Gait phase triggered deep brain stimulation in Parkinson’s disease

Abstract

Letter to the EditorGait disorder is a particularly disabling and treatment refractory symptom of Parkinson's disease (PD), contributing to higher fall risk [1] and restrictions of daily activities [2]. Although Parkinsonian gait can improve with deep brain stimulation (DBS) of the subthalamic nucleus (STN) or globus pallidus internus (GPi) [3], gait is not considered to be adequately treated [4].Two "closed-loop" DBS alternatives have been proposed: adaptive DBS (aDBS), where stimulation varies with local field potential (LFP) power (e.g. beta-band 13e30 Hz) [5], and responsive DBS (rDBS), where stimulation is entrained to a specific phase of the pathological movement (e.g. tremor) [6]. Two studies have evaluated aDBS effect on gait [7,8], and none has evaluated rDBS effect on gait.Beta-band power is modulated with the gait cycle [9]. We hypothesize that rDBS timed to gait events might allow, or even enhance, this normal, physiological beta modulation, improving gait. We developed and tested a rDBS system delivering short duration pulse trains at specific gait phases in real-time. To assess the accuracy of stimulation delivery, gait phases were aligned with stimulation artifacts collected from a surface EMG electrode on the neck. To measure efficacy of this rDBS system, we assessed spatial and temporal gait metrics.Sixteen PD individuals with bilateral DBS leads (13 STN, 3 GPi) and Medtronic SC, PC, or RC implantable neural stimulators (INSs) were enrolled. All gave informed consent according to a University of Minnesota Institutional Review Board approved protocol. Data from four participants (all STN) were excluded due to technical difficulties (stimulation not delivered at the target gait phase). Detailed participant demographics are in Table S1.Participants walked on an instrumented treadmill (C-Mill, Motek Medical, Netherlands) for one-minute trials. Each trial was under one of five conditions: off-stimulation, continuous stimulation, stimulation triggered on ipsilateral heel-strike (IHS), on contralateral heel-strike (CHS), or on contralateral toe-off (CTO).

Wearable sensor-driven responsive deep brain stimulation for essential tremor

“…EMG electrodes are bilaterally placed during recordings. These muscles were chosen due to their role in flexion and extension of both the wrist and forearms, which are locations of tremors in ET [37,38]. (b) Data were collected from participants while performing tremor provoking tasks (kinetic or postural tasks) beginning in the DBS-off state.…”

“…In addition to invasive LFP-based rDBS, there is increasing interest in non-invasive approaches with peripheral sensors [27,28,[33][34][35][36][37], which are capable of directly measuring motor symptoms, such as tremor [27,28,38], and decoding relevant behavioral states, such as movement [27,33], gait events [37,39,40], or sleep [41]. However, sensor-based studies have been limited to offline approaches [34,35], have solely reported clinical [33,36] or objective [27,28,37,38,42] measurements of symptom severity, and have demonstrated feasibility in a scarce number of participants. Here, in a prospective study of 10 human participants with ET, we aimed to develop an rDBS system using wearable sensors tailored for electromyography (EMG).…”

Gait-Phase Modulates Alpha and Beta Oscillations in the Pedunculopontine Nucleus

“…Recently, another independent study reported that compared with continuous DBS, gait phase triggered responsive DBS (rDBS) targeting STN or globus pallidus internus (GPi) only lead to significant improvement on gait in 3 out of 12 participants (Louie et al, 2021). However, the stimulation was only switched ON for 12% of each cycle at fixed gait phase, which might not be enough to enhance the alternating pattern of the brain activities during stepping.…”

Multidimensional Bayesian Estimation for Deep Brain Stimulation Using the SafeOpt Algorithm

“…Consequently, we regard this as our most important finding, since it shows the feasibility of those experiments. Our gait measurement protocol 19 achieved 20 measurements in a single session, and that number could easily have been increased, by eliminating a lengthy set-up procedure which was specific to those experiments. Moreover, the SafeOpt algorithm can be adapted to multiple sessions on different days, with each session resuming where the algorithm left off on the preceding session.…”

“…The median over all 27 patients was 1.8%,1.6% for the left and right foot, respectively. Next, from our previously published study of DBS effects 19 we obtained an effect size for the therapeutic effect of DBS on stride length, using a similar one-minute walking protocol. As Figure 1E in that paper shows, the effect size was about 5%, i.e.…”