Subthalamic deep brain stimulation at individualized frequencies for Parkinson disease

Abstract

Objectives: The oscillation model of Parkinson disease (PD) states that, in the subthalamic nucleus (STN), increased θ (4-10 Hz) and β (11-30 Hz) frequencies were associated with worsening whereas γ frequencies (31-100 Hz) were associated with improvement of motor symptoms. However, the peak STN frequency in each band varied widely from subject to subject. We hypothesized that STN deep brain stimulation (DBS) at individualized γ frequencies would improve whereas θ or β frequencies would worsen PD motor signs.

Methods: We prospectively studied 13 patients with PD. STN local field potential (LFP) was recorded after electrode implantations, in the OFF and then in ON dopaminergic medication states while patients performed wrist movements. Six individual peak frequencies of the STN LFP power spectra were obtained: the greatest decrease in θ and β and greatest increase in γ frequencies in the ON state (MED) and during movements (MOVE). Eight DBS frequencies were applied including 6 MED and MOVE frequencies, high frequency (HF) used for chronic stimulation, and no stimulation. The patients were assessed using the motor Unified Parkinson's Disease Rating Scale (mUPDRS).

Results: STN DBS at γ frequencies (MED and MOVE) and HF significantly improved mUPDRS scores compared to no stimulation and both γ frequencies were not different from HF. DBS at θ and β frequencies did not worsen mUPDRS scores compared to no stimulation.

Conclusion: Short-term administration of STN DBS at peak dopamine-dependent or movement-related γ frequencies were as effective as HF for reducing parkinsonian motor signs but DBS at θ and β frequencies did not worsen PD motor signs.

Classification of evidence: This study provides Class III evidence that STN DBS at patient-specific γ frequencies and at usual high frequencies both improved mUPDRS scores compared to no stimulation and did not differ in effect.

Figure 1. Examples of dopamine-dependent and movement-related power spectra of the subthalamic nucleus (STN)

Data were recorded from right STN of patient 5. Power spectra were derived from deep brain stimulation (DBS) electrode contact pair 2–3. (A) Resting frequency spectra between 1 and 100 Hz in the OFF and ON dopaminergic medication states. Individualized dopamine-dependent frequencies for this patient were 10 Hz for the θ band which showed the greatest reduction in spectral power between 4 and 10 Hz in the ON compared to OFF states, 26.5 Hz for the β band which was the frequency with greatest reduction between 11 and 30 Hz in the ON compared to OFF states, and 48 Hz for the γ band which showed the greatest increase between 31 and 100 Hz in the ON compared to OFF states. (B) Movement-related spectra between 1 and 100 Hz in the premovement (−4 to −3.5 s) and the movement execution (0 to 0.5 s) periods from an average of 79 trials of self-initiated wrist movements in the ON dopaminergic medication state. Individualized movement-related frequencies for this patient were 9 Hz for the θ band which showed the greatest reduction between 4 and 10 Hz in the movement compared to premovement periods, 30 Hz for the β band which showed the greatest reduction between 11 and 30 Hz in the movement compared to premovement periods, and 80 Hz for the γ band which showed the greatest increase between 31 and 100 Hz in the movement compared to premovement periods.

Figure 2. The effects of deep brain stimulation (DBS) frequencies and medication states on hemibody and axial motor Unified Parkinson's Disease Rating Scale (mUPDRS) scores

(A) Hemibody and axial mUPDRS scores for 8 DBS frequencies in the OFF and ON dopaminergic medication states rated by the live rater. (B) Averaged hemibody and axial mUPDRS scores without rigidity for 8 DBS frequencies in the OFF and ON dopaminergic medication states rated by the video raters. The black bars represent mUPDRS scores obtained in the OFF dopaminergic medication state while the green bars represent the ON dopaminergic medication states. HF = high frequencies used for chronic STN DBS; MED = individualized dopamine-dependent frequencies; MOVE = individualized movement-related frequencies; STIM OFF = subthalamic nucleus DBS turned off. * p < 0.05. Error bar indicates 1 SEM.

Figure 3. The effects of deep brain stimulation (DBS) frequencies on tapping speed

The black bars represent motor Unified Parkinson's Disease Rating Scale scores obtained in the OFF dopaminergic medication state while the green bars represent the ON dopaminergic medication states. HF = high frequencies used for chronic DBS; MED = individualized dopamine-dependent frequencies; MOVE = individualized movement-related frequencies; STIM OFF = subthalamic nucleus DBS turned off. * p < 0.05. Error bar indicates 1 SEM.