Poster No:
1790
Submission Type:
Abstract Submission
Authors:
Bethany Facer1, Corey Ratcliffe1, Antonella Macerollo2, Simon Keller1
Institutions:
1University of Liverpool, Liverpool, Merseyside, 2The Walton Centre, Aintree University Hospital, Liverpool, Merseyside
First Author:
Co-Author(s):
Introduction:
Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder, primarily affecting the substantia nigra and other areas of the basal ganglia (Braak et al, 2003). The disease presents with clinical heterogeneity and symptoms beyond motor impairment, and likely impact multiple brain areas. Fixel-based analysis (FBA), measures intra-axonal volume specific to fibre populations (fibre density (FD)), the macroscopic cross-sectional size of fibre bundles (FC), and combined metrics (FDC). Previous studies have identified increased FC in the corticospinal tract in tremor-dominant PD (TD-PD) (Andica et al, 2021). However, the dentato-rubro-thalamic tract (DRTT)-a key pathway connecting the cerebellum to the thalamus-remains underexplored (Párraga et al, 2016). The DRTT is clinically significant as it is often targeted in deep brain stimulation to alleviate tremor symptoms (Coenen et al, 2020). This study aims to investigate whether white matter microstructural abnormalities of the DRTT exist in patients with de-novo PD using FBA.
Methods:
Data was obtained from the Parkinson's Progression Markers Initiative, including DTI and clinical data from individuals with de novo PD. Patients were stratified into tremor-dominant (TD) and postural instability gait difficulty (PIGD) groups to examine motor phenotype-specific white matter alterations (Stebbins et al, 2013). Data preprocessing and FBA were performed using MRtrix3. A DRTT mask was delineated on the white matter population template, defined by manual inclusion ROIs placed on the superior cerebellar peduncle, red nucleus, and primary motor cortex, and exclusion ROIs applied to the corpus callosum (Kwon et al, 2011). The mask was converted to a binary image containing only fixels corresponding with the template space DRTT. Age, sex, and intracranial volume were included as covariates in models. GLMs were conducted using fixelcfestats to assess between-group differences in fixels across the whole brain followed by the DRTT. Connectivity-clustered family-wise error corrected fixel metric outputs and standardised effect sizes (ES) were overlaid on the template and visually inspected for anatomical consistency, and for local maxima. We used a lenient threshold of p < .200 for trending due to the stringency of FWE and the minimal number of permutations used by fixelcfestats at this point.
Results:
A total of 65 controls (24 females; mean age 60.3 ± 10.9), 103 tremor-dominant PD (TD-PD) patients (39 females; mean age 61.5 ± 8.9), and 31 PIGD-PD patients (9 females; mean age 64.1 ± 9.1) were included. There were no significant differences in age or sex across groups. In an exploratory whole brain analysis, patients with TD-PD showed significantly larger fibre cross-section (FC, p = .015, ES = 0.931) and trending increases in fibre density and cross-section (FDC, p =.078, ES = 0.795) in the cerebellum compared to controls. Controls exhibited trending higher FD values compared to patients with PIGD-PD (p = .149, ES = 1.062) in the occipital lobe and TD-PD (p = .172; ES = 0.844) in the parietal lobe. In the DRTT specific analysis, trending higher FC values were observed in PIGD-PD relative to controls (p = .124, ES = 0.711) localised to fixels in the right projection from the superior cerebellar peduncle up to the point of decussation.
Conclusions:
Consistent with previous studies, we observed whole-brain differences in FC and FDC between TD-PD and controls (Andica et al, 2021). This study extends prior findings, as the increased DRTT FC observed in PIGD-PD compared to controls could suggest a potential compensatory mechanism, with a larger fibre bundle cross section in this tract potentially mitigating tremor symptoms.
Disorders of the Nervous System:
Neurodegenerative/ Late Life (eg. Parkinson’s, Alzheimer’s) 2
Lifespan Development:
Aging
Modeling and Analysis Methods:
Diffusion MRI Modeling and Analysis
Neuroanatomy, Physiology, Metabolism and Neurotransmission:
White Matter Anatomy, Fiber Pathways and Connectivity 1
Novel Imaging Acquisition Methods:
Diffusion MRI
Keywords:
Aging
Degenerative Disease
Open Data
WHITE MATTER IMAGING - DTI, HARDI, DSI, ETC
1|2Indicates the priority used for review
By submitting your proposal, you grant permission for the Organization for Human Brain Mapping (OHBM) to distribute your work in any format, including video, audio print and electronic text through OHBM OnDemand, social media channels, the OHBM website, or other electronic publications and media.
I accept
The Open Science Special Interest Group (OSSIG) is introducing a reproducibility challenge for OHBM 2025. This new initiative aims to enhance the reproducibility of scientific results and foster collaborations between labs. Teams will consist of a “source” party and a “reproducing” party, and will be evaluated on the success of their replication, the openness of the source work, and additional deliverables. Click here for more information.
Propose your OHBM abstract(s) as source work for future OHBM meetings by selecting one of the following options:
I do not want to participate in the reproducibility challenge.
Please indicate below if your study was a "resting state" or "task-activation” study.
Other
Healthy subjects only or patients (note that patient studies may also involve healthy subjects):
Patients
Was this research conducted in the United States?
No
Were any human subjects research approved by the relevant Institutional Review Board or ethics panel?
NOTE: Any human subjects studies without IRB approval will be automatically rejected.
Yes
Were any animal research approved by the relevant IACUC or other animal research panel?
NOTE: Any animal studies without IACUC approval will be automatically rejected.
Not applicable
Please indicate which methods were used in your research:
Diffusion MRI
For human MRI, what field strength scanner do you use?
3.0T
Which processing packages did you use for your study?
Other, Please list
-
MRtrix3
Provide references using APA citation style.
Andica, C., Kamagata, K., Saito, Y., Uchida, W., Fujita, S., Hagiwara, A., Akashi, T., Wada, A., Ogawa, T., Hatano, T., Hattori, N., & Aoki, S. (2021). Fiber-specific white matter alterations in early-stage tremor-dominant Parkinson’s disease. Npj Parkinson’s Disease, 7(1), 51.
Braak, H., Tredici, K. D., Rüb, U., de Vos, R. A. I., Jansen Steur, E. N. H., & Braak, E. (2003). Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiology of Aging, 24(2), 197–211.
Coenen, V. A., Sajonz, B., Prokop, T., Reisert, M., Piroth, T., Urbach, H., Jenkner, C., & Reinacher, P. C. (2020). The dentato-rubro-thalamic tract as the potential common deep brain stimulation target for tremor of various origin: An observational case series. Acta Neurochirurgica, 162(5), 1053–1066.
Kwon, H. G., Hong, J. H., Hong, C. P., Lee, D. H., Ahn, S. H., & Jang, S. H. (2011). Dentatorubrothalamic tract in human brain: Diffusion tensor tractography study. Neuroradiology, 53(10), 787–791.
Párraga, R. G., Possatti, L. L., Alves, R. V., Ribas, G. C., Türe, U., & de Oliveira, E. (2016). Microsurgical anatomy and internal architecture of the brainstem in 3D images: surgical considerations. Journal of Neurosurgery, 124(5), 1377-1395.
Stebbins, G. T., Goetz, C. G., Burn, D. J., Jankovic, J., Khoo, T. K., & Tilley, B. C. (2013). How to identify tremor dominant and postural instability/gait difficulty groups with the movement disorder society unified Parkinson’s disease rating scale: Comparison with the unified Parkinson’s disease rating scale. Movement Disorders, 28(5), 3.
No