Objective: We aimed to demonstrate the parallel neural mechanisms underlying the effects of combining standard levodopa treatment with the DopApp digital intervention on motor and non-motor symptoms in Parkinson’s disease (PD).

Background: PD is defined by the progressive degeneration of dopaminergic neurons within the nigrostriatal pathway, leading to a complex interplay of motor and non-motor symptoms. Previous studies have suggested that these clinical manifestations result from disruptions in the structural and functional integrity of segregated cortico-basal neural circuits. This parallel circuits model processes distinct types of information simultaneously via the thalamic relay.

Method: Thirty-two PD patients treated with Levodopa participated in a prospective, double-blind, randomized, placebo-controlled trial. The 3-week digital treatment included a proprietary daily protocol of brief interactive interventions including multisensory motor, psychological and cognitive training. Patients were assessed pre- and post-treatment using MDS-UPDRS and resting-state fMRI scans. A bivariate group-level regression analysis with UPDRS covariates was used to identify brain functional connectivity correlations.

Results: Seed-to-voxel analysis revealed a significant increase in group-by-time connectivity between bilateral ventral lateral thalamus (VLT) nuclei and the primary motor cortex (M1) (pFDR < 0.05)[figure1]. These increases correlated with improved UPDRS part-III (clinician motor examination) scores (r = -0.72, p<0.05). Additionally, we observed increased connectivity in a parallel circuit between anteroventral nuclei of the thalamus (AVT) and the caudate, with the medial prefrontal (mPFC) and the orbitofrontal cortex (OFC) (pFDR<0.05)[figure1]. These increases correlated with improved UPDRS part-II scores, which reflects self-perception of motor experiences of daily living (r =-0.75, p<0.05).

Conclusion: Combining pharmaceutical and non-pharmaceutical approaches increased connectivity in both motor and limbic neural circuits.  The distinct correlation between parallel neural pathways and clinician-rated versus self-rated symptoms highlights the benefit of this approach in improving both motor and non-motor symptoms in PD.

Figure 1

« Back to 2025 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/improving-motor-and-non-motor-symptoms-in-parkinsons-disease-a-combined-pharmaceutical-and-digital-approach-targeting-parallel-neural-circuits/