{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T15:37:07Z","timestamp":1784907427057,"version":"3.55.0"},"reference-count":53,"publisher":"SAGE Publications","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAD"],"published-print":{"date-parts":[[2021,11,23]]},"abstract":"<jats:p>Background: Prior research, primarily with young adults, suggests transcranial direct current stimulation (tDCS) effects are driven by the primary excitatory and\/or inhibitory neurotransmitters, glutamate, and gamma-aminobutyric acid (GABA), respectively. Objective: We examined the neurometabolic mechanisms of tDCS in older adults with and without mild cognitive impairment (MCI). Methods: We used data from a double-blind, cross-over, randomized controlled trial (NCT01958437) in 32 older adults to evaluate high definition (HD)-tDCS-induced changes in glutamate and GABA via magnetic resonance spectroscopy (MRS). Participants underwent MRS following two counterbalanced HD-tDCS sessions (one active, one sham) that targeted the right superior parietal cortex (center anode at P2) and delivered 2mA for 20 minutes. Results: Relative to sham, and when co-varying for MRS voxel overlap and right superior parietal volume, active HD-tDCS significantly increased GABA and decreased the ratio of glutamate to GABA. No changes were observed in a left prefrontal control MRS voxel. Although we did not find a significant correlation between strength of delivered current (measured via MRI-based computational modeling) and neurometabolite change, there was a robust positive relationship between the volume of right superior parietal cortex and neurometabolite change. Conclusion: Our preliminary findings of increased GABA and reduced glutamate\/GABA ratio raise the possibility that (HD-)tDCS effects differ by age. Moreover, age- and disease-related regional brain volume loss may be especially important to consider when planning future studies. Replication would emphasize the importance of developing population-specific tDCS parameters that consider structural and physiologic changes associated with \u201cnormal\u201d and pathological aging.<\/jats:p>","DOI":"10.3233\/jad-201091","type":"journal-article","created":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T22:28:51Z","timestamp":1633127331000},"page":"1091-1102","source":"Crossref","is-referenced-by-count":18,"title":["Effects of High Definition-Transcranial Direct Current Stimulation on Local GABA and Glutamate Levels Among Older Adults with and without Mild Cognitive Impairment: An Exploratory Study"],"prefix":"10.1177","volume":"84","author":[{"given":"Ketrin","family":"Lengu","sequence":"first","affiliation":[{"name":"Neuropsychology Section, Mental Health Service, VA Ann Arbor Healthcare System, Ann Arbor, MI, USA"},{"name":"Research Program on Cognition and Neuromodulation-Based Interventions (RP-CNBI), Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shannon","family":"Ryan","sequence":"additional","affiliation":[{"name":"Research Program on Cognition and Neuromodulation-Based Interventions (RP-CNBI), Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott J.","family":"Peltier","sequence":"additional","affiliation":[{"name":"Functional MRI Laboratory, University of Michigan, Ann Arbor, MI, USA"},{"name":"Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Troy","family":"Tyszkowski","sequence":"additional","affiliation":[{"name":"Research Program on Cognition and Neuromodulation-Based Interventions (RP-CNBI), Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anson","family":"Kairys","sequence":"additional","affiliation":[{"name":"Research Program on Cognition and Neuromodulation-Based Interventions (RP-CNBI), Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Giordani","sequence":"additional","affiliation":[{"name":"Research Program on Cognition and Neuromodulation-Based Interventions (RP-CNBI), Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin M.","family":"Hampstead","sequence":"additional","affiliation":[{"name":"Neuropsychology Section, Mental Health Service, VA Ann Arbor Healthcare System, Ann Arbor, MI, USA"},{"name":"Research Program on Cognition and Neuromodulation-Based Interventions (RP-CNBI), Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","reference":[{"key":"10.3233\/JAD-201091_ref1","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1016\/j.neuroimage.2013.07.083","article-title":"Battery powered thought: Enhancement of attention, learning, and memory in healthy adults using transcranial direct current stimulation","volume":"85","author":"Coffman","year":"2014","journal-title":"Neuroimage"},{"key":"10.3233\/JAD-201091_ref2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fnhum.2017.00112","article-title":"Transcranial electrical stimulation and behavior change: The intermediary influence of the brain","volume":"11","author":"Harty","year":"2017","journal-title":"Front Hum Neurosci"},{"key":"10.3233\/JAD-201091_ref3","first-page":"1","article-title":"Can transcranial direct current stimulation alone or combined with cognitive training be used as a clinical intervention to improve cognitive functioning in persons with mild cognitive impairment? 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