Category: Parkinson's disease: Neuroimaging
Objective: To determine whether people with Parkinson’s disease (PwPD) with fatigue, and those without fatigue, experience differences in white matter structural connectivity (SC).
Background: Fatigue is a common non-motor symptom that affects about half of PwPD1. Previous fMRI studies of PwPD with fatigue have shown alterations in functional connectivity (FC), specifically in the postcentral gyrus, precentral gyrus, and supplementary motor region (SMA)2–9. It remains unclear whether these changes in FC are in part due to changes in white matter integrity. Only two studies examined local, voxel-wise white matter microstructural alterations using Tract-Based Spatial Statistics (TBSS), yielding conflicting results10,11. Neither studies assessed the whole brain connectome with SC using probabilistic tractography.
Method: 22 PwPD (Hoehn & Yahr 2-3) were recruited and classified, based on the mean Multidimensional Fatigue Inventory [MFI] score (fatigue ≥ 48 averaged over 3 visits) into fatigue (n=11; mean MFI score: 56; mean age 63 years, 3 females) or non-fatigue (n=11; mean MFI score: 40; mean age 64 years, 6 females) groups. Diffusion-weighted magnetic resonance imaging was collected on a 3T Prisma Siemens scanner. Probabilistic tractography estimated whole brain SC between brain regions by creating 64 x 64 connectome matrices. Group-wise differences for SC were assessed using threshold-free network-based statistics (TFNBS). TBSS analysis was conducted to extract fractional anisotropy (FA) and mean diffusivity (MD) to assess white matter microstructural integrity. Group-wise differences for FA and MD were examined using Threshold-Free Cluster Enhancement (TFCE).
Results: Preliminary analyses showed no significant group-wise differences in SC (TFNBS, FWE-corrected, permutation-based, p < 0.05) or FA and MD metrics (TFCE, FWE-corrected, permutation-based, p < 0.05). Currently exploring seed-based analysis connecting regions between the postcentral gyrus, precentral gyrus, and SMA.
Conclusion: No studies in PwPD with fatigue used probabilistic tractography. Although no significant differences were found in the whole-brain SC analysis, investigating white matter at the network level provides insight into whether fatigue in PD is associated with widespread white matter changes. Additionally, understanding the differences in structure will allow clinicians to make more informed treatment decisions based on the presented symptoms12,13.
References: 1. Siciliano M, Trojano L, Santangelo G, De Micco R, Tedeschi G, Tessitore A. Fatigue in Parkinson’s disease: A systematic review and meta-analysis. Movement Disorders. 2018;33(11):1712-1723. doi:10.1002/mds.27461
2. Li J, Yuan Y, Wang M, et al. Alterations in regional homogeneity of resting-state brain activity in fatigue of Parkinson’s disease. J Neural Transm. 2017;124(10):1187-1195. doi:10.1007/s00702-017-1748-1
3. Zhang JJ, Ding J, Li JY, et al. Abnormal Resting-State Neural Activity and Connectivity of Fatigue in Parkinson’s Disease. CNS Neuroscience & Therapeutics. 2017;23(3):241-247. doi:10.1111/cns.12666
4. Shan A, Zhang H, Gao M, et al. Aberrant voxel-based degree centrality and functional connectivity in Parkinson’s disease patients with fatigue. CNS Neuroscience & Therapeutics. 2023;29(9):2680-2689. doi:10.1111/cns.14212
5. Siciliano M, De Micco R, Giordano A, et al. Supplementary motor area functional connectivity in “drug-naïve” Parkinson’s disease patients with fatigue. J Neural Transm. 2020;127(8):1133-1142. doi:10.1007/s00702-020-02219-6
6. Tessitore A, Giordano A, De Micco R, et al. Functional connectivity underpinnings of fatigue in “Drug-Naïve” patients with Parkinson’s disease. Movement Disorders. 2016;31(10):1497-1505. doi:10.1002/mds.26650
7. Hou Y, Zhang L, Ou R, et al. Resting-state fMRI study on drug-naïve early-stage patients with Parkinson’s disease and with fatigue. Parkinsonism & Related Disorders. 2022;105:75-82. doi:10.1016/j.parkreldis.2022.11.009
8. Zabala-Gómez O, Ibarretxe-Bilbao N, Tijero B, et al. Fatigue brain network functional connectivity in Parkinson’s disease. Neuroscience. 2025;579:122-128. doi:10.1016/j.neuroscience.2025.06.001
9. Di Vico IA, Moretto M, Tamanti A, et al. Molecular-Informed Network Analysis Unveils Fatigue-Related Functional Connectivity in Parkinson’s Disease. Movement Disorders. 2025;40(8):1561-1571. doi:10.1002/mds.30214
10. Kluger BM, Zhao Q, Tanner JJ, et al. Structural brain correlates of fatigue in older adults with and without Parkinson’s disease. NeuroImage: Clinical. 2019;22:101730. doi:10.1016/j.nicl.2019.101730
11. Kang SY, Bang M, Hong JY, et al. Neural and dopaminergic correlates of fatigue in Parkinson’s disease. J Neural Transm. 2020;127(3):301-309. doi:10.1007/s00702-019-02130-9
12. Loução R, Kocher M, Brandt GA, et al. Structural Connectivity of the Basal Ganglia from Patient-Individual Tractography Is Key for Understanding the Effects of Deep Brain Stimulation in Parkinson’s Disease. Stereotact Funct Neurosurg. 2025;103(4):279-294. doi:10.1159/000546716
13. Du J, Zhou X, Liang Y, et al. Levodopa responsiveness and white matter alterations in Parkinson’s disease: A DTI-based study and brain network analysis: A cross-sectional study. Brain and Behavior. 2022;12(12):e2825. doi:10.1002/brb3.2825
To cite this abstract in AMA style:
JY. Park, E. Morales, J. Bedime, C. Mvomo, S. Perfetto, F. Parent-L’Ecuyer, I. Sierra, H. Lajeunesse, A. Parent, M. Sharp, A. Rochette, A. Potvin-Desrochers, C. Paquette. Examining the Impact of Fatigue on White Matter tracts in Parkinson’s Disease [abstract]. Mov Disord. 2026; 41 (suppl 1). https://www.mdsabstracts.org/abstract/examining-the-impact-of-fatigue-on-white-matter-tracts-in-parkinsons-disease/. Accessed October 1, 2026.« Back to 2026 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/examining-the-impact-of-fatigue-on-white-matter-tracts-in-parkinsons-disease/