Transcranial Magnetic Stimulation in Nonfluent/Agrammatic Variant Primary Progressive Aphasia

Overview

Nonfluent/agrammatic variant primary progressive aphasia (nf/avPPA) is a fatal neurodegenerative disease that begins with isolated language deficits. There is currently no cure or treatment for this disease. Repetitive Transcranial Magnetic Stimulation (rTMS), a noninvasive neuromodulatory technique, is effective in major depression, and studied in many other conditions including nf/avPPA. Here the investigators propose to study the feasibility and change in language and brain function of a newer rTMS protocol (intermittent theta-burst stimulation, iTBS) using a randomized, blinded crossover design: participants will receive active or sham iTBS for two weeks and then switch groups without them or clinicians knowing their group. The investigators hypothesize that brain function and performance with language tasks will change after active iTBS.

This study is a randomized controlled blinded cross-over treatment trial that involves 20 iTBS treatment sessions (10 active treatment sessions; 10 sham treatment sessions) and the study will last between 6 weeks. There will be 20 treatment visits (Monday-Friday) each lasting 10-40 minutes. Whether the participant is randomly assigned to active or sham treatment, the participant will receive daily 10 minute session of iTBS treatment. Some sessions will include behavioral and neurophysiological measures. In addition, participants will complete cognitive testing, and neuro-imaging, including functional magnetic resonance (fMRI), functional near infrared spectroscopy (fNIRS) and electroencephalography (EEG) prior to the commencement of iTBS/sham treatment and at post-treatment. Safety and tolerability will be evaluated during daily iTBS treatments. After 10 iTBS treatment visits over 2 weeks, a clinical assessment will be done to see if the participants are responding to the iTBS treatment with a targeted language assessment and neuro-imaging as described above. After 2 weeks of "wash-out", where the subjects do not receive any treatments, the participants will undergo another 2 weeks of iTBS treatment. On the first iTBS session after the 2-week washout period, participants will undergo a targeted language assessment and EEG/fNIRS. At the final iTBS session at 6 weeks, subjects will again undergo a targeted language assessment, EEG/fNIRS, and fMRI. At that point, after 6 weeks, the cross-over study is finished.