Poster C38, Friday, August 17, 10:30 am – 12:15 pm, Room 2000AB
BDNF Genotype and tDCS Interaction in Aphasia Therapy
Julius Fridriksson1, Jordan Elm2, Brielle Stark1, Alexandra Basilakos1, Chris Rorden3, Souvik Sen4, Mark George5,6,7, Leonardo Bonilha7;1University of South Carolina Department of Communication Sciences and Disorders, 2Medical University of South Carolina Department of Public Health Sciences, 3University of South Carolina Department of Psychology, 4University of South Carolina Department of Neurology, 5Medical University of South Carolina Department of Psychiatry, 6Ralph H. Johnson VA Medical Center, Charleston, 7Medical University of South Carolina Department of Neurology
Using a double blinded randomized controlled trial, we evaluated the extent to which brain stimulation (anodal transcranial direct current stimulation [A-tDCS]) applied during speech therapy, was a futile adjunctive intervention to improve speech production (naming) in individuals with chronic post-stroke aphasia. This futility design evaluated a null hypothesis of 'A-tDCS results in better treatment outcome than sham tDCS.' 74 patients with chronic aphasia (following left hemisphere stroke) received 3 weeks of speech-language therapy coupled with either A-tDCS or sham tDCS. Thirty-four subjects were randomized to receive A-tDCS (10 F; age, M=60±11yrs; education, M=15±3yrs) and 40 sham tDCS (12 F; age, M=60±10yrs; education, M=14±2yrs). The primary outcome was the ability to name common objects (performance on a sample of treated items [Naming 80] and the Philadelphia Naming Test [PNT]), assessed before and after therapy. Secondary outcomes included change in the number of correctly named items at 4- and 24-weeks post-treatment. We also acquired whole blood samples from participants (N=67) to identify how expression of the val66met polymorphism, reflecting atypical expression of blood derived neurotrophic factor (BDNF), modulated the effect of tDCS on naming ability post-treatment. If the null hypothesis was rejected at a one-sided significance level of 0.10, then A-tDCS would be unlikely to be effective for aphasia treatment and would not be considered for further study. We report results for outcomes adjusted for baseline aphasia severity, naming ability and treatment site. Immediately post-therapy, the A-tDCS group showed a mean adjusted improvement of 13.9 correctly named items and the sham tDCS group, 8.2 items (one-sided p=0.89). At 4-weeks post-treatment, the A-tDCS group showed an adjusted mean change from baseline of 16.8 correctly named items compared to the sham tDCS group's 9.4 correctly named items (p=0.94) and at 24-weeks post-treatment, the A-tDCS group showed an adjusted mean change from baseline of 14.9 items compared to the sham tDCS group's 7.1 items (p=0.90). Those without the val66met polymorphism (N=37) were significantly less severe at baseline than those expressing the Met allele (N=30) (p=0.01) but the groups did not significantly differ on other demographic factors. We therefore included aphasia severity as a cofactor in a general linear model of fixed effects, where our dependent factor was proportional change (actual change as a proportion of possible change) on the naming measures at immediately post-treatment, 4-weeks post and 24-weeks post. There was a significant interaction of genotype and tDCS group [Naming 80: F(1,61)=4.99, p=0.03; PNT: F(1,62)=5.14, p=0.027], where those without the Met allele receiving A-tDCS exhibited greater proportional change in correct naming over the course of the study. We failed to reject the primary futility null hypothesis, suggesting that a larger trial may be warranted to further evaluate the effects of A-tDCS on aphasia treatment. Carriers of the Met allele have been previously shown to display a reduced response to noninvasive brain stimulation protocols (Cheeran et al., 2008) and our results suggest that those not expressing the polymorphism show increased effect of A-tDCS on primary outcome, suggesting that typical BDNF is a mediator of tDCS effect.
Topic Area: Language Therapy