectral peaks in the LFPs were classified and the absence of artifacts confirmed. The distribution of phase angles between beta LFP and spiking of individual beta-bursting neurons were explored. FindingsBilateral beta LFP expression was observed in 47{middle dot}25% of patients, and in 65{middle dot}59% of hemispheres. LFP-synchronized neuronal spiking clustered in two-thirds of neurons at a primary and in one-third at a secondary LFP phase (182{middle dot}84{degrees} phase shifted). This applied on the group level and for individual patients across different DBS centers. InterpretationBeta-informed approaches mandate reliable biomarker expression, a requirement not met by slightly more than half of herein investigated patients. This is particularly troublesome for intraoperative guidance wherein the cause of biomarker absence, including DBS lead misplacement or a balanced ratio of phasic and antiphasic spiking neurons, cannot be determined, decreasing insight and increasing doubt. Although beta LFPs remain a valuable biomarker, routine clinical practice should not rely on beta alone; instead, multiple biomarkers (i.e. beta-gamma coupling, finely tuned gamma and/or cortico-cortical beta-band coupling) should be evaluated simultaneously to increase robustness. FundingMaximilian Scherer received funding from the Alexander von Humboldt-Foundation. Thomas Koeglsperger has been supported by the Munich Clinician Scientist Program.