Sequencing and Initiation in Speech Production: Investigating Speech Sequencing in Neurotypical Speakers, Persons Who Stutter, and Persons With Primary Progressive Aphasia
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 278
- 试验地点
- 6
- 主要终点
- Change from baseline in production error rate
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 6 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Sub-syllabic learning and anodal tDCS of 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 the training, continuous anodal transcranial direct current stimulation (tDCS) will be applied to the the subject's right cerebellum.
干预措施: Learning of non-native phoneme combinations: 1 training session (Behavioral)
Sub-syllabic learning and sham tDCS
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.
干预措施: Sham tDCS (Other)
Multisyllabic learning in children
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.
干预措施: Learning of novel multisyllabic nonwords (Behavioral)
Sub-syllabic learning in PPA
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.
干预措施: Learning of non-native phoneme combinations: 8 training sessions (Behavioral)
Sub-syllabic learning and fMRI
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.
干预措施: Learning of non-native phoneme combinations: 6 training sessions (Behavioral)
Sub-syllabic learning and anodal tDCS of inferior frontal sulcus
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.
干预措施: Learning of non-native phoneme combinations: 1 training session (Behavioral)
Sub-syllabic learning and anodal tDCS of inferior frontal sulcus
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.
干预措施: Anodal tDCS (Other)
Sub-syllabic learning and anodal tDCS of 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 the training, continuous anodal transcranial direct current stimulation (tDCS) will be applied to the the subject's right cerebellum.
干预措施: Anodal tDCS (Other)
Sub-syllabic learning and sham tDCS
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.
干预措施: Learning of non-native phoneme combinations: 1 training session (Behavioral)
Multisyllabic learning and fMRI in adults
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.
干预措施: Learning of novel multisyllabic nonwords (Behavioral)
结局指标
主要结局
Change from baseline in production error rate
时间窗: Evaluated at Baseline and immediately following intervention
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
时间窗: Evaluated at Baseline and immediately following intervention
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
时间窗: Evaluated at Baseline and immediately following intervention
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
时间窗: Evaluated at Baseline and immediately following intervention
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
时间窗: Evaluated at Baseline and immediately following intervention
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.
次要结局
- Cortical white matter connectivity(Evaluated during the MRI scanning procedure)
- Stuttering Severity(Evaluated at Baseline)
- Cortical morphometry(Evaluated during the MRI scanning procedure)
- Working memory test scores(Evaluated at Baseline)
- Forward digit span(Evaluated at Baseline)
研究者
Frank Guenther
Professor
Boston University Charles River Campus