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
Affiliations: [a] Neuropsychology Section, Mental Health Service, VA Ann Arbor Healthcare System, Ann Arbor, MI, USA
| [b] Research Program on Cognition and Neuromodulation-Based Interventions (RP-CNBI), Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA
| [c] Functional MRI Laboratory, University of Michigan, Ann Arbor, MI, USA
| [d] Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA
Correspondence:
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Correspondence to: Benjamin M. Hampstead, University of Michigan, 2101 Commonwealth Blvd Ste C, Ann Arbor, MI 48105, USA. Tel.: +1 800 525 5188; Fax: +1 734 936 9262; E-mail: bhampste@med.umich.edu.
Abstract: 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 “normal” and pathological aging.
