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The relation between baseline brain volumes and response to tDCS in individuals with Primary Progressive Aphasia

Vânia De Aguiar1*, Yi Zhao2, Andreia V. Faria3, Bronte Ficek1, Kimberly T. Webster1, Haley Wendt1, Zeyi Wang2, Argye Hillis1, 4, 5, Constantine Frangakis2, Brian Caffo2 and Kyrana Tsapkini1
  • 1 School of Medicine, Johns Hopkins University, Department of Neurology, United States
  • 2 Bloomberg School of Public Health, Johns Hopkins, Department of Biostatistics, United States
  • 3 School of Medicine, Johns Hopkins University, Department of Radiology, United States
  • 4 Johns Hopkins University, Department of Cognitive Science, United States
  • 5 Johns Hopkins University, Department of Physical Medicine and Rehabilitation, United States

BACKGROUND. Individuals with Primary Progressive Aphasia (PPA) may benefit from receiving transcranial direct current stimulation (tDCS) paired with behavioral interventions. However, there is substantial variability in response to stimulation in the healthy population, post-stroke aphasia, and PPA (Shah-Basak et al., 2015; Tsapkini, Frangakis, Gomez, Davis, & Hillis, 2014). In the current study, we identified brain regions within spelling and learning networks that are associated with stimulation effects. We aimed to determine whether stimulation effects were associated with relative atrophy of areas within and/or beyond the stimulated region. The identified brain regions will reflect the neural networks and cognitive processes susceptible to tDCS-related enhancement. METHOD. Twenty-two individuals with PPA received either anodal tDCS or Sham (randomized), with simultaneous written naming/spelling therapy, daily for a period of approximately 3 weeks. Stimulation was delivered for the first 20 min of each session, at 2mA, with the anode over the left Inferior Frontal Gyrus (IFG), and the cathode over the right cheek. T1-weighted MPRAGE scans were collected at baseline. Volumes of 21 anatomical regions of interest (ROI), and their right hemisphere (RH) homologues, were extracted using MRIcloud (Mori et al., 2016) and normalized by intra-cerebral volume. Spelling accuracy (% of correctly spelled letters) for both treated and untreated words was assessed before and after therapy, in a written naming/spelling task. A modified outcome approach (Tian et al., 2014) was implemented to target interactions between stimulation and volumetric data, with pre-therapy letter accuracy and Global Atrophy for adjustment. We identify brain regions that moderate the stimulation effect (difference in treatment response in tDCS vs. Sham conditions), chosen based on the increment of cross-validated coefficient of determination (R2). RESULTS. Effects of tDCS on change for treated words were associated with the volume of the right Lingual Gyrus (LG) (delta R2=0.428, Coeff.=0.679, p<0.001), right IFG triangularis (delta R2=0.257, Coeff.=0.451, p<0.001), and left Angular Gyrus (AG) (delta R2=0.103, Coeff.=-0.309, p<0.01). For untreated words, none of the ROIs met the statistical criteria. DISCUSSION AND CONCLUSION. Stimulation effects for treated words were positively correlated with brain volume of the right IFG (homologous to the stimulated area) and the right LG. Individuals with larger volumes in these two RH regions who received tDCS benefited more from therapy than those receiving Sham. These results are in line with Jokel et al. (2016), who showed that increases in RH recruitment are associated with larger gains after naming therapy in svPPA. Furthermore, the right LG is involved in directing attention to global shapes of words (Mechelli, Humphreys, Mayall, Olson, & Price, 2000). Hence, these results indicate that stimulation effects are associated with volumes of RH areas, that may help to compensate for existing spelling impairments. In addition, individuals with smaller left AG volumes who received tDCS benefited more treatment than those receiving Sham. This suggests that the left AG may be an effective stimulation target even in individuals with greater degeneration, especially given its white-matter connectivity to the stimulated left IFG. Note: The first two authors contributed equally to the work.

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Acknowledgements

This work was supported by grants from the Science of Learning Institute at Johns Hopkins University and by the National Institutes of Health (National Institute of Deafness and Communication Disorders) through award R01 DC014475 to KT. AH was supported by NIH (NIDCD) through awards R01 DC05375, R01 DC011317 and P50 DC014664. We are grateful to our participants for their unfailing commitment and interest in our study. We also thank referring physicians.

References

Jokel, R., Kielar, A., Anderson, N. D., Black, S. E., Rochon, E., Graham, S., … Tang-Wai, D. F. (2016). Behavioural and neuroimaging changes after naming therapy for semantic variant primary progressive aphasia. Neuropsychologia, 89, 191–216.
Mechelli, A., Humphreys, G. W., Mayall, K., Olson, A., & Price, C. J. (2000). Differential effects of word length and visual contrast in the fusiform and lingual gyri during. Proceedings of the Royal Society of London B: Biological Sciences, 267(1455), 1909–1913.
Mori, S., Wu, D., Ceritoglu, C., Li, Y., Kolasny, A., Vaillant, M. A., … Miller, M. I. (2016). MRICloud: Delivering High-Throughput MRI Neuroinformatics as Cloud-Based Software as a Service. Computing in Science & Engineering, 18(5), 21–35.
Shah-Basak, P. P., Norise, C., Garcia, G., Torres, J., Faseyitan, O., & Hamilton, R. H. (2015). Individualized treatment with transcranial direct current stimulation in patients with chronic non-fluent aphasia due to stroke. Frontiers in Human Neuroscience, 9.
Tian, L., Alizadeh, A. A., Gentles, A. J., & Tibshirani, R. (2014). A Simple Method for Estimating Interactions between a Treatment and a Large Number of Covariates. Journal of the American Statistical Association, 109(508), 1517–1532.
Tsapkini, K., Frangakis, C., Gomez, Y., Davis, C., & Hillis, A. E. (2014). Augmentation of spelling therapy with transcranial direct current stimulation in primary progressive aphasia: Preliminary results and challenges. Aphasiology, 28((8–9), 1112–1130.

Keywords: primary progressive aphasia, spelling therapy, transcranial direct current stimulation (tDCS), neuroanatomical predictors of outcome, Brain volumes

Conference: Academy of Aphasia 56th Annual Meeting, Montreal, Canada, 21 Oct - 23 Oct, 2018.

Presentation Type: oral presentation

Topic: not eligible for a student prize

Citation: De Aguiar V, Zhao Y, Faria AV, Ficek B, Webster KT, Wendt H, Wang Z, Hillis A, Frangakis C, Caffo B and Tsapkini K (2019). The relation between baseline brain volumes and response to tDCS in individuals with Primary Progressive Aphasia. Conference Abstract: Academy of Aphasia 56th Annual Meeting. doi: 10.3389/conf.fnhum.2018.228.00096

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Received: 30 Apr 2018; Published Online: 22 Jan 2019.

* Correspondence: PhD. Vânia De Aguiar, School of Medicine, Johns Hopkins University, Department of Neurology, Baltimore, MD, United States, deaguiar@jhmi.edu