Fronto-caudate and callosal microstructural alterations: unveiling multimodal MRI biomarkers in early Parkinson’s disease

Ángela Bernabéu-Sanz; Sandra Morales; Valery Naranjo; Eduardo Fernandez

doi:10.1093/bjr/tqag024

journal article Open Access Jan 31, 2026

Fronto-caudate and callosal microstructural alterations: unveiling multimodal MRI biomarkers in early Parkinson’s disease

Ángela Bernabéu-Sanz

Sandra Morales

Valery Naranjo

Eduardo Fernandez

The British Journal of Radiology Vol. 99 No. 1180 pp. 802-811 · Oxford University Press (OUP)

View at Publisher Save 10.1093/bjr/tqag024

Abstract

Abstract

Objectives
This study investigated grey and white matter alterations and their association with motor and cognitive symptoms in early-stage Parkinson’s disease (PD).

Methods
Thirty-one early-stage PD patients and 30 matched healthy controls underwent multimodal MRI (VBM, DTI) and comprehensive clinical/neuropsychological assessments. We assessed grey matter atrophy, white matter microstructure, and caudate-cortical connectivity.

Results
Parkinson’s disease (PD) patients showed selective deficits in memory (FCSRT total recall, P-FDR = .014) and processing speed (SDMT, P-FDR = .025). Voxel-based morphometry (VBM) revealed bilateral caudate atrophy (left, P-FDR = .024; right, P-FDR = .026). Diffusion tensor imaging (DTI) demonstrated widespread microstructural alterations in corpus callosum and major association tracts. Disease duration negatively correlated with corpus callosum streamline counts (superior parietal P-FDR = .02; posterior parietal P-FDR = .004). UPDRS negatively correlated with fractional anisotropy (FA) in occipital (P-FDR = .002) and temporal (P-FDR = .0017) corpus callosum segments. Reduced caudate-cortical streamline density in frontal regions correlated with UPDRS/FCSRT scores; caudate-cingulum streamlines correlated with Mini-Mental State Examination (MMSE) attention/calculation.

Conclusions
Our findings suggest early functionally relevant degeneration of fronto-caudate and interhemispheric pathways in PD. These structural changes correlate with specific cognitive and motor impairments, and are candidate imaging biomarkers for early PD progression and/or cognitive vulnerability.

Advances in Knowledge
This is the first tractography study to evaluate connectivity between the caudate nuclei and different frontal lobe regions, unveiling specific white matter alterations in early PD. Our findings suggest that caudate atrophy, though not directly correlated with clinical variables, may underlie or result from impaired caudate-cortical connectivity, potentially accounting for some of the multifaceted PD symptoms.

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Details

Published: Jan 31, 2026
Vol/Issue: 99(1180)
Pages: 802-811
License: View

Authors

�

Ángela Bernabéu-Sanz

Inscanner SL Magnetic Resonance Department, , Calle San Pedro Poveda 10 , Alicante, CP 03010,; Instituto de Bioingeniería, Universidad Miguel Hernández de Elche, Avenida de la Universidad s/n , CP 03202 Elche,

S

Sandra Morales

Instituto Universitario de Investigación en Tecnología Centrada en el Ser Humano, HUMAN-tech, Universitat Politècnica de València (UPV) , Camino de Vera s/n , Valencia, CP 46022,

V

Valery Naranjo

Instituto Universitario de Investigación en Tecnología Centrada en el Ser Humano, HUMAN-tech, Universitat Politècnica de València (UPV) , Camino de Vera s/n , Valencia, CP 46022,

E

Eduardo Fernandez

Instituto de Bioingeniería, Universidad Miguel Hernández de Elche, Avenida de la Universidad s/n , CP 03202 Elche,; CIBER-BBN , Avenida Monforte de Lemos 3-5, Pabellón 11, Planta 0 , Madrid, CP 28029

Funding

Generalitat Valenciana

Spanish Ministerio de Ciencia, Innovación y Universidades Award: CIPROM/2023/25

BRAIM Award: IDI-20130020

CRUE-Universitat Politècnica de València

Cite This Article

Ángela Bernabéu-Sanz, Sandra Morales, Valery Naranjo, et al. (2026). Fronto-caudate and callosal microstructural alterations: unveiling multimodal MRI biomarkers in early Parkinson’s disease. The British Journal of Radiology, 99(1180), 802-811. https://doi.org/10.1093/bjr/tqag024

Fronto-caudate and callosal microstructural alterations: unveiling multimodal MRI biomarkers in early Parkinson’s disease

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