A fundamental problem in the study of learning is that learning-related cha
nges may be confounded by nonspecific time effects. There are several strat
egies for handling this problem. This problem may be of greater significanc
e in functional magnetic resonance imaging (fMRI) compared to positron emis
sion tomography (PET). Using the general linear model, we describe, compare
, and discuss two approaches for separating learning-related from nonspecif
ic time effects. The first approach makes assumptions on the general behavi
or of nonspecific effects and explicitly models these effects, i.e., nonspe
cific time effects are incorporated as a linear or nonlinear confounding co
variate in the statistical model. The second strategy makes no a priori ass
umption concerning the form of nonspecific time effects, but implicitly con
trols for nonspecific effects using an interaction approach, i.e., learning
effects are assessed with an interaction contrast. The two approaches depe
nd on specific assumptions and have specific limitations. With certain expe
rimental designs, both approaches may be used and the results compared, len
ding particular support to effects that are independent of the method used.
A third and perhaps better approach that sometimes may be practically unfe
asible is to use a completely temporally balanced experimental design. The
choice of approach may be of particular importance when learning-related ef
fects are studied with fMRI. Hum. Brain Mapping 7:234-243, 1999. (C) 1999 W
iley-Liss, Inc.