title: The medial forebrain bundle as a deep brain stimulation target for treatment resistant depression: A review of published data.
abstract: BACKGROUND
  Despite a wide variety of therapeutic interventions for major depressive disorder (MDD), treatment resistant depression (TRD) remains to be prevalent and troublesome in clinical practice. In recent years, deep brain stimulation (DBS) has emerged as an alternative for individuals suffering from TRD not responding to combining antidepressants, multiple adjunctive strategies and electroconvulsive therapy (ECT). Although the best site for TRD-DBS is still unclear, pilot data suggests that the medial forebrain bundle (MFB) might be a key target to accomplish therapeutic efficacy in TRD patients.
  
  
  OBJECTIVE
  To explore the anatomic, electrophysiologic, neurocognitive and treatment data supporting the MFB as a target for TRD-DBS.
  
  
  RESULTS
  The MFB connects multiple targets involved in motivated behavior, mood regulation and antidepressant response. Specific phenomenology associated with TRD can be linked specifically to the superolateral branch (sl) of the MFB (slMFB). TRD patients who received DBS-slMFB reported high response/remission rates with an improvement in functioning and no significant adverse outcomes in their physical health or neurocognitive performance.
  
  
  CONCLUSIONS
  The slMFB is an essential component of a network of structural and functional pathways connecting different areas possibly involved in the pathogenesis of mood disorders. Therefore, the slMFB should be considered as an exciting therapeutic target for DBS therapy to achieve a sustained relief in TRD patients.
  
  
  CONCLUSIONS
  There is an urgent need for clinical trials exploring DBS-slMFB in TRD. Further efforts should pursue measuring baseline pro-inflammatory cytokines, oxidative stress, and cognition as possible biomarkers of DBS-slMFB response in order to aid clinicians in better patient selection.
authors.affiliation: UT Center of Excellence on Mood Disorders, The University of Texas Health Science Center at Houston, Houston, TX, USA; Department of Psychiatry, Pontificia Universidad Javeriana School of Medicine, Bogotá, Colombia. Electronic address: Juan.F.GalvezFlorez@uth.tmc.edu.
authors.forename: Juan F
authors.initials: JF
authors.lastname: Gálvez
authors.affiliation: Department of Physical Medicine and Rehabilitation, TIRR Memorial Hermann Neuro-Recovery Research Center, Houston, TX, USA. Electronic address: Zafer.Keser@uth.tmc.edu.
authors.forename: Zafer
authors.initials: Z
authors.lastname: Keser
authors.affiliation: UT Center of Excellence on Mood Disorders, Department of Psychiatry and Behavioral Sciences, University of Texas Health Science Center, Houston, TX, USA. Electronic address: Benson.Irungu@uth.tmc.edu.
authors.forename: Benson
authors.initials: B
authors.lastname: Mwangi
authors.affiliation: The University of Texas Health Science Center at Houston, TX, USA. Electronic address: Amna.a.ghouse@uth.tmc.edu.
authors.forename: Amna A
authors.initials: AA
authors.lastname: Ghouse
authors.affiliation: The University of Texas Health Science Center at Houston, TX, USA. Electronic address: Albert.J.Fenoy@uth.tmc.edu.
authors.forename: Albert J
authors.initials: AJ
authors.lastname: Fenoy
authors.affiliation: The University of Texas Health Science Center at Houston, TX, USA. Electronic address: Paul.E.Schulz@uth.tmc.edu.
authors.forename: Paul E
authors.initials: PE
authors.lastname: Schulz
authors.affiliation: UT Center of Excellence on Mood Disorders, Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston, USA. Electronic address: Marsal.sanches@uth.tmc.edu.
authors.forename: Marsal
authors.initials: M
authors.lastname: Sanches
authors.affiliation: Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston, TX, USA. Electronic address: Joao.L.DeQuevedo@uth.tmc.edu.
authors.forename: Joao
authors.initials: J
authors.lastname: Quevedo
authors.affiliation: Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston, TX, USA. Electronic address: Sudhakar.Selvaraj@uth.tmc.edu.
authors.forename: Sudhakar
authors.initials: S
authors.lastname: Selvaraj
authors.affiliation: The University of Texas Health Science Center at Houston, TX, USA. Electronic address: prashant.gajwani@uth.tmc.edu.
authors.forename: Prashant
authors.initials: P
authors.lastname: Gajwani
authors.affiliation: Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston, TX, USA. Electronic address: Giovana.b.zuntasoares@uth.tmc.edu.
authors.forename: Giovana
authors.initials: G
authors.lastname: Zunta-Soares
authors.affiliation: Department of Diagnostic and Interventional Imaging, Magnetic Resonance Imaging Research Division, Diffusion Tensor Imaging Lab, University of Texas Health Science Center at Houston, Houston, TX, USA. Electronic address: Khader.M.Hasan@uth.tmc.edu.
authors.forename: Khader M
authors.initials: KM
authors.lastname: Hasan
authors.affiliation: The University of Texas Health Science Center at Houston, TX, USA. Electronic address: Jair.C.Soares@uth.tmc.edu.
authors.forename: Jair C
authors.initials: JC
authors.lastname: Soares
mesh_terms: D000818:Animals; D046690:Deep Brain Stimulation / Q000009:adverse effects / Q000379:methods*; D061218:Depressive Disorder, Treatment-Resistant / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy*; D006801:Humans; D008474:Medial Forebrain Bundle / Q000473:pathology / Q000503:physiopathology*; D009434:Neural Pathways / Q000473:pathology / Q000503:physiopathology
keywords: Deep brain stimulation (DBS); Medial forebrain bundle (MFB); Neuromodulation; Psychiatry; Treatment resistance depression (TRD)