Brain blood-flow change with acute vagus nerve stimulation in treatment-refractory major depressive disorder

Abstract

Background Existing neuroimaging studies of vagus nerve stimulation (VNS) in treatment resistant major depression (TRMD) suggest that many brain regions (e.g., prefrontal cortex, thalamus, cingulate cortex, insular cortex) associated with mood disorders undergo alterations in blood flow/metabolism. Objective/Hypothesis Positron emission tomography (PET oxygen-15 labeled water or PET [15O] H2O) was used to identify changes in regional cerebral blood flow (rCBF) in response to immediate VNS in 13 subjects with TRMD. We hypothesized rCBF changes along the afferent pathway of the vagus and in regions associated with depression (e.g., orbitofrontal cortex, amygdala, insular cortex). Methods Six 90-second PET [15O] H2O scans were performed on 13 subjects in a VNS off-on sequence. Following normalization for global uptake and realignment to standard atlas space, statistical t-images (p < 0.005) were used to evaluate rCBF change. Results VNS induced significant rCBF decreases in the left and right lateral orbitofrontal cortex and left inferior temporal lobe. Significant increases were found in the right dorsal anterior cingulate, left posterior limb of the internal capsule/medial putamen, the right superior temporal gyrus, and the left cerebellar body. Post-hoc analysis found small to moderate correlations between baseline acute change in rCBF and antidepressant response following 12 months of VNS. Conclusions Regions undergoing rCBF change in response to acute VNS are consistent with the known afferent pathway of the vagus nerve and models of brain network in depression. Larger studies assessing the correlation between acute stimulation patterns and antidepressant outcomes with VNS are needed.

Neuropathological and neuromorphometric abnormalities in bipolar disorder: View from the medial prefrontal cortical network

“…The lateral OFC receives afferent projections from the nucleus tractus solitarius, the principal terminus of interoceptive inputs from the vagus nerve, and potentially acts through the perigenual ACC to regulate visceromotor activity (Conway et al, 2012;Thayer et al, 2012). The reciprocal relationship between the vagus nerve and the mPFC may have implications for the regulation of the immune system, which is putatively disturbed in mood disorders (Dantzer et al, 2008;Irwin and Cole, 2011;Miller et al, 2009;Padmos et al, 2008;Savitz et al, 2013a).…”

Effect of transcutaneous auricular vagus nerve stimulation on major depressive disorder: A nonrandomized controlled pilot study

“…The vagus nerve is a mixed nerve composed of approximately 80% afferent fibers. It is speculated that the antidepressant effects of VNS are attributed partially to the projection of afferent fibers to the nucleus tractus solitaries (NTS), which is further connected both directly and indirectly with brain structures such as amygdala, hypothalamus, insula, thalamus, orbitofrontal cortex, and other limbic regions responsible for mood and anxiety regulation (Conway et al, 2012; Conway et al, 2006; Lomarev et al, 2002; Mu et al, 2004). An animal study (He et al, 2013) has shown that stimulating the auricular branches of the vagus nerve can significantly suppress epileptiform activity via the NTS in rats, which further endorses the effect of taVNS.…”

“…More recently, brain-imaging tools have been applied to investigate the fMRI signal change evoked by VNS (Conway et al, 2013; Conway et al, 2012; Conway et al, 2006; Landau et al, 2015) and taVNS (Dietrich et al, 2008; Kraus et al, 2007; Kraus et al, 2013). In a previous study (Kraus et al, 2013), Kraus and colleagues investigated the anterior and posterior wall of the auditory canal separately.…”

Vagus Nerve Stimulation in Ischemic Stroke: Old Wine in a New Bottle

“…In patients with treatment-refractory major depressive disorder, CBF decreases (left and right lateral orbitofrontal cortex, left inferior temporal lobe) and increases (right dorsal anterior cingulated, left posterior limb of internal capsule/medial putamen, right superior temporal gyrus, left cerebellar body) were seen in different anatomical regions after VNS (32). …”