Neurochemical effects of theta burst stimulation as assessed by magnetic resonance spectroscopy

Abstract

Continuous theta burst stimulation (cTBS) is a novel transcranial stimulation technique that causes significant inhibition of synaptic transmission for <or=1 h when applied over the primary motor cortex (M1) in humans. Here we use magnetic resonance spectroscopy to define mechanisms mediating this inhibition by noninvasively measuring local changes in the cortical concentrations of gamma-aminobutyric acid (GABA) and glutamate/glutamine (Glx). cTBS to the left M1 led to an increase in GABA compared with stimulation at a control site without significant change in Glx. This direct evidence for increased GABAergic interneuronal activity is framed in terms of a new hypothesis regarding mechanisms underlying cTBS.

FIG. 1.

A: experimental protocol. A baseline magnetic resonance spectroscopy (MRS) acquisition was performed after the motor hotspot had been identified in each subject. After this was complete, the subjects were removed from the scanner and a 40-s train of theta burst stimulation (TBS) pulses were applied, either to the motor hotspot (M1; verum stimulation) or to the vertex (Cz; control stimulation). The subjects were then repositioned in the scanner and a poststimulation MRS spectrum was acquired. This commenced after a period of about 20 min of scanner setup. B: typical 2 × 2 × 2-cm voxel placed within the hand region of the left primary motor cortex.

FIG. 2.

A: typical locations for the prestimulation voxel (yellow) and the poststimulation voxel (blue). The substantial overlap between the 2 is shown in green. B: plot showing the high correlation between the amount of gray matter within the voxel of interest before and after stimulation (r² = 0.88, P < 0.01).

FIG. 3.

A: typical γ-aminobutyric acid (GABA)–optimized spectrum acquired. Insets show representative GABA and N-acetylaspartate (NAA) peaks before and after stimulation in the same subject. Glx, composite measure of glutamate and glutamine. B: percentage change in GABA:NAA ratio from baseline. Verum stimulation leads to a significant increase in GABA:NAA ratio, compared with control. C: percentage change in creatine signal for baseline. There is no significant change with either stimulation condition.