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

Publisher: National Academy of Sciences Country of Publication: United States NLM ID: 7505876 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1091-6490 (Electronic) Linking ISSN: 00278424 NLM ISO Abbreviation: Proc Natl Acad Sci U S A Subsets: MEDLINE

Original Publication: Washington, DC : National Academy of Sciences

Parkinson Disease*/physiopathology ; Parkinson Disease*/drug therapy ; Subthalamic Nucleus*/physiopathology ; Subthalamic Nucleus*/drug effects ; Speech*/physiology ; Speech*/drug effects ; Language*; Humans ; Male ; Female ; Middle Aged ; Aged ; Magnetic Resonance Imaging ; Dopamine/metabolism ; Nerve Net/drug effects ; Nerve Net/physiopathology ; Cognition/drug effects ; Dopamine Agents/pharmacology ; Dopamine Agents/therapeutic use

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.
Competing Interests: Competing interests statement:The authors declare no competing interest.

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AG071837 HHS | NIH | National Institute on Aging (NIA); NS086085 HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS); MH121069 HHS | NIH | National Institute of Mental Health (NIMH); R01 MH121069 United States MH NIMH NIH HHS; R01 NS086085 United States NS NINDS NIH HHS; P30 AG066515 United States AG NIA NIH HHS; NS115114 HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS); K99 AG071837 United States AG NIA NIH HHS; RF1 NS086085 United States NS NINDS NIH HHS; AARFD-21-848178 Alzheimer's Association (AA); P50 AG047366 United States AG NIA NIH HHS; DC017950-S1 HHS | NIH | National Institute on Deafness and Other Communication Disorders (NIDCD); AARGD-NTF-21-850781 Alzheimer's Association (AA); R01 NS115114 United States NS NINDS NIH HHS; AARFD-21-849349 Alzheimer's Association (AA); R21 DC017950 United States DC NIDCD NIH HHS

Keywords: dopamine; functional connectivity; language; speech; subthalamic nuclei

Date Created: 20240520 Date Completed: 20240520 Latest Revision: 20241121

20241121

PMC11145286

10.1073/pnas.2316149121

38768342