Chronic vagus nerve stimulation for treatment-resistant depression decreases resting ventromedial prefrontal glucose metabolism

Abstract

Vagus nerve stimulation (VNS) is used as an adjunctive therapy for treatment-resistant depression (TRD). Its mechanism of action is not fully understood. Longitudinal measurement of changes in brain metabolism associated with VNS can provide insights into this new treatment modality. Eight severely depressed outpatients who were highly treatment-resistant underwent electrical stimulation of the left vagus nerve for approximately one year. The main outcome measures were resting regional brain glucose uptake measured with positron emission tomography (PET) and the 24-item Hamilton Depression Scale. The most significant and extensive change over one year of chronic VNS localized to the ventromedial prefrontal cortex extending from the subgenual cingulate to the frontal pole. This region continued to decline in metabolism even toward the end of the study. Clinically, this cohort showed a trend for improvement. No correlations surfaced between change in glucose uptake and depression scores. However, the sample size was small; none remitted; and the range of depression scores was limited. Chronic VNS as adjunctive therapy in patients with severe TRD produces protracted and robust declines in resting brain activity within the ventromedial prefrontal cortex, a network with dense connectivity to the amygdala and structures monitoring the internal milieu.

Group differences in MEG-ICA derived resting state networks: Application to major depressive disorder

“…Connectomic diffusion tensor imaging studies also found alterations in sgACC connectivity (Korgaonkar et al, 2014). Deep brain stimulation targeting the sgACC resulted in robust relief from depressive symptoms (Mayberg et al, 2005), and vagus nerve stimulation (Pardo et al, 2008) and antidepressant treatment also normalized sgACC metabolism (Drevets et al, 2002a; Kennedy et al, 2007). Since our group IC map did not contain an sgACC node, we view this group difference as somewhat analogous to group differences in inter-network connectivity, although sgACC is visible in the unthresholded maps shown in Figure 2 B and C.…”

Adjunctive vagus nerve stimulation for treatment-resistant bipolar disorder: managing device failure or the end of battery life

“…In 2005, she was implanted with a VNS device (Model 102, Cyberonics, Houston, Texas, USA). Because of reports that the effects of VNS may take many months with brain metabolic changes evolving even beyond 1 year,1 2 she was advised that major antidepressant effects from VNS might take 1 to 2 years. She would need to continue intensive psychiatric management.…”

“…Adjunctive vagus nerve stimulation (VNS) is indicated for treatment-resistant major depression or bipolar disorder, when either the patient cannot tolerate conventional treatments, or when unresponsive to medications or convulsive seizure therapy. It has become clear that VNS can take a long time to improve mood (eg, 1 year or more1 2). However, little is known about what happens to mood-disordered patients in remission who stop VNS treatment.…”

Targeted electrode-based modulation of neural circuits for depression

“…Across studies of chronic antidepressant treatment using commonly prescribed medications, prefrontal cortical changes are the most consistently reported, with normalization of frontal cortex overactivity and underactivity both described (62,(70)(71)(72). Additionally, changes are also seen in limbic and subcortical regions, including the subgenual cingulate, amygdala, hippocampus, posterior cingulate cortex, and insula, with decreased activity most commonly observed (70,71,(74)(75)(76)(77). The time course of these medication effects and differences between responders and nonresponders have provided additional localizing clues as to critical brain changes mediating depression remission.…”