Assessing differential effects of single and accelerated low-frequency rTMS to the visual cortex on GABA and glutamate concentrations

Background The application of repetitive transcranial magnetic stimulation (rTMS) for therapeutic use in visual-related disorders and its underlying mechanisms in the visual cortex is under-investigated. Additionally, there is little examination of rTMS adverse effects particularly with regards to visual and cognitive function. Neural plasticity is key in rehabilitation and recovery of function; thus, effective therapeutic strategies must be capable of modulating plasticity. Glutamate and gamma-aminobutyric acid (GABA)-mediated changes in the balance between excitation and inhibition are prominent features in visual cortical plasticity. Objectives and method: We investigated the effects of low-frequency (1 Hz) rTMS to the visual cortex on altering levels of neurotransmitters GABA and glutamate to determine the therapeutic potential of 1 Hz rTMS for visual-related disorders. Two rTMS regimes commonly used in clinical applications were investigated: participants received rTMS to the visual cortex either in a single 20-min session or five accelerated 20-min sessions (not previously investigated at the visual cortex). Proton (H-1) magnetic resonance spectroscopy for in vivo quantification of GABA (assessed via GABA+) and glutamate (assessed via Glx) concentrations was performed pre- and post-rTMS. Results: GABA+ and Glx concentrations were unaltered following a single session of rTMS to the visual cortex. One day of accelerated rTMS significantly reduced GABA+ concentration for up to 24 hr, with levels returning to baseline by 1-week post-rTMS. Basic visual and cognitive function remained largely unchanged. Conclusion: Accelerated 1 Hz rTMS to the visual cortex has greater potential for approaches targeting plasticity or in cases with altered GABAergic responses in visual disorders. Notably, these results provide preliminary insight into a critical window of plasticity with accelerated rTMS (e.g., 24 hr) in which adjunct therapies may offer better functional outcome. We describe detailed procedures to enable further exploration of these protocols.