Transcranial Direct Stimulation (tDCS) and Behavioral Intervention in Aphasia

Specific Aims Aim 1: Identify and quantify the effects of a-tDCS to the left dorsolateral
prefrontal cortex (DLPFC) in conjunction with intensive behavioral treatment on naming in
non-fluent aphasia. a-tDCS (2mA for 20 minutes) will be applied over the left DLPFC with
cathode over the right orbit. Pre and post treatment behavioral measures of naming and
working memory will be used to quantify and compare differences. Hypothesis 1: a-tDCS will
result in improvements in naming accuracy, naming response times, and working memory (WM) in
participants with non-fluent aphasia.

Aim 2: Compare the effects of a-tDCS applied to the left DLPFC before behavioral treatment to
during behavioral treatment in non-fluent aphasia. a-tDCS (2mA for 20 minutes) will be
applied over the left DLPFC with cathode over the right orbit. Pre and post treatment
behavioral measures of naming and working memory will be used to quantify and compare
functional differences between conditions. Hypothesis 1: a-tDCS to the DLPFC during treatment
will result in a greater improvement of naming accuracy, naming response time and WM in
participants with non-fluent aphasia.

Significance The findings from the proposed study will lay the foundation for a larger
clinical trial which will in turn have a significant impact on individuals with aphasia given
that naming deficits are a common symptom in this population. As the presence of naming
deficits has a negative relationship to emotional well-being and functional communication
26-30, treatment that improves naming deficits will positively influence quality of life in
many of these individuals. The approach taken to remediate naming deficits in aphasia is to
treat impaired WM systems on the premise that certain cognitive processes underlie linguistic
functions in aphasia. This approach represents a departure from most behavioral-based naming
treatment approach, but reflects a growing recognition that WM systems in individuals with
aphasia impact their linguistic performance 5, 31. The addition of a-tDCS as a
neuromodulation tool to increase cortical excitability (upregulate) the working memory center
to target naming is a novel approach. In addition, this study will further elucidate the
optimal timing of a-tDCS in order to achieve the most beneficial outcomes, which have not yet
been reported. These findings, along with other related studies, will shape future clinical
practice guidelines as more studies adopt a concurrent cognitive-linguistic approach to treat
linguistic deficits in aphasia.

Design & Methodology Participants. Four individuals with aphasia will be recruited. These
participants must meet the following inclusionary/exclusionary criteria: a) completion of
high school or GED; b) normal or corrected-to-normal vision; c) adequate hearing acuity for
1:1 conversational exchanges; d) use of English as primary language; e) a vascular lesion in
the dominant left hemisphere verified by an MRI scan within six months of the start of the
study. These participants must also meet the following exclusionary criteria: a) no previous
history of neurological- or psychiatric-based illnesses or disease, language or learning
disabilities, or alcohol/substance abuse; b) no history of seizures; c) no metal implants in
the head (except dental fillings); d) no lesion in the left DLPFC confirmed by MRI; e) no
current pregnancy. Pre-Test Behavioral Measures. Participants will be seen between 2-3
sessions to undergo comprehensive cognitive-linguistic testing prior to initiation of
treatment. Testing will take place at the University of Minnesota (UMN) Clinical
Translational Science Institute (CTSI). Behavioral test measures will include the WAB 32 in
order to obtain the WAB Aphasia Quotient (WAB AQ), Boston Naming Test (BNT) 33 and the
Apraxia Battery for Adults (ABA-2) 34. The WAB AQ will provide a general classification of
aphasia subtype, scores from the BNT will provide the level of severity of naming impairment,
and ABA-2 performance will be used to assess severity of apraxia of speech (AoS). To assess
the integrity of the phonological store, participants will be tested for the effects of
phonological similarity using both auditory and visual presentation 35, 36. To assess the
integrity of subvocal rehearsal processes, participants will be tested for the effects of
word length on both auditory and visual span 37; the effects of articulatory suppression on
recall performance 37, 38; and rhyme judgments 39-41. Protocols that have been adapted for
individuals with aphasia will be followed42-45. These tests will be used to distinguish
behavioral evidence of deficient subvocal rehearsal processes from deficient phonological
short-term store. Individuals with a range of moderate to moderately severe nonfluent
aphasia, a range of moderate to moderately severe anomia, and a range of mild to no AoS will
be chosen for the study. Baseline probes will also be obtained prior to the initiation of the
study. Stability of baseline performance, defined as no more than 20% difference between
scores,will be obtained over three consecutive sessions in order to establish experimental
control. Post-Test Behavioral Measures. Participants will also be seen for post-treatment
testing following the implementation of the treatment protocol. Testing will take place in
the participant's home. Post-treatment behavioral measures will include BNT, the ABA-2, WM
tasks, and naming treatment and control items. It is anticipated that only one session will
be needed for post-treatment testing. An adverse events survey will also be provided to
assess the participant's level of discomfort during use of tDCS. tDCS Protocol. Each
participant will be seated comfortably in a chair. A swim cap will be placed on the
participant's head to identify cranial landmarks for accurate electrode placement. The area
referred to as F3 by the International 10/20 system for electroencephalogram electrode
placement46 has been established as the optimal location for targeting the left DLPFC25,
47-49. The F3 region will be located by marking the vertex (the midpoint between left and
right tragus and midpoint between nasion and inion), measuring the head circumference. When
these measurements are entered into the Beam F3 Locator Software50, additional values are
provided to reliably identify the location of F3. Once F3 has been established, two saline
soaked surface sponge electrodes (352cm) will be prepared and placed. For optimal anodal
stimulation to the DLPFC, the anode will be placed over F3 and the cathode will be placed
over the right supraorbital region23, 24, 47, 48. A current of 2mA will be delivered for 20
minutes 24 by a multichannel transcranial current stimulator (Starstim, Neuroelectrics
Corporation; Cambridge, MA). a-tDCS will be applied before and during behavioral treatment in
the design specified below.

Treatment Design. Two treatment conditions will be presented in a counter-balanced order in a
cross-over design. The non-prime (NONPRIME) condition will consist of 40 minutes of naming
treatment only, followed by an additional 20 minutes of concurrent naming treatment with
a-tDCS. The primed (PRIME) condition will consist of presentation of a-tDCS for 20 minutes
prior to naming treatment, while the subject sits quietly and comfortably in a chair. After
the 20-minute priming period, the a-tDCS will be removed and the participant will receive
naming treatment for 60 minutes. Both conditions will be presented over four consecutive
days. Two participants will receive NON-PRIME-PRIME sequence, with a one-month washout period
between the two conditions. Two other participants will receive PRIME-NON-PRIME sequence,
with a one-month washout period between the two conditions. Naming reaction time will be
immediately evaluated after each treatment day.

Inclusion Criteria:

- completion of high school or GED, normal or corrected-to-normal vision, adequate
hearing acuity for 1:1 conversational exchanges, use of English as primary language, a
vascular lesion in the dominant left hemisphere verified by an MRI scan within six
months of the start of the study

Exclusion Criteria:

- no previous history of neurological- or psychiatric-based illnesses or disease,
language or learning disabilities, or alcohol/substance abuse; no history of seizures;
no metal implants in the head (except dental fillings); no lesion in the left DLPFC
confirmed by MRI; no current pregnancy.