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

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.

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.