We hypothesize patients who have difficulty with word recall (naming pictures) due to a stroke will experience greater benefit in word recall after receiving a combination of transcranial direct current stimulation (tDCS) and traditional behavioral treatment. This study will investigate the effects of the timing of tDCS in relationship to the behavioral treatment to determine the most optimal protocol. Transcranial direct current stimulation involves placing two electrodes on your scalp and sending a very small electrical current to excite the brain cells of the target site.

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.

The protocol for sharing individual participant data with other researchers has not yet been determined as data collection is in progress.

2 months

Each participant was asked if they experienced headache or itchy/tingly sensation at site of stimulation during and/or after tDCS sessions.