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Investigating Speech Sequencing in Neurotypical Speakers and Persons With Disordered Speech

Primary Purpose

Stuttering, Developmental, Aphasia, Primary Progressive

Status

Not yet recruiting

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

Learning of non-native phoneme combinations: 6 training sessions

Learning of non-native phoneme combinations: 1 training session

Learning of novel multisyllabic nonwords

Anodal tDCS

Sham tDCS

Learning of non-native phoneme combinations: 8 training sessions

About this trial

This is an interventional basic science trial for Stuttering, Developmental focused on measuring Stuttering, Developmental, Magnetic Resonance Imaging, Transcranial Direct Current Stimulation, Speech Motor Learning, Speech Disorders, Neurocomputational Modeling

Eligibility Criteria

6 Years - undefined (Child, Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria

Healthy individuals with no history of neurological, speech, or hearing disorders (other than stuttering in studies that involve adults who stutter).
To maximize the uniformity of prior exposure to the speech stimuli that will be used, only native speakers of American English will be recruited, and only those with limited exposure to a second language will be enrolled.
All adult participants will also pass a standard pure-tone hearing screening at a 25dB hearing level threshold at 500, 1k, 2k, and 4kHz frequencies.
All participating children will pass a hearing screening at a 20 dB threshold at 500, 1k, 2k, and 4k Hz.
Participants in experiments that require them to read orthographic stimuli must have normal or corrected-to-normal vision (MRI-safe corrective glasses are available at the Boston University Cognitive Neuroimaging Center for use during neuroimaging).
Participating children will complete additional speech, language, hearing, and cognitive tests to ensure that they are within normal performance ranges for their age with the exception of stuttering for children in the children who stutter (CWS) group.
Persons who stutter will be evaluated formally by a speech-language pathologist to assess stuttering severity and to ensure the absence of other speech or language disorders. PWS will have no history of neurological disorder other than stuttering, and will demonstrate very mild to severe stuttering according to the Stuttering Severity Instrument for Children and Adults - 4th Edition (SSI-4: PRO-ED, Inc.), that is confirmed by clinical reports and expressed concern by the subject and/or guardian.
Participants with primary progressive aphasia (PPA) will have been diagnosed through the Massachusetts General Hospital Frontotemporal Disorders Unit (MGH-FTD) by an experienced neurologist in coordination with a speech-language pathologist.
Participants with PPA will have a score of 1.0 or lower on the Clinical Dementia Rating scale (i.e., mild cognitive impairment or mild dementia) to ensure cognitive levels are sufficient to complete the task.
All participants with PPA must have a recent clinical assessment and T1 structural neuroimaging scan through the MGH-FTD Unit for eligibility for this study.

Exclusion Criteria

Participants in studies that involve tDCS or MRI scanning will have no contraindications specific to those procedures. For the tDCS study, this includes individuals who have a metallic implant in the head or electrically sensitive devices implanted in the body, a history of seizures, significant scalp lesions, or pregnancy.
For MRI studies, this includes a history of seizures, severe claustrophobia, the presence of magnetically or mechanically active implant, ferromagnetic material embedded in any part of the body, or pregnancy).
All participants will perform a standardized nonword repetition pre-test (the Dollaghan and Campbell Nonword Repetition Task) to assess working memory performance. Participants who perform more than 2 standard deviations below the norm for their age range will be deemed to be unable to perform the experimental task and released from further participation.
Participating children will have no history of neurological disorder other than stuttering, and will demonstrate very mild to severe stuttering according to the Stuttering Severity Instrument for Children and Adults, 4th Edition, that is confirmed by clinical reports and expressed concern by the subject and/or guardian.
Children under the age of 6 and over the age of 8 will not enrolled in this study.
Participants with PPA will not be eligible for this study if they are taking any medications that would be expected to affect speech or language.

Sites / Locations

Massachusetts General Hospital
Boston University
University of Michigan

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm Type

Experimental

Sham Comparator

Experimental

Arm Label

Sub-syllabic learning and fMRI

Sub-syllabic learning and anodal tDCS of inferior frontal sulcus

Sub-syllabic learning and anodal tDCS of cerebellum

Sub-syllabic learning and sham tDCS

Multisyllabic learning and fMRI in adults

Multisyllabic learning in children

Sub-syllabic learning in PPA

Arm Description

60 adults with neurotypical speech development will participate in this arm. Subjects will learn novel 1-syllable nonsense words formed by non-native phoneme combinations during 6 training sessions over 2 days. Following training, subjects will participate in a functional magnetic resonance imaging (fMRI) session on a third day to measure brain activity associated with producing the words learned during training and with a set of unfamiliar words also formed by non-native phoneme combinations.

35 adults with neurotypical speech development will participate in this arm. Subjects will learn novel 1-syllable nonsense words formed by non-native phoneme combinations. During the training, anodal transcranial direct current stimulation (tDCS) will be applied to the the subject's left inferior frontal sulcus.

35 adults with neurotypical speech development will participate in this arm. Subjects will learn novel 1-syllable words formed by non-native phoneme combinations. During the training, continuous anodal transcranial direct current stimulation (tDCS) will be applied to the the subject's right cerebellum.

35 adults with neurotypical speech development will participate in this arm. Subjects will learn novel 1-syllable words formed by non-native phoneme combinations. During training, Sham transcranial direct current stimulation stimulation (tDCS) will be delivered to the subject's brain.

30 adults persistent developmental stuttering (AWS) and 30 adults with neurotypical speech development (ANS) will participate in this arm. Subjects will learn nonsense words formed by novel combinations of 3 syllables that are legal in American English during 6 training sessions over 2 days. Following training, subjects will participate in a functional magnetic resonance imaging (fMRI) session on a third day to measure brain activity associated with producing the words formed by pairing 2 learned 3-syllable strings learned during training and those formed by pairing 2 unfamiliar 3-syllable strings. Behavioral measures extracted from the data will be used to compare performance before and after training and across the AWS and ANS participants.

45 children with persistent developmental stuttering (CWS) and 45 children with neurotypical speech development (CNS) will participate in this arm. Subjects will learn nonsense words formed by novel combinations of 2 syllables that are legal in American English during 6 training sessions over 2 days. Behavioral measures extracted from the data will be used to compare performance before and after training and across the CWS and CNS participants.

30 adults with primary progressive aphasia (PPA) will participate in this arm. Subjects will learn novel 1-syllable nonsense words formed by non-native phoneme combinations during 8 training sessions over 2 days. Following training, subjects will complete a behavioral test to compare their performance on the words learned during training with a set of unfamiliar words also formed by non-native phoneme combinations.

Outcomes

Primary Outcome Measures

Change from baseline in production error rate

Investigators will compare mean error rates when producing newly learned speech sequences versus novel speech sequences of the same length in each arm. This measure will be used to test hypotheses regarding speech motor learning and brain activity and how these compare in persons with persistent developmental stuttering and persons with neurotypical speech.

Change from baseline in utterance duration

Investigators will measure changes in utterance duration before and after speech sequence training to test hypotheses concerning differences in the neural mechanisms responsible for speed/duration improvements compared to improvements in accuracy (i.e., reductions in error rate).

Change from baseline in reaction time

Investigators will measure the time interval between the prompt to begin speech and the subject's speech onset. Mean reaction time will be compared for learned and novel nonwords in persons with persistent developmental stuttering and persons with neurotypical speech.

Percentage of words stuttered

Investigators will compare the percentage of words stuttered under different experimental conditions. This measure will be used to test hypotheses regarding the effect of speech motor learning on stuttering rate and the relationship between stuttering rate and brain activity.

Brain activity measured with functional magnetic resonance imaging

Investigators will measure blood oxygen level dependent (BOLD) brain activity when producing speech utterances in different experimental conditions in adults with persistent developmental stuttering and those with neurotypical speech.

Secondary Outcome Measures

Cortical white matter connectivity

Diffusion-weighted MRI will be collected and used to identify relationships between white matter connectivity and behavioral measures.

Cortical morphometry

Structural MRI will be collected and used to identify relationships between cortical morphometry and behavioral measures.

Working memory test scores

The Comprehensive Test of Phonological Processing (CTOPP) Second Edition working memory subtest scores for each participant will be used to identify correlations between working memory capacity, task performance, and brain measures in all studies.

Forward digit span

Scores from the Forward Digit Span task from the Uniform Data Set neuropsychological test battery will be used for each participant with PPA to identify correlations between phonological working memory and task performance.

Stuttering Severity

The Stuttering Severity Instrument, 4th Edition, will be administered to persons show stutter to identify correlations between stuttering severity and task performance and functional and structural brain measures.

Full Information

NCT ID

NCT05437159

First Posted

June 1, 2022

Last Updated

February 6, 2023

Sponsor

Boston University Charles River Campus

Collaborators

National Institute on Deafness and Other Communication Disorders (NIDCD), University of Michigan, Massachusetts General Hospital

1. Study Identification

Unique Protocol Identification Number

NCT05437159

Brief Title

Investigating Speech Sequencing in Neurotypical Speakers and Persons With Disordered Speech

Official Title

Sequencing and Initiation in Speech Production: Investigating Speech Sequencing in Neurotypical Speakers, Persons Who Stutter, and Persons With Primary Progressive Aphasia

Study Type

Interventional

2. Study Status

Record Verification Date

February 2023

Overall Recruitment Status

Not yet recruiting

Study Start Date

March 2023 (Anticipated)

Primary Completion Date

May 2026 (Anticipated)

Study Completion Date

May 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Boston University Charles River Campus

Collaborators

National Institute on Deafness and Other Communication Disorders (NIDCD), University of Michigan, Massachusetts General Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

Persistent developmental stuttering affects more than three million people in the United States, and it can have profound adverse effects on quality of life. Despite its prevalence and negative impact, stuttering has resisted explanation and effective treatment, due in large part to a poor understanding of the neural processing impairments underlying the disorder. The overall goal of this study is to improve understanding of the brain mechanisms involved in speech motor planning and how these are disrupted in neurogenic speech disorders, like stuttering. The investigators will do this through an integrated combination of experiments that involve speech production, functional MRI, and non-invasive brain stimulation. The study is designed to test hypotheses regarding the brain processes involved in learning and initiating new speech sound sequences and how those processes compare in persons with persistent developmental stuttering and those with typical speech development. These processes will be studied in both adults and children. Additionally, these processes will be investigated in patients with neurodegenerative speech disorders (primary progressive aphasia) to further inform the investigators understanding of the neural mechanisms that support speech motor sequence learning. Together these experiments will result in an improved account of the brain mechanisms underlying speech production in fluent speakers and individuals who stutter, thereby paving the way for the development of new therapies and technologies for addressing this disorder.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Stuttering, Developmental, Aphasia, Primary Progressive

Keywords

Stuttering, Developmental, Magnetic Resonance Imaging, Transcranial Direct Current Stimulation, Speech Motor Learning, Speech Disorders, Neurocomputational Modeling

7. Study Design

Primary Purpose

Basic Science

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

315 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Sub-syllabic learning and fMRI

Arm Type

Experimental

Arm Description

Arm Title

Sub-syllabic learning and anodal tDCS of inferior frontal sulcus

Arm Type

Experimental

Arm Description

Arm Title

Sub-syllabic learning and anodal tDCS of cerebellum

Arm Type

Experimental

Arm Description

Arm Title

Sub-syllabic learning and sham tDCS

Arm Type

Sham Comparator

Arm Description

Arm Title

Multisyllabic learning and fMRI in adults

Arm Type

Experimental

Arm Description

Arm Title

Multisyllabic learning in children

Arm Type

Experimental

Arm Description

Arm Title

Sub-syllabic learning in PPA

Arm Type

Experimental

Arm Description

Intervention Type

Behavioral

Intervention Name(s)

Learning of non-native phoneme combinations: 6 training sessions

Intervention Description

Each trial of the training sessions will follow a simple reaction time protocol in which a nonsense syllable containing novel consonant clusters (e.g., GDADK) is produced as quickly and accurately as possible after an auditory prompt presented via earphones. During each training session, the participant will practice producing a set of 8 stimuli (the Fully Learned stimuli). Each of the 8 Fully Learned stimuli will be produced 60 times over the 6 training sessions.

Intervention Type

Behavioral

Intervention Name(s)

Learning of non-native phoneme combinations: 1 training session

Intervention Description

Each trial of the training sessions will follow a simple reaction time protocol in which a nonsense syllable containing novel consonant clusters (e.g., GDADK) is produced as quickly and accurately as possible after an auditory prompt presented via earphones. During the training session, the participant will practice producing a set of 3 stimuli (the Fully Learned stimuli). Each of the 3 Fully Learned stimuli will be produced 60 times.

Intervention Type

Behavioral

Intervention Name(s)

Learning of novel multisyllabic nonwords

Intervention Description

Each trial of the training sessions (total of 6 training sessions over 2 days) will follow a simple reaction time protocol in which a nonword stimulus formed by 2 or 3 syllables that are legal in American English is presented auditorily to the participant, who then produces the stimulus as quickly and accurately as possible. During training, each participant will repeatedly produce 6 nonwords, with each nonword produced a total of 60 times over the 6 training sessions.

Intervention Type

Device

Intervention Name(s)

Anodal tDCS

Intervention Description

Continuous anodal tDCS is delivered to a speech processing area of the brain during a 19-minute speech training session. The tDCS stimulation will ramp up to its maximum value (2 milliamperes) in the minute prior to the training session and maintained at that level throughout the session.

Intervention Type

Device

Intervention Name(s)

Sham tDCS

Intervention Description

Sham tDCS stimulation is delivered to a speech processing area of the brain during a 19-minute speech training session. During the minute prior to training onset, the tDCS stimulator is ramped up to 2 milliamperes and then back down to 0.

Intervention Type

Behavioral

Intervention Name(s)

Learning of non-native phoneme combinations: 8 training sessions

Intervention Description

Each trial of the training sessions will follow a simple reaction time protocol in which a nonsense syllable containing novel consonant clusters (e.g., GDADK) is produced as quickly and accurately as possible after an auditory prompt presented via earphones. During each training session, the participant will practice producing a set of 3 stimuli (the Fully Learned stimuli). Each of the 3 Fully Learned stimuli will be produced 120 times over the 8 training sessions.

Primary Outcome Measure Information:

Title

Change from baseline in production error rate

Description

Time Frame

Evaluated at Baseline and immediately following intervention

Title

Change from baseline in utterance duration

Description

Time Frame

Evaluated at Baseline and immediately following intervention

Title

Change from baseline in reaction time

Description

Time Frame

Evaluated at Baseline and immediately following intervention

Title

Percentage of words stuttered

Description

Time Frame

Evaluated at Baseline and immediately following intervention

Title

Brain activity measured with functional magnetic resonance imaging

Description

Time Frame

Evaluated at Baseline and immediately following intervention

Secondary Outcome Measure Information:

Title

Cortical white matter connectivity

Description

Diffusion-weighted MRI will be collected and used to identify relationships between white matter connectivity and behavioral measures.

Time Frame

Evaluated during the MRI scanning procedure

Title

Cortical morphometry

Description

Structural MRI will be collected and used to identify relationships between cortical morphometry and behavioral measures.

Time Frame

Evaluated during the MRI scanning procedure

Title

Working memory test scores

Description

Time Frame

Evaluated at Baseline

Title

Forward digit span

Description

Time Frame

Evaluated at Baseline

Title

Stuttering Severity

Description

Time Frame

Evaluated at Baseline

10. Eligibility

Sex

All

Minimum Age & Unit of Time

6 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria Healthy individuals with no history of neurological, speech, or hearing disorders (other than stuttering in studies that involve adults who stutter). To maximize the uniformity of prior exposure to the speech stimuli that will be used, only native speakers of American English will be recruited, and only those with limited exposure to a second language will be enrolled. All adult participants will also pass a standard pure-tone hearing screening at a 25dB hearing level threshold at 500, 1k, 2k, and 4kHz frequencies. All participating children will pass a hearing screening at a 20 dB threshold at 500, 1k, 2k, and 4k Hz. Participants in experiments that require them to read orthographic stimuli must have normal or corrected-to-normal vision (MRI-safe corrective glasses are available at the Boston University Cognitive Neuroimaging Center for use during neuroimaging). Participating children will complete additional speech, language, hearing, and cognitive tests to ensure that they are within normal performance ranges for their age with the exception of stuttering for children in the children who stutter (CWS) group. Persons who stutter will be evaluated formally by a speech-language pathologist to assess stuttering severity and to ensure the absence of other speech or language disorders. PWS will have no history of neurological disorder other than stuttering, and will demonstrate very mild to severe stuttering according to the Stuttering Severity Instrument for Children and Adults - 4th Edition (SSI-4: PRO-ED, Inc.), that is confirmed by clinical reports and expressed concern by the subject and/or guardian. Participants with primary progressive aphasia (PPA) will have been diagnosed through the Massachusetts General Hospital Frontotemporal Disorders Unit (MGH-FTD) by an experienced neurologist in coordination with a speech-language pathologist. Participants with PPA will have a score of 1.0 or lower on the Clinical Dementia Rating scale (i.e., mild cognitive impairment or mild dementia) to ensure cognitive levels are sufficient to complete the task. All participants with PPA must have a recent clinical assessment and T1 structural neuroimaging scan through the MGH-FTD Unit for eligibility for this study. Exclusion Criteria Participants in studies that involve tDCS or MRI scanning will have no contraindications specific to those procedures. For the tDCS study, this includes individuals who have a metallic implant in the head or electrically sensitive devices implanted in the body, a history of seizures, significant scalp lesions, or pregnancy. For MRI studies, this includes a history of seizures, severe claustrophobia, the presence of magnetically or mechanically active implant, ferromagnetic material embedded in any part of the body, or pregnancy). All participants will perform a standardized nonword repetition pre-test (the Dollaghan and Campbell Nonword Repetition Task) to assess working memory performance. Participants who perform more than 2 standard deviations below the norm for their age range will be deemed to be unable to perform the experimental task and released from further participation. Participating children will have no history of neurological disorder other than stuttering, and will demonstrate very mild to severe stuttering according to the Stuttering Severity Instrument for Children and Adults, 4th Edition, that is confirmed by clinical reports and expressed concern by the subject and/or guardian. Children under the age of 6 and over the age of 8 will not enrolled in this study. Participants with PPA will not be eligible for this study if they are taking any medications that would be expected to affect speech or language.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Frank H Guenther, PhD

Phone

6173535765

guenther@bu.edu

First Name & Middle Initial & Last Name or Official Title & Degree

Barbara Holland

Phone

6173536181

splab@bu.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Frank H Guenther, PhD

Organizational Affiliation

Boston University

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Soo-Eun Chang, PhD

Organizational Affiliation

University of Michigan

Official's Role

Principal Investigator

Facility Information:

Facility Name

Massachusetts General Hospital

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02129

Country

United States

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Bradford Dickerson, MD

Phone

617-726-8689

brad.dickerson@mgh.harvard.edu

First Name & Middle Initial & Last Name & Degree

Bradford Dickerson, MD

Facility Name

Boston University

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02215

Country

United States

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Frank H Guenther, PhD

Phone

617-353-5765

guenther@bu.edu

First Name & Middle Initial & Last Name & Degree

Barbara Holland, MA

Phone

617-353-6181

splab@bu.edu

First Name & Middle Initial & Last Name & Degree

Frank H Guenther, PhD

First Name & Middle Initial & Last Name & Degree

Jason A Tourville, PhD

First Name & Middle Initial & Last Name & Degree

Alfonso Nieto-Castonon, PhD

First Name & Middle Initial & Last Name & Degree

Tyler K Perrachione, PhD

First Name & Middle Initial & Last Name & Degree

Hilary Miller, MS

Facility Name

University of Michigan

City

Ann Arbor

State/Province

Michigan

ZIP/Postal Code

48109

Country

United States

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Soo-Eun Chang, PhD

Phone

734-232-0300

sooeunc@med.umich.edu

First Name & Middle Initial & Last Name & Degree

Soo-Eun Chang, PhD

12. IPD Sharing Statement

Learn more about this trial

Investigating Speech Sequencing in Neurotypical Speakers and Persons With Disordered Speech

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