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.

The efficacy of deep brain stimulation (DBS) in Parkinson's disease (PD) has been convincingly demonstrated in studies that compare motor performance with and without stimulation, but characterization of performance at intermediate stimulation amplitudes has been limited. This study investigated the effects of changing DBS amplitude in order to assess dose-response characteristics, inter-subject variability, consistency of effect across outcome measures, and day-to-day variability. Eight subjects with PD and bilateral DBS systems were evaluated at their clinically determined stimulation (CDS) and at three reduced amplitude conditions: approximately 70%, 30%, and 0% of the CDS (MOD, LOW, and OFF, respectively). Overall symptom severity and performance on a battery of motor tasks - gait, postural control, single-joint flexion-extension, postural tremor, and tapping - were assessed at each condition using the motor section of the Unified Parkinson's Disease Rating Scale (UPDRS-III) and quantitative measures. Data were analyzed to determine whether subjects demonstrated a threshold response (one decrement in stimulation resulted in ≥ 70% of the maximum change) or a graded response to reduced stimulation. Day-to-day variability was assessed using the CDS data from the three testing sessions. Although the cohort as a whole demonstrated a graded response on several measures, there was high variability across subjects, with subsets exhibiting graded, threshold, or minimal responses. Some subjects experienced greater variability in their CDS performance across the three days than the change induced by reducing stimulation. For several tasks, a subset of subjects exhibited improved performance at one or more of the reduced conditions. Reducing stimulation did not affect all subjects equally, nor did it uniformly affect each subject's performance across tasks. These results indicate that altered recruitment of neural structures can differentially affect motor capabilities and demonstrate the need for clinical consideration of the effects on multiple symptoms across several days when selecting DBS parameters.