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 γ‐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 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 (1H) 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.