Bilateral adaptive deep brain stimulation is effective in Parkinson's disease

Abstract

Introduction & objectives: Adaptive 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.

Methods: We 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.

Results: UPDRS 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.

Conclusion: Bilateral aDBS can improve both axial and limb symptoms and can track the need for stimulation across drug states.

Figure 1

Screen shot of 15 s bilateral adaptive deep brain stimulation (aDBS) in patient 1. Bottom two traces are local field potentials (LFPs) after first stage analogue filtering (LFPf1; 3–37 Hz). Third and fourth traces from bottom show LFPs after second stage digital filtering around patient specific β peak (LFPf2; 20±3 Hz). The two traces above are the online readouts of the filtered β amplitude after rectification, smoothing and thresholding. The top two traces show bursts of ramped stimulation in response to β amplitude threshold crossing. Blue and red traces are from left and right electrodes, respectively. Note stimulation across the two sides is discontinuous and independent.

Figure 2

Group mean blinded UPDRS motor scores in the two experimental conditions and their SEs. *Indicates significance with p<0.05. Red circles depict individual data. DBS, deep brain stimulation; UPDRS, Unified Parkinson's Disease Rating Scale.

Figure 3

Per cent ToS during prolonged aDBS after levodopa administration at time 0 and its dependency on β power. (A) Grey blocks indicate the periods of stable ToS as identified by change-point analysis (p<0.01). The vertical extent of the blocks denotes the confidence limits of blocks between significant change points and these blocks are centred on the mean of the stable period. The vertical arrows denote when clinical improvement due to levodopa was first manifest. ToS dropped at the onset of the clinical effect of levodopa. Note that prior to this, ToS was stable for about 30 min or more, suggesting that the progressive drop in ToS at the very outset of aDBS plateaued with continued aDBS. (B) Scatter plots of β power and ToS per 10 s block. Grey line is the product of linear regression. aDBS, adaptive deep brain stimulation; STN, subthalamic nucleus; ToS, time on stimulation.