Neural Networks and Language Recovery in Aphasia From Stroke: fMRI Studies

March 21, 2022 updated by: VA Office of Research and Development
The purpose of this research is to utilize functional magnetic resonance imaging (fMRI) to investigate brain reorganization for language behavior in stroke patients with aphasia. A primary focus of the study is on recovery of nonfluent propositional speech and naming in chronic aphasia patients. The fMRI technique is used to examine activation in the left hemisphere (LH) and right hemisphere (RH), during recovery of specific language behaviors in chronic nonfluent aphasia patients.

Study Overview

Status

Completed

Conditions

Detailed Description

PURPOSE: The purpose of this 4-year fMRI research is to study brain reorganization for language in patients with left hemisphere (LH) stroke who have chronic nonfluent aphasia. This fMRI research is fundamental and critical to the PI's NIH RO1 grant, Transcranial Magnetic Stimulation (TMS) to Improve Speech in nonfluent aphasia, which was recently renewed for 5 years, 2006-11. There is no overlap in the studies. The NIH grant provides the TMS (real and sham). This VA grant provides 4 different fMRI tasks performed pre- and post- a series of TMS treatments (real and sham) - Overt Naming fMRI; Overt Propositional Speech fMRI; and Nonverbal Semantic Decision tasks for Nouns, and for Actions.

The investigators have observed that application of TMS to an anterior portion of right (R) Broca's homologue (pars triangularis, PTr), results in significantly improved picture naming ability at 2 and 8 Mo. after the last (10th) TMS treatment, in aphasia patients who began TMS at 5-11 years poststroke. Also, half of these nonfluent aphasia patients improved their Phrase Length in propositional speech, post-TMS.

RATIONALE: The investigators and others have observed that patients with chronic, nonfluent aphasia (poor, hesitant speech) have overactivation of R hemisphere (RH) cortical language homologues. The investigators hypothesize this represents a maladaptive plasticity and probably poor active inhibition during speech. Slow, 1 Hz TMS can be used to suppress cortical excitability. The goal is to use 1 Hz TMS to inhibit/suppress the overactivation in RH language homologues. The investigators' early TMS research has shown that suppression of R PTr in these patients is associated with improved speech. The fMRI studies proposed in this VA grant will help to investigate the neurophysiological changes underlying improvement post- TMS in propositional speech and in nonverbal semantic decision tasks. The new MRI technique, diffusion tensor imaging (DTI) will be used to study WM pathways subjacent to cortex treated with TMS.

DESIGN: Randomized, sham-control, incomplete crossover design with 32 patients (16 mild-moderate; 16 severe nonfluent), half receive real TMS series only; half, sham TMS 1st, and real 2nd. Language, Neuropsych. testing, and fMRIs are performed at Entry, and at 2 Mo. post-10 real or sham TMS treatments; and at 6 Mo. post real. There are 4 Projects: 1) fMRI during overt naming and propositional speech (Overt Picture Naming and Picture Descriptions/Story Telling; 2) fMRI during a Nonverbal Semantic Decision Task with Superordinate Noun Icons; 3) fMRI during a Nonverbal Semantic Decision Task with Action and Object Icons; 4) DTI. DTI is performed only at Entry (all subjects). Normal controls (n=8) do not receive TMS; they are studied with fMRI at Entry, at 2 and 6 Mo. later.

HYPOTHESES: Following the real TMS to suppress R PTr, there will be less overactivation on fMRI (better modulation) in RH language homologues, and new LH activation (including L perilesional areas and L SMA). This will be associated with improved propositional speech (BDAE) and nonverbal semantic decision ability at 2 and 6 Mo. post-real TMS. No language or fMRI changes are expected post-sham TMS. The fMRIs performed 3x with the normal controls are not expected to show change, but will document the neural networks for the fMRI tasks.

Study Type

Observational

Enrollment (Actual)

62

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02130
        • VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

45 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Chronic stroke patients with nonfluent aphasia

Description

Inclusion Criteria:

  • Aphasia patients with a single, unilateral, left hemisphere stroke.
  • Patients must be native speakers of English
  • Patients must be at least 6 months poststroke and produce mild-severe nonfluent speech. Minimum Language requirements: 2-4 word phrase length on elicited propositional speech
  • Auditory Comprehension a the 25th percentile or higher on the BDAE subtests for Word Comprehension and Commands, sufficient to cooperate during testing
  • The ability to name a minimum of 3 items on the Boston Naming Test at entry into study.
  • Patients must understand the nature of the study and give informed consent.
  • Normal right-handed controls with no history of neurological disease or substance abuse; age, education and gender-matched to the Aphasia cases.

Exclusion Criteria:

  • Patients with more than one stroke in the left hemisphere or patients with bilateral strokes.
  • Each participant must be able to have an MRI scan.
  • MRI is contraindicated for pregnant women.
  • Patients will be excluded if they have the following:
  • Intracranial metallic bodies from prior neurosurgical procedure, implanted pacemaker, medication pump, vagal stimulator, deep brain stimulator, TENS unit or ventriculoperitoneal shunt
  • Past history of seizures within one year or unexplained loss of consciousness Family history of epilepsy
  • Acute, unstable medical conditions
  • History of substance abuse (within last 6 months)
  • Abnormal neurological exam, other than as signs of the condition being studied
  • Abnormal MRI, or history of known structural brain abnormality other than as signs of the condition studied in the present protocol.
  • Administration of investigational drug within 5 halflives of the drug prior to testing.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Chronic Stroke patients with Nonfluent Aphasia
patients with left hemisphere (LH) stroke who have chronic nonfluent aphasia

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cerebral Activation in the Left and Right Brain Hemispheres
Time Frame: Out to 6 months, from baseline entry
Cerebral Activation in the Left and Right Brain Hemispheres
Out to 6 months, from baseline entry

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

VA Office of Research and Development

Collaborators

Boston University

Investigators

  • Principal Investigator: Margaret Naeser, PhD, VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 1, 1999

Primary Completion (Actual)

December 1, 2016

Study Completion (Actual)

December 31, 2021

Study Registration Dates

First Submitted

April 25, 2007

First Submitted That Met QC Criteria

April 26, 2007

First Posted (Estimate)

April 27, 2007

Study Record Updates

Last Update Posted (Actual)

March 24, 2022

Last Update Submitted That Met QC Criteria

March 21, 2022

Last Verified

March 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MHBB-006-06S

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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