Longitudinal Changes in Depressive Circuitry in Response to Neuromodulation Therapy

Area of Science:

• Neuroscience
• Psychiatry
• Medical Technology

Background:

• Major depressive disorder (MDD) is a global health concern.
• Non-invasive therapies like repetitive transcranial magnetic stimulation (rTMS) show promise for MDD.
• Neural circuit changes induced by rTMS require further characterization.

Purpose of the Study:

• To investigate if brain regions targeted by deep brain stimulation (DBS) for MDD respond to rTMS.
• To determine if functional connectivity (FC) measures can predict clinical response to rTMS in MDD patients.

Main Methods:

• Administered 20 rTMS sessions to the left-dorsolateral prefrontal cortex (L-DLPFC) in five MDD patients over 4 weeks.
• Acquired magnetoencephalography (MEG) recordings and Montgomery-Asberg depression rating scale (MADRS) assessments.
• Measured changes in power spectral density (PSD) and functional connectivity (FC) using MEG source imaging and coherence.

Main Results:

• Four out of five patients met clinical response criteria (≥40% MADRS decrease).
• Increased gamma power at L-DLPFC correlated with symptom improvement.
• Altered delta and gamma band connectivity between L-DLPFC and other brain regions (amygdala, pACC, sACC) correlated with symptom improvement.

Conclusions:

• rTMS modulates activity in depressive circuits targeted by DBS, and MEG can detect these modulations.
• Gamma oscillations and altered functional connectivity may underlie rTMS therapeutic effects.
• MEG-based response prediction could inform patient selection for DBS surgery.