The effect of intermittent theta-burst stimulation over the dorsomedial prefrontal cortext on brain activity in depression

Sammanfattning: Repetitive transcranial magnetic stimulation is an emerging alternative for treatment-resistant depression, with ongoing developments in stimulation protocols and treatment targets. As such, intermittent theta-burst stimulation (iTBS) delivered over the dorsomedial prefrontal cortex (dmPFC) has shown promise, however establishing a need for neuroimaging studies to further understand the treatment mechanisms. This thesis aims to explore the effects of dmPFC-iTBS on brain activity in depression, using data from a randomized controlled trial and two add-on brain imaging studies with shared methodology. Study I investigated the prefrontal blood oxygenation (oxy-Hb) response during, as well as before and after iTBS sessions at the first, fifth, and final day of treatment. Oxy-Hb was assessed using functional near-infrared spectroscopy (fNIRS). Study II examined patients’ cognitive performance and concurrent prefrontal oxy-Hb before and after a full iTBS treatment course, again using fNIRS. The patient data were also compared to a sample of healthy controls. Study III assessed whether iTBS modulates functional brain activity during an emotional picture anticipation paradigm, using functional magnetic resonance imaging (fMRI). Study IV investigated the functional connectivity of the brain network behind the oxy-Hb response observed in study I. This was done by using the fNIRS optode locations as seeds in a resting-state fMRI analysis before and after a full iTBS treatment course. In summary, brain activity was modulated by iTBS both in an acute and delayed matter. Patients receiving active iTBS had increased prefrontal oxy-Hb levels during the fifth and final iTBS session, suggesting that this modulation was being built up during the treatment course (study I). Resting-state functional connectivity of this prefrontal cortex region to the insula or, when adding oxy-Hb change as a regressor, the posterior parietal cortex was modulated after active, but not sham, iTBS (study IV). Likewise, amygdala activation during exposure to picture stimuli of negative valence was reduced after active, but not sham, iTBS (study III). While patients displayed cognitive deficits compared to healthy controls before treatment start, active iTBS did not alter their cognitive performance or concurrent prefrontal oxy-Hb (study II).