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The goal of this project is to investigate whether transcranial electrical stimulation and sensory stimulation affect language outcomes in individuals with primary progressive aphasia (PPA). The main questions it aims to answer are:
Does transcranial alternating current stimulation (tACS) affect verbal short-term memory (STM) in individuals with PPA? Does a single session of multisensory stimulation affect verbal STM in individuals with PPA? Researchers will compare active tACS to sham tACS (a fake stimulation condition) to see if active tACS improves verbal STM. Researchers will compare pre-multisensory stimulation to post-stimulation performance to see if multisensory stimulation improves verbal STM.
Participants will:
Undergo EEG, MRI (anatomical and functional) May complete a cognitive exam Undergo tACS over 3 separate sessions Undergo multisensory stimulation Complete language tasks before, during and/or after stimulation
The primary objective of the current project is to examine the effects of tACS and multisensory stimulation on verbal STM outcomes in individuals with PPA. The selection of parameters will be guided on the basis of oscillatory brain activity using language task-based or task-free EEG paradigms. Neuroimaging (MRI and functional MRI) will guide spatial targets of tACS. A secondary objective is to explore sources of individual variability in response to stimulation and whether these factors could offer insight into disease progression. This proof-of-concept, pilot project will generate essential preliminary data to help refine hypotheses for future clinical trials aimed at assessing the efficacy of these intervention strategies in predicting and treating (as in delaying) disease progression.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| tACS or multisensory stimulation | Experimental | All participants in a within-subject design will receive high-Definition-tACS, delivered via a battery operated alternating current stimulator (Soterix) using two center-surround montages. Targets of stimulation will be localized based on the 10-10 International EEG system with center electrodes placed at a frontal and a temporoparietal site. The current is turned on and increased in a ramplike fashion over approximately 30 seconds. Participants will undergo tACS with frequencies ranging from 4-40Hz for 20-minutes with 2 milliampere (mA) peak-to-peak intensity. For sham stimulation, tACS is turned off after the first 30 seconds. All participants will receive light and/or sound flicker stimulation using an off-the-shelf app for 20 minutes. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| tACS or multisensory stimulation | Device | Active or sham tACS Light and/or sound flickers |
|
| Measure | Description | Time Frame |
|---|---|---|
| Changes in STM capacity assessed using a verbal STM task | Improvement in STM capacity with in-phase tACS and worsening of STM capacity with anti-phase tACS compared to sham tACS | Changes monitored over pre, during and immediately after 20 minutes of tACS |
| Changes in STM capacity with multisensory stimulation using a verbal STM task | Improvement in STM capacity post-stimulation compared to pre-stimulation | Changes monitored pre and immediately after 20 minutes of stimulation |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Sidney Schoenrock, MA | Contact | 414-955-7579 | sschoenrock@mcw.edu |
| Name | Affiliation | Role |
|---|---|---|
| Priyanka Shah-Basak, PhD | Medical College of Wisconsin | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Medical College of Wisconsin | Recruiting | Milwaukee | Wisconsin | 53226 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37625524 | Background | Hu J, Zheng L, Guan Z, Zhong K, Huang F, Huang Q, Yang J, Li W, Li S. Sensory gamma entrainment: Impact on amyloid protein and therapeutic mechanism. Brain Res Bull. 2023 Oct 1;202:110750. doi: 10.1016/j.brainresbull.2023.110750. Epub 2023 Aug 23. | |
| 27929004 | Background | Iaccarino HF, Singer AC, Martorell AJ, Rudenko A, Gao F, Gillingham TZ, Mathys H, Seo J, Kritskiy O, Abdurrob F, Adaikkan C, Canter RG, Rueda R, Brown EN, Boyden ES, Tsai LH. Gamma frequency entrainment attenuates amyloid load and modifies microglia. Nature. 2016 Dec 7;540(7632):230-235. doi: 10.1038/nature20587. |
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| ID | Term |
|---|---|
| D018888 | Aphasia, Primary Progressive |
| ID | Term |
|---|---|
| D003704 | Dementia |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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In a within-subject design, participants will receive in-phase tACS, anti-phase tACS and sham tACS with spatial targets and tACS frequency guided by baseline fMRI and EEG results. Participants will also undergo multisensory stimulation using light and/or sound flickers provided in the gamma range during a session separate from tACS.
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Participants and personnel scoring the outcomes will be blinded.
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| 30879788 | Background | Martorell AJ, Paulson AL, Suk HJ, Abdurrob F, Drummond GT, Guan W, Young JZ, Kim DN, Kritskiy O, Barker SJ, Mangena V, Prince SM, Brown EN, Chung K, Boyden ES, Singer AC, Tsai LH. Multi-sensory Gamma Stimulation Ameliorates Alzheimer's-Associated Pathology and Improves Cognition. Cell. 2019 Apr 4;177(2):256-271.e22. doi: 10.1016/j.cell.2019.02.014. Epub 2019 Mar 14. |
| 37510481 | Background | McNett SD, Vyshedskiy A, Savchenko A, Durakovic D, Heredia G, Cahn R, Kogan M. A Feasibility Study of AlzLife 40 Hz Sensory Therapy in Patients with MCI and Early AD. Healthcare (Basel). 2023 Jul 17;11(14):2040. doi: 10.3390/healthcare11142040. |
| 39267112 | Background | Tang Y, Xing Y, Sun L, Wang Z, Wang C, Yang K, Zhu W, Shi X, Xie B, Yin Y, Mi Y, Wei T, Tong R, Qiao Y, Yan S, Wei P, Yang Y, Shan Y, Zhang X, Jia J, Teipel SJ, Howard R, Lu J, Li C, Zhao G. TRanscranial AlterNating current stimulation FOR patients with mild Alzheimer's Disease (TRANSFORM-AD): a randomized controlled clinical trial. Alzheimers Res Ther. 2024 Sep 12;16(1):203. doi: 10.1186/s13195-024-01570-0. |
| 37715232 | Background | Altomare D, Benussi A, Cantoni V, Premi E, Rivolta J, Cupidi C, Martorana A, Santarnecchi E, Padovani A, Koch G, Borroni B. Home-based transcranial alternating current stimulation (tACS) in Alzheimer's disease: rationale and study design. Alzheimers Res Ther. 2023 Sep 15;15(1):155. doi: 10.1186/s13195-023-01297-4. |
| D001037 |
| Aphasia |
| D013064 | Speech Disorders |
| D007806 | Language Disorders |
| D003147 | Communication Disorders |
| D019954 | Neurobehavioral Manifestations |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |