Document Type

Article

Publication Date

2026

DOI

10.3390/cells15010037

Publication Title

Cells

Volume

15

Issue

1

Pages

37

Abstract

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that leads to the gradual loss of motor control, typically resulting in paralysis and death within 3 to 5 years of diagnosis. ALS shares neuropathological and genetic associations with fronto-temporal dementia (FTD), a neurodegenerative condition primarily impacting cognitive functions. These two conditions are increasingly viewed as manifestations of a single molecular disease process that affects distinct brain systems, impacting motor neuronal pathways in ALS and fronto-cortical functions in FTD. However, this simple dichotomy belies the complexity of these conditions. In particular, patients with primary motor ALS can also experience significant cognitive deficits. Investigating the pathobiological and neurophysiological underpinnings of these impairments is essential for a comprehensive understanding of ALS and may open avenues for targeted therapies to alleviate these debilitating symptoms. Moreover, the biophysical correlates of cognitive deficits in ALS may serve as sensitive biomarkers for evaluating potential therapeutics. In this narrative review, we begin with an overview of the clinical features and genetics of ALS, followed by a review of the associated cognitive deficits that are adjunctive to motor decline. We then highlight neuroimaging studies from our laboratory and the broader literature, using EEG and other modalities that are beginning to uncover systems-level brain disruptions potentially underlying cognitive impairment in motor-dominant ALS.

Rights

© 2025 by the authors.

This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International (CC BY 4.0) License.

Data Availability

Article states: "No new data were created or analyzed in this study." 

Original Publication Citation

Borgheai, S. B., Achorn, B. E., Zisk, A. H., Hosni, S. M., Richter, K. E. G., Menniti, F. S., & Shahriari, Y. (2026). A comprehensive overview of neurophysiological correlates of cognitive impairment in amyotrophic lateral sclerosis. Cells, 15(1), Article 37. https://doi.org/10.3390/cells15010037

ORCID

0000-0002-6159-0257 (Hosni)

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