Adaptive DBS in a Parkinson's patient with chronically implanted DBS: A proof of principle

Abstract

Preliminary evidence from patients with Parkinson's disease (PD) suggests that deep brain stimulation (DBS) might work better, more efficiently, and with fewer side effects when applied in an adaptive manner (aDBS)1-4 In each of these studies aDBS was delivered according to the amplitude of beta oscillations (13-30 Hz) in the subthalamic nucleus (STN), which itself has been shown to correlate with contralateral akinesia and rigidity (AR).5 The key limitations in these clinical aDBS studies are that they have been conducted in the immediate postoperative phase. In this period, clinical testing and stimulation titration are complicated by the "stun" effect, and the optimal chronic DBS settings are not yet known. Furthermore, AR has thus far only been assessed with ordinal clinical scores, a limited and subjective rating system. To circumvent these limitations, we applied aDBS in a PD patient who had been chronically implanted with DBS and already titrated to optimal stimulation parameters and assessed bradykinesia with a validated digital task. aDBS was applied during battery replacement surgery in a 68-year-old patient with a 27-year history of Parkinson's disease who had been implanted with bilateral STN electrodes for 14 years. The patient gave consent to the research protocol, which was approved by the local ethics committee. Bipolar local field potential (LFP) amplitude in the beta range ± 3 Hz was used as biomarker in such a way that conventional DBS was provided only when beta amplitude exceeded an estimated median value (for methods see references 1, 3, and 4). aDBS was applied for 12 minutes to the right STN (contralateral to the most affected side) with matched stimulation parameters to optimized conventional DBS (cDBS), namely, 2.8V, 60-microsecond pulse width, and 135 Hz (with 250-millisecond ramping at onset and offset). Bradykinesia was assessed using a tablet-based version of the validated bradykinesia, akinesia, incoordination (BRAIN) task.6 The BRAIN task assesses the velocity of alternating finger movements between 2 buttons

An update on adaptive deep brain stimulation in Parkinson's disease

“…Moreover, a recent study demonstrated the feasibility and beneficial effects on motor symptoms of aDBS over the course of 8 hours in akinetic‐rigid PD patients . Previous studies had already shown that aDBS was applicable and effective in a freely moving and a chronically implanted PD patient …”

“…21 Previous studies had already shown that aDBS was applicable and effective in a freely moving 22 and a chronically implanted PD patient. 23 Nevertheless, beta-LFPs in the STN are not (easily) detectable in all patients, 8 although this long-standing assumption has been contradicted recently. 24 Second, changes in beta-LFPs do not clearly capture all main symptoms of PD.…”

Toward Electrophysiology-Based Intelligent Adaptive Deep Brain Stimulation for Movement Disorders

“…A closed-loop stimulation strategy first was shown to be effective in a non-human primate model of PD via recording in motor cortex and the globus pallidus (GPi) and stimulating in the GPi [192]. The translational nature of this approach recently has attracted many multidisciplinary research groups bringing neurologists, neurosurgeons, engineers, and neuroscientists together with the aim to improve therapeutic outcome in DBS [49,50,137,181,[193][194][195][196][197][198]. The first studies in human PD patients utilized pathological increases in STN beta activity to trigger stimulation with fixed DBS parameters, where stimulation ceased after sufficient beta signal suppression was achieved [194,[199][200][201].…”

“…The translational nature of this approach recently has attracted many multidisciplinary research groups bringing neurologists, neurosurgeons, engineers, and neuroscientists together with the aim to improve therapeutic outcome in DBS [49,50,137,181,[193][194][195][196][197][198]. The first studies in human PD patients utilized pathological increases in STN beta activity to trigger stimulation with fixed DBS parameters, where stimulation ceased after sufficient beta signal suppression was achieved [194,[199][200][201]. This approach resulted in similar or better symptom alleviation compared with conventional DBS and a reduction of dyskinesia symptoms [181,195,201] and stimulation-induced side effects [202].…”

“…Notwithstanding the impact of piloting aDBS studies for the field of human neuralnetwork neurosurgery, the STN-LFP beta power approach has several limitations that raise questions about its usefulness for adoption in a clinical real-life setting. Most importantly, sensing from the same lead that delivers stimulation is suboptimal in many ways: (i) signal quality deteriorates with stimulation; (ii) bipolar sensing leaves only 2 of 4 available stimulation contacts that necessarily should reside in an optimal target location [181,194,195,200,202]; (iii) common mode rejection, through which an LFP signal is less perturbed by DBS when sensing contacts are distributed symmetrically around the stimulation contact, may require symmetric current spread, potentially obliterating the additional benefit directional current steering [149,150,152]; and (iv) that approach may force DBS target planning to include consideration of biomarker location rather than enabling independent optimal targeting of both sensing and stimulation electrodes. Here, using additional ECoG recordings for closed-loop sensing, which has been reported to be safe [206], could have striking advantages: (i) compatibility with any DBS electrode design; (ii) optimal signal to noise ratio; (iii) placement of the sensing electrode independent of the DBS target (e.g., white matter tracts for tremor); (iv) coverage of large areas (potentially more than one location; many contacts); (v) reduction of stimulation artifacts; and (vi) preservation of the number of potential stimulation contacts in the DBS target.…”