Exploring habenular structural connectivity in Parkinson's disease: insights from 7 T MRI study

Background PD is marked by both motor and non-motor symptoms, with its pathophysiology involving many neural pathways and brain regions beyond the dopaminergic system. While mainly gray matter changes have been noted, white matter changes also exist in PD. Habenula, known for its role in reward processing, mood regulation, motor functions, and cognition, is of interest due to its connection to mood disorders in PD. This study aims to explore diffusion metrics and structural connectivity changes in the habenula of newly diagnosed PD patients using 7 T MRI. Methods 84 PDs and 38 HCs were recruited from Maastricht University Medical Centre. Clinical, demographic, and total Beck Depression Inventory (BDI) scores were recorded. A 7 T brain MRI was conducted. Diffusion metrics and structural connectivity were evaluated. Results The mean diffusion metrics of Hb were not significantly different between the groups. However, in PD patients, there was an increase in mean structural connectivity from the right Hb to the right hippocampus ( p = 0.006) and the right fusiform gyrus ( p = 0.007). On the left side, enhanced connectivity was observed with the left pallidum ( p = 0.040) and left accumbens ( p = 0.009). In the PD group, a significant correlation was found between the BDI total score and increased structural connectivity from the right Hb to the left cingulate isthmus ( R 2 = 0.090, p = 0.003). Conclusion This pioneering study examines diffusion metrics and structural connectivity of Hb in PD patients using high-resolution 7 T MRI. Our findings highlight the habenula's potential role in PD pathophysiology, with altered connectivity suggesting early neurodegenerative or compensatory processes. These results underscore the importance of the habenula as a biomarker for PD and its potential as a therapeutic target.