Objective: Brain–computer interfaces (BCIs) could potentially be used to interact with pathological brain signals to intervene and ameliorate their effects in disease states. Here, we provide proof-of-principle of this approach by using a BCI to interpret pathological brain activity in patients with advanced Parkinson disease (PD) and to use this feedback to control when therapeutic deep brain stimulation (DBS) is delivered. Our goal was to demonstrate that by personalizing and optimizing stimulation in real time, we could improve on both the efficacy and efficiency of conventional continuous DBS.Methods: We tested BCI-controlled adaptive DBS (aDBS) of the subthalamic nucleus in 8 PD patients. Feedback was provided by processing of the local field potentials recorded directly from the stimulation electrodes. The results were compared to no stimulation, conventional continuous stimulation (cDBS), and random intermittent stimulation. Both unblinded and blinded clinical assessments of motor effect were performed using the Unified Parkinson's Disease Rating Scale.Results: Motor scores improved by 66% (unblinded) and 50% (blinded) during aDBS, which were 29% (p = 0.03) and 27% (p = 0.005) better than cDBS, respectively. These improvements were achieved with a 56% reduction in stimulation time compared to cDBS, and a corresponding reduction in energy requirements (p < 0.001). aDBS was also more effective than no stimulation and random intermittent stimulation.Interpretation BCI-controlled DBS is tractable and can be more efficient and efficacious than conventional continuous neuromodulation for PD. Ann Neurol 2013;74:449–457

Introduction & objectivesAdaptive deep brain stimulation (aDBS) uses feedback from brain signals to guide stimulation. A recent acute trial of unilateral aDBS showed that aDBS can lead to substantial improvements in contralateral hemibody Unified Parkinson’s Disease Rating Scale (UPDRS) motor scores and may be superior to conventional continuous DBS in Parkinson’s disease (PD). We test whether potential benefits are retained with bilateral aDBS and in the face of concurrent medication.MethodsWe applied bilateral aDBS in 4 patients with PD undergoing DBS of the subthalamic nucleus. aDBS was delivered bilaterally with independent triggering of stimulation according to the amplitude of β activity at the corresponding electrode. Mean stimulation voltage was 3.0±0.1 volts. Motor assessments consisted of double-blinded video-taped motor UPDRS scores that included both limb and axial features.ResultsUPDRS scores were 43% (p=0.04; Cohen’s d=1.62) better with aDBS than without stimulation. Motor improvement with aDBS occurred despite an average time on stimulation (ToS) of only 45%. Levodopa was well tolerated during aDBS and led to further reductions in ToS.ConclusionBilateral aDBS can improve both axial and limb symptoms and can track the need for stimulation across drug states.

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

HighlightsSetup for MEG and intracranial recordings during Deep Brain Stimulation is described.Phantom experiment showed correct recovery of oscillatory sources despite artefacts.The method is applied to real data from a patient with Parkinson's Disease.Cortico-subthalamic coherence profiles on and off stimulation were comparable.

Adaptive deep brain stimulation (aDBS) has the potential to improve the treatment of Parkinson's disease by optimizing stimulation in real time according to fluctuating disease and medication state. In the present realization of adaptive DBS we record and stimulate from the DBS electrodes implanted in the subthalamic nucleus of patients with Parkinson's disease in the early post-operative period. Local field potentials are analogue filtered between 3 and 47 Hz before being passed to a data acquisition unit where they are digitally filtered again around the patient specific beta peak, rectified and smoothed to give an online reading of the beta amplitude. A threshold for beta amplitude is set heuristically, which, if crossed, passes a trigger signal to the stimulator. The stimulator then ramps up stimulation to a pre-determined clinically effective voltage over 250 msec and continues to stimulate until the beta amplitude again falls down below threshold. Stimulation continues in this manner with brief episodes of ramped DBS during periods of heightened beta power.Clinical efficacy is assessed after a minimum period of stabilization (5 min) through the unblinded and blinded video assessment of motor function using a selection of scores from the Unified Parkinson's Rating Scale (UPDRS). Recent work has demonstrated a reduction in power consumption with aDBS as well as an improvement in clinical scores compared to conventional DBS. Chronic aDBS could now be trialed in Parkinsonism.