Deep brain stimulation can suppress pathological synchronisation in parkinsonian patients

Abstract

Background: Although deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a highly effective therapeutic intervention in severe Parkinson's disease, its mechanism of action remains unclear. One possibility is that DBS suppresses local pathologically synchronised oscillatory activity.

Methods: To explore this, the authors recorded from DBS electrodes implanted in the STN of 16 patients with Parkinson's disease during simultaneous stimulation (pulse width 60 μs; frequency 130 Hz) of the same target using a specially designed amplifier. The authors analysed data from 25 sides.

Results: The authors found that DBS progressively suppressed peaks in local field potential activity at frequencies between 11 and 30 Hz as voltage was increased beyond a stimulation threshold of 1.5 V. Median peak power had fallen to 54% of baseline values by a stimulation intensity of 3.0 V.

Conclusion: The findings suggest that DBS can suppress pathological 11-30 Hz activity in the vicinity of stimulation in patients with Parkinson's disease. This suppression occurs at stimulation voltages that are clinically effective.

Figure 1

Power autospectra of local field potential (LFP) recorded between contacts 1 and 3 from left subthalamic nucleus deep brain stimulation (DBS) electrode in case 1. Log power autospectra show a peak centred at 8.6 Hz (left vertical arrow), which is unaffected by amplifier type or DBS applied to contact 2 (pulse-width 60 μs; frequency 130 Hz), and a peak centred around 25 Hz (right vertical arrow), which is unaffected by amplifier type but which is suppressed by DBS applied to contact 2 at 2.5 V (130 Hz). The latter was also the threshold for the suppression of contralateral rigidity and bradykinesia as determined by clinical examination using stimulation of the same contact pair performed at a different time on the same day. Two kinds of amplifier were used: Digitimer D360 and our custom-built amplifier. Frequency resolution is 1 Hz. Autospectra averaged over 110 s recorded during same experimental session, but not simultaneously.

Figure 2

Effect of deep brain stimulation (DBS) of right subthalamic nucleus on local field potential (LFP) in case 5. (A) Power autospectrum of LFP recorded without stimulation. There is a large peak arrowed at 13.6 Hz. (B) Frequency-time log power spectrum of LFP (contact pair 02). Frequency resolution 0.39 Hz. Power, as in (A), shown over the pass band of the amplifier (4–40 Hz). Red bars along the time axis denote periods of DBS at 2.0–3.0 V. Dyskinesias of the contralateral foot were noted at voltages of 2.0 V and above. Note suppression of spectral peak with stimulation ≥2.0 V, with evidence of a temporary increase in the power of the peak with stimulation at 1.5 V and a delayed return of the peak after stimulation at 3.0 V is terminated. (C) Timing and voltage of DBS applied at contact 1. In total, four peaks (on three sides from two patients) between 11 and 30 Hz demonstrated an initial but temporary increase in power before the onset of suppression, as stimulation voltages were progressively increased (see outliers in figure 3).

Figure 3

Summary box plot of power suppression of beta band peaks during stimulation at different voltages. Power is expressed as a percentage from baseline (without deep brain stimulation). There is a progressive suppression of power of spectral peaks of local field potential between 11 and 30 Hz with increasing voltages. The bottom and top of the boxes are the 25th and 75th percentile, and the band near the middle of the box is the 50th percentile (the median). The whiskers represent one SD above and below the mean of the data. Interrupted lines link medians. Shaded boxes are different from 100% (Mann–Whitney U tests p<0.05, corrected for multiple testing). Peaks with outlying power levels at a given stimulation voltage are denoted by asterisks. The outliers above 150% at 1.5 and 2.0 V are those sides, like those illustrated in figure 2, in which there was a temporary increase in the power of the peak as stimulation voltage was incrementally increased. Peak power suppressed thereafter as stimulation voltage was increased still further.