Abstract
Adaptive deep brain stimulation uses feedback about the state of neural circuits to control stimulation rather than delivering fixed stimulation all the time, as currently performed. In patients with Parkinson's disease, elevations in beta activity (13-35 Hz) in the subthalamic nucleus have been demonstrated to correlate with clinical impairment and have provided the basis for feedback control in trials of adaptive deep brain stimulation. These pilot studies have suggested that adaptive deep brain stimulation may potentially be more effective, efficient and selective than conventional deep brain stimulation, implying mechanistic differences between the two approaches. Here we test the hypothesis that such differences arise through differential effects on the temporal dynamics of beta activity. The latter is not constantly increased in Parkinson's disease, but comes in bursts of different durations and amplitudes. We demonstrate that the amplitude of beta activity in the subthalamic nucleus increases in proportion to burst duration, consistent with progressively increasing synchronization. Effective adaptive deep brain stimulation truncated long beta bursts shifting the distribution of burst duration away from long duration with large amplitude towards short duration, lower amplitude bursts. Critically, bursts with shorter duration are negatively and bursts with longer duration positively correlated with the motor impairment off stimulation. Conventional deep brain stimulation did not change the distribution of burst durations. Although both adaptive and conventional deep brain stimulation suppressed mean beta activity amplitude compared to the unstimulated state, this was achieved by a selective effect on burst duration during adaptive deep brain stimulation, whereas conventional deep brain stimulation globally suppressed beta activity. We posit that the relatively selective effect of adaptive deep brain stimulation provides a rationale for why this approach could be more efficacious than conventional continuous deep brain stimulation in the treatment of Parkinson's disease, and helps inform how adaptive deep brain stimulation might best be delivered.
Highlights
Deep brain stimulation (DBS) is a well-established treatment option for advanced Parkinson’s disease (Deuschl et al, 2006; Hariz, 2012)
We investigated the effect of adaptive DBS compared to no stimulation and conventional DBS on bursts of beta activity in 13 patients (16 hemispheres) with advanced Parkinson’s disease undergoing DBS surgery of the subthalamic nucleus (STN) (Table 1)
For the post hoc comparison between adaptive DBS and no stimulation (noStim) we found that the number of short bursts (200–300 ms and 300–400 ms) was higher during adaptive DBS compared to noStim [t(15) = 2.750, P = 0.045; t(15) = 3.126, P = 0.049]
Summary
Deep brain stimulation (DBS) is a well-established treatment option for advanced Parkinson’s disease (Deuschl et al, 2006; Hariz, 2012). In a first proof-of-principle study in patients with Parkinson’s disease, it was shown that using the beta band activity as a feedback signal for unilateral adaptive DBS led to an improvement in contralateral motor performance superior to that achieved with conventional DBS, while battery consumption was reduced by about half (Little et al, 2013). This has been followed by a further patient series confirming the efficacy of bilateral adaptive DBS (Little et al, 2015) and a case report demonstrating a reduction in dyskinesias in Parkinson’s disease with adaptive DBS using a different control algorithm (Rosa et al, 2015). In acute trials, it has recently been shown that speech intelligibility is preserved during adaptive DBS, while speech deterioration was observed during conventional DBS (Little et al, 2016)
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