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.
Subject(s)
Brain Mapping/methods , Cerebral Cortex/anatomy & histology , Cerebral Cortex/physiology , Cognition/physiology , Evoked Potentials/physiology , Image Interpretation, Computer-Assisted/methods , Magnetic Resonance Imaging/methods , Adult , Female , Humans , MaleABSTRACT
fMRI and structural equation modeling (SEM) were used to study effective connectivity inside the working memory network in patients at the earliest stage of multiple sclerosis (MS), while performing paced auditory serial addition test (PASAT), a sensitive task to reveal subtle cognitive impairments related to working memory and information speed processing. The path model used for SEM included bilateral connections between left and right BA 46, left and right BA 40, left and right anterior cingulate cortex (ACC), left BA 44 and left BA 40, right BA 44 and right BA 40, and unidirectional ipsilateral connections from BA 46 to BA 44, from ACC to BA 46, and from ACC to BA 44. Experimental data from the two groups fit accurately the working memory model, in patients [chi20(2) = 13, P = 0.877] as well as in controls [chi20(2) = 13.54, P = 0.853]. The omnibus test indicated a significant difference of model fits in patients and in controls [chi40(2) = 160.07, P < 0.0001]. Connectivity strengths from right BA 46 to left BA 46, from left ACC to left BA 46 were lower in patients than in controls, and higher from right ACC to right BA 46, from left to right and from right to left ACC (stacked model). Effective connectivity inside the working memory network appears altered in patients at the earliest stage of MS. Modulation of effective connectivity is present in patients inside the executive subsystems of working memory, and could be related to adaptive cognitive control processes that may limit the clinical manifestation of MS.
