Magnetic resonance study of the influence of tissue damage and cortical reorganization on PASAT performance at the earliest stage of multiple sclerosis

Abstract

We sought to determine the influence of tissue damage and the potential impact of cortical reorganization on the performance to the Paced Auditory Serial Addition Test (PASAT) in patients at the earliest stage of multiple sclerosis (MS). Magnetization transfer ratio (MTR) imaging and functional magnetic resonance imaging (fMRI) experiments using PASAT as paradigm were carried out in 18 patients with clinically isolated syndrome suggestive of MS (CISSMS) compared to 18 controls. MTR histogram analyses showed structural abnormalities in patients involving the normal-appearing white matter (NAWM) but also the gray matter (GM). Mean PASAT scores were significantly lower in the group of patients taken as a whole, and were correlated with the mean NAWM MTR value. No correlation was observed between PASAT scores and GM MTR. However, in the subgroup of patients with normal PASAT performance (n = 9), fMRI showed larger activations in bilateral Brodmann area 45 (BA45) and right BA44 compared to that in controls (n = 18). In these areas with potentially compensatory reorganization, the whole group of patients (n = 18) showed significantly greater activation than controls (n = 18). Activation in the right BA45 was inversely correlated with the mean NAWM MTR and the peak position of GM MTR histograms of patients. This study indicates that even at the earliest stage of MS, cortical reorganization is present inside the executive system of working memory and could tend to limit the determinant functional impact of NAWM injury on the execution of the PASAT.

Figure 1

MTR histograms in CISSMS patients and controls. A: NAWM MTR histogram. B: GM MTR histogram.

Figure 2

Cortical activation during PASAT in healthy controls (n = 18; one‐sample t‐test, P < 0.01, k > 5.)

Figure 3

A: Relative increase in cortical activation during PASAT of CISSMS patients (n = 18) in comparison to healthy controls (n = 18) (two‐sample t‐test, P < 0.01, k > 5). B: Relative increase in cortical activation during PASAT of CISSMS patients with normal performance (Group A, n = 9) in comparison to 18 healthy controls (two‐sample t‐test, P < 0.005, k > 5). Significant differences (confirmed by individual statistics in these surviving regions, P < 0.05, Mann‐Whitney U‐test) were obtained in the left and right lateral prefrontal cortices (right and left BA45, right BA44).

Figure 4

A: Scatterplot of NAWM MTR vs. PASAT in CISSMS (n = 18). B: Scatterplot of activations in right BA 45/46 vs. NAWM MTR in CISSMS. C: Scatterplot of activations in right BA45/46 vs. GM MTR peak position in CISSMS.