Compensatory cortical activation observed by fMRI during a cognitive task at the earliest stage of multiple sclerosis

Abstract

Recent functional magnetic resonance imaging (fMRI) studies have suggested that functional cortical changes seen in patients with early relapsing-remitting multiple sclerosis (MS) can have an adaptive role to limit the clinical impact of tissue injury. To determine whether cortical reorganization occurs during high cognitive processes at the earliest stage of multiple sclerosis (MS), we performed an fMRI experiment using the conventional Paced Auditory Serial Addition Test (PASAT) as paradigm in a population of ten patients with clinically isolated syndrome suggestive of multiple sclerosis (CISSMS). At the time of the fMRI exploration, mean disease duration was 6.8 Ϯ 3.3 months. We compared these results to those obtained in a group of ten education-, age-, and sex-matched healthy controls. Subjects were explored on a 1.5 T MRI system using single-shot gradient-echo EPI sequence. Performances of the two groups during PASAT recorded inside the MR scanner were not different. Statistical assessment of brain activation was based on the random effect analysis (between-group analysis two-sample t-test P Ͻ 0.005 confirmed by individual analyses performed in the surviving regions P Ͻ 0.05 Mann Whitney U-test). Compared to controls, patients showed significantly greater activation in the right frontopolar cortex, the bilateral lateral prefrontal cortices, and the right cerebellum. Healthy controls did not show greater activation compared to CISSMS patients. The present study argues in favor of the existence of compensatory cortical activations at the earliest stage of MS mainly located in regions involved in executive processing in patients performing PASAT. It also suggests that fMRI can evidence the active processes of neuroplasticity contributing to mask the clinical cognitive expression of brain pathology at the earliest stage of MS. Hum. Brain

Structural and functional MRI correlates of Stroop control in benign MS

“…Since only the corrected answers were modelled in the statistical analysis and task performance was similar between patients and controls, we can reasonably rule out a possible influence of cognitive impairment and different task performance between patients and controls on our fMRI results. These results are in agreement with those of previous studies which assessed fMRI patterns of activation during the performance of cognitive tasks in patients at the earliest stages of the disease [Audoin et al, 2003] and in those with relapsing course [Hillary et al, 2003;Mainero et al, 2004;Staffen et al, 2002]. Our results are partially in contrast with those of a previous study [Parry et al, 2003] of a mixed group of patients with relapsing remitting (RR) and secondary progressive (SPM) MS, where an increased activation of the L frontal cortex and a decreased activation of the R frontal cortex were found in patients in comparison with controls.…”

“…The conventional SPM analysis exclusively showed an increased activation of all the previous areas in BMS patients when contrasted to controls, thus not allowing to disclose any difference in the behaviour of the different areas. The notion that increased recruitment of areas of the R hemisphere is a critical aspect for a reorganisation inside the cognitive network is in line with previous activation [Audoin et al, 2003;Hillary et al, 2003;Mainero et al, 2004;Staffen et al, 2002] and connectivity studies [Cader et al, 2006] performed on patients with clinically isolated syndromes suggestive of MS and RRMS, as well as with many studies of the motor network [Filippi and Rocca, 2004] showing that recruitment of homologous regions in the two hemisphere is one of the main compensatory mechanisms, at least at the beginning of the disease. This is the first study showing that this mechanism is working also in patients with BMS.…”

Functional MRI in investigating cognitive impairment in multiple sclerosis

“…Working memory has been the most extensively studied domain by means of the Paced Auditory Serial Addition Test (PASAT) or the Paced Visual Serial Addition Task. [7][8][9][10][11][12][13] In patients with a clinically isolated syndrome (CIS) suggestive of MS, an altered pattern of cortical activations has been described during PASAT performance, confirming the presence of cortical reorganization at the earliest clinical stage of disease. 10 An increased recruitment of several cortical areas during PASAT has also been shown in patients with relapsing-remitting (RR) MS and mild cognitive impairment, 11 suggesting that an impaired cognitive task performance in these patients could reflect a decreased function of canonical task-specific areas in the absence of adequate compensatory strategies.…”

Neuroimaging - Clinical Applications

“…At later stages, bilateral activation of these regions is first observed, followed by a widespread recruitment of additional areas, which are usually recruited by healthy subjects in the performance of more complex or novel tasks . Similarly, fMRI studies investigating various cognitive domains in MS patients have shown altered patterns of cortical activation (Audoin et al, 2003;Staffen et al, 2002;Hillary et al, 2003;Li et al, 2004;Cader et al, 2006). Moreover a relationship between cortical activation and fatigue has been shown in several studies suggesting that the underlying mechanism of this common but poorly understood symptom may be the deficiency of neuronal compensation (Filippi et al, 2002;White et al, 2009).…”