A longitudinal study on deep brain stimulation of the medial forebrain bundle for treatment-resistant depression

Abstract

Deep brain stimulation (DBS) to the superolateral branch of the medial forebrain bundle (MFB) has been reported to lead to rapid antidepressant effects. In this longitudinal study, we expand upon the initial results we reported at 26 weeks (Fenoy et al., 2016), showing sustained antidepressant effects of MFB DBS on six patients with treatment-resistant depression (TRD) over 1 year. The Montgomery-Åsberg Depression Rating Scale (MADRS) was used as the primary assessment tool. Deterministic fiber tracking was used to individually map the target area; analysis was performed to compare modulated fiber tracts between patients. Intraoperatively, upon stimulation at target, responders reported immediate increases in energy and motivation. An insertional effect was seen during the 4-week sham stimulation phase from baseline (28% mean MADRS reduction, p = 0.02). However, after 1 week of initiating stimulation, three of six patients had a > 50% decrease in MADRS scores relative to baseline (43% mean MADRS reduction, p = 0.005). One patient withdrew from study participation. At 52 weeks, four of remaining five patients have > 70% decrease in MADRS scores relative to baseline (73% mean MADRS reduction, p = 0.007). Evaluation of modulated fiber tracts reveals significant common orbitofrontal connectivity to the target region in all responders. Neuropsychological testing and 18F-fluoro-deoxyglucose-positron emission tomography cerebral metabolism evaluations performed at baseline and at 52 weeks showed minimal changes and verified safety. This longitudinal evaluation of MFB DBS demonstrated rapid antidepressant effects, as initially reported by Schlaepfer et al. (2013), and supports the use of DBS for TRD.

Deep Brain Stimulation Is Effective for Treatment-Resistant Depression: A Meta-Analysis and Meta-Regression

“…Thirteen studies were excluded because they did not compare active to sham stimulation [31][32][33][34][35][36][37][38][39][40][41][42][43], and one study was excluded as it included only three patients [44]. Therefore, 12 studies [15][16][17][18][19][20][21][22][23][24][25] (186 unique patients) were included in the meta-analysis and meta-regression ( Table 1). The Raymaekers et al study was analyzed as two separate studies, because this study included two anatomically distinct stimulation targets, and both targets were evaluated with blinded stimulation periods.…”

“…Multiple human trials have explored the efficacy of DBS for TRD. Anatomic targets have included the ventral anterior limb of the internal capsule (vALIC) [15], ventral capsule/ventral striatum (VC/VS) [16], subcallosal cingulate (SCC) [17][18][19][20][21][22], inferior thalamic peduncle (ITP) [23], medial forebrain bundle (MFB) [24,25], and lateral habenula [26]. Reports regarding the efficacy of DBS for TRD have been mixed, with some studies demonstrating encouraging results, while others have shown a lack of efficacy relative to sham stimulation.…”

The Utility of Diffusion Tensor Imaging in Neuromodulation: Moving Beyond Conventional Magnetic Resonance Imaging

“…Subsequently, a specific part of the MFB that has the maximum traffic of fibers–the supero‐lateral branch of the MFB–was proposed as a new DBS target . And as discussed in the previous section, deterministic tractography has been shown to help guide targeting of this particular tract with good clinical outcomes . In addition, whole‐brain activation volume probabilistic tractography has been shown to identify a combination of white matter tracts passing through the SCC target that mediate successful response to DBS for depression .…”

Deep Brain Stimulation for the Treatment of Resistant Depression: Systematic Review of the Literature

“…Increased depression was associated with battery depletion in four patients, and accidental deactivation in three. 101 Evaluation of the tractographies showed that responders typically have their active contacts exclusively situated in the center of the triangle, with no contact with the nuclear environment. Thus, every treatment should be based on individual slMFB (tractography) geometry.…”