Using Transcranial Direct Current Stimulation to Reveal Mechanisms of Language Loss and to Treat Progressive Aphasia Associated with FTD and Related Dementias
Abstract
Primary progressive aphasia (PPA) refers to a debilitating disorder of language loss associated with deterioration in portions of the brain that process language, typically in the left hemisphere. Two types of PPA — nonfluent/agrammatic (naPPA) and semantic variant (svPPA) — together affect up to 40% of patients with frontotemporal degeneration (FTD), one of the Fiscal Year 2019 Peer Reviewed Medical Research Program topic areas. Both of these FTD-associated PPA variants profoundly impact communication abilities and impose a significant burden of suffering on patients and their caregivers. Unfortunately, behavioral language treatments for PPA have only shown modest results, and pharmacologic approaches are ineffective. In recent years, a small body of evidence has suggested that combining transcranial direct current stimulation (tDCS) — a form of safe, noninvasive brain stimulation — with behavioral language therapy may hold out promise as a potential treatment. Recent years have also seen important advances in network science that have enabled us to more fully understand how complex, dynamic systems like the brain operate. Leveraging these advances, this proposal focuses on how the language network of the brain is impacted by PPA and also by tDCS. We posit that the language deficits associated with PPA can be conceptualized as resulting from the degeneration of centers of connectivity in the language network, referred to here as hubs. The rationale of employing tDCS in this context is to enhance the effectiveness of remaining language network connections. We also pair stimulation with speech therapy because it is believed that tDCS selectively reinforces neural circuits for the mental operations and behaviors performed at or near the time of stimulation. Our early studies are promising and provide support for further exploration of tDCS paired with speech therapy as an intervention for PPA. Our preliminary work also reveals network analysis to be a powerful tool for capturing language system changes in persons with PPA and may prove to be a useful framework for characterizing the neural effects of tDCS in PPA. The main objectives of this proposal are to further develop tDCS as a novel clinical intervention for FTD-associated PPAs and to employ network neuroscience tools to elucidate both the neural underpinnings of aphasia symptoms in PPA and the mechanisms by which tDCS may enhance language performance in these disorders. To accomplish these objectives, we will conduct a double-blind, sham (i.e., placebo) controlled, two-armed crossover study in which subjects with naPPA and svPPA will undergo language testing and structural and functional brain imaging before and after receiving 10 sessions (Monday-Friday x 2 weeks) of either real or sham tDCS over the left hemisphere of the brain paired with a language therapy. Language testing and brain imaging will be repeated immediately after completion of treatment and then 3 months following the end of treatment. We will pursue our study objectives by accomplishing four aims. First, we will determine whether tDCS paired with behavioral language therapy improves language performance in naPPA and svPPA. We predict that, compared to sham stimulation paired with language therapy, tDCS paired with language therapy will lead to improved language performance persisting at least 12 weeks after stimulation. Second, we will apply cutting-edge network analysis to functional and structural brain imaging data to relate changes in connectivity within the language network to the symptoms of PPA. We predict that degeneration-induced changes in the connectivity of language network hubs will determine baseline aphasia severity in persons with PPA. Third, we will then use the same network analytical approach to determine how tDCS plus language therapy influences the connectivity of hubs in the language network. We predict that tDCS with language therapy will strengthen hub conn
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010490
Entities
People
- Roy Hamilton
Organizations
- United States Army
- University of Pennsylvania