Neural Predictors and Longitudinal Neural Correlates of Deep Transcranial Magnetic Stimulation for Treating Major Depression

• 21-item Hamilton Depression Rating Scale (HAM-D21) [ Time Frame: week 5 ] [ Designated as safety issue: No ]
  Pre-post neuromodulation changes on HAM-D21 scores
  
  

• 21-item Hamilton Depression Rating Scale (HAM-D21) [ Time Frame: week 5 ] [ Designated as safety issue: No ]
  Response to treatment is defined as a ≥ 50% reduction in the scores of the HAM-D21. Remission is defined as a HAM-D21 score ≤ 8.
  
  
• Quick Inventory of Depressive Symptomatology - Self-Report (QIDS-SR) [ Time Frame: week 5 ] [ Designated as safety issue: No ]
  Response is defined as a ≥ 50% reduction in the scores of the QIDS-SR. Remission is defined as a QIDS-SR score ≤ 5.
  
  

Standard high frequency repetitive transcranial magnetic stimulation (HF-rTMS) is a noninvasive method able to modulate neuronal activity in superficial brain regions through the induction of weak electric currents produced by changing magnetic fields. Studies have shown HF-rTMS to be effective in treating major depressive disorder (MDD), although clinical effects are often highly variable and there are several negative trials in the literature. One reason for these discrepant results might be that standard HF-rTMS only enables direct stimulation of superficial brain areas and, consequently, it is possible that the stimulation of deeper brain regions might produce superior and more reliable results. Recently, a novel form of HF-rTMS (called deep transcranial magnetic stimulation or DTMS) that allows direct stimulation of larger and deeper brain regions has been shown to be effective for treating MDD. Contrary to standard HF-rTMS, to date there is no data on the neurobiological effects of DTMS, and in this study we will investigate this issue in subjects with MDD. More specifically, we aim at identifying possible neural predictors of clinical improvement after DTMS and at clarifying the impact of DTMS in brain activity over time. We will apply DTMS over the left dorsolateral prefrontal cortex and will compare it with standard HF-rTMS in terms of its effectiveness and brain effects. For this, 80 subjects with at least moderate MDD will be randomized to receive daily DTMS or standard HF-rTMS treatment for 4 weeks, and will undergo functional magnetic resonance imaging (fMRI) before and after treatment (i.e., at baseline and week 5). During the fMRI sessions, we will use a Self-Referential Processing Task and the N-Back Task. Furthermore, subjects will be clinically assessed in 3 occasions: at baseline and at weeks 5 and 9. Our results could help identify which depressed patients would be best candidates for receiving either standard HF-rTMS or DTMS, and which areas of the brain should be targeted by these neuromodulation techniques.