Novel fMRI working memory paradigm accurately detects cognitive impairment in multiple sclerosis

Flavia Nelson, Mohammad A. Akhtar, Edward Zuandnandiga, Carlos A. Perez, Khader M. Hasan, Jeffrey Wilken, Jerry S. Wolinsky, Ponnada A. Narayana, Joel L. Steinberg

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


Background: Cognitive impairment (CI) cannot be diagnosed by magnetic resonance imaging (MRI). Functional magnetic resonance imaging (fMRI) paradigms, such as the immediate/delayed memory task (I/DMT), detect varying degrees of working memory (WM). Preliminary findings using I/DMT showed differences in blood oxygenation level dependent (BOLD) activation between impaired (MSCI, n = 12) and non-impaired (MSNI, n = 9) multiple sclerosis (MS) patients. Objectives: The aim of the study was to confirm CI detection based on I/DMT BOLD activation in a larger cohort of MS patients. The role of T2 lesion volume (LV) and Expanded Disability Status Scale (EDSS) in magnitude of BOLD signal was also sought. Methods: A total of 50 patients (EDSS mean (m) = 3.2, disease duration (DD) m = 12 years, and age m = 40 years) underwent the Minimal Assessment of Cognitive Function in Multiple Sclerosis (MACFIMS) and I/DMT. Working memory activation (WMa) represents BOLD signal during DMT minus signal during IMT. CI was based on MACFIMS. Results: A total of 10 MSNI, 30 MSCI, and 4 borderline patients were included in the analyses. Analysis of variance (ANOVA) showed MSNI had significantly greater WMa than MSCI, in the left prefrontal cortex and left supplementary motor area (p = 0.032). Regression analysis showed significant inverse correlations between WMa and T2 LV/EDSS in similar areas (p = 0.005, 0.004, respectively). Conclusion: I/DMT-based BOLD activation detects CI in MS. Larger studies are needed to confirm these findings. andcopy; SAGE Publications.

Original languageEnglish (US)
Pages (from-to)836-847
Number of pages12
JournalMultiple Sclerosis
Issue number6
StatePublished - May 1 2017


  • BOLD
  • Cognitive impairment
  • fMRI
  • multiple sclerosis
  • working memory

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