This is a resubmission for the competing continuation renewal of our research on the therapeutic utility of repetitive transcranial magnetic stimulation (rTMS) to improve speech in chronic, nonfluent and severe aphasia. Functional MRI studies in these patients have shown """"""""over-activation"""""""" in right (R) perisylvian language homologues; possibly representing a maladaptive plasticity. Our hypothesis is that suppression of this over-activation with IMS may improve speech. Significant improvement in picture naming was observed immediately following rTMS for 10 min. to suppress R pars triangularis (R BA 45), with decreased reaction time (RT). rTMS to 3 other R ROIs produced no improvement. In a later phase, we applied 1-Hz rTMS to R BA 45 for 20 min. daily, 10 days. Significant improvement in picture naming was observed at 2 Mo. post- TMS; and at 8 Mo.post-TMS, despite no individualized speech therapy. Pilot studies with sham rTMS have shown no effect. We propose a blinded, sham-controlled, incomplete crossover design, over a 5-Yr. period (20 mild-moderate nonfluent; 20 severe nonfluent patients) with fMRI to study mechanisms of action of TMS. To insure recruitment of an adequate number of patients, we have added a second site, the Univ. of PA, where half of the patients will be studied. We have developed an overt naming fMRI BOLD paradigm for use with nonfluent patients. Pilot data indicate that pre-rTMS, there is over-activation in R frontal areas (including R inferior frontal gyrus, R BA 45; and motor cortex-mouth), with little activation in temporal lobe and poor naming performance. Post-rTMS where 1-Hz rTMS was applied to R BA 45 for 20 min. daily, 10 days, improved naming was associated with less over-activation in R BA 45 and M1-mouth, with new temporal lobe activation. Overt naming fMRI will be obtained pre-real/sham rTMS, and at 2 Mo. post-real/sham rTMS. Those receiving sham rTMS are then crossed-over to real-rTMS. We hypothesize that patients who receive real rTMS will have significant improvement in picture naming at 2 Mo. post-real rTMS, versus those who receive sham rTMS. Only the real rTMS group will show suppression of R BA 45 on fMRI. Relevance to public health: The U.S. population is increasing in age; thus, an increase in stroke and need for sophisticated treatment. The number of people with aphasia in the U.S. today is estimated to be 1 million; 80,000 new cases each year. This research has direct clinical relevance for aphasia patients. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
2R01DC005672-04A2
Application #
7103871
Study Section
Language and Communication Study Section (LCOM)
Program Officer
Cooper, Judith
Project Start
2002-07-05
Project End
2011-03-31
Budget Start
2006-04-01
Budget End
2007-03-31
Support Year
4
Fiscal Year
2006
Total Cost
$508,327
Indirect Cost
Name
Boston University
Department
Neurology
Type
Schools of Medicine
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02118
Martin, Paula I; Treglia, Ethan; Naeser, Margaret A et al. (2014) Language improvements after TMS plus modified CILT: Pilot, open-protocol study with two, chronic nonfluent aphasia cases. Restor Neurol Neurosci 32:483-505
Papeo, Liuba; Pascual-Leone, Alvaro; Caramazza, Alfonso (2013) Disrupting the brain to validate hypotheses on the neurobiology of language. Front Hum Neurosci 7:148
Garcia, Gabriella; Norise, Catherine; Faseyitan, Olufunsho et al. (2013) Utilizing repetitive transcranial magnetic stimulation to improve language function in stroke patients with chronic non-fluent aphasia. J Vis Exp :e50228
Naeser, Margaret A; Martin, Paula I; Ho, Michael et al. (2012) Transcranial magnetic stimulation and aphasia rehabilitation. Arch Phys Med Rehabil 93:S26-34
Turkeltaub, Peter E; Coslett, H Branch; Thomas, Amy L et al. (2012) The right hemisphere is not unitary in its role in aphasia recovery. Cortex 48:1179-86
Medina, Jared; Norise, Catherine; Faseyitan, Olufunsho et al. (2012) Finding the Right Words: Transcranial Magnetic Stimulation Improves Discourse Productivity in Non-fluent Aphasia After Stroke. Aphasiology 26:1153-1168
Turkeltaub, Peter E; Benson, Jennifer; Hamilton, Roy H et al. (2012) Left lateralizing transcranial direct current stimulation improves reading efficiency. Brain Stimul 5:201-207
Naeser, Margaret A; Martin, Paula I; Theoret, Hugo et al. (2011) TMS suppression of right pars triangularis, but not pars opercularis, improves naming in aphasia. Brain Lang 119:206-13
Hamilton, Roy H; Sanders, Linda; Benson, Jennifer et al. (2010) Stimulating conversation: enhancement of elicited propositional speech in a patient with chronic non-fluent aphasia following transcranial magnetic stimulation. Brain Lang 113:45-50
Naeser, Margaret A; Martin, Paula I; Lundgren, Kristine et al. (2010) Improved language in a chronic nonfluent aphasia patient after treatment with CPAP and TMS. Cogn Behav Neurol 23:29-38

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