Based on single-cell recordings in primates, the relationship between neuro
nal activity and force magnitude is thought to be monotonic, at least for a
subset of pyramidal cells in the motor cortex. Functional neuroimaging stu
dies have also suggested a monotonic relationship between cerebral activati
on and force magnitude. In order to more precisely define this relationship
and to characterize the activation pattern(s) associated with the modulati
on of static force, we studied 40 normal subjects using [O-15]water PET and
a simple visuomotor task-application of static force on a micro force sens
or with the thumb and index finger of the right hand. When our experimental
design did not produce the expected result (evidence of a relationship bet
ween cerebral activation and force magnitude in ten subjects), we made seri
al changes in the experimental protocol, including the addition of control
(baseline) trials, and increased the number of subjects in an effort to inc
rease our sensitivity to variations in force magnitude. We compared univari
ate and multivariate data-analytic strategies, but we relied on our multiva
riate results to elucidate the interaction of attentional and motor network
s. We found that increasing the number of subjects from 10 to 20 resulted i
n an increase in statistical power and a more stable (i.e., more replicable
) but qualitatively similar result, and that the inclusion of control trial
s 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 a
nd that failure to detect such variation may result from unanticipated neur
obehavioral effects. (C) 2001 Academic Press.