Pallidal stimulation: Effect of pattern and rate on bradykinesia in the non-human primate model of Parkinson's disease

Deep brain stimulation (DBS) involves the delivery of continuous, fixed-frequency electrical pulses to specific brain regions; however the reliance of therapeutic benefit on the fixed-frequency nature of the stimulation pattern is currently unknown. To address this, we investigated the effect of changes in the pattern and frequency of DBS in the internal segment of the globus pallidus (GPi) on bradykinesia in a single, hemi-parkinsonian monkey. Therapeutic parameters (i.e., contacts, pulse width, amplitude) were established for fixed-frequency stimulation at 135 Hz based on improved movement times during a reach and retrieval task. Thereafter, the pattern and frequency of stimulation were varied to assess the effect of variability, bursting and oscillatory patterns of stimulation on bradykinesia. During fixed-frequency stimulation, performance improved as a function of increasing pulse rate (P < 0.01). Using a temporally irregular pattern at the same average frequency failed to alter therapeutic benefit relative to the fixed-frequency condition. Introducing an 80 Hz burst pattern (20 bursts/s at 4 pulses/burst) improved bradykinesia (P < 0.01) relative to both “OFF” and 80 Hz fixed-frequency conditions, yielding results comparable to fixed-frequency stimulation at 135 Hz with 40% less current drain. Compared to burst and fixed-frequency stimulations, oscillatory patterns at 4 and 8 Hz were less effective. These results suggest that lower frequency stimulation delivered in a regular bursting pattern may be equally effective and require lower energy than higher frequency continuous patterns of stimulation, thereby prolonging battery life and call into question the role of bursting activity in the pathogenesis of bradykinesia.