Neurocognitive Mechanisms of Sentence Production Impairment in Aphasia (sentence)

The proposed research is relevant to public health because stroke is a leading cause of long-term disability among older adults and communication impairments resulting from stroke have a significant negative impact on quality of life. By seeking to better understand post-stroke aphasia, this project lays the groundwork for development of new interventions, and aligns with NIDCD's priority areas 1 (understanding normal function), 2 (understanding diseases), and 3 (improving diagnosis, treatment, and prevention).

Study Overview

• Status: Recruiting
• Conditions: Stroke; Healthy Aging; Aphasia, Acquired
• Intervention / Treatment: Behavioral: Language Condition

Detailed Description

Post-stroke agrammatic aphasia (PSA-G) is characterized by a cluster of symptoms (fragmented sentences, errors in functional morphology, a dearth of verbs, and slow speech rate), yet extant theories and language interventions focus on individual symptoms. This single-symptom theoretical and intervention focus results in limited gains in functional communication. The long-term goal of this research is to improve the clinical effectiveness of interventions for PSA-G.

As a first step towards this goal, this project's objective is to advance the theoretical framework of PSA-G by addressing two critical gaps. The first gap is in the mechanistic understanding of how lexical, grammatical, motoric, and cognitive processes work together to enable fluent sentence production and how this breaks down in PSA-G. The second gap is in the understanding of neural mechanisms underlying how sentence production planning normally unfolds over time and what crucial spatiotemporal alterations give rise to PSA-G versus other variants of post-stroke aphasia with predominantly lexico-semantic deficits (PSA-LS). The central hypothesis is that agrammatic language production results from spatiotemporal alterations in the neural dynamics of morphosyntactic and phonomotor processes, causing a cumulative processing bottleneck at the point of articulatory planning. This Synergistic Processing Bottleneck Model of Agrammatism will be tested with two specific aims.

Specific Aim 1 will elucidate the relative contribution of syntactic and non-syntactic processes towards sentence production in aphasia by using speed metrics and a path modeling framework. The expected outcomes of this aim are an improved understanding of the extent to which delays in different linguistic processes underlying the agrammatic symptom cluster impair fluent sentence production in aphasia generally, and in PSA-G versus PSA-LS more specifically.

Specific Aim 2 will determine the neural mechanisms underlying sentence production across language deficit profiles. Magnetoencephalography (MEG) will be used to compare alterations in timecourse and functional connectivity of key perilesional and contralesional syntactic hubs across increasingly demanding morphosyntactic production tasks. The expected outcome of this aim is a spatiotemporally specified neural model of sentence production in neurotypical, PSA-G, and PSA-LS speakers.

The significance this research is that it will forward an empirically established multidimensional model of sentence production, which will lay the foundation for developing more targeted and effective language interventions for agrammatic aphasia. It will also contribute to a better understanding of agrammatism in neurodegenerative aphasias. The innovative aspects of this project include: a novel multidimensional theoretical framework that incorporates non-syntactic dimensions of phonomotor planning, processing capacity and speed, and neurophysiological dynamics; direct comparisons between PSA-G and PSA-LS groups; and MEG analysis of spoken language with simultaneous electromyographic measurement.

• Study Type: Interventional
• Enrollment (Estimated): 350
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Yasmeen Faroqi-Shah, PhD; Phone Number: 3014054229; Email: yfshah@umd.edu
• Study Contact Backup: Name: Robert Slevc, PhD; Phone Number: (301) 405-5835; Email: slevc@umd.edu

Study Locations

• United States
  • Maryland
    • College Park, Maryland, United States, 20742
      • Recruiting
      • University of Maryland
      • Contact: Robert Slevc, PhD; Phone Number: (301) 405-5835; Email: slevc@umd.edu
      • Contact: Yasmeen Faroqi-Shah, PhD; Phone Number: 301-405-4229; Email: yfshah@umd.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Study Population

The study population consists of community-dwelling adults who either have a diagnosis of acquired aphasia or are neurologically healthy. Participants need to be able to participate in the study via videoconferencing for behavioral studies and/or travel to the University of Maryland, College Park campus for neuroimaging studies.

Description

Inclusion Criteria:

• At least 18 years of age
• Persons with acquired aphasia are defined as those with a language impairment following left hemisphere brain injury (most likely a stroke).
• Neurotypical adults need to be either young (ages 18-30 years) or older (> 60 years)
• Native (or primary) speakers of English

Exclusion Criteria:

• Prior neurological or psychiatric diagnoses or developmental disabilities before the onset of aphasia
• do not speak English fluently

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Language condition; All participants will receive this arm. In this arm, the intervention involves asking participants to speak and understand words and sentences with different linguistic manipulations such as morphological, semantic, phonological priming, predictability of the subject and object nouns associated with verbs, naming of verbs and nouns, production of sentences with past, future or present tense. Accuracy, response times and brain activity are the outcome measures.

Behavioral: Language Condition; The intervention involves asking participants to speak and understand words and sentences with different linguistic manipulations such as morphological, semantic, phonological priming, predictability of the subject and object nouns associated with verbs, naming of verbs and nouns, production of sentences with past, future or present tense. Accuracy, response times and brain activity are the outcome measures.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Accuracy	Response accuracy for each experimental condition will be measured	through the completion of the study, an average of 1 year
Response time	Response times for each experimental condition will be measured	through the completion of the study, an average of 1 year
Brain activity	Patterns of brain activity (using magnetoencephalography and MRI) will be measured for each experimental condition	through the completion of the study, an average of 1 year

Collaborators and Investigators

• Sponsor: University of Maryland, College Park
• Collaborators: McMaster University
• Investigators: Principal Investigator: Yasmeen Faroqi-Shah, PhD, University of Maryland

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2024
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): June 1, 2029

Study Registration Dates

• First Submitted: May 1, 2024
• First Submitted That Met QC Criteria: May 6, 2024
• First Posted (Actual): May 8, 2024

Study Record Updates

• Last Update Posted (Actual): September 3, 2024
• Last Update Submitted That Met QC Criteria: August 28, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Language Disorders; Communication Disorders; Speech Disorders; Aphasia
• Other Study ID Numbers: 2044118-1

Drug and device information, study documents

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