Objective: Following the combination of standard levodopa treatment with a digital intervention in Parkinson’s disease (PD), we assessed the associations between neuroplasticity within the limbic system, differences in motivated behaviors and changes in psychological symptoms.

Background: PD is characterized by a progressive degeneration of dopaminergic neurons within the nigrostriatal pathway, leading to a complex interplay of motor and non-motor symptoms. Current PD medications typically have limited or no effect on non-motor symptoms.  Previous studies have suggested that non-motor symptoms may be related to the degeneration of limbic circuits, which contribute to the pathogenesis of depression, reduced motivation, impaired decision making, emotional dysregulation, and other psychiatric aspects of the disease.​

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 clinical and psychological scales, as well as resting-state fMRI scans. Daily behavioral data on app usage was analyzed to derive self-motivation and self-engagement scores.

Results: We observed a group-by-time increase in functional connectivity in key functional regions in the basal ganglia-limbic network (pFDR<0.05). Specifically, we found: Increased connectivity between the caudate and the mPFC and Increased connectivity among the globus pallidus internus, caudate, mPFC, ACC, and the insula. While changes in orbitofrontal and ventromedial prefrontal cortex connectivity correlated with self-motivation scores, increased connectivity in the amygdala, caudate, and insula were associated with self-engagement and BDI-II depression scores [figure1].

Conclusion: Our findings demonstrate the potential of combining levodopa treatment with a novel digital intervention to stimulate neuroplasticity in the basal ganglia and limbic networks, supporting motivated behaviors and emotional regulation in PD.

Figure 1

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MDS Abstracts - https://www.mdsabstracts.org/abstract/combining-pharmaceutical-and-digital-treatment-approaches-in-parkinsons-disease-modulates-of-the-limbic-system-supporting-emotional-regulation-and-motivated-behaviors/