How Sample Size Impacts Probabilistic Stimulation Maps in Deep Brain Stimulation

Probabilistic stimulation maps of deep brain stimulation (DBS) effect based on voxel-wise statistics (p-maps) have increased in literature over the last decade. These p-maps require correction for Type-1 errors due to multiple testing based on the same data. Some analyses do not reach overall significance, and this study aims to evaluate the impact of sample size on p-map computation. A dataset of 61 essential tremor patients treated with DBS was used for the investigation. Each patient contributed with four stimulation settings, one for each contact. From the dataset, 5 to 61 patients were randomly sampled with replacement for computation of p-maps and extraction of high- and low-improvement volumes. For each sample size, the process was iterated 20 times with new samples generating in total 1140 maps. The overall p-value corrected for multiple comparisons, significance volumes, and dice coefficients (DC) of the volumes within each sample size were evaluated. With less than 30 patients (120 simulations) in the sample, the variation in overall significance was larger and the median significance volumes increased with sample size. Above 120 simulations, the trends stabilize but present some variations in cluster location, with a highest median DC of 0.73 for n = 57. The variation in location was mainly related to the region between the high- and low-improvement clusters. In conclusion, p-maps created with small sample sizes should be evaluated with caution, and above 120 simulations in single-center studies are probably required for stable results.Funding Agencies|Swedish Foundation for Strategic Research [SSF BD15-0032]; Swedish Research Council [VR 2016-03564]