The purpose of this study is to examine whether repetitive transcranial magnetic stimulation (rTMS) can be used to improve speech in chronic stroke patients with aphasia. Aphasia patients can have problems with speech production. The rTMS procedure allows painless, noninvasive stimulation of human cortex from outside the head. Chronic aphasia patients have been observed in our functional magnetic resonance brain imaging studies to have excess brain activation in brain areas possibly related to language on the right side of the brain (opposite side to where the stroke took place). It is expected that suppression of activity in the directly targeted brain region will have an overall modulating effect on the neural network for naming (and propositional speech) and will result in behavioral improvement.
OBJECTIVE: The purpose of this research is to investigate whether repetitive transcranial magnetic stimulation (rTMS) can improve speech in chronic stroke patients with aphasia. TMS allows painless, noninvasive stimulation of brain cortex (1 cm x 1 cm). Slow (1 Hz) rTMS appears to decrease excitability in the targeted cortical region of interest (ROI) leading to measurable behavioral effects. Chronic aphasia patients have been observed in our fMRI work (and others) to have increased activation in right (R) Broca's and other R language homologues during language tasks. It is hypothesized that suppression of activity in a directly targeted right hemisphere (RH) ROI will have an overall modulating effect on functionally connected elements of the distributed neural network for naming (and propositional speech), and will result in behavioral improvement. RESEARCH PLAN AND METHODS: Nonfluent aphasia patients (\>6 Mo. poststroke) will be studied. The rTMS treatments in Boston take place at the Berenson-Allen Center for Noninvasive Brain Stimulation, Beth Israel Deaconess Medical Center, Harvard Medical School under the supervision of Alvaro Pascual-Leone, M.D., Ph.D. and additional patients will be studied at the Hospital of the University of Pennsylvania, H. Branch Coslett, M.D., who is a P.I. on that subcontract. This is a blinded, randomized, sham-control, incomplete crossover design. Naming and language tests are obtained pre- and post- rTMS. Treatment Design: Multiple Baseline Language Evaluations (x3) are performed at Entry (Boston Naming Test, BNT; and Boston Diagnostic Aphasia Exam, BDAE). Primary Outcome Measures are BNT; and Number of Words per Longest Phrase Length (cookie theft picture description) from the BDAE. Patients are randomly assigned to receive a series of either Sham rTMS followed by a series of Real rTMS; OR they receive only the series of Real rTMS. The Sham series is identical to the Real, however, no magnetic pulse is emitted from the coil, although the patient hears the same clicking sound emitted from the coil. Due to space limitation here, only the Real rTMS treatment schedule is described. There are two rTMS Phases: During Phase 1, the single, best RH cortical ROI to suppress with rTMS to improve picture naming, is determined for each patient. Real rTMS (1 Hz, 90% motor threshold) is applied for 10 minutes, in separate rTMS sessions, to each of 4 different RH cortical ROIs (R ant. BA 45; R post. BA 45; R BA 44 and R M1, mouth). Snodgrass \& Vanderwart (S\&V, 1980) Picture Naming is tested immediately before and after each ROI has been suppressed with rTMS. The single RH ROI which is associated with at least a 2 SD improvement (above S\&V Naming, tested 3x at Baseline), immediately following 10 minutes of rTMS to suppress that cortical area, is considered to be the Best Response ROI for that patient. During Phase 2, the Best Response ROI from Phase 1 is suppressed for 20 minutes, 5 days per week, 2 weeks. All patients receive follow-up BNT and BDAE testing at 2 months following the 10th Real (or Sham) rTMS treatment.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
63
10 rTMS treatments (90% of motor threshold, 20 minutes, at 1 Hz) to specific right hemisphere area of brain cortex; 5 days per week for 2 weeks at the Berenson-Allen Center for Noninvasive Brain Stimulation, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA; or at the Neurology Department, Hospital of the University of Pennsylvania, Philadelphia, PA.
VA Boston Healthcare System, Jamaica Plain Campus, Boston University Aphasia Research Center (12-A), 150 So. Huntington Ave.
Boston, Massachusetts, United States
Berenson-Allen Center for Noninvasive Brain Stimulation, 330 Brookline Ave, Kirstein Bldg., Dept. of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School
Boston, Massachusetts, United States
Department of Neurology, Hospital of the University of Pennsylvania, 3 W. Gates Bldg.
Philadelphia, Pennsylvania, United States
Picture Naming
Pictures named correctly on Boston Naming Test (BNT), First 20 Pictures
Time frame: Baseline and 2 months after the last rTMS treatment session
Phrase Length
Longest Number of Words per Phrase Length, for elicited propositional speech for BDAE Cookie Theft Picture Description
Time frame: Baseline and 2 months after the last rTMS treatment session
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