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Functional connectivity and cognitive decline in MS patients- a cross-sectional study (P4.341)

Objective: To identify and characterize MRI measures associated with memory impairment Background: Spontaneous low-frequency BOLD oscillations can be measured by functional connectivity and “resting state” (rs) neural networks multiple sclerosis (MS) patients which have a relationship to patients’ disease burden, cognitive deficits and gender. Design/Methods: Patients underwent an rs-fMRI scan: 132 repetitions of 31–4mm thick axial slices acquired with TE/TR=29ms/2800 ms, 128×128 matrix, 256mm × 256mm FOV, receive bandwidth = 1446Hz/pixel, and an inscanner verbal episodic memory task. Average activation during the “correct recognition” condition of the verbal episodic memory task identified the left dorsal lateral prefrontal cortex (DLPFC) region. The left DLPFC voxel with the highest average activation marked the center of an in-plane ROI and seeded individual whole-brain correlation rs-fMRI maps. rs-fMRI maps were created using the linearly detrended average time series of voxels in the DLPFC ROI and calculating a cross-correlation with the linearly detrended time series of each voxel. The correlation at each voxel was converted to a Student’s t and normalized. A measure of performance on a verbal episodic memory task was correlated on a voxel-wise basis with left DLPFC rs-fMRI maps. Correlation maps were thresholded at p = 0.01 with a cluster size of 621, for an effective voxel-wise p of 4×10-5. Results: 51 MS patients (age: 43.8±8.9, 16 males, EDSS: median 2, range 1–6.5) had useable rs-fMRI data. Performance on a verbal episodic memory task showed a significant correlation to connectivity from the left DLPFC to the left and right MTG (r = 0.405, p = 0.0032 and r = 0.449, p = 0.0009, respectively). These relationships remained significant when age, education, and disease duration were used as covariates in a partial correlation. Conclusions: These results suggest that rs-fMRI from the left DLPFC to the bilateral temporal lobes decreases as patients experience a decline in verbal episodic memory. Study Supported by: National MS Society Grant Disclosure: Dr. Stone has nothing to disclose. Dr. Koenig has nothing to disclose. Dr. Lin has nothing to disclose. Dr. Bermel has received personal compensation for activities with Biogen, Novartis, Genzyme, Genentech. Dr. Bermel has received research support from Biogen and Genentech. Dr. Rao has received personal compensation for activities with Novartis, Biogen Idec, and Genzyme Corp. Dr. Rao has received personal compensation in an editorial capacity for the American Psychological Association. Dr. Rao has received research support from Biogen Idec and Novartis. Dr. Lowe has nothing to disclose. Dr. Phillips has nothing to disclose.