Serial Vagus Nerve Stimulation Functional MRI in Treatment-Resistant Depression

Abstract

Vagus nerve stimulation (VNS) therapy has shown antidepressant effects in open acute and long-term studies of treatment-resistant major depression. Mechanisms of action are not fully understood, although clinical data suggest slower onset therapeutic benefit than conventional psychotropic interventions. We set out to map brain systems activated by VNS and to identify serial brain functional correlates of antidepressant treatment and symptomatic response. Nine adults, satisfying DSM-IV criteria for unipolar or bipolar disorder, severe depressed type, were implanted with adjunctive VNS therapy (MRI-compatible technique) and enrolled in a 3-month, doubleblind, placebo-controlled, serial-interleaved VNS/functional MRI (fMRI) study and open 20-month follow-up. A multiple regression mixed model with blood oxygenation level dependent (BOLD) signal as the dependent variable revealed that over time, VNS therapy was associated with ventro-medial prefrontal cortex deactivation. Controlling for other variables, acute VNS produced greater right insula activation among the participants with a greater degree of depression. These results suggest that similar to other antidepressant treatments, BOLD deactivation in the ventro-medial prefrontal cortex correlates with the antidepressant response to VNS therapy. The increased acute VNS insula effects among actively depressed participants may also account for the lower dosing observed in VNS clinical trials of depression compared with epilepsy. Future interleaved VNS/fMRI studies to confirm these findings and further clarify the regional neurobiological effects of VNS.

Comparison of ΔFosB Immunoreactivity Induced by Vagal Nerve Stimulation with That Caused by Pharmacologically Diverse Antidepressants

“…Results of imaging studies in patients with epilepsy or depression who are treated with VNS also show widespread effects on subcortical and cortical regions, with short-term VNS producing increases in blood flow in the hypothalamus, thalamus, and insular cortex but decreases in the hippocampus and posterior cingulate gyrus (Chae et al, 2003). Longterm VNS produced both increased (Kosel et al, 2011) and decreased (Nahas et al, 2007) changes in blood flow in cortical regions although subcortical regions were activated (Henry et al, 2004). Inconsistent results were also obtained in the amygdala (Zobel et al, 2005;Conway et al, 2006).…”

Brain–Gut Relationship on Mucosal Inflammation in the Gastrointestinal Tract

“…39 It has been demonstrated that depression results in autonomic imbalance, with impaired parasympathomimetic functions. 40 Experimental findings also confirm that impaired cholinergic function may play a causal role in gut inflammation; disease activity index, macroscopic and histologic scores, myeloperoxidase activity, level of serum amyloid-P, and colonic tissue levels of IL-1b, interleukin-6 (IL-6), and TNF-a were increased significantly in vagotomized mice in DSS and hapten-induced colitis when compared with sham-operated mice that received DSS or the hapten. 41 These results suggest that vagal nerve is likely to exert a tonic inhibition on acute inflammation.…”

Neurocircuitry of Mood Disorders

“…Functional imaging studies in depressed humans indicate that metabolism and blood flow decrease in the sgACC/ ventromedial PFC in response to chronic treatment with antidepressant drugs, vagus nerve stimulation, or deep brain stimulation of the sgACC or anterior capsule (Mayberg et al, 1999(Mayberg et al, , 2005Drevets et al, 2002a;Van Laere et al, 2006;Nahas et al, 2007;Conway et al, 2006). Activity in the broader limbic-thalamo-cortical circuitry also decreases during effective treatment with antidepressant drugs or electroconvulsive therapy (Drevets et al, 2002a(Drevets et al, , 2004a.…”