Objective: To investigate thalamic subnuclei volume and macrostructural white matter changes in Parkinson’s disease (PD) depression.

Background: Depression is the most common neuropsychiatric feature of Parkinson’s Disease (PD) but a clear understanding of the neural correlates of PD depression has remained elusive. The thalamus may be relevant as previous work has demonstrated functional connectivity [1] and white matter microstructural [2] changes as well as noradrenergic denervation [3] involving this structure in PD depression. Our study utilised an automated thalamic segmentation technique that enables the thalamus to be studied in more specific detail at the level of its constituent subnuclei [4].

Method: We used structural and diffusion weighted imaging on 76 participants with PD to evaluate the relationship between PD depression and grey and white matter thalamic changes. We used a thalamic segmentation method to divide the thalamus into 50 constituent nuclei [4]. We assessed longitudinal change in subnuclei volumes and macrosturctural white matter integrity by extracting volumes and using fixel based analyses [5] to calculate mean fibre cross sections (FC) for afferent and efferent fibres at each subnuclei, at baseline and 18-month follow-up. We used a generalised linear mixed model to evaluate the relationship between depression and both nuclei volume and mean FC for each of the 50 thalamic subnuclei.

Results: We found that depression scores were associated with right pulvinar anterior (PuA) nucleus volume loss over time. Antidepressant use was associated with higher right PuA volume suggesting a possible effect of treatment. Depression scores were associated with decreases in white matter tract macrostructure across 43 of the 50 tracts connected to thalamic subnuclei.

Conclusion: We demonstrate that depression is associated with right thalamic PuA volume loss and widespread thalamic white matter macrostructural changes over time. Further, we found that antidepressants may protect against right PuA volume loss. Our work provides mechanistic insights for depression in PD and highlights potential therapeutic targets.

References: 1) Cardoso EF, Maia FM, Fregni F, Myczkowski ML, Melo LM, Sato JR, et al. Depression in Parkinson’s disease: convergence from voxel-based morphometry and functional magnetic resonance imaging in the limbic thalamus. Neuroimage. 2009;47(2):467-72. 2) Li W, Liu J, Skidmore F, Liu Y, Tian J, Li K. White matter microstructure changes in the thalamus in Parkinson disease with depression: A diffusion tensor MR imaging study. AJNR Am J Neuroradiol. 2010;31(10):1861-6. 3) Remy P, Doder M, Lees A, Turjanski N, Brooks D. Depression in Parkinson’s disease: loss of dopamine and noradrenaline innervation in the limbic system. Brain. 2005;128(Pt 6):1314-22. 4) Iglesias JE, Insausti R, Lerma-Usabiaga G, Bocchetta M, Van Leemput K, Greve DN, et al. A probabilistic atlas of the human thalamic nuclei combining ex vivo MRI and histology. Neuroimage. 2018;183:314-26. 5) Raffelt DA, Tournier JD, Smith RE, Vaughan DN, Jackson G, Ridgway GR, et al. Investigating white matter fibre density and morphology using fixel-based analysis. Neuroimage. 2017;144(Pt A):58-73.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/longitudinal-change-in-thalamic-white-matter-macrostructure-and-volume-in-parkinsons-disease-depression/