Accelerated intermittent theta burst stimulation in major depression induces decreases in modularity: A connectome analysis.

Karen Caeyenberghs,Chris Baeken,Romain Duprat,Peter H Wilson,Debby Klooster,Alexander Leemans,Hadi Hosseini

doi:10.1162/netn_a_00060

Abstract

Accelerated intermittent theta burst stimulation (aiTBS) is a noninvasive neurostimulation technique that shows promise for improving clinical outcome in patients suffering from treatment-resistant depression (TRD). Although it has been suggested that aiTBS may evoke beneficial neuroplasticity effects in neuronal circuits, the effects of aiTBS on brain networks have not been investigated until now. Fifty TRD patients were enrolled in a randomized double-blind sham-controlled crossover trial involving aiTBS, applied to the left dorsolateral prefrontal cortex. Diffusion-weighted MRI data were acquired at each of three time points (T1 at baseline; T2 after the first week of real/sham aiTBS stimulation; and T3 after the second week of treatment). Graph analysis was performed on the structural connectivity to examine treatment-related changes in the organization of brain networks. Changes in depression severity were assessed using the Hamilton Depression Rating Scale (HDRS). Baseline data were compared with 60 healthy controls. We observed a significant reduction in depression symptoms over time (p < 0.001). At T1, both TRD patients and controls exhibited a small-world topology in their white matter networks. More importantly, the TRD patients demonstrated a significantly shorter normalized path length (pAUC = 0.01), and decreased assortativity (pAUC = 0.035) of the structural networks, compared with the healthy control group. Within the TRD group, graph analysis revealed a less modular network configuration between T1 and T2 in the TRD group who received real aiTBS stimulation in the first week (p < 0.013). Finally, there were no significant correlations between changes on HDRS scores and reduced modularity. Application of aiTBS in TRD is characterized by reduced modularity, already evident 4 days after treatment. These findings support the potential clinical application of such noninvasive brain stimulation in TRD.

Highlights

Major depressive disorder (MDD) is a worldwide mental health problem (WHO) and is characterized by affective, cognitive, and somatic symptoms impeding the daily life and activities of the patient
Treatment-resistant depression: Depressed patients who do not respond to mainstream treatment, e.g., medication or therapy
The majority of studies using repetitive transcranial magnetic techniques for clinically depressed patients have already shown that a series of daily sessions of high-frequency (HF)-rTMS delivered on the left dorsolateral prefrontal cortex (DLPFC) or low-frequency (LF)-rTMS applied to the right DLPFC are effective in reducing depressive symptoms (Lefaucheur et al, 2014)

Summary

Introduction

Major depressive disorder (MDD) is a worldwide mental health problem (WHO) and is characterized by affective, cognitive, and somatic symptoms impeding the daily life and activities of the patient. More recent studies have examined whether accelerated stimulation paradigms can yield higher response rates and reduce the total time of treatment, with promising results (Holtzheimer et al, 2010; Baeken et al, 2013) For example, in our recent randomized, shamcontrolled crossover accelerated intermittent theta burst (aiTBS) study in TRD patients (Desmyter et al, 2016; Duprat et al, 2016), we showed significant (acute) reductions in depression severity symptoms and suicide ideation Despite these promising results, the underlying neurobiological mechanisms supporting these treatment-related changes remain unclear. Functional connectivity alterations are associated with the pathophysiology of MDD, future

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