A longitudinal fMRI study of the paced auditory serial addition task

The paced auditory serial addition task (PASAT) is a test of working memory and attention that is frequently abnormal in MS and is used serially to assess cognitive dysfunction as part of the MS Functional Composite in clinical trials. Previous studies using functional (fMRI) during PASAT performance have shown significant differences in activation patterns between healthy controls and MS patients matched for performance, but serial fMRI measures have not been reported. A confound is that learning effects are common with repeated PASAT testing, diminishing over successive trials. After measuring PASAT performance weekly for four weeks in 10 healthy controls to eliminate practice effects, we assessed brain activity using fMRI at baseline and after six months to determine the reproducibility of activation patterns in healthy controls during PASAT performance. Results showed that scores improved during the first three testing trials and stabilized subsequently. Brain activation during PASAT performance was seen in left frontal and parietal regions consistent with previous reports. After a six-month interval, PASAT performance and fMRI activity were stable, suggesting that serial fMRI during PASAT performance could be used as an outcome measure in trials assessing cognitive decline in clinical populations once practice effects are eliminated.