Optimizing Targeted Interventions for Primary Progressive Aphasia

点击翻译按钮获取中文摘要

PROJECT SUMMARY/ABSTRACT Treatment options for primary progressive aphasia (PPA), a communication disorder associated with fronto- temporal dementia (FTD) or Alzheimer’s Disease (AD) pathology, are extremely limited, and the psychosocial and economic impacts of PPA are devastating. Knowledge of modifiable brain targets has not been harnessed to catalyze meaningful treatment outcomes. Transcranial electrical stimulation (tES) allows systematic investi- gations of the effects of brain target engagement and has strong clinical translational potential. While tES re- search in PPA is encouraging, the over-reliance on tES protocols and recovery models used for stroke-induced aphasia, rather than the development of approaches motivated by PPA neurobiology, has prevented vertical progress in PPA treatment development. The fundamental underlying pathophysiology of progressive aphasia warrants tailored approaches to intervention. There is a critical need for rigorous investigations that facilitate identification of treatments capable of engaging modifiable brain targets for prophylaxis, restitution, and overall improved disease management in PPA and other AD/ADRD. Failure to meet this need will unnecessarily delay treatment advancements for clinical populations with no time to waste. The long-term goal of both the parent grant and this supplement is to optimize neurorehabilitation for aphasia, whether due to stable or progressive etiology, with clinically translatable brain-based treatments. The overall objective of this project is to strengthen the impact of a current project on tES in stroke-induced aphasia (R01DC018282) by identifying and optimizing adjunctive treatments that engage brain targets in people with PPA. This requires a neurotargeting foundation grounded in PPA (rather than stroke) neurobiology and disease trajectory. Innovative pipelines developed in the parent grant will be leveraged and combined with innovations in brain target selection specific to PPA and its three consensus-based variants to develop essential tES tools and guidelines. Two specific aims will be pursued: 1) Develop pipelines and guidelines for targeted modulation of intact cortex for each PPA variant; and 2) Use EEG to identify networks for targeting with tES for each PPA variant. Under the first aim, a shareable pipeline for E-field modeling of multi-electrode transcranial direct current stimulation (tDCS) will be developed, as will a normative dataset of modeled E-field distributions. Under the second aim, spectral EEG differences between controls and people with PPA will be localized, laying the groundwork for future research with tran- scranial alternating current stimulation (tACS). These contributions will be significant because the anticipated development and sharing of resources will advance the validity and inferential precision of tES research for PPA and other AD/ADRD, supporting development of future grant applications specific to neuromodulatory ad- juvant treatments in these clinical populations who are in desperate need of innovations.