Subthalamic nucleus-language network connectivity predicts dopaminergic modulation of speech function in Parkinson's disease

• 成果类型: Article
• 署名作者: Cai, Weidong; Young, Christina B.; Yuan, Rui; Lee, Byeongwook; Ryman, Sephira; Kim, Jeehyun; Yang, Laurice; Levine, Taylor F.; Henderson, Victor W.; Poston, Kathleen L.; Menon, Vinod
• 署名单位: Stanford University; Stanford University; Stanford University; Stanford University; Stanford University
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-10922
• DOI: 10.1073/pnas.2316149121
• 发表日期: 2024-05-28
• 关键词: deep brain-stimulation; cognitive function; sensorimotor cortex; nonmotor symptoms; motor cortex; inhibition; parcellation; ORGANIZATION; integration; reveals

摘要

Speech impediments are a prominent yet understudied symptom of Parkinson's disease (PD). While the subthalamic nucleus (STN) is an established clinical target for treating motor symptoms, these interventions can lead to further worsening of speech. The interplay between dopaminergic medication, STN circuitry, and their downstream effects on speech in PD is not yet fully understood. Here, we investigate the effect of dopaminergic medication on STN circuitry and probe its association with speech and cognitive functions in PD patients. We found that changes in intrinsic functional connectivity of the STN were associated with alterations in speech functions in PD. Interestingly, this relationship was characterized by altered functional connectivity of the dorsolateral and ventromedial subdivisions of the STN with the language network. Crucially, medication - induced changes in functional connectivity between the STN's dorsolateral subdivision and key regions in the language network, including the left inferior frontal cortex and the left superior temporal gyrus, correlated with alterations on a standardized neuropsychological test requiring oral responses. This relation was not observed in the written version of the same test. Furthermore, changes in functional connectivity between STN and language regions predicted the medication's downstream effects on speech - related cognitive performance. These findings reveal a previously unidentified brain mechanism through which dopaminergic medication influences speech function in PD. Our study sheds light into the subcortical - cortical circuit mechanisms underlying impaired speech control in PD. The insights gained here could inform treatment strategies aimed at mitigating speech deficits in PD and enhancing the quality of life for affected individuals. Significance While dopaminergic medications effectively treat motor symptoms in Parkinson's disease (PD), their impact on speech-a critical yet often overlooked nonmotor symptom-has been ambiguous. Our study elucidates a neural mechanism revealing that such dopamine modulates functional connectivity between specific subdivisions of the subthalamic nuclei (STN) and language networks. We found this connectivity to be uniquely correlated with changes in speech functions, especially those requiring vocal responses, while remaining dissociated from cognitive tasks that required manual responses. Our work offers insights into the neurocircuitry governing speech in PD and lays the foundation for targeted, more efficacious treatment strategies, thereby filling a crucial gap in our understanding of dopaminergic modulation of speech functions in PD.