Striatal representations and network correlates of digital motor scores in Parkinson’s disease

Digital health technology (DHT) enables to detect and quantify charateristics motor dysfunction in Parkinson’s disease (PD). However, the understanding of the relationship between dopaminergic nigrostriatal denervation and quantitative composite digital motor scores (DMS) captured by DHT remains largely limited to date.

In this hybrid PET-MRI study, we used simultaneously acquired PET with ¹¹ C-d-threo-methylphenidate ( ¹¹ C-dMP-PET) – a tracer of presynaptic dopamine transporters – and resting-state-fMRI (rs-fMRI) to investigate this relationship and to explore associated neural network correlates in PD.

Seventeen PD patients and 39 healthy controls underwent ¹¹ C-dMP-PET and rs-fMRI. Quantitative composite DMS for arm swing, gait and balance were calculated using DHT-derived parameters. Voxel-based correlation analysis of ¹¹ C-dMP-PET binding potential (BP _NP ) was performed for each DMS and resulting clusters were used for seed-based functional connectivity analyses.

We found that DMS of arm swing, gait and balance exhibit differential striatal representations associated with dopaminergic denervation as assessed by ¹¹ C-dMP-PET. Specifically, lower BP _NP correlated with higher (i. e. more pathologic) arm swing DMS in the central putamen and higher balance DMS in the right caudate, whereas the most robust correlation was observed for lower BP _ND with higher gait DMS in the right caudate and anteromedial putamen. Seed-based functional connectivity analysis revealed lower functional connectivity in a frontostriatal network encompassing the basal ganglia and medial frontal regions associated to pathological gait DMS in PD.

Taken together, our study demonstrates striatal representations of key domains of PD motor dysfunction captured by DHT. Highlighting the complex interplay of gait motor control, we show that gait dysfunction is associated with dopaminergic denervation in the anteromedial executive subregion of the striatum and frontostriatal connectivity changes in regions involved in planning and initiation of movement sequences. Therefore, our study provides first preliminary insights into the relationship of dopaminergic degeneration and DMS encouraging further investigation in larger cohorts and longitudinal studies to construct and validate digital motor biomarkers obtained from DHT as outcome measures in clinical trials in PD.

Abbreviated summary

Using ¹¹ C-d-threo-methylphenidate-PET and resting-state-fMRI, Roeben et al. investigate the relationship between dopaminergic denervation and digital motor scores (DMS) in Parkinson’s disease. They show that gait DMS are associated with dopaminergic denervation in the anteromedial executive striatum and frontostriatal connectivity changes in regions involved in planning and initiation of movement sequences.