Tractography-assisted deep brain stimulation of the superolateral branch of the medial forebrain bundle (slMFB DBS) in major depression

Abstract

BackgroundDeep brain stimulation (DBS) of the superolateral branch of the medial forebrain bundle (slMFB) emerges as a - yet experimental - treatment for major depressive disorder (MDD) and other treatment refractory psychiatric diseases. First experiences have been reported from two open label pilot trials in major depression (MDD) and long-term effectiveness for MDD (50 months) has been reported.ObjectiveTo give a detailed description of the surgical technique for DBS of the superolateral branch of the medial forebrain bundle (slMFB) in MDD.MethodsSurgical experience from bilateral implantation procedures in n = 24 patients with MDD is reported. The detailed procedure of tractography-assisted targeting together with detailed electrophysiology in 144 trajectories in the target region (recording and stimulation) is described. Achieved electrode positions were evaluated based on postoperative helical CT and fused to preoperative high resolution anatomical magnetic resonance imaging (MRI; Philips Medical Systems, Best, Netherlands), including the pre-operative diffusion tensor imaging (DTI) tractographic information (StealthViz DTI, Medtronic, USA; Framelink 5.0, Medtronic, USA). Midcommissural point (MCP) coordinates of effective contact (EC) location, together with angles of entry into the target region were evaluated. To investigate incidental stimulation of surrounding nuclei (subthalamic nucleus, STN; substantia nigra, SNr; and red nucleus, RN) as a possible mechanism, a therapeutic triangle (TT) was defined, located between these structures (based on MRI criteria in T2) and evaluated with respect to EC locations.ResultsBilateral slMFB DBS was performed in all patients. We identified an electrophysiological environment (defined by autonomic reaction, passive microelectrode recording, acute effects and oculomotor effects) that helps to identify the proper target site on the operation table. Postoperative MCP-evaluation of effective contacts (EC) shows a significant variability with respect to localization. Evaluation of the TT shows that responders will typically have their active contacts inside the triangle and that surrounding nuclei (STN, SNr, RN) are not directly hit by EC, indicating a predominant white matter stimulation. The individual EC position within the triangle cannot be predicted and is based on individual slMFB (tractography) geometry. There was one intracranial bleeding (FORESEE I study) during a first implantation attempt in a patient who later received full bilateral implantation. Typical oculomotor side effects are idiosyncratic for the target region and at inferior contacts.ConclusionThe detailed surgical procedure of slMFB DBS implantation has not been described before. The slMFB emerges as an interesting region for the treatment of major depression (and other psychiatric diseases) with DBS. So far it has only been successfully researched in open label clinical case series and in 15 patients published. Stimulation probably achieves its effect through direct white-matter modulation of slMFB...

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“…As a result of successfully identifying the target site, which cannot be properly visualized on standard MRI, six out of the seven patients obtained rapid antidepressant response. This finding has since been replicated and recent long‐term data on this target have shown sustained antidepressant effects . The MFB, which forms part of the reward system, has also been tried as a target for DBS in patients with OCD .…”

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“…Thus, every treatment should be based on individual slMFB (tractography) geometry. 97 A case report presented a patient with TRD and nervous anorexia who was treated with DBS and showed great response. However, after 10 months, she presented blurred vision and was reoperated with electrodes placed on the BNST.…”

“…This makes this target the most promising of the open-label trials selected. 97 The MFB is the most rapid to produce response, most probably because it lies at the center of the reward pathway, 14,91,109 with acute effects also more pronounced on the NAcc. 87 Nonetheless, whenever acute responses are present, the insertional effect (possibly related to acute inflammatory mediators 11 or glial released neurotransmitters 12,32 in early time-points must be considered.…”

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“…Likewise, the superolateral branch of the medial forebrain bundle (slMFB) seems to be anatomically and functionally connected with DBS targets used to treat major depressive disorder (MDD), such as the NAc/ALIC [103]. In another study, tractography was useful for localizing and implanting DBS targeting the slMFB, serving to modulate subcortical and cortical reward-related pathways assumed to be dysfunctional in MDD [104]. The results showed, indeed, that direct white-matter modulation of slMFB fibers achieved desirable anti-depressive effects.…”