Thalamic white matter macrostructure and subnuclei volumes in Parkinson’s disease depression

Abstract

Depression is a common non-motor feature of Parkinsons disease (PD) which confers significant morbidity and is challenging to treat. The thalamus is a key component in the basal ganglia-thalamocortical network critical to the pathogenesis of PD and depression but the precise thalamic subnuclei involved in PD depression have not been identified. We performed structural and diffusion-weighted imaging (DWI) on 76 participants with PD to evaluate the relationship between PD depression and grey and white matter thalamic subnuclear changes. We used a thalamic segmentation method to divide the thalamus into its 50 constituent subnuclei (25 each hemisphere). Fixel-based analysis was used to calculate mean fibre cross-section (FC) for white matter tracts connected to each subnucleus. We assessed volume and FC at baseline and 14–20 months follow-up. A generalised linear mixed model was used to evaluate the relationship between depression, subnuclei volume and mean FC for each thalamic subnucleus. We found that depression scores in PD were associated with lower right pulvinar anterior (PuA) subnucleus volume. Antidepressant use was associated with higher right PuA volume suggesting a possible protective effect of treatment. After follow-up, depression scores were associated with reduced white matter tract macrostructure across almost all tracts connected to thalamic subnuclei. In conclusion, our work implicates the right PuA as a relevant neural structure in PD depression and future work should evaluate its potential as a therapeutic target for PD depression.

Rohan Bhome

PhD Student

Rohan Bhome is a consultant old age psychiatrist with a clinical and research interest in the neuropsychiatric symptoms of neurodegenerative disorders, which cause significant morbidity but are poorly understood and difficult to treat. Jointly based at the Dementia Research Centre (DRC) and Centre for Medical Image Computing (CMIC), and co-supervised by James Cole and Rimona Weil, his PhD, funded by the Wolfson foundation and Eisai, aims to investigate the neural mechanisms in Dementia with Lewy bodies (DLB) using advanced neuroimaging techniques including Quantitative Susceptibility Mapping, Fixel Based Analysis and Normative modelling. He hopes to identify novel neuroimaging biomarkers that could potentially enhance future clinical trials in DLB by improving stratification and monitoring of response to treatment.

James H Cole

Professor of Neuroimage Computing

My research interests include neuroimaging, ageing and neurodegenerative diseases