Effects of Deep Brain Stimulation Amplitude on Motor Performance in Parkinson’s Disease

Background: The efficacy of deep brain stimulation (DBS) in Parkinson’s disease has been convincingly demonstrated in studies comparing motor performance with and without stimulation, but characterization of the stimulation dose-response curves has been limited.

Methods: In a series of case studies, eight subjects with Parkinson’s disease and bilateral DBS systems were evaluated at their clinically determined stimulation (CDS) and at three reduced amplitudes, ie, approximately 70%, 30%, and 0% of the CDS (MOD, LOW, and OFF, respectively). Performance was assessed using the motor section of the Unified Parkinson’s Disease Rating Scale (UPDRS-III), which includes subscores for tremor, bradykinesia, gait, posture, and tapping. Data at the reduced settings were analyzed to determine if individual subjects demonstrated a threshold-like response, which was defined as a dose-response curve in which one decrement in stimulation accounted for ≥70% of the maximum change observed. Day-to-day variability was assessed using the CDS data from the three different days.

Results: In the dose-response curves, two subjects exhibited a threshold-like response, four exhibited a graded change, and two did not exhibit substantial changes. For some subjects, variability in CDS performance across the three days exceeded the change observed when reducing amplitude to the MOD setting. Comparisons across this set of eight subjects demonstrated that the mean UPDRS-III and all but one subscore significantly increased (performance degraded) when amplitude was reduced from CDS to the LOW and OFF conditions, but there were no significant changes when amplitude was reduced from CDS to the MOD condition.

Conclusion: Individual differences in the DBS dose-response curves may provide opportunities to optimize clinical performance. Day-to-day variability in motor performance cautions against the use of a single UPDRS measurement in clinical selection of DBS settings.