Primary progressive aphasia (PPA) is a relatively common clinical neurodegenerative syndrome that first and foremost affects language abilities. PPA usually has an early onset (50-60 years of age), detrimentally affecting work and family life. Spoken and written word production deficits are the earliest affected language skills with significant prognostic and diagnostic value for its course. There is no available treatment for affected individuals. Behavioral language therapy and naming and spelling interventions in particular have shown modest but encouraging gains, which, however, do not generalize to untrained items and do not sustain over time. Transcranial Direct Current Stimulation (tDCS) is a relatively new, safe, non-invasive, non-painful electrical stimulation of the brain; it has been shown to improve language and cognitive abilities in healthy controls and individuals with stroke and dementia when administered during language therapy. Repetitive and consecutive sessions of tDCS are thought to induce a type of long-term potentiation in the brain that affects synaptic connectivity. There is only one published study (by our group) supporting that tDCS coupled with spelling therapy has beneficial effects in people with PPA. In this project we propose to investigate the behavioral and neuromodulatory effects of tDCS during a combination of spoken and written word production therapy in PPA participants over time.
In Specific Aim 1, we will test the hypothesis that anodal tDCS, when administered in combination with spoken and written word production therapy, will improve performance of individuals with PPA more than behavioral spoken and written word production therapy alone. We also hypothesize that improvements will be sustained over time and generalize to other language and cognitive functions subserved by the stimulated brain areas and will positively affect the quality of life of participants. In Speciic Aim 2, we test the hypothesis that changes in functional connectivity as measured by resting-state fMRI are greater after tDCS coupled with spoken and written word production intervention than after behavioral spoken and written word production intervention alone while controlling for gray matter volume and white matter tract loss as measured by volumetric and diffusion tensor imaging (DTI). Study results may help optimize future interventions in individuals with PPA or other neurodegenerative disease by providing novel treatment alternatives in a neurodegenerative syndrome with no proven effective treatment. A better understanding of the behavioral as well as functional connectivity changes due to tDCS will offer insights into ways of impeding neurodegeneration that may improve quality of life for individuals with PPA and other dementias.

Public Health Relevance

PPA is a clinical neurodegenerative syndrome that is mainly characterized by language deficits for which there is no treatment available. Spoken and written word production deficits are the earliest affected language functions with great prognostic and diagnostic value for the progress of the disease. In this project we will evaluate the effectiveness of transcranial direct current stimulation (tDCS)-a relatively new technique of brain stimulation-coupled to a language intervention that combines treatment for both the spoken and written word production; we will also monitor the effects of interventions and neuromodulation in the brain by studying changes in functional connectivity using resting-state fMRI while controlling for gray matter volume and white matter loss.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
1R01DC014475-01
Application #
8861556
Study Section
Language and Communication Study Section (LCOM)
Program Officer
Cooper, Judith
Project Start
2015-04-02
Project End
2020-03-31
Budget Start
2015-04-02
Budget End
2016-03-31
Support Year
1
Fiscal Year
2015
Total Cost
$768,672
Indirect Cost
$271,086
Name
Johns Hopkins University
Department
Neurology
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21205
Tsapkini, Kyrana; Webster, Kimberly T; Ficek, Bronte N et al. (2018) Electrical brain stimulation in different variants of primary progressive aphasia: A randomized clinical trial. Alzheimers Dement (N Y) 4:461-472
Riello, Marianna; Faria, Andreia V; Ficek, Bronte et al. (2018) The Role of Language Severity and Education in Explaining Performance on Object and Action Naming in Primary Progressive Aphasia. Front Aging Neurosci 10:346
Ficek, Bronte N; Wang, Zeyi; Zhao, Yi et al. (2018) The effect of tDCS on functional connectivity in primary progressive aphasia. Neuroimage Clin 19:703-715
Oeltzschner, Georg; Snoussi, Karim; Puts, Nicolaas A et al. (2018) Effects of eddy currents on selective spectral editing experiments at 3T. J Magn Reson Imaging 47:673-681
Rofes, Adrià; Mandonnet, Emmanuel; de Aguiar, Vânia et al. (2018) Language processing from the perspective of electrical stimulation mapping. Cogn Neuropsychol :1-23
Sebastian, Rajani; Tsapkini, Kyrana; Tippett, Donna C (2016) Transcranial direct current stimulation in post stroke aphasia and primary progressive aphasia: Current knowledge and future clinical applications. NeuroRehabilitation 39:141-52
Sebastian, Rajani; Saxena, Sadhvi; Tsapkini, Kyrana et al. (2016) Cerebellar tDCS: A Novel Approach to Augment Language Treatment Post-stroke. Front Hum Neurosci 10:695
Tippett, Donna C; Hillis, Argye E; Tsapkini, Kyrana (2015) Treatment of Primary Progressive Aphasia. Curr Treat Options Neurol 17:362
Tsapkini, Kyrana; Frangakis, Constantine; Gomez, Yessenia et al. (2014) Augmentation of spelling therapy with transcranial direct current stimulation in primary progressive aphasia: Preliminary results and challenges. Aphasiology 28:1112-1130