title: Axonal pathways linked to therapeutic and nontherapeutic outcomes during psychiatric deep brain stimulation.
abstract: OBJECTIVE
  The underlying hypothesis of our work is that specific clinical neuropsychiatric benefits can be achieved by selective activation of specific axonal pathways during deep brain stimulation (DBS). As such, the goal of this study was to develop a method for identifying axonal pathways whose activation is most likely necessary for achieving therapeutic benefits during DBS.
  
  
  METHODS
  Our approach combined clinical data, diffusion tensor tractography, and computer models of patient-specific neurostimulation to identify particular axonal pathways activated by DBS and determine their correlations with individual clinical outcome measures. We used this method to evaluate a cohort of seven treatment-resistant depression patients treated with DBS of the ventral anterior internal capsule and ventral striatum (VC/VS).
  
  
  RESULTS
  Clinical responders exhibited five axonal pathways that were consistently activated by DBS. All five pathways coursed lateral and medial to the VS or dorsal and lateral to the nucleus accumbens; however, details of their specific trajectories differed. Similarly, one common pathway was identified across nonresponders.
  
  
  CONCLUSIONS
  Our method and preliminary results provide important background for studies aiming to expand scientific characterization of neural circuitry associated with specific psychiatric outcomes from DBS. Furthermore, identification of pathways linked to therapeutic benefit provides opportunities to improve clinical selection of surgical targets and stimulation settings for DBS devices.
authors.affiliation: Department of Biomedical Engineering, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
authors.forename: J Luis
authors.initials: JL
authors.lastname: Lujan
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Chaturvedi
authors.forename: Donald A
authors.initials: DA
authors.lastname: Malone
authors.forename: Ali R
authors.initials: AR
authors.lastname: Rezai
authors.forename: Andre G
authors.initials: AG
authors.lastname: Machado
authors.forename: Cameron C
authors.initials: CC
authors.lastname: McIntyre
mesh_terms: D000328:Adult; D001369:Axons; D001931:Brain Mapping; D002986:Clinical Trials as Topic; D003198:Computer Simulation; D046690:Deep Brain Stimulation; D003863:Depression / Q000473:pathology* / Q000628:therapy; D056324:Diffusion Tensor Imaging; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008959:Models, Neurological; D009434:Neural Pathways / Q000166:cytology*; D016896:Treatment Outcome; D055815:Young Adult