Subthalamic Nucleus Deep Brain Stimulation in Speech Study

Parkinson Disease Clinical Trial

— SiSS  

Official title:

Role of Subthalamic Nucleus in Speech and Movement Among People With Parkinson's Disease as Revealed by Intraoperative Recordings and Deep Brain Stimulation

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05493670
• Other study ID #: 202001213
• Secondary ID: R01DC017718
• Status: Recruiting
• Start date: October 15, 2020
• Est. completion date: July 2025

Study information

• Verified date: December 2023
• Source: University of Iowa
• Contact: Jeremy Greenlee, MD
• Phone: 319-356-2771
• Email: jeremy-greenlee[@]uiowa.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Parkinson's disease (PD) patients treated with deep brain stimulation (DBS) of the subthalamic nucleus (STN) have unpredictable and varied speech outcomes after this treatment. Our research will prospectively document speech performance before, during and 6- and 12-months after STN-DBS in 80 surgically treated patients and compared with 40 non-surgical controls with Parkinson's disease. This study will provide unique insights into the role of STN in speech production, document speech outcome in a comprehensive fashion, identify factors that predict functional communication ability 12 months after STN-DBS, and test the feasibility of low frequency DBS in reversing DBS-induced speech declines in order to optimize treatment strategies for those living with Parkinson's disease.

Description:

Aim 1. Define the mechanistic role of STN in speech using direct intraoperative brain recordings. For the first time, we will define STN neuronal physiology for both speech and limb tasks. Through multichannel microelectrode recording (MER) during awake STN-DBS implantation surgery, we will test the hypothesis suggested by our pilot data that STN firing rate during speech will be significantly different from the firing rate during a limb motor task.

Aim 2. Advance understanding of speech outcomes associated with STN-DBS. Intelligibility will serve as the primary functional communication outcome, with communication participation as a secondary metric. Acoustic measures of articulation, phonatory-respiratory behavior and tempo-fluency will be obtained.

Aim 2A. Determine differential effects of DBS stimulation (ON vs. OFF) on speech outcomes. ON vs. OFF stimulation changes in acoustic measures of speech will be used to inform potential reasons for observed changes in intelligibility.

Aim 2B. Define longitudinal effects of STN-DBS on speech outcomes. Speech outcomes and limb measures obtained pre-surgery will be compared to those at 6 and 12 months post-surgery when DBS stimulation is ON. Change in communication participation also will be defined. The control group studied at similar time points will control for disease progression.

Aim 2C. Determine associations between acoustic measures and intelligibility in STN-DBS.

Aim 3. Explore factors associated with changes in intelligibility post STN-DBS. As initial endeavors to guide future studies, we will:

Aim 3A. Use our metrics from Aims 1 and 2 (e.g. disease-specific characteristics, microelectrode recording data, pre-operative intelligibility) to identify factors that predict intelligibility at 12 months following STN-DBS.

Aim 3B. Test the feasibility of manipulating DBS stimulation parameters to improve intelligibility in a subset of participants with DBS-induced intelligibility declines.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: July 2025
• Est. primary completion date: July 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years to 84 Years

Eligibility

Inclusion Criteria:

For inclusion in this study, participants must

• have a confirmed diagnosis of idiopathic Parkinson's disease and no atypical Parkinsonism features

• experience significant motor fluctuations

• currently taking and responsive to dopaminergic medications (e.g. Levodopa)

• use English as their primary language

• lack significant cognitive impairment and be able to consent to participate

Exclusion Criteria:

• Significant hearing loss/reliance on hearing aids

Related Conditions & MeSH terms

• Dysarthria
• Parkinson Disease

Locations

Country	Name	City	State
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa

Sponsors (6)

Lead Sponsor	Collaborator
Jeremy Greenlee	National Institute on Deafness and Other Communication Disorders (NIDCD), National Institutes of Health (NIH), Northwestern University, University at Buffalo, University of Pittsburgh

Country where clinical trial is conducted

United States, 

References & Publications (11)

Dayal V, Limousin P, Foltynie T. Subthalamic Nucleus Deep Brain Stimulation in Parkinson's Disease: The Effect of Varying Stimulation Parameters. J Parkinsons Dis. 2017;7(2):235-245. doi: 10.3233/JPD-171077. — View Citation

Dromey C, Kumar R, Lang AE, Lozano AM. An investigation of the effects of subthalamic nucleus stimulation on acoustic measures of voice. Mov Disord. 2000 Nov;15(6):1132-8. doi: 10.1002/1531-8257(200011)15:63.0.co;2-o. — View Citation

Hebb AO, Darvas F, Miller KJ. Transient and state modulation of beta power in human subthalamic nucleus during speech production and finger movement. Neuroscience. 2012 Jan 27;202:218-33. doi: 10.1016/j.neuroscience.2011.11.072. Epub 2011 Dec 6. — View Citation

Lipski WJ, Alhourani A, Pirnia T, Jones PW, Dastolfo-Hromack C, Helou LB, Crammond DJ, Shaiman S, Dickey MW, Holt LL, Turner RS, Fiez JA, Richardson RM. Subthalamic Nucleus Neurons Differentially Encode Early and Late Aspects of Speech Production. J Neurosci. 2018 Jun 13;38(24):5620-5631. doi: 10.1523/JNEUROSCI.3480-17.2018. Epub 2018 May 22. — View Citation

Pal PK, Lee CS, Samii A, Schulzer M, Stoessl AJ, Mak EK, Wudel J, Dobko T, Tsui JK. Alternating two finger tapping with contralateral activation is an objective measure of clinical severity in Parkinson's disease and correlates with PET. Parkinsonism Relat Disord. 2001 Oct;7(4):305-309. doi: 10.1016/s1353-8020(00)00048-1. — View Citation

Seifried C, Weise L, Hartmann R, Gasser T, Baudrexel S, Szelenyi A, van de Loo S, Steinmetz H, Seifert V, Roeper J, Hilker R. Intraoperative microelectrode recording for the delineation of subthalamic nucleus topography in Parkinson's disease. Brain Stimul. 2012 Jul;5(3):378-387. doi: 10.1016/j.brs.2011.06.002. Epub 2011 Jul 8. — View Citation

Sidtis D, Sidtis JJ. Subcortical Effects on Voice and Fluency in Dysarthria: Observations from Subthalamic Nucleus Stimulation. J Alzheimers Dis Parkinsonism. 2017;7(6):392. doi: 10.4172/2161-0460.1000392. Epub 2017 Oct 30. — View Citation

Sidtis JJ, Alken AG, Tagliati M, Alterman R, Van Lancker Sidtis D. Subthalamic Stimulation Reduces Vowel Space at the Initiation of Sustained Production: Implications for Articulatory Motor Control in Parkinson's Disease. J Parkinsons Dis. 2016 Mar 19;6(2):361-70. doi: 10.3233/JPD-150739. — View Citation

Skodda S. Effect of deep brain stimulation on speech performance in Parkinson's disease. Parkinsons Dis. 2012;2012:850596. doi: 10.1155/2012/850596. Epub 2012 Nov 21. — View Citation

Sturman MM, Vaillancourt DE, Metman LV, Bakay RA, Corcos DM. Effects of five years of chronic STN stimulation on muscle strength and movement speed. Exp Brain Res. 2010 Sep;205(4):435-43. doi: 10.1007/s00221-010-2370-8. Epub 2010 Aug 10. — View Citation

Tourville JA, Guenther FH. The DIVA model: A neural theory of speech acquisition and production. Lang Cogn Process. 2011 Jan 1;26(7):952-981. doi: 10.1080/01690960903498424. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Neuron Firing Rate	DBS-STN participants will complete simple speech and motor tasks during surgery while the surgeon records neuron firing rate using Microelectrode Recording (MER).	Intraoperatively
Secondary	Speech Intelligibility with DBS ON	Speech intelligibility will be measured using the Sentence Intelligibility Test (SIT). Speech intelligibility ratings are measured as percentages, with lower percentages indicating more severe speech impairments.	Speech intelligibility with DBS ON will be measured at the 6 month follow up and 12 month follow up for the DBS-STN group.
Secondary	Speech Intelligibility (stimulation OFF or not applicable)	Speech intelligibility will be measured using the Sentence Intelligibility Test (SIT). Speech intelligibility ratings are measured as percentages, with lower percentages indicating more severe speech impairments.	Speech intelligibility without stimulation will be measured at baseline, 6 month, and 12 month visits for all participants.