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Commentary on the Article: “Feasibility and Findings from a Novel Working Memory fMRI Paradigm in Multiple Sclerosis” by Nelson F. and Steinberg J.

(Article DOI :

In the realm of neuroscientific research, particularly in the study of Multiple Sclerosis (MS), the innovative use of functional MRI (fMRI) to assess cognitive impairments offers both challenges and opportunities. The study by Nelson and Steinberg makes a notable contribution to this field by implementing a novel fMRI paradigm, the immediate memory task/delayed memory task (IMT/DMT), aimed at evaluating working memory functions in MS patients. This commentary aims to critically analyze the study’s methodology, findings, and its implications for future research.

Methodological Review:

The IMT/DMT paradigm introduces a dynamic assessment of working memory by varying the memory load and delay, which represents a significant advancement over static tasks like the n-back paradigm. The inclusion of 10 MS patients, while small, is appropriate for a pilot study, especially considering the detailed neuropsychological screening and exclusion criteria to control confounding variables. However, the study’s impact is somewhat limited by its sample size and the lack of a control group. Future studies could enhance validity by including a matched control group to ascertain whether the observed brain activations are specific to MS or are characteristic of general cognitive processes under stress.

Analysis of Findings:

The study’s results indicate significant BOLD activation in brain areas known to be involved in working memory during both 3-digit and 5-digit memory loads. This suggests that the IMT/DMT paradigm can effectively stimulate and measure brain functions related to working memory in MS. However, the lack of increased activation for the 7-digit task might point to a ceiling effect in cognitive load or potentially to a specific impairment in MS that warrants further investigation.

Implications for Future Research:

One of the more intriguing aspects of this study is its potential applicability in routine clinical assessments of MS. If further studies confirm these findings, the IMT/DMT could be a valuable tool in the early diagnosis of cognitive impairment in MS, potentially leading to earlier and more targeted interventions. Moreover, the study’s approach to manipulating task difficulty and memory delay offers a model that could be adapted for other neurological conditions, thereby broadening its applicability.


Nelson and Steinberg’s study provides compelling preliminary evidence that the IMT/DMT fMRI paradigm can assess working memory in MS with a high degree of sensitivity. While acknowledging the limitations inherent in an initial study, its novel approach lays a promising foundation for further research. As the authors suggest, subsequent studies should aim to include larger, more diverse cohorts and control groups to fully establish the paradigm’s efficacy and reliability.

This study is a step forward in the nuanced understanding of MS and cognitive function, potentially impacting both diagnostic processes and therapeutic strategies for this complex condition.