HD-tDCS + Language Therapy for Primary Progressive Aphasia
Trial Summary
What is the purpose of this trial?
AD afflicts over 5.5. million Americans and is one of the most expensive diseases worldwide. In AD the variant in which language functions are most affected are referred to as 'logopenic variant Primary Progressive Aphasia' (lvPPA). Language deficits dramatically impair communication and quality of life for both patients and caregivers. PPA usually has an early onset (50-65 years of age), detrimentally affecting work and family life. Studies have identified verbal short-term memory/working memory (vSTM/WM) as a primary deficit and cause of language impairment. In the first cycle of this award, the investigators asked the question of whether language therapy effects could be augmented by electrical stimulation. The investigators conducted the largest to-date randomized, double-blind, sham-controlled, crossover, clinical trial to determine the effects of transcranial direct current stimulation (tDCS) in PPA. The investigators found that tDCS over the left inferior frontal gyrus (L_IFG), one of the major language hubs in the brain, significantly enhanced the effects of a written naming and spelling intervention. In addition, findings demonstrated that tDCS modulates functional connectivity between the stimulated area and other networks (e.g. functionally and structurally connected areas), and that tDCS modulates the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). In terms of tDCS, the investigators have been identified several predictors to determine the beneficience of tDCS including (a) PPA variant, (b) initial performance on cognitive/language tasks, particularly vSTM/WM, and (c) initial white-matter integrity and structure. These findings support the notion that tDCS benefits generalize beyond the treatment tasks and has led to the important question of the present study: How can we implement treatments to product benefits that maximally generalize to untrained but vital language/cognitive functions. To address the above question, the investigators will test recent neuroplasticity theories that claim that the benefits of neuromodulation to language-specific areas generalize to other language functions within the language network, while neuromodulation of a domain-general/multiple-demands area generalizes to both domain-general, executive and language functions. The two areas to be stimulated will be the supramarginal gyrus (SMG) and left dorsolateral prefrontal cortex (DLPFC) respectively. The left supramarginal gyrus (L_SMG) in particular, specializes in phonological processing, namely phonological verbal short-term memory (vSTM), i.e., the ability to temporarily store phonological (and graphemic) information in order. The domain of vSTM affects many language tasks (repetition, naming, syntax), which makes it an ideal treatment target and the L_SMG an ideal stimulation target, since generalization of tDCS effects to other language tasks is driven by the function (computation) of the stimulated area. By testing a fundamental principle of neuromodulation in a devastating neurodegenerative disorder, the investigators will significantly advance the field of neurorehabilitation in early-onset dementias. Aim 1: To determine whether vSTM/WM behavioral therapy combined with high definition (HD)-tDCS over the L_SMG will induce more generalization to language-specific tasks than to executive tasks, whereas stimulation over the LDPFC will induce equivalent generalization to both executive and language-specific tasks. Aim 2: To understand the mechanism of tDCS by measuring tDCS-induced changes in network functional connectivity (FC) and GABA in the LSMG and LDPFC. The investigators will carry out resting-state functional magnetic resonance imaging (rsfMRI), (MPRAGE), diffusion-weighted imaging (DWI), perfusion imaging (pCASL), and magnetic resonance spectroscopy (MRS), before, after, and 3-months post-intervention. Aim 3: To identify the neural, cognitive, physiological, clinical and demographic characteristics (biomarkers) that predict sham, tDCS, and tDCS vs. sham effects on vSTM and related language tasks in PPA. The investigators will evaluate neural (functional and structural connectivity, cortical volume, neuropeptides, and perfusion), cognitive (memory, attention, executive) and language functions, clinical (severity), physiological (sleep), and demographic (age, gender) characteristics, and the investigators will analyze the effects on vSTM and other language/cognitive outcomes immediately after intervention and at 3 months post-intervention.
Will I have to stop taking my current medications?
The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.
What data supports the effectiveness of the treatment HD-tDCS + Language Therapy for Primary Progressive Aphasia?
Research suggests that transcranial direct current stimulation (tDCS), when combined with language therapy, can improve language abilities in people with primary progressive aphasia (PPA). Studies have shown improvements in speech production and grammatical comprehension, indicating that tDCS may help enhance language performance in some individuals with PPA.12345
Is HD-tDCS safe for humans?
How does the HD-tDCS treatment for Primary Progressive Aphasia differ from other treatments?
The HD-tDCS treatment is unique because it uses a non-invasive electrical stimulation technique to target specific brain areas involved in language, potentially enhancing the effects of language therapy. Unlike traditional drug treatments, this approach directly stimulates brain activity to improve language function in patients with Primary Progressive Aphasia.23457
Research Team
Kyrana Tsapkini, PhD
Principal Investigator
Johns Hopkins University
Eligibility Criteria
This trial is for right-handed individuals aged 50-80 with Primary Progressive Aphasia or dementia, who have completed at least high school and are proficient in English. They must be diagnosed at specialized clinics based on consensus criteria. Healthy controls matched by age and education may also participate.Inclusion Criteria
Exclusion Criteria
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
Treatment
Participants receive either Sham or active HD-tDCS combined with Language/Cognitive Interventions
Washout
A washout period between crossover phases to eliminate carryover effects
Follow-up
Participants are monitored for changes in language and cognitive functions post-intervention
Treatment Details
Interventions
- High-definition active tDCS (HD-tDCS) (Device)
- Sham (Device)
Find a Clinic Near You
Who Is Running the Clinical Trial?
Johns Hopkins University
Lead Sponsor
National Institute on Aging (NIA)
Collaborator