Functional MRI study of PASAT in normal subjects

Abstract

The paced auditory serial addition test (PASAT) is routinely used to evaluate the cognitive part of the multiple sclerosis functional composite (MSFC) score, the new reference index of patient disability. PASAT is sensitive to subtle cognitive impairment related to MS, although the cognitive components of this test still remain unclear. In order to better characterize brain systems involved during this complex task, functional magnetic resonance imaging (fMRI) experiments were conducted during PASAT in a population of ten normal subjects. The paradigm consisted of a series of 61 single-digit numbers delivered every 3 s. After each number, subjects were asked to overt vocalize the result of the addition of the two last numbers heard. A control task consisting of the repetition of the same series of single-digit numbers was used. Statistical group analysis was performed using the random effect procedure (SPM 99). Cortical activation was observed in the left prefrontal cortex, the supplementary motor area, the lateral premotor cortex, the cingulate gyrus, the left parietal lobe, the left superior temporal gyrus, the left temporal pole, and visual associative areas. fMRI activations underlying PASAT were consistent with an involvement of verbal working memory and the semantic memory retrieval network which could be related to arithmetic fact retrieval. This study on normal subjects could provide a base for the understanding of the potential abnormal cortical activation in MS patients performing this test for a cognitive evaluation.

Functional magnetic resonance imaging correlates of cognitive performance in patients with a clinically isolated syndrome suggestive of multiple sclerosis at presentation: an activation and connectivity study

“…In line with the results of previous studies [9,10,12], when compared to HC, CIS patients showed an increased recruitment of several regions mainly located in the frontal and parietal lobes, bilaterally. All of these regions contribute to different aspects of working memory processing and the majority of them have been demonstrated to have a load-depending activity during working memory tasks [29,30].…”

“…They also had an increased connectivity between the R IFG and R IPL and between the L and R IPL compared to both CP patients and healthy controls, thus indicating an increased task demand for the R hemisphere in these patients. The notion that an increased recruitment of areas of the R hemisphere has a critical role for cognitive performance of MS patients agrees with previous activation [33,9,34] and connectivity [14] studies performed in patients with CIS and RRMS, as well as with several studies of the motor network (for a review, see Filippi and Rocca [36], which showed that a recruitment of homologous regions of the two hemispheres is one of the main compensatory mechanisms, at least at the earliest clinical phases of the disease. Differently from previous studies, which found abnormalities of brain recruitment in patients without overt clinical impairment [ 37, 38] our analysis did not reveal any abnormality of activation and connectivity between CP CIS patients and HC.…”

“…It requires defining an a priori model, usually chosen among possible alternative models using a Bayesian model selection procedure [28]. In our case, this model was established based on brain areas known to be related to working memory, as shown by several previous fMRI studies [9,10,12]. The areas selected were: the left (L) and right (R) middle third of the middle frontal gyrus (MFG), the L and R inferior frontal gyrus (IFG), the L and R anterior cingulate cortex (ACC), and the L and R inferior parietal lobe (IPL).…”

“…Some of these studies have suggested that, at least in some cases, an altered pattern of brain recruitment might contribute to limit the clinical consequences of tissue damage F o r P e e r R e v i e w [9,10,11]. Brain reorganization has also been observed in CIS patients when performing cognitive [12] and motor tasks [13].…”

“…To examine possible early fMRI cognition-associated abnormalities, we studied a sample of CIS patients using an adapted version of the Paced Auditory Serial Addition Test (PASAT), which has been previously applied in several fMRI studies of patients with definite MS [9,10,12]. This task is sensitive to abnormalities of working memory and information processing speed.…”