Abstract
Background: The efficacy of deep brain stimulation (DBS) therapy in Parkinson’s disease (PD) patients is highly dependent on the precise localization of the target structures such as subthalamic nucleus (STN). Most commonly, microelectrode single unit activity (SUA) recordings are performed to refine the target. This process is heavily experience based and can be technically challenging. Local field potentials (LFPs), representing the activity of a population of neurons, can be obtained from the same microelectrodes used for SUA recordings and allow flexible online processing with less computational complexity due to lower sampling rate requirements. Although LFPs have been shown to contain biomarkers capable of predicting patients’ symptoms and differentiating various structures, their use in the localization of the STN in the clinical practice is not prevalent.Methods: Here we present, for the first time, a randomized and double-blinded pilot study with intraoperative online LFP processing in which we compare the clinical benefit from SUA- versus LFP-based implantation. Ten PD patients referred for bilateral STN-DBS were randomly implanted using either SUA or LFP guided targeting in each hemisphere. Although both SUA and LFP were recorded for each STN, the electrophysiologist was blinded to one at a time. Three months postoperatively, the patients were evaluated by a neurologist blinded to the intraoperative recordings to assess the performance of each modality. While SUA-based decisions relied on the visual and auditory inspection of the raw traces, LFP-based decisions were given through an online signal processing and machine learning pipeline.Results: We found a dramatic agreement between LFP- and SUA-based localization (16/20 STNs) providing adequate clinical improvement (51.8% decrease in 3-month contralateral motor assessment scores), with LFP-guided implantation resulting in greater average improvement in the discordant cases (74.9%, n = 3 STNs). The selected tracks were characterized by higher activity in beta (11–32 Hz) and high-frequency (200–400 Hz) bands (p < 0.01) of LFPs and stronger non-linear coupling between these bands (p < 0.05).Conclusion: Our pilot study shows equal or better clinical benefit with LFP-based targeting. Given the robustness of the electrode interface and lower computational cost, more centers can utilize LFP as a strategic feedback modality intraoperatively, in conjunction to the SUA-guided targeting.
Highlights
Deep brain stimulation (DBS) is an effective treatment option for patients suffering from various neurological disorders such as Parkinson’s disease (PD) (Benabid et al, 2008; Groiss et al, 2009; Schiefer et al, 2011; Hariz, 2012, 2014; Odekerken et al, 2013; Gunduz et al, 2017; Lee et al, 2018)
The single unit activity (SUA)-predicted tracks were determined by the longest span of background and spiking activity (Figures 2A,B) whereas the longest span of in-subthalamic nucleus (STN) votes of the classifier were considered in Local field potentials (LFPs)-based selection (Figures 2C–F)
The randomized decision modality was SUA for the right hemisphere of patient 10 (Figure 2, right panel) suggesting implantation in the medial track, intraoperative computed tomography (CT) favored the center track as the target, which was used as the final implantation location
Summary
Deep brain stimulation (DBS) is an effective treatment option for patients suffering from various neurological disorders such as Parkinson’s disease (PD) (Benabid et al, 2008; Groiss et al, 2009; Schiefer et al, 2011; Hariz, 2012, 2014; Odekerken et al, 2013; Gunduz et al, 2017; Lee et al, 2018). SUA is used to identify cells with firing characteristics consistent with STN neurons and response characteristics confirming the motor sub-territory of the STN based on a variety of visual and auditory cues (Hutchison et al, 1998; Magnin et al, 2001; Rodriguez-Oroz et al, 2001; Abosch et al, 2002; Benazzouz et al, 2002) This procedure is subjective, heavily experience-based and depends critically on the neurosurgeon’s or electrophysiologist’s ability to recognize the STN (Benazzouz et al, 2002; Benabid et al, 2009; Marceglia et al, 2010; Abosch et al, 2013). LFPs have been shown to contain biomarkers capable of predicting patients’ symptoms and differentiating various structures, their use in the localization of the STN in the clinical practice is not prevalent
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