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


Journal

Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876

Informations de publication

Date de publication:
28 May 2024
Historique:
medline: 20 5 2024
pubmed: 20 5 2024
entrez: 20 5 2024
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 38768342
doi: 10.1073/pnas.2316149121
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

e2316149121

Subventions

Organisme : NIA NIH HHS
ID : P50 AG047366
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG066515
Pays : United States
Organisme : HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS)
ID : NS086085
Organisme : HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS)
ID : NS115114
Organisme : HHS | NIH | National Institute of Mental Health (NIMH)
ID : MH121069
Organisme : HHS | NIH | National Institute on Aging (NIA)
ID : AG071837
Organisme : Alzheimer's Association (AA)
ID : AARFD-21-849349
Organisme : Alzheimer's Association (AA)
ID : AARGD-NTF-21-850781
Organisme : HHS | NIH | National Institute on Deafness and Other Communication Disorders (NIDCD)
ID : DC017950-S1
Organisme : Alzheimer's Association (AA)
ID : AARFD-21-848178

Déclaration de conflit d'intérêts

Competing interests statement:The authors declare no competing interest.

Auteurs

Weidong Cai (W)

Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA 94305.
Wu Tsai Neurosciences Institute, Stanford University School of Medicine, Stanford, CA 94305.

Christina B Young (CB)

Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305.

Rui Yuan (R)

Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA 94305.

Byeongwook Lee (B)

Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA 94305.

Sephira Ryman (S)

Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305.

Jeehyun Kim (J)

Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305.

Laurice Yang (L)

Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305.

Taylor F Levine (TF)

Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305.

Victor W Henderson (VW)

Wu Tsai Neurosciences Institute, Stanford University School of Medicine, Stanford, CA 94305.
Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305.
Department of Epidemiology and Population Health, Stanford University School of Medicine, Stanford, CA 94305.

Kathleen L Poston (KL)

Wu Tsai Neurosciences Institute, Stanford University School of Medicine, Stanford, CA 94305.
Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305.
Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA 94305.

Vinod Menon (V)

Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA 94305.
Wu Tsai Neurosciences Institute, Stanford University School of Medicine, Stanford, CA 94305.
Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305.

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