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SCIENTIFIC LITERATURE · PPR

Caudate Integrity Shapes Neural Responses to Working Memory Manipulation in Early Parkinson’s Disease

· 2026-07-17

DOI: 10.21203/rs.3.rs-10307910/v1

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Research overview

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Abstract Cognitive processes with a high executive demand, such as the manipulation of working memory (WM), are often affected in Parkinson’s disease (PD). While this process critically depends on frontostriatal circuits involving the caudate nucleus, the relationship between dopamine availability, iron load, and task-related activation remains poorly understood. Here, 25 individuals with early PD and 35 healthy controls (HC) underwent an established fMRI WM manipulation paradigm, iron load and dopamine transporter density imaging. Associations between task-related activation and markers of caudate integrity were assessed. Both groups demonstrated robust and similar WM manipulation-related activation. Within the PD group, neural activation was positively associated with caudate dopamine transporter density and inversely correlated with iron load with the later accounting for a larger proportion of explained variance in neural activation. These findings indicate that WM-related activation is not primarily characterized by overt group-level abnormalities, but rather by interindividual variability linked to caudate integrity.

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