Continuous and intermittent theta burst stimulation to the visual cortex do not alter GABA and glutamate concentrations measured by magnetic resonance spectroscopy

Background: Theta burst stimulation (TBS), a form of repetitive transcranial magnetic stimulation (rTMS), uses repeated high-frequency bursts to non-invasively modulate neural processes in the brain. An intermittent TBS (iTBS) protocol is generally considered "excitatory," while continuous TBS (cTBS) is considered "inhibitory." However, the majority of work that has led to these effects being associated with the respective protocols has been done in the motor cortex, and it is well established that TMS can have variable effects across the brain.

Objectives and method: We investigated the effects of iTBS and cTBS to the primary visual cortex (V1) on composite levels of gamma-aminobutyric acid + co-edited macromolecules (GABA+) and glutamate + glutamine (Glx) since these are key inhibitory and excitatory neurotransmitters, respectively. Participants received a single session of cTBS, iTBS, or sham TBS to V1. GABA+ and Glx were quantified in vivo at the stimulation site using spectral-edited proton magnetic resonance spectroscopy (¹ H-MRS) at 3T. Baseline pre-TBS GABA+ and Glx levels were compared to immediate post-TBS and 1 h post-TBS levels.

Results: There were no significant changes in GABA+ or Glx following either of the TBS conditions. Visual cortical excitability, measured using phosphene thresholds, remained unchanged following both cTBS and iTBS conditions. There was no relationship between excitability thresholds and GABA+ or Glx levels. However, TBS did alter the relationship between GABA+ and Glx for up to 1 h following stimulation.

Conclusions: These findings demonstrate that a single session of TBS to the visual cortex can be used without significant effects on the tonic levels of these key neurotransmitters; and add to our understanding that TBS has differential effects at visual, motor, and frontal cortices.