Parkinson’s Disease Research Report: Subthalamic Nucleus–Language Network Functional Connectivity Predicts Dopaminergic Modulation of Speech Function

Background

Parkinson’s disease (PD) is primarily characterized by motor impairments, but it also involves non-motor symptoms including speech disorders, severely affecting patients’ quality of life. Although dopaminergic medication has significant effects in alleviating motor symptoms, its influence on speech function remains unclear. This study investigates how dopamine modulates the functional connectivity between the subthalamic nucleus (STN) and the language network to understand its regulation of speech function. The study aims to fill the critical knowledge gap regarding dopaminergic modulation of speech function in PD patients and provide a foundation for developing more effective treatment strategies.

Paper Source

This study entitled “Subthalamic nucleus–language network connectivity predicts dopaminergic modulation of speech function in Parkinson’s disease” was written by Weidong Cai and his team, who are affiliated with multiple institutions including the Department of Psychiatry and Behavioral Sciences at Stanford University. The paper was published on May 20, 2024, in the journal PNAS (Proceedings of the National Academy of Sciences of the United States of America).

Research Methods

Subjects and Design

The study recruited 27 PD patients and 44 healthy controls (HC). PD patients underwent functional magnetic resonance imaging (fMRI) scans before and after dopamine medication, while healthy controls underwent a single scan. Using a self-control study design, each PD patient was assessed and completed various tasks, including the Movement Disorder Society-sponsored Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) motor function assessment, Symbol Digit Modalities Test (SDMT), and resting-state fMRI scans before and after medication.

Functional Connectivity Analysis

The fMRI data analysis included extracting time series from the subthalamic nucleus and analyzing its connectivity with ten major brain functional networks. A consensus clustering method was used to perform functional partitioning of the subthalamic nucleus, and the canonical correlation analysis (CCA) model was applied to evaluate the impact of dopaminergic medication on functional connectivity and PD patient behavior.

Functional Partitioning of the Subthalamic Nucleus

Through the analysis of brain functional connectivity structure, the study identified three internal functional subdivisions of the subthalamic nucleus: dorsolateral, central, and ventromedial. These subdivisions have specific white matter projections to different cortical regions, contributing to functions in motor control, cognition, and emotional processing.

Results

Effects of Dopaminergic Medication on Motor and Cognitive Function

Dopaminergic medication significantly improved PD patients’ motor function (MDS-UPDRS scores) but had little effect on the Symbol Digit Modalities Test (SDMT). However, the speech recognition part (oral SDMT) showed that the medication’s impact on speech function was significantly higher than on the written SDMT. This indicates that the medication primarily affects speech function rather than general cognitive ability.

Relationship Between Functional Connectivity Changes and Behavioral Improvement

Functional connectivity analysis revealed that dopaminergic medication significantly altered the functional connectivity between the subthalamic nucleus and the language network, especially with the Left Inferior Frontal Cortex (LIFC) and Left Superior Temporal Gyrus (LSTG). These changes in functional connectivity were highly correlated with the improvement in oral SDMT performance in PD patients.

Specificity of Subthalamic Nucleus Functional Subdivisions

Specifically, the connectivity between the dorsolateral and ventromedial subdivisions of the subthalamic nucleus and the language network influenced different behavioral outcomes. The dorsolateral subdivision primarily involved motor function, while the ventromedial subdivision was associated with emotional processing. These findings unveil how dopamine influences speech function through specific neural pathways.

Predictive Analysis Model

A multivariable regression analysis model demonstrated that analyzing the functional connectivity changes induced by dopaminergic medication can accurately predict the post-medication speech performance in PD patients. This provides strong support for the future development of personalized treatment based on dopaminergic regulation.

Conclusions and Significance

This study is the first to reveal how dopaminergic medication influences speech function in PD patients by modulating the functional connectivity between the subthalamic nucleus and the language network, offering a new neural mechanism to explain this process. It not only fills a research gap concerning the non-motor symptoms of dopaminergic medication but also provides a scientific basis for developing more effective treatment strategies aimed at improving the quality of life for PD patients. In future research, further exploration of the effects of dopaminergic medication on other cognitive and emotional functions is needed, as well as the application of these findings in clinical practice to help PD patients better manage their symptoms.