title: Quantitative analysis of axonal fiber activation evoked by deep brain stimulation via activation density heat maps.
abstract: BACKGROUND
  Cortical modulation is likely to be involved in the various therapeutic effects of deep brain stimulation (DBS). However, it is currently difficult to predict the changes of cortical modulation during clinical adjustment of DBS. Therefore, we present a novel quantitative approach to estimate anatomical regions of DBS-evoked cortical modulation.
  
  
  METHODS
  Four different models of the subthalamic nucleus (STN) DBS were created to represent variable electrode placements (model I: dorsal border of the posterolateral STN; model II: central posterolateral STN; model III: central anteromedial STN; model IV: dorsal border of the anteromedial STN). Axonal fibers of passage near each electrode location were reconstructed using probabilistic tractography and modeled using multi-compartment cable models. Stimulation-evoked activation of local axon fibers and corresponding cortical projections were modeled and quantified.
  
  
  RESULTS
  Stimulation at the border of the STN (models I and IV) led to a higher degree of fiber activation and associated cortical modulation than stimulation deeply inside the STN (models II and III). A posterolateral target (models I and II) was highly connected to cortical areas representing motor function. Additionally, model I was also associated with strong activation of fibers projecting to the cerebellum. Finally, models III and IV showed a dorsoventral difference of preferentially targeted prefrontal areas (models III: middle frontal gyrus; model IV: inferior frontal gyrus).
  
  
  CONCLUSIONS
  The method described herein allows characterization of cortical modulation across different electrode placements and stimulation parameters. Furthermore, knowledge of anatomical distribution of stimulation-evoked activation targeting cortical regions may help predict efficacy and potential side effects, and therefore can be used to improve the therapeutic effectiveness of individual adjustments in DBS patients.
authors.affiliation: Department of Biomedical Engineering, Cleveland Clinic Foundation Cleveland, OH, USA ; Department of Neurology, Medical Faculty, Heinrich-Heine University Düsseldorf Düsseldorf, Germany ; Medical Faculty, Institute of Clinical Neuroscience and Medical Psychology, Heinrich-Heine-University Düsseldorf Düsseldorf, Germany.
authors.forename: Christian J
authors.initials: CJ
authors.lastname: Hartmann
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 Neurologic Surgery, Mayo Clinic Rochester, MN, USA ; Department of Physiology and Biomedical Engineering, Mayo Clinic Rochester, MN, USA.
authors.forename: J Luis
authors.initials: JL
authors.lastname: Lujan
keywords: axonal activation; computational model; cortical excitability; deep brain stimulation; individualized medicine