Acute neuromodulatory effects of 1 Hz rTMS on the central autonomic network in depression: A concurrent TMS-fMRI study.

BACKGROUND

Major depressive disorder (MDD) is associated with significant autonomic dysregulation and dysfunction of the central autonomic network (CAN), comprised of cortical and subcortical brain regions involved in autonomic modulation. Repetitive transcranial magnetic stimulation (rTMS) is an effective intervention for depression, and has been shown to induce changes in heart rate variability (HRV), hypothesized to be due to trans-synaptic modulation of the CAN. However, evidence for the mechanism by which rTMS modulates CAN activity is lacking. This study employed a concurrent rTMS-fMRI design to address this knowledge gap.

METHODS

MDD patients underwent the following scanning sequence: 1) 5 min rsfMRI, 2) 5 min concurrent rTMS-fMRI, where low-frequency rTMS (LFT) was administered in-scanner to the right dorsolateral prefrontal cortex (R-DLPFC), followed by 3) 5 min rsfMRI run, all with simultaneous electrocardiogram recording. Patients subsequently underwent a 4-week course of daily LFT to the R-DLPFC. We assessed changes in HRV, temporal correlations between HRV and blood‑oxygen-level-dependent (BOLD) activity and CAN nodes, and coupling between functional connectivity (FC) and HRV during TMS-fMRI compared to rsfMRI.

RESULTS

TMS-fMRI led to an increase in temporal correlation between BOLD signal in the right posterior insula (r-pIns) and HRV, and between r-pIns-midbrain FC and HRV; HRV decreased during TMS-fMRI. These changes were not present immediately after TMS-fMRI. There were weak correlation trends (non-statistically significant) between increased CAN activity and treatment outcomes.

CONCLUSIONS

LFT acutely increases CAN-heart connectivity, and leads to transient decrease in HRV. Further research is warranted to investigate the relationship of CAN-biomarkers with clinical outcomes.

CLINICALTRIALS: govidentifier:NCT03642522.