Effects of changes in experimental design on PET studies of isometric force

Based on single-cell recordings in primates, the relationship between neuronal activity and force magnitude is thought to be monotonic, at least for a subset of pyramidal cells in the motor cortex. Functional neuroimaging studies have also suggested a monotonic relationship between cerebral activation and force magnitude. In order to more precisely define this relationship and to characterize the activation pattern(s) associated with the modulation of static force, we studied 40 normal subjects using [(15)O]water PET and a simple visuomotor task-application of static force on a micro force sensor with the thumb and index finger of the right hand. When our experimental design did not produce the expected result (evidence of a relationship between cerebral activation and force magnitude in ten subjects), we made serial changes in the experimental protocol, including the addition of control (baseline) trials, and increased the number of subjects in an effort to increase our sensitivity to variations in force magnitude. We compared univariate and multivariate data-analytic strategies, but we relied on our multivariate results to elucidate the interaction of attentional and motor networks. We found that increasing the number of subjects from 10 to 20 resulted in an increase in statistical power and a more stable (i.e., more replicable) but qualitatively similar result, and that the inclusion of control trials in a 10-subject group did not enhance our ability to discern significant brain-behavior relationships. Our results suggest that sample sizes greater than 20 may be required to detect parametric variation in some instances and that failure to detect such variation may result from unanticipated neurobehavioral effects.