Individualized theta-burst stimulation modulates hippocampal activity and connectivity in patients with major depressive disorder

Abstract

Background

While intermittent theta-burst stimulation (iTBS) has been shown to improve symptoms of major depressive disorder (MDD), research has been largely limited to targeting the dorsolateral prefrontal cortex (DLPFC). New approaches utilize patients’ individual resting state fMRI data in order to identify superficial cortical stimulation targets functionally connected to deeper brain regions, thus enabling the modulation of previously inaccessible targets for antidepressant therapy.

Objective

To improve iTBS treatment of MDD by inducing plasticity in the hippocampus through stimulation of an individually mapped, functionally interconnected site in the parietal cortex.

Methods

Fifty-three MDD patients were randomized to three treatment groups and underwent 15 sessions of iTBS to the left DLPFC. This was augmented by adding a second daily session of (i) stimulation over individualized parietal targets functionally connected to the hippocampus, (ii) left DLPFC stimulation, or (iii) sham stimulation. To evaluate the improvement of treatment, we assessed depression severity, neuropsychological performance, functional connectivity and neural activation during an associative memory paradigm pre- vs. post-treatment.

Results

Augmentation of left DLPFC stimulation by parieto-hippocampal stimulation increased functional connectivity between hippocampus and DLPFC as well as encoding-related hippocampal activation; the latter was associated with better performance during a spatial planning task dependent on prefrontal and hippocampal contributions. Depressive symptoms improved in all groups after treatment, with best clinical outcomes following twice-daily left DLPFC stimulation.

Conclusion

Functional connectivity-guided stimulation of the hippocampus may serve as an adjunct to iTBS in order to target the cognitive symptoms of MDD.