Post-Stroke Aphasia and Repetitive Transcranial Magnetic Stimulation (rTMS) Treatment Study

Aphasia after stroke is associated with high mortality, significant motor impairment, and
severe limitations in social participation. During the past decade, therapies administered by
stroke teams have made great strides to limit the motor impairments caused by stroke.
Unfortunately, progress in aphasia rehabilitation has not experienced the same rapid
advancement. This proposal is based on preliminary evidence from our recently completed pilot
study which showed that navigated excitatory repetitive transcranial magnetic stimulation
(nerTMS) targeted to residual activity in the affected hemisphere has a significant
beneficial effect on post-stroke aphasia recovery.1 The main aim of this study is to conduct
a double-blind, sham-controlled, dose-response nerTMS treatment trial in subjects with
chronic aphasia. By conducting this comparative trial, we will provide clinical (qualitative
and quantitative) and imaging evidence that nerTMS improves language function after stroke
when compared to standard treatment (ST). The findings will have implications for patients
with post-stroke aphasia in that once the study is completed and the results are available,
rehabilitation specialists may be able to change their practice pattern by offering an
additional tool to aid patients in recovering their language skills with improved
participation in society and enhanced quality of life.

To fill the gap in our therapeutic arsenal for aphasia, we propose a study with the following
specific aims: (1) to determine the comparative efficacy and optimal dosing of nerTMS on
aphasia recovery using a randomized, double-blind, sham-controlled study design. Subjects
(15/group) will be randomly assigned to 4 treatment groups: (a) 3 weeks of nerTMS, (b) 1 week
of ST + 2 weeks of nerTMS, (c) 2 weeks of ST +1 week of nerTMS, or (d) 3 weeks of ST (control
group). This design will allow systematic evaluation of the efficacy of nerTMS and will
determine its most optimal dose for language recovery. Short- and long-term outcomes will be
evaluated with aphasia testing (AT) and fMRI; (2) to use fMRI to assess changes in language
lateralization in response to nerTMS. We will examine the relationship between the degree of
pre-nerTMS language lateralization (fMRI) with the post-nerTMS language outcomes (AT) and
determine whether fMRI language lateralization can predict AT performance following nerTMS
targeted to the left middle cerebral artery (LMCA) stroke areas; (3) to explore the possible
synergistic effect of constraint induced aphasia therapy (CIAT) plus nerTMS on aphasia
recovery in a group of 20 LMCA stroke patients. These subjects will receive 2 weeks of nerTMS
enhanced by 1 hour of daily CIAT; both therapies will be administered in an open-label
fashion. Patients will be evaluated with fMRI and AT as above and compared to the arm "b" of
the double-blind study and to CIAT data collected in an ongoing study (R01 NS048281). This
aim will gather preliminary data regarding the possible synergistic effects of nerTMS and
behavioral intervention.

Inclusion Criteria:

- Age ≥ 19 years

- LMCA stroke as indicated by the presence of aphasia and MRI lesion in the LMCA
distribution

- Moderate aphasia (Token Test score between 40th and 90th percentile)

- Fluency in English

- Provision of written informed consent by the patient and/or the next of kin

Exclusion Criteria:

- Age less than 18 years

- Underlying degenerative or metabolic disorder or supervening medical illness

- Severe depression or other psychiatric disorder

- Positive pregnancy test in women of childbearing age

- Any contraindication to MRI/fMRI at 3T (i.e., intracranial metal implants,
claustrophobia)

- Any contraindication to nerTMS (e.g., seizures or epilepsy)