Functional Correlates of Impaired Working Memory in MS Patients: A Multicentre Study (P6.123)

OBJECTIVE: To assess the functional MRI (fMRI) correlates of frontal lobe dysfunction in multiple sclerosis (MS) patients with and without cognitive impairment. Background. BACKGROUND: Cognitive impairment in MS seems to be associated with a disconnection between the frontal lobes and other regions subserving cognitive functioning. DESIGN/METHODS: This study was conducted at six European sites using 3.0 Tesla scanners. FMRI scans during a N-back task were acquired from 42 right-handed relapsing remitting (RR) MS patients and 52 sex-matched right-handed healthy controls (HC). MS patients underwent the Rao battery and the Wisconsin Card Sorting test. Patients with at least two abnormal tests were considered as cognitively impaired (CI). FMRI data were analysed modelling regions showing a load-dependent activation/deactivation with increasing task difficulty. FMRI activity was compared between HC and all MS, as well as between HC, cognitively preserved (CP) and CI patients. Correlations of fMRI activity with clinical, neuropsychological and conventional MRI variables were also assessed. RESULTS: Twenty-two MS patients were cognitively preserved (CP) and 20 (47%) were CI. Task-related activations/deactivations were found in similar regions for HC and MS. Compared to HC, MS showed a reduction of fMRI activity with increasing task difficulty in the bilateral parietal, left inferior frontal and left middle frontal regions. While CP showed fMRI patterns similar to those detected in HC, CI patients had a distributed reduced fMRI activity (in bilateral parietal and frontal regions, and in the bilateral insula) and fMRI deactivations (in the bilateral precuneus, posterior cingulate cortex and parahyppocampal gyrus) compared to HC and CP patients. A failure of activation of frontal regions was correlated with a longer disease duration, higher T2/T1-lesion volumes, lower Z-score of global cognitive, attention-executive and visual functions. CONCLUSIONS: This multicenter study support the theory that preserved fMRI activity of the frontal lobe is associated with a better cognitive profile in MS. Study Supported by: