Transcranial Magnetic Stimulation (TMS) has been demonstrated to improve language function in subjects with chronic aphasia in a number of small studies, many of which did not include a control group. Although the treatment appears promising, data to date do not permit an adequate assessment of the utility of the technique. We propose to study the effects of TMS combined with Constraint Induced Language Therapy (CILT) in 75 subjects with chronic aphasia. Subjects will be randomized in a 2:1 ratio to TMS with CILT or sham TMS with CILT. One Hz TMS at 90% motor threshold will be delivered to the right inferior frontal gyrus for 20 minutes in 10 sessions over 2 weeks; language therapy will be provided for one hour immediately after the conclusion of each session of TMS. Change from baseline in the Western Aphasia Battery Aphasia Quotient at 6 months after the end of TMS treatment will serve as the primary outcome measure. A secondary aim is to identify anatomic and behavioral predictors of response to treatment. Finally, a third aim is to identify the mechanism underlying the beneficial effect of the treatment using a variety of imaging techniques. Subjects who have no contraindication to the MRI will undergo fMRI imaging prior to and at 6 months after therapy. Using modern network analyses and robust machine learning techniques we will identify changes in the strengths of connections between nodes in the language network to address specific hypotheses regarding the effects of TMS and CILT on brain organization that are associated with beneficial response to treatment.
Although Transcranial Magnetic Stimulation (TMS) has been demonstrated to improve language function in subjects with aphasia in many small studies, its general clinical utility has not been established. We propose to study the effects of TMS combined with Constraint Induced Language Therapy in a double-blinded study of 75 subjects with chronic aphasia. Additional aims are to identify anatomic and behavioral predictors of response to treatment and identify the mechanisms underlying the beneficial effect of using modern neuroimaging techniques.