Feasibility and Findings from a Novel Working Memory fMRI Paradigm in Multiple Sclerosis.

BACKGROUND Functional MRI (fMRI) basic cognitive paradigms such as the n-back have been shown to detect cognitive impairment (CI) in Multiple Sclerosis (MS). The immediate memory task/delayed memory task (IMT/DMT) detects varying degrees of working memory (WM) by alternating three levels of complexity and two levels of WM delay. This paradigm has not been evaluated in MS nor validated against standard neuropsychological (NP) testing. OBJECTIVE To evaluate the correlation between WM function and blood oxygen level dependent (BOLD) activation on fMRI in MS patients undergoing the IMT/DMT. To compare IMT/DMT behavioral scores to NP scores. METHODS 10 MS patients with no history of CI underwent the Minimal Assessment of Cognitive Function in MS (MACFIMS) and an fMRI session where they performed the IMT/DMT. Working-memory ("wmem") activation was defined as the BOLD signal during DMT blocks for a particular condition (3, 5, or 7 digits per stimuli) minus the BOLD signal during IMT blocks for that condition. Areas of statistically significant Family Wise Error (FWE) -corrected cluster-level BOLD activation were identified using SPM8 Random Effects t-test. IMT/DMT behavioral data and MACFIMS scores were compared. RESULTS The 3-digit as well as the 5-digit wmem showed significant fMRI BOLD activation. The 3-digit wmem, activation was found in portions of the bilateral superior and mid frontal cortex, supplementary motor area, pre and post central gyrus, bilateral superior and inferior parietal lobule, inferolateral pre-frontal cortex, cuneus, insula and cingulate regions. The 5 digit wmen activation was seen in the inferior medial frontal and medial orbitofrontal cortex. IMT/DMT behavioral scores were within normal range and consistent with MACFIMS. CONCLUSION IMT/DMT, a novel fMRI working memory paradigm, is associated with BOLD activation in areas of the brain related to cognitive function in patients with MS. Both MACFIMS and IMT/DMT scores were in agreement and supported intact cognitive function.