Subgenual Anterior Cingulate-Medial Orbitofrontal Functional Connectivity in Medication-Resistant Major Depression: A Neurobiological Marker for Accelerated Intermittent Theta Burst Stimulation Treatment?

Abstract

Background: Accelerated repetitive transcranial magnetic stimulation paradigms have been shown to result in fast decreases in depressive symptoms and suicidal ideation. Although the subgenual anterior cingulate cortex (sgACC) region has been put forward as a possible biological marker, so far, no studies evaluated the clinical effects of accelerated intermittent theta burst stimulation (aiTBS) on sgACC functional connectivity (FC).

Methods: Fifty patients with treatment-resistant depression were enrolled in this registered randomized double-blind sham-controlled crossover aiTBS treatment study. All received 20 iTBS sessions applied to the left dorsolateral prefrontal cortex (5 daily sessions spread over 4 days). Forty-four complete resting-state functional magnetic resonance imaging scans were collected. Baseline resting-state functional magnetic resonance imaging scans were compared with a matched healthy control group. Besides depression severity, all patients were also assessed with the Scale for Suicide Ideation and the Beck Hopelessness Scale.

Results: Our main resting-state functional magnetic resonance imaging findings indicate that a positive sgACC FC correlation with the medial orbitofrontal cortex could distinguish aiTBS responders from nonresponders at baseline. Beneficial aiTBS treatment strengthened sgACC-medial orbitofrontal cortex FC patterns. Moreover, this increased FC pattern was associated with a decrease in feelings of hopelessness.

Conclusions: Clinical response to aiTBS treatment is not only characterized by stronger FC patterns between the sgACC and the medial orbitofrontal cortex, but it is also associated with decreases in hopelessness. Our observations provide a possible neurobiological explanation why accelerated repetitive transcranial magnetic stimulation paradigms may result in prompt attenuation of negative thinking in depressed patients.

Trial registration: ClinicalTrials.gov NCT01832805.

Keywords: Accelerated iTBS; Functional connectivity; Major depressive disorder; Orbitofrontal cortex; Subgenual anterior cingulate cortex; Treatment resistance.