Brain activity is contingent on neuropsychological function in an fMRI study of Verbal Working Memory in Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease that causes progressive degeneration of neurons in motor and non-motor regions, affecting multiple cognitive domains. To contribute to the growing research field that employs structural and functional neuroimaging to investigate the effect of ALS on different working memory components, we conducted a functional magnetic resonance imaging (fMRI) study exploring the localization and intensity of alterations in neural activity. Being the first study to specifically address verbal working memory via fMRI in the context of ALS, we employed the verbal n-back task with 0-back and 2-back conditions. Despite ALS patients showing unimpaired accuracies (p = 0.724) and reaction times (p = 0.0785), there was significantly increased brain activity of frontotemporal and parietal regions in the 2-back minus 0-back contrast in patients compared to controls using nonparametric statistics with 5000 permutations and a T-threshold of 2.5. This increased brain activity during working memory performance was largely associated with better neuropsychological function within the ALS group, suggesting a compensatory effect. This study therefore adds to the current knowledge on neural correlates of working memory in ALS and contributes to a more nuanced understanding of hyperactivity during cognitive processes in fMRI studies of ALS. ### Competing Interest Statement All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf. SP has received honorariums by Desitin Pharma, Cytokinetics, Inc., Biogen an Novartis. The other authors declare no conflicts of interest. ### Funding Statement SP is funded by German Neuromuscular Society and Federal Ministry of Education and Research (BMBF). JM is funded by the federal state of Saxony-Anhalt and the European Regional Development Fund (ERDF) in the Center for Behavioral Brain Sciences (CBBS, ZS/2016/04/78113). XK has been funded by the German Neuromuscular Society. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethical committee of the medical faculty of the University of Magdeburg All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes The participants have not consented to data sharing, therefore the individual data is not available.