Intermittent theta-burst stimulation moderates interaction between increment of N-Acetyl-Aspartate in anterior cingulate and improvement of unipolar depression

Highlights

• First controlled ¹H-MRS study of iTBS effects in major depression.

• ITBS is know to be associated with favorable clinical improvement.

• If iTBS applied, higher NAA concentrations in ACC predict favorable BDI reduction.

• Prefrontal iTBS might act through modulation of ACC neuronal viability.

Abstract

Background

Intermittent theta-burst stimulation (iTBS), a novel repetitive transcranial magnetic stimulation (rTMS) technique, appears to have antidepressant effects when applied over left dorsolateral prefrontal cortex (DLPFC). However, its underlying neurobiological mechanisms are unclear. Proton magnetic resonance spectroscopy (¹H-MRS) provides in vivo measurements of cerebral metabolites altered in major depressive disorder (MDD) like N-acetyl-aspartate (NAA) and choline-containing compounds (Cho). We used MRS to analyse effects of iTBS on the associations between the shifts in the NAA and Cho levels during therapy and MDD improvement.

Methods

In-patients with unipolar MDD (N = 57), in addition to treatment as usual, were randomized to receive 20 iTBS or sham stimulations applied over left DLPFC over four weeks. Single-voxel ¹H-MRS of the anterior cingulate cortex (ACC) was performed at baseline and follow-up. Increments of concentrations, as well as MDD improvement, were defined as endpoints. We tested a moderated mediation model of effects using the PROCESS macro (an observed variable ordinary least squares and logistic regression path analysis modeling tool) for SPSS.

Results

Improvement of depressive symptoms was significantly associated with decrease of Cho/NAA ratio, mediated by NAA. iTBS had a significant moderating effect enhancing the relationship between NAA change and depression improvement.

Conclusions

Our findings suggest a potential neurochemical pathway and mechanisms of antidepressant action of iTBS, which may moderate the improvement of metabolic markers of neuronal viability. iTBS might increase neuroplasticity, thus facilitating normalization of neuronal circuit function.