Structural brain changes in the development of essential tremor: toward early diagnosis.

Overview

1. Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom
2. EleKin Research Group, System Engineering and Automation Department, University of the Basque Country UPV/EHU, Donostia-San Sebastian, Spain
3. NTT DATA Europe and LATAM, Arlington, VA, United States
4. Data and Signal Processing Research Group, University of Vic-Central University of Catalonia, Barcelona, Spain
5. Instituto de Biomedicina de Sevilla (IBiS) HUVR/CSIC/Universidad de Sevilla/CIBERSAM, ISCIII, Dpto. de Fisiología Médica y Biofísica, Sevilla, Spain
6. The Alan Turing Institute, British Library, London, United Kingdom
7. CITA Alzheimer Foundation, Donostia-San Sebastián, Spain
8. Departamento de Ciencias Médicas Básicas, Instituto de Medicina Molecular Aplicada (IMMA) Nemesio Díez, Facultad de Medicina, Universidad San Pablo-CEU, CEU Universities, Madrid, Spain
9. Neurodegenerative Disorders Area, Biodonostia Health Research Institute, Donostia-San Sebastián, Spain
10. Movement Disorders Unit, Department of Neurology, University Hospital Donostia, San Sebastián, Spain
11. Biomedical Research Networking Centre Consortium for the Area of Neurodegenerative Diseases (CIBERNED), Madrid, Spain

Abstract

Background: Essential tremor (ET) is the most common movement disorder. Its etiology and neuropathology remain controversial, but could be clarified with neuroimaging.

Objectives: This study investigated brain structures derived from T1-weighted MRI associated with tremor severity in analyses focusing on the motor circuit and whole-brain to test competing hypotheses.

Methods: Structural MRI at 3T was acquired from 50 ET participants and 50 healthy controls (HC). Voxel-based morphometry and surface-based processing generated measures of brain structure. Three two-group comparisons were undertaken: 1) HC versus ET participants; 2) HC versus ET participants with low tremor; and 3) HC versus ET participants with high tremor. For ET participants, correlations with tremor severity were also explored.

Results: Within the motor circuit and across the whole brain, no significant case–control differences were observed after correction. Likewise, vertex-wise analyses of cortical volume, cortical thickness, and gyrification did not reveal significant differences. Uncorrected voxel-wise analyses suggested subtle reductions in the cerebellum and the motor circuit, particularly in ET participants with greater tremor severity. However, these effects were generally small and not consistently observed across analyses.

Conclusion: The present analysis showed that ET severity was associated with weak structural differences, mainly within the motor circuit, although these findings did not survive correction. Consistent with previous literature, structural MRI abnormalities in ET appeared subtle and heterogeneous across studies, potentially becoming more detectable in patients with more severe symptoms. Although not designed to assess disease progression directly and noting that no finding survived correction for multiple comparisons, the direction of uncorrected exploratory trends within the motor circuit is consistent with the hypothesis of progressive structural alterations; however, this interpretation remains speculative and requires replication in larger, longitudinal cohorts.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Data availability statement

The datasets generated by and/or analysed during the current study are not publicly available due to ethics and privacy requirements, but they are available from the corresponding author upon reasonable request. All the code is open source upon reasonable request.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Version 2, 28 September 2026

• Funding: added Eusko Jaurlaritza; Euskal Herriko Unibertsitatea

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, pages, dates, 12 authors, 5 keywords, 56 references.

Cite

This paper

Lopez-de-Ipina, K., Sánchez-Méndez, J. I., Solé-Casals, J., Romero-Garcia, R., Fernandez, E., Poologaindran, A., García-Sebastian, M., Martinez-Lague, P., Requejo, C., Martí-Massó, J., Bergareche, A., & Suckling, J. (2026). Structural brain changes in the development of essential tremor: toward early diagnosis. Frontiers in aging neuroscience, 18, 1767582. https://doi.org/10.3389/fnagi.2026.1767582

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