title: Tractography Activation Patterns in Dorsolateral Prefrontal Cortex Suggest Better Clinical Responses in OCD DBS.
abstract: BACKGROUND
  Medication resistant obsessive-compulsive disorder (OCD) patients can be successfully treated with Deep Brain Stimulation (DBS) which targets the anterior limb of the internal capsule (ALIC) and the nucleus accumbens (NA). Growing evidence suggests that in patients who respond to DBS, axonal fiber bundles surrounding the electrode are activated, but it is currently unknown which discrete pathways are critical for optimal benefit. Our aim was to identify axonal pathways mediating clinical effects of ALIC-NA DBS.
  
  
  METHODS
  We created computational models of ALIC-NA DBS to simulate the activation of fiber tracts and to identify connected cerebral regions. The pattern of activated axons and their cortical targets was investigated in six OCD patients who underwent ALIC-NA DBS.
  
  
  RESULTS
  Modulation of the right anterior middle frontal gyrus (dorsolateral prefrontal cortex) was associated with an excellent response. In contrast, non-responders showed high activation in the orbital part of the right inferior frontal gyrus (lateral orbitofrontal cortex/anterior ventrolateral prefrontal cortex). Factor analysis followed by step-wise linear regression indicated that YBOCS improvement was inversely associated with factors that were predominantly determined by gray matter activation results.
  
  
  CONCLUSIONS
  Our findings support the hypothesis that optimal therapeutic results are associated with the activation of distinct fiber pathways. This suggests that in DBS for OCD, focused stimulation of specific fiber pathways, which would allow for stimulation with lower amplitudes, may be superior to activation of a wide array of pathways, typically associated with higher stimulation amplitudes.
authors.affiliation: Department of Biomedical Engineering, Cleveland Clinic FoundationCleveland, OH, USA; Department of Neurology, Medical Faculty, Institute of Clinical Neuroscience and Medical Psychology, Heinrich-Heine University DüsseldorfDüsseldorf, Germany.
authors.forename: Christian J
authors.initials: CJ
authors.lastname: Hartmann
authors.affiliation: Department of Neurologic Surgery, Mayo ClinicRochester, MN, USA; Department of Physiology and Biomedical Engineering, Mayo ClinicRochester, MN, USA.
authors.forename: J Luis
authors.initials: JL
authors.lastname: Lujan
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University Cleveland, OH, USA.
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Chaturvedi
authors.affiliation: Department of Psychiatry, Friedman Brain Institute and Mount Sinai School of Medicine New York, NY, USA.
authors.forename: Wayne K
authors.initials: WK
authors.lastname: Goodman
authors.affiliation: Department of Neurology and Neurosurgery, Center for Movement Disorders and Neurorestoration, University of Florida Gainesville, FL, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Okun
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University Cleveland, OH, USA.
authors.forename: Cameron C
authors.initials: CC
authors.lastname: McIntyre
authors.affiliation: Department of Neurology, Wake Forest University School of Medicine Winston-Salem, NC, USA.
authors.forename: Ihtsham U
authors.initials: IU
authors.lastname: Haq
keywords: clinical efficacy; deep brain stimulation; obsessive-compulsive disorder; tractography; simulation
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