Category: Parkinson's Disease: Neuroimaging
Objective: We tested whether inter- and intra-individual differences in clinical severity are determined by cortical compensation, and not just by basal ganglia dysfunction.
Background: Motor symptoms in Parkinson’s disease (PD) are often attributed to basal ganglia dysfunction and dopamine depletion. However, dopamine depletion takes place years prior to symptom onset and is a poor predictor of clinical progression[3-7]. It is therefore unlikely to be the sole determinant of motor symptoms. Functional MRI studies demonstrate that PD is associated with potentially compensatory increases in parieto-premotor activity[8-9]. However, beneficial effects of altered parieto-premotor function on motor behavior remain to be confirmed.
Method: 353 PD patients and 60 healthy controls from the Personalized Parkinson Project performed an action selection task that is sensitive to bradykinesia during functional MRI. 326 patients and 56 healthy controls returned at two-year follow-up. The relationship between individual differences in brain activity and clinical severity was investigated in two ways. First, we compared brain activity between clinical subtypes of PD, which were defined according to a previously validated phenotyping strategy[12-14]. Second, brain activity was directly correlated with bradykinesia severity, measured with the MDS-UPDRS III. We also quantified the relationship between two-year change in bradykinesia and brain activity.
Results: PD patients had reduced basal ganglia compared to healthy controls. However, basal ganglia activity did not differ between subtypes and did not predict bradykinesia severity. In contrast, the relatively benign mild-motor predominant subtype was characterized by increased parieto-premotor activity compared to both a more severely affected diffuse-malignant subtype and healthy controls. Consistently, parieto-premotor activity inversely correlated with bradykinesia severity. Additionally, two-year change in superior parietal cortex activity inversely correlated with bradykinesia progression.
Conclusion: In conclusion, our findings strongly support a compensatory role of the parieto-premotor cortex and indicates that decline in cortical compensation may be a critical determinant of clinical severity and progression in PD. Treatments that maintain or enhance cortical compensation may serve as a valuable complement to traditional dopaminergic medication.
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To cite this abstract in AMA style:M. Johansson, I. Toni, R. Kessels, B. Bloem, R. Helmich. Clinical severity in Parkinson’s disease is determined by decline in cortical compensation [abstract]. Mov Disord. 2023; 38 (suppl 1). https://www.mdsabstracts.org/abstract/clinical-severity-in-parkinsons-disease-is-determined-by-decline-in-cortical-compensation/. Accessed September 23, 2023.
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MDS Abstracts - https://www.mdsabstracts.org/abstract/clinical-severity-in-parkinsons-disease-is-determined-by-decline-in-cortical-compensation/