Deep brain stimulation of the medial forebrain bundle: Distinctive responses in resistant depression.
Treatment resistant depression (TRD) is a serious, disabling disease. Deep brain stimulation (DBS) to the superolateral branch of the medial forebrain bundle (MFB), as proposed by Schlaepfer et al. (2013), has led to rapid anti-depressant response but has not been replicated.



In this interim analysis of an ongoing pilot study of ten subjects, we assessed the efficacy of MFB-DBS in a cohort of four TRD patients over a 52-week period using the Montgomery-Åsberg Depression Rating Scale (MADRS) as the primary assessment tool. Implanted patients entered a 4-week single-blinded sham stimulation period prior to stimulation initiation. Deterministic fiber tracking analysis was performed to compare modulated fiber tracts between patients.



Intraoperatively, responder patients displayed immediate increased signs of energy and motivation upon stimulation at target. There was no significant mean change in mood during sham stimulation phase. Three of 4 patients had >50% decrease in MADRS scores at 7 days post-stimulation initiation relative to baseline. One patient withdrew from study participation. At 26 weeks, two of 3 remaining patients continue to have >80% decrease in MADRS scores. One patient failed to have response; evaluation of modulated fiber tracts revealed reduced frontal connectivity to the target region.



This is an interim report, with limited conclusions.



This study of MFB-DBS shows similar rapid anti-depressant effects within the first week of stimulation as initially reported by Schlaepfer et al. (2013). Implementation of anhedonia measurements would greatly augment characterization of the striking motivational effects observed. We urge others to pursue this target to further prove efficacy. ClinicalTrials.gov (identifier: NCT02046330) https://clinicaltrials.gov/ct2/show/NCT02046330.
Department of Neurosurgery, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA. Electronic address: albert.j.fenoy@uth.tmc.edu.
Albert J
AJ
Fenoy
Department of Neurology, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA.
Paul
P
Schulz
Center of Excellence on Mood Disorders, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, University of Texas Health Science Center at Houston, TX, USA.
Sudhakar
S
Selvaraj
Department of Neurology, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA.
Christina
C
Burrows
Center of Excellence on Mood Disorders, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, University of Texas Health Science Center at Houston, TX, USA.
Danielle
D
Spiker
Center of Excellence on Mood Disorders, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, University of Texas Health Science Center at Houston, TX, USA.
Bo
B
Cao
Center of Excellence on Mood Disorders, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, University of Texas Health Science Center at Houston, TX, USA.
Giovanna
G
Zunta-Soares
Center of Excellence on Mood Disorders, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, University of Texas Health Science Center at Houston, TX, USA.
Prashant
P
Gajwani
Center of Excellence on Mood Disorders, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, University of Texas Health Science Center at Houston, TX, USA.
Joao
J
Quevedo
Center of Excellence on Mood Disorders, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, University of Texas Health Science Center at Houston, TX, USA.
Jair
J
Soares
D000328:Adult; D000339:Affect / Q000502:physiology; D046690:Deep Brain Stimulation; D061218:Depressive Disorder, Treatment-Resistant / Q000628:therapy*; D056324:Diffusion Tensor Imaging; D005260:Female; D006801:Humans; D008297:Male; D008474:Medial Forebrain Bundle / Q000502:physiology*; D008875:Middle Aged; D009042:Motivation / Q000502:physiology; D059906:Neuroimaging; D010865:Pilot Projects; D016896:Treatment Outcome
Clinical trial; Deep brain stimulation; Diffusion tensor imaging; Medial forebrain bundle; Tractography; Treatment resistant depression