Investigating Subcortical Contributions to Speech Sequencing in Deep Brain Stimulator Recipients

This study will examine how two important brain circuits - one involving the subthalamic nucleus (STN) and one involving the ventral intermediate nucleus of the thalamus (VIM) - contribute to learning and producing speech sequences. Participants will include two groups: 1. individuals with Parkinson's disease who have deep brain stimulation (DBS) devices targeting the STN and 2. individuals with essential tremor who have DBS devices targeting the VIM.

Participants will complete speech tasks involving the learning and repetition of novel sound sequences. During some parts of the study, DBS stimulation will be temporarily turned on or off in a controlled research setting. This will allow researchers to examine how stimulation affects both the learning of new speech sequences and the production of previously learned sequences. All STN participants and most VIM participants will also be equipped with a cutting-edge DBS system, the Percept PC, which will enable the recording of deep brain activity during the tasks.

The results of this study will improve our understanding of how different brain circuits support speech learning and production. In particular, this study will help to differentiate the roles of the STN and VIM in learning the ordering of speech sounds within a syllable from learning of speech sequences containing multiple syllables. This knowledge may help guide future approaches to optimizing DBS settings to improve both movement and speech outcomes in individuals with neurological disorders, as well as provide greater general insight into how these brain structures contribute to speech production and learning.

Study Overview

• Status: Recruiting
• Conditions: Essential Tremor; Parkinson's Disease (PD)
• Intervention / Treatment: Behavioral: Phoneme sequence learning; Other: Cessation and re-enabling of stimulation of the STN; Behavioral: Multisyllabic sequence learning; Other: Cessation and re-enabling of stimulation of the VIM thalamic nucleus

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Frank H Guenther, Ph.D.; Phone Number: 617-353-5765; Email: guenther@bu.edu
• Study Contact Backup: Name: Barbara G Holland, MA; Phone Number: 617-353-6181; Email: bobbieh@bu.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Massachusetts General Hospital
      • Principal Investigator: Todd Herrington, MD, PHD
      • Contact: Todd Herrington, MD, PHD; Phone Number: 6177265532; Email: therrington@mgh.harvard.edu
      • Sub-Investigator: Zeyang Yu, PHD
      • Sub-Investigator: Robert Richardson, MD, PHD
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Boston University
      • Contact: Frank H Guenther, Ph.D.; Phone Number: 617-353-5765; Email: guenther@bu.edu
      • Contact: Barbara G Holland, MA; Email: bobbieh@bu.edu
      • Principal Investigator: Frank H Guenther, Ph.D.
      • Sub-Investigator: Alfonso Nieto-Castanon, Ph.D.
      • Sub-Investigator: Andrew Meier, Ph.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Native speakers of American English
• Adults at least 18 years of age
• A clinically established diagnosis of Parkinson's disease or essential tremor
• Able to provide informed consent in the judgment of the investigator
• Treated with deep brain stimulation of the subthalamic nucleus (Parkinson's disease) or ventral intermediate nucleus of the thalamus (essential tremor)
• Stable Parkinson's disease or essential tremor medication regimen for at least one month
• Stable DBS program settings for at least one month
• Nominal DBS system function, including normal impedances at therapeutic DBS contacts, and adequate battery life or adequate IPG charging status for therapy
• For DBS sensing, implanted with Medtronic Percept PC or Percept RC implantable pulse generator
• Corrected vision adequate to easily read text presented during speech motor task

Exclusion Criteria:

• Cognitive impairment (Montreal Cognitive Assessment (MoCA; Nesreddine et al., 2005) score < 25) or active psychotic or behavioral symptoms that would, in the judgment of the investigator, preclude proper participation in the study
• Hearing impairment that interferes with accurate perception of the speech motor learning stimulus (25dB hearing level threshold at 500, 1k, 2k, and 4kHz frequencies)
• Language impairment (aphasia) or speech articulation impairment (dysarthria) that precludes performance of the speech motor learning task
• Neurological disorder that interferes with speech motor learning
• Inability to tolerate symptoms when DBS is off
• Orthodontia or atypical oral structure (e.g., cleft palate) that interferes with speech
• Pregnancy
• For participants in the sub-syllabic sequence learning study (Study C.2.1), experience with the following languages: Hebrew, Polish, Lithuanian, Romanian, Georgian, Tepehua, Hungarian, and Pima

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Subthalamic nucleus with subsyllabic learning arm; Arm 1: subjects with implanted STN deep brain stimulators will undergo learning tasks involving non-English sound sequences while their stimulators are turned on and off	Behavioral: Phoneme sequence learning; Approximately half of subjects enrolled in the study will participate in this intervention. Subjects will read aloud monosyllabic sequences that are presented orthographically on a screen. Each sequence is formed by a non-native consonant cluster followed by a vowel and final consonant (CCVC). Speech trials will be grouped into blocks. After a Familiarization block, subjects will produce a set of twelve CCVCs in a Pretest block. Subjects will then repeatedly produce two of those CCVCs in one Training block, and two other CCVCs in a subsequent Training block. Following training, subjects will produce all four trained CCVCs and four additional novel CCVCs in each of two Test blocks. Washout blocks, during which no speech task trials are completed, will follow the Pretest, Training, and first Test block to allow subjects to rest and to complete standardized testing.; Other: Cessation and re-enabling of stimulation of the STN; 20 adults with Parkinson's disease (PD) who have deep brain stimulator (DBS) implants in the subthalamic nucleus (STN). Stimulation of the STN will be intermittently turned off while subjects complete speech sequence learning tasks. After no more than 35 minutes, stimulation will be re-enabled with normal clinical parameters for each participant.
Experimental: Subthalamic nucleus with multisyllabic learning arm; Arm 2: subjects with implanted STN deep brain stimulators will undergo learning tasks involving syllable sequences while their stimulators are turned on and off	Other: Cessation and re-enabling of stimulation of the STN; 20 adults with Parkinson's disease (PD) who have deep brain stimulator (DBS) implants in the subthalamic nucleus (STN). Stimulation of the STN will be intermittently turned off while subjects complete speech sequence learning tasks. After no more than 35 minutes, stimulation will be re-enabled with normal clinical parameters for each participant.; Behavioral: Multisyllabic sequence learning; Approximately half of subjects enrolled in the study will participate in this intervention. Subjects will read aloud sequences that are presented orthographically on a screen. Speech trials will be grouped into blocks. After a Familiarization block, subjects will produce 2- and 7-syllable sequences in an Assessment block to determine the appropriate length sequence for the remainder of the intervention. Subjects will produce a set of eight sequences in a Pretest block. Subjects will then repeatedly produce two of those sequences in one Training block and two other sequences in a subsequent Training block. Following training, subjects will produce all four trained sequences and two additional novel sequences in each of two Test blocks. Washout blocks, during which no speech task trials are completed, will follow the Pretest, Training, and first Test Block to allow subjects to rest and to complete standardized testing.
Experimental: Ventral intermediate thalamus with subsyllabic learning arm; Arm 3: subjects with implanted VIM deep brain stimulators will undergo learning tasks involving non-English sound sequences while their stimulators are turned on and off	Behavioral: Phoneme sequence learning; Approximately half of subjects enrolled in the study will participate in this intervention. Subjects will read aloud monosyllabic sequences that are presented orthographically on a screen. Each sequence is formed by a non-native consonant cluster followed by a vowel and final consonant (CCVC). Speech trials will be grouped into blocks. After a Familiarization block, subjects will produce a set of twelve CCVCs in a Pretest block. Subjects will then repeatedly produce two of those CCVCs in one Training block, and two other CCVCs in a subsequent Training block. Following training, subjects will produce all four trained CCVCs and four additional novel CCVCs in each of two Test blocks. Washout blocks, during which no speech task trials are completed, will follow the Pretest, Training, and first Test block to allow subjects to rest and to complete standardized testing.; Other: Cessation and re-enabling of stimulation of the VIM thalamic nucleus; 20 adults with essential tremor who have deep brain stimulator (DBS) implants in the ventral intermediate nucleus (VIM) of the thalamus will participate in this intervention. Stimulation of the VIM will be intermittently turned off (DBS OFF state) while subjects complete speech sequence learning tasks. After no more than 35 minutes, stimulation will be re-enabled with normal clinical parameters for each participant.
Experimental: Ventral intermediate thalamus with multisyllabic learning arm; Arm 4: subjects with implanted VIM deep brain stimulators will undergo learning tasks involving syllable sequences while their stimulators are turned on and off	Behavioral: Multisyllabic sequence learning; Approximately half of subjects enrolled in the study will participate in this intervention. Subjects will read aloud sequences that are presented orthographically on a screen. Speech trials will be grouped into blocks. After a Familiarization block, subjects will produce 2- and 7-syllable sequences in an Assessment block to determine the appropriate length sequence for the remainder of the intervention. Subjects will produce a set of eight sequences in a Pretest block. Subjects will then repeatedly produce two of those sequences in one Training block and two other sequences in a subsequent Training block. Following training, subjects will produce all four trained sequences and two additional novel sequences in each of two Test blocks. Washout blocks, during which no speech task trials are completed, will follow the Pretest, Training, and first Test Block to allow subjects to rest and to complete standardized testing.; Other: Cessation and re-enabling of stimulation of the VIM thalamic nucleus; 20 adults with essential tremor who have deep brain stimulator (DBS) implants in the ventral intermediate nucleus (VIM) of the thalamus will participate in this intervention. Stimulation of the VIM will be intermittently turned off (DBS OFF state) while subjects complete speech sequence learning tasks. After no more than 35 minutes, stimulation will be re-enabled with normal clinical parameters for each participant.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in speech sequencing accuracy	Investigators will evaluate recordings of speech productions to identify errors. This will be used to compare sequence accuracy before and after practice of novel sequences with DBS in the ON and OFF states.	Day 1
Speech production duration	Investigators will inspect recordings of speech productions to identify production duration. This will be used to test hypotheses regarding differences in sequence duration before and after practice of novel sequences and with DBS in the ON and OFF states.	Day 1
Beta power during speech production	Investigators will extract beta band (12-20 Hz) power from neural recordings taken while subjects practice and rehearse novel speech sequences. This will be used to test hypotheses regarding differences in beta power before and after practice of novel sequences and with DBS in the ON and OFF states.	Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Forward Digit Span	The forward digit span subtest of the Comprehensive Test of Phonological Awareness, 2nd Edition will be administered to all participants. Scores will be used to identify correlations between working memory capacity and other outcome measures.	Baseline
Cognitive Assessment	The Montreal Cognitive Assessment (MoCa) test will be administered to all participants. Scores will be used to determine study eligibility and to identify correlations between cognitive capacity and other outcome measures. Score range: 0-30, higher score indicates higher cognitive performance.	Baseline
Essential tremor severity	Participants with essential tremor will complete The Essential Tremor Rating and Assessment Scale (TETRAS) in both the DBS ON and OFF states to assess disease severity and to identify correlations between severity and other outcome measures. Score range: 0-64, lower score indicates less severe tremor.	Day 1
Parkinson's disease severity	Part III (motor examination) of the Movement Disorder Society-sponsored revision of the Unified Parkinson's disease Ratings Scale (UPDRS part 3) will be administered to participants with Parkinson's disease in both the DBS ON and OFF states to assess disease severity and to identify correlations between severity and other outcome measures. Score range: 0-132, lower scores indicate lower motor symptom severity.	Day 1

Collaborators and Investigators

• Sponsor: Boston University Charles River Campus
• Collaborators: Massachusetts General Hospital; National Institute on Deafness and Other Communication Disorders (NIDCD)
• Investigators: Principal Investigator: Frank H Guenther, Ph.D., Boston University

Study record dates

Study Major Dates

• Study Start (Actual): February 18, 2026
• Primary Completion (Estimated): August 1, 2030
• Study Completion (Estimated): August 1, 2030

Study Registration Dates

• First Submitted: March 3, 2026
• First Submitted That Met QC Criteria: March 3, 2026
• First Posted (Actual): March 6, 2026

Study Record Updates

• Last Update Posted (Actual): March 9, 2026
• Last Update Submitted That Met QC Criteria: March 6, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Parkinson's Disease; Essential Tremor; Deep Brain Stimulation; Stuttering; Speech Disorders; Neurocomputational Modeling
• Additional Relevant MeSH Terms: Synucleinopathies; Neurologic Manifestations; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurobehavioral Manifestations; Neurodegenerative Diseases; Movement Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Communication Disorders; Language Disorders; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Parkinson Disease; Speech Disorders; Essential Tremor; Stuttering
• Other Study ID Numbers: Guenther_8238; R01DC022949 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: All planned analyses will be carried out by research staff who are already facilitating the study.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No