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

Background: Existing neuroimaging studies of vagus nerve stimulation (VNS) in treatment resistant major depression (TRMD) suggest that many brain regions (eg, 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 [(15)O] H(2)O) 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 (eg, orbitofrontal cortex, amygdala, insular cortex).

Methods: Six 90-second PET [(15)O] H(2)O scans were performed on 13 subjects in a VNS off-on sequence. After normalization for global uptake and realignment to standard atlas space, statistical t images (P < .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 after 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.