Investigating Subcortical Contributions to Speech Sequencing in Deep Brain Stimulator Recipients

Purpose

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.

Conditions

  • Parkinson's Disease (PD)
  • Essential Tremor

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

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 Design

Phase
N/A
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Basic Science
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
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
  • 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.
  • 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.

Recruiting Locations

Massachusetts General Hospital
Boston, Massachusetts 02215
Contact:
Todd Herrington, MD, PHD
6177265532
therrington@mgh.harvard.edu

More Details

Status
Recruiting
Sponsor
Boston University Charles River Campus

Study Contact

Frank H Guenther, Ph.D.
617-353-5765
guenther@bu.edu