A Mechanistic Insight into Sources of Error of Visual Working Memory in Multiple Sclerosis
Ahmad Pourmohammadi1, Ali Motahharynia2, Armin Adibi2, Vahid Shaygannejad2, Fereshteh Ashtari2, Iman Adibi2, Mehdi Sanayei3
1Columbia University, 2Isfahan University of Medical Sciences, 3Institute For Research In Fundamental Sciences (IPM)
Objective:
To investigate the mechanisms underlying working memory (WM) dysfunction in relapsing and progressive multiple sclerosis (MS) and develop a sensitive cognitive biomarker for WM impairment in MS patients.
Background:
WM is one of the most affected cognitive domains in MS, which is mainly studied by the previously established binary model for information storage (slot model). However, recent observations based on the continuous reproduction paradigms have shown that assuming dynamic allocation of WM resources (resource model) instead of the binary hypothesis will give more accurate predictions in WM assessment and new insights into the organization of the WM system.
Design/Methods:
We assessed visual WM in 121 MS patients (61 relapsing-remitting and 60 secondary progressive) and 73 controls using memory-guided localization and Sequential paradigm with bar stimuli. Recall error, recall precision, and reaction times were compared across groups. Hierarchical regression and ROC analyses evaluated confounding effects and classification accuracy of our tests across groups. For the sequential paradigm we used the Mixture Model to further investigate the sources of error in recalling information and uncover the involved mechanisms in visual WM impairment.
Results:
Our results demonstrated an overall increase in recall error and decreased recall precision in MS. While sequential paradigms were better in distinguishing healthy control from relapsing-remitting MS, memory-guided localization were more accurate in discriminating MS subtypes (relapsing-remitting from secondary progressive), providing evidence about the underlying mechanisms of WM dysfunction in progressive states of the disease. Furthermore, computational modeling of the results from the sequential paradigm determined that imprecision in decoding information and swap error (mistakenly reporting the feature of other presented items) was responsible for WM dysfunction in MS.
Conclusions:
This study provides a sensitive approach for assessing WM dysfunction in MS and reveals distinct mechanisms of WM impairment, offering potential as a cognitive biomarker for disease progression.
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