Tractography Analysis of White Matter Pathways Associated with Speech Impairment in Parkinson's Disease

Abstract

Purpose: Parkinson’s disease (PD) is a progressive neurodegenerative disorder affecting multiple systems. Speech disorders, stemming from motor and nonmotor deficits, affect up to 89% of PD patients. This study examines the arcuate fasciculus (AF) and frontal aslant tract (FAT), white matter pathways linked to verbal fluency, which have not been previously assessed in PD. Methods: We included publicly available high-quality diffusion-weighted images (DWI) acquired with 120 gradient directions (b = 2500 s/mm²) from 27 PD patients (Age: 66 ± 8, 14 M, 13 F) and 26 age-, sex-, and education-matched controls (Age: 64 ± 8, 14 M, 12 F), processed using the Generalized Q-sampling Imaging (GQI) model (DSI Studio software) for white matter pathway reconstruction. The Automatic Fiber Tracking (AutoTrack) option in DSI Studio was used for virtual dissection of the AF and FAT. Diffusion metrics of mean diffusivity (MD), radial diffusivity (RD), axial diffusivity (AD), fractional anisotropy (FA), quantitative anisotropy (QA), and track volume measures were obtained and analyzed. Results: No significant correlation was observed between quantitative anisotropy and verbal fluency measures across PD and control groups. However, male PD patients exhibited reduced left FAT volume and significantly lower QA in bilateral FAT and left AF. Microstructural changes in the FAT were observed in male PD patients, but no correlation was found between verbal fluency scores and QA. Conclusion: Our results suggest a more severe impact on the microstructure of the FAT in male PD patients compared to females.

Keywords

• diffusion MRI
• parkinson
• arcuate fasciculus
• frontal aslant tract
• speech impairment

References

1. 1.Zhang Y, Burock MA. Diffusion Tensor Imaging inParkinson's Disease and Parkinsonian Syndrome: ASystematic Review. Frontiers in Neurology.2020;11:531993..
2. 2.Dashtipour K, Tafreshi A, Lee J, Crawley B. Speechdisorders in Parkinson's disease: pathophysiology,medical management and surgical approaches.Neurodegener Dis Manag. 2018;8:337-48.
3. 3. Curry DW, Stutz B, Andrews ZB, Elsworth JD. TargetingAMPK Signaling as a Neuroprotective Strategy inParkinson's Disease. J Parkinsons Dis. 2018;8:161-81.
4. 4.Yang K, Wu Z, Long J, et al. White matter changes inParkinson’s disease. npj Parkinson's Disease.2023;9:150.
5. 5.Dick AS, Garic D, Graziano P, Tremblay P. The frontalaslant tract (FAT) and its role in speech, language andexecutive function. Cortex. 2019;111:148-63.
6. 6.Ivanova M, Zhong A, Turken A, Baldo J, Dronkers NF.Functional Contributions of the Arcuate Fasciculus toLanguage Processing. Frontiers in Human Neuroscience.2021;15:1--672665.
7. 7.Eggermont JJ: Chapter 11 - Predictive coding in music,speech, and language. In: Brain Responses to AuditoryMismatch and Novelty Detection. edn. Edited byEggermont JJ: Academic Press; 2023: 345-76.
8. 8.Oestreich LKL, Whitford TJ, Garrido M. Prediction ofSpeech Sounds Is Facilitated by a Functional Fronto-Temporal Network. Frontiers in neural circuits.2018;12:43.

9. 9.La Corte E, Eldahaby D, Greco E, et al. The FrontalAslant Tract: A Systematic Review for NeurosurgicalApplications. Frontiers in Neurology. 2021;12:641586.
10. 10.Zhong AJ, Baldo JV, Dronkers NF, Ivanova MV. Theunique role of the frontal aslant tract in speech andlanguage processing. NeuroImage clinical.2022;34:103020.
11. 11.Cerri S, Mus L, Blandini F. Parkinson’s Disease inWomen and Men: What’s the Difference? Journal ofParkinson's Disease. 2019;9:501-15.
12. 12.Ziegler E, Rouillard M, André E, et al. Mapping trackdensity changes in nigrostriatal and extranigralpathways in Parkinson's disease. Neuroimage.2014;99:498-508.
13. 13.Kennedy DN, Haselgrove C, Riehl J, Preuss N,Buccigrossi R. The NITRC image repository. NeuroImage.2016;124:1069-73.
14. 14.Yeh FC, Verstynen TD, Wang Y, Fernández-MirandaJC, Tseng WY. Deterministic diffusion fiber trackingimproved by quantitative anisotropy. PLoS One.2013;8:e80713.
15. 15.Yeh F-C. Shape analysis of the human associationpathways. NeuroImage. 2020;223:117329.
16. 16.Hobson DE, Lang AE, Martin WRW, et al. ExcessiveDaytime Sleepiness and Sudden-Onset Sleep inParkinson Disease: A Survey by the Canadian MovementDisorders Group. JAMA : the journal of the AmericanMedical Association. 2002;287:455-63.
17. 17.Dick AS, Bernal B, Tremblay P. The LanguageConnectome: New Pathways, New Concepts. TheNeuroscientist. 2014;20:453-67.
18. 18.Dragoy O, Zyryanov A, Bronov O, et al. Functionallinguistic specificity of the left frontal aslant tract forspontaneous speech fluency: Evidence fromintraoperative language mapping. Brain and Language.2020;208:104836.
19. 19.Catani M, Mesulam MM, Jakobsen E, et al. A novelfrontal pathway underlies verbal fluency in primaryprogressive aphasia. Brain. 2013;136:2619-28.
20. 20.Schmitz J, Güntürkün O, Ocklenburg S. Building anasymmetrical brain: The molecular perspective.Frontiers in psychology. 2019;10:982.
21. 21.Ortug A, Guo Y, Feldman HA, et al. Autism-associatedbrain differences can be observed in utero using MRI.Cerebral Cortex. 2024;34(4):bhae117.
22. 22.Cholerton B, Johnson CO, Fish B, et al. Sex differencesin progression to mild cognitive impairment anddementia in Parkinson's disease. Parkinsonism RelatDisord. 2018;50:29-36.
23. 23.Szewczyk-Krolikowski K, Tomlinson P, Nithi K, et al.The influence of age and gender on motor and non-motorfeatures of early Parkinson's disease: Initial findingsfrom the Oxford Parkinson Disease Center (OPDC) discovery cohort. Parkinsonism & Related Disorders. 2014;20:99-105.
24. 24.Park KM, Kim KT, Lee DA, Cho YW. Correlation ofDiffusion Tensor Tractography with Restless LegsSyndrome Severity. Brain Sci. 2023;13:1560.
25. 25.Huang SH, Li MJ, Yeh FC, et al. Differential andcorrelational tractography as tract-based biomarkers inmild traumatic brain injury: A longitudinal MRI study.NMR Biomed. 2023;36:e4991.
26. 26.Ivanova MV, Isaev DY, Dragoy OV, et al. Diffusion-tensor imaging of major white matter tracts and theirrole in language processing in aphasia. Cortex.2016;85:165-81.
27. 27.Karagulle Kendi AT, Lehericy S, Luciana M, Ugurbil K,Tuite P. Altered Diffusion in the Frontal Lobe inParkinson Disease. American Journal of Neuroradiology. 2008;29:501-5.
28. 28.Ding J, Middleton EL, Mirman D. Impaired discoursecontent in aphasia is associated with frontal white matterdamage. Brain Communications. 2023;5:fcad310.
29. 29.Kinoshita M, de Champfleur NM, Deverdun J, Met al.Role of fronto-striatal tract and frontal aslant tract inmovement and speech: an axonal mapping study. BrainStructure and Function. 2015;220:3399-412.
30. 30.Li M, Zhang Y, Song L, et al. Structural connectivitysubserving verbal fluency revealed by lesion-behaviormapping in stroke patients. Neuropsychologia.2017;101: