Stimulating the Aging Brain Using Brain and Sensory Stimulation

Official title

Stimulating the Aging Brain: Noninvasive Brain and Sensory Stimulation Strategies in Aging

Overview

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

Detailed description

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.

Interventions

• Device tACS or multisensory stimulation
  Active or sham tACS Light and/or sound flickers

Primary outcome measures

• Changes in STM capacity assessed using a verbal STM task [Time frame: Changes monitored over pre, during and immediately after 20 minutes of tACS]
• Changes in STM capacity with multisensory stimulation using a verbal STM task [Time frame: Changes monitored pre and immediately after 20 minutes of stimulation]

Eligibility criteria

Inclusion criteria

• Clinical exam supports diagnosis of PPA and/or MCI with no report of difficulty functioning in basic or instrumental activities of daily living.
• Completed clinical cognitive exam within 6 months of study baseline visit OR neuropsychological research battery within 6 months of study baseline visit.

Exclusion criteria

• Evidence of dementia at baseline
• Known history of neoplasm, symptomatic stroke, moderate to severe traumatic brain injury, or other significant neurologic event
• Age <45 years.
• Evidence of severe psychiatric illness (e.g., bipolar disorder, schizophrenia).
• Presence of cardiac stimulators or pacemakers
• Any other implants near the scalp or in the eye
• Contraindications to MRI or stimulation
• Pregnancy
• History of ongoing or unmanaged seizures
• History of dyslexia or other developmental learning disabilities

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Basic science

Study locations

United States · 1 center

• Medical College of Wisconsin — Milwaukee

Publications

• 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. PMID 37625524
• 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. PMID 27929004
• 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. PMID 30879788
• 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. PMID 37510481
• 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/s13195-0 PMID 39267112
• 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. PMID 37715232

Identifiers

NCT: NCT07650188 · PRO00056114

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗