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Functional reorganization during cognitive function tasks in patients with amyotrophic lateral sclerosis

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Abstract

Cognitive deficits, especially in the domains of social cognition and executive function including verbal fluency, are common in amyotrophic lateral sclerosis (ALS) patients. There is yet sparse understanding of pathogenesis of the underlying, possibly adaptive, cortical patterns. To address this issue, 65 patients with ALS and 33 age-, gender- and education-matched healthy controls were tested on cognitive and behavioral deficits with the Edinburgh Cognitive and Behavioural ALS Screen (ECAS). Using functional magnetic resonance imaging (fMRI), cortical activity during social cognition and executive function tasks (theory of mind, verbal fluency, alternation) adapted from the ECAS was determined in a 3 Tesla scanner. Compared to healthy controls, ALS patients performed worse in the ECAS overall (p < 0.001) and in all of its subdomains (p < 0.02), except memory. Imaging revealed altered cortical activation during all tasks, with patients consistently showing a hyperactivation in relevant brain areas compared to healthy controls. Additionally, cognitively high performing ALS patients consistently exhibited more activation in frontal brain areas than low performing patients and behaviorally unimpaired patients presented with more neuronal activity in orbitofrontal areas than behaviorally impaired patients. In conclusion, hyperactivation in fMRI cognitive tasks seems to represent an early adaptive process to overcome neuronal cell loss in relevant brain areas. The hereby presented cortical pattern change might suggest that, once this loss passes a critical threshold and no cortical buffering is possible, clinical representation of cognitive and behavioral impairment evolves. Future studies might shed light on the pattern of cortical pattern change in the course of ALS.

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Acknowledgments

The authors would like to thank Sonja Fuchs, Ines Schulthess (née Röll) and Jan Luitjens for their assistance with data collection as well as all those who participated in the study.

This is an EU Joint Programme – Neurodegenerative Disease Research (JPND; 01ED1405) project. The project is supported through the following organizations under the aegis of JPND – www.jpnd.eu, e.g. Germany, Bundesministerium für Bildung und Forschung (BMBF, FKZ), Sweden, Vetenskaprådet Sverige, and Poland, Narodowe Centrum Badan i Rozwoju (NCBR). This work was additionally supported by the BMBF (#01GM1103A).

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  1. Department of Neurology, University of Ulm, Oberer Eselsberg 45, 89081, Ulm, Germany

    Jürgen Keller, Sarah Böhm, Helena E. A. Aho-Özhan, Markus Loose, Martin Gorges, Jan Kassubek, Ingo Uttner, Albert C. Ludolph & Dorothée Lulé

  2. Psychology-PPLS, Euan MacDonald Centre for Motor Neuron Disease Research & Anne Rowling Regenerative Neurology Clinic, University of Edinburgh, 7 George Square, Edinburgh, EH89JZ, UK

    Sharon Abrahams

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  1. Jürgen Keller
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The experimental protocol was approved by the Ethics Committee of the University of Ulm (Statement No. 19/12).

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Keller, J., Böhm, S., Aho-Özhan, H.E.A. et al. Functional reorganization during cognitive function tasks in patients with amyotrophic lateral sclerosis. Brain Imaging and Behavior 12, 771–784 (2018). https://doi.org/10.1007/s11682-017-9738-3

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