Resting-State EEG Oscillations in Amyotrophic Lateral Sclerosis (ALS): Toward Mechanistic Insights and Clinical Markers

Overview

Journal J Clin Med

Date 2025 Jan 25

PMID 39860557

Authors

James Chmiel

Marta Stepien-Slodkowska

Affiliations

Soon will be listed here.

Abstract

Amyotrophic lateral sclerosis (ALS) is a complex, progressive neurodegenerative disorder characterized by the degeneration of motor neurons in the brain, brainstem, and spinal cord. Several neuroimaging techniques can help reveal the pathophysiology of ALS. One of these is the electroencephalogram (EEG), a noninvasive and relatively inexpensive tool for examining electrical activity of the brain with excellent temporal precision. This mechanistic review examines the pattern of resting-state EEG activity. With a focus on publications published between January 1995 and October 2024, we carried out a comprehensive search in October 2024 across a number of databases, including PubMed/Medline, Research Gate, Google Scholar, and Cochrane. The literature search yielded 17 studies included in this review. The studies varied significantly in their methodology and patient characteristics. Despite this, a common biomarker typical of ALS was found-reduced alpha power. Regarding other oscillations, the findings are less consistent and sometimes contradictory. As this is a mechanistic review, three possible explanations for this biomarker are provided. The main and most important one is increased cortical excitability. In addition, due to the limitations of the studies, recommendations for future research on this topic are outlined to enable a further and better understanding of EEG patterns in ALS. Most studies included in this review showed alpha power deficits in ALS patients, reflecting pathological hyperexcitability of the cerebral cortex. Future studies should address the methodological limitations identified in this review, including small sample sizes, inconsistent frequency-band definitions, and insufficient functional outcome measures, to solidify and extend current findings.

References

Sitaram R, Ros T, Stoeckel L, Haller S, Scharnowski F, Lewis-Peacock J . Closed-loop brain training: the science of neurofeedback. Nat Rev Neurosci. 2016; 18(2):86-100. DOI: 10.1038/nrn.2016.164. View

OHare L, Tarasi L, Asher J, Hibbard P, Romei V . Excitation-Inhibition Imbalance in Migraine: From Neurotransmitters to Brain Oscillations. Int J Mol Sci. 2023; 24(12). PMC: 10299141. DOI: 10.3390/ijms241210093. View

Ilieva H, Polymenidou M, Cleveland D . Non-cell autonomous toxicity in neurodegenerative disorders: ALS and beyond. J Cell Biol. 2009; 187(6):761-72. PMC: 2806318. DOI: 10.1083/jcb.200908164. View

Malekmohammadi M, Elias W, Pouratian N . Human thalamus regulates cortical activity via spatially specific and structurally constrained phase-amplitude coupling. Cereb Cortex. 2014; 25(6):1618-28. PMC: 4447821. DOI: 10.1093/cercor/bht358. View

Bjelica B, Bartels M, Hesebeck-Brinckmann J, Petri S . Non-motor symptoms in patients with amyotrophic lateral sclerosis: current state and future directions. J Neurol. 2024; 271(7):3953-3977. PMC: 11233299. DOI: 10.1007/s00415-024-12455-5. View

Vucic S, van den Bos M, Menon P, Howells J, Dharmadasa T, Kiernan M . Utility of threshold tracking transcranial magnetic stimulation in ALS. Clin Neurophysiol Pract. 2018; 3:164-172. PMC: 6275211. DOI: 10.1016/j.cnp.2018.10.002. View

Berro L, Overton J, Reeves-Darby J, Rowlett J . Alprazolam-induced EEG spectral power changes in rhesus monkeys: a translational model for the evaluation of the behavioral effects of benzodiazepines. Psychopharmacology (Berl). 2021; 238(5):1373-1386. PMC: 8177744. DOI: 10.1007/s00213-021-05793-z. View

Klimesch W, Freunberger R, Sauseng P . Oscillatory mechanisms of process binding in memory. Neurosci Biobehav Rev. 2009; 34(7):1002-14. DOI: 10.1016/j.neubiorev.2009.10.004. View

Verstraete E, Veldink J, van den Berg L, van den Heuvel M . Structural brain network imaging shows expanding disconnection of the motor system in amyotrophic lateral sclerosis. Hum Brain Mapp. 2013; 35(4):1351-61. PMC: 6869230. DOI: 10.1002/hbm.22258. View

10.

Xie M, Pallegar P, Parusel S, Nguyen A, Wu L . Regulation of cortical hyperexcitability in amyotrophic lateral sclerosis: focusing on glial mechanisms. Mol Neurodegener. 2023; 18(1):75. PMC: 10585818. DOI: 10.1186/s13024-023-00665-w. View

11.

Aiyer R, Novakovic V, Barkin R . A systematic review on the impact of psychotropic drugs on electroencephalogram waveforms in psychiatry. Postgrad Med. 2016; 128(7):656-64. DOI: 10.1080/00325481.2016.1218261. View

12.

Maksimovic K, Youssef M, You J, Sung H, Park J . Evidence of Metabolic Dysfunction in Amyotrophic Lateral Sclerosis (ALS) Patients and Animal Models. Biomolecules. 2023; 13(5). PMC: 10216611. DOI: 10.3390/biom13050863. View

13.

Secco A, Tonin A, Rana A, Jaramillo-Gonzalez A, Khalili-Ardali M, Birbaumer N . EEG power spectral density in locked-in and completely locked-in state patients: a longitudinal study. Cogn Neurodyn. 2021; 15(3):473-480. PMC: 8131474. DOI: 10.1007/s11571-020-09639-w. View

14.

Dukic S, Fasano A, Coffey A, Buxo T, McMackin R, Chipika R . Electroencephalographic β-band oscillations in the sensorimotor network reflect motor symptom severity in amyotrophic lateral sclerosis. Eur J Neurol. 2024; 31(4):e16201. PMC: 11235881. DOI: 10.1111/ene.16201. View

15.

Iyer P, Egan C, Pinto-Grau M, Burke T, Elamin M, Nasseroleslami B . Functional Connectivity Changes in Resting-State EEG as Potential Biomarker for Amyotrophic Lateral Sclerosis. PLoS One. 2015; 10(6):e0128682. PMC: 4474889. DOI: 10.1371/journal.pone.0128682. View

16.

Van de Steen F, Pinotsis D, Devos W, Colenbier N, Bassez I, Friston K . Dynamic causal modelling shows a prominent role of local inhibition in alpha power modulation in higher visual cortex. PLoS Comput Biol. 2022; 18(12):e1009988. PMC: 9829170. DOI: 10.1371/journal.pcbi.1009988. View

17.

Jensen O, Kaiser J, Lachaux J . Human gamma-frequency oscillations associated with attention and memory. Trends Neurosci. 2007; 30(7):317-24. DOI: 10.1016/j.tins.2007.05.001. View

18.

Hardiman O, Al-Chalabi A, Chio A, Corr E, Logroscino G, Robberecht W . Amyotrophic lateral sclerosis. Nat Rev Dis Primers. 2017; 3:17071. DOI: 10.1038/nrdp.2017.71. View

19.

Hohmann M, Fomina T, Jayaram V, Emde T, Just J, Synofzik M . Case series: Slowing alpha rhythm in late-stage ALS patients. Clin Neurophysiol. 2018; 129(2):406-408. DOI: 10.1016/j.clinph.2017.11.013. View

20.

Arnold F, Putka A, Raychaudhuri U, Hsu S, Bedlack R, Bennett C . Revisiting Glutamate Excitotoxicity in Amyotrophic Lateral Sclerosis and Age-Related Neurodegeneration. Int J Mol Sci. 2024; 25(11). PMC: 11171854. DOI: 10.3390/ijms25115587. View