title: The tremor network targeted by successful VIM deep brain stimulation in humans.
abstract: OBJECTIVE
  Deep brain stimulation (DBS) of the ventral intermediate nucleus of thalamus (VIM) is a treatment option in medically intractable tremor, such as essential tremor or tremor-dominant Parkinson disease (PD). Although functional studies demonstrated modulation of remote regions, the structural network supporting this is as yet unknown. In this observational study, we analyzed the network mediating clinical tremor modulation.
  
  
  METHODS
  We studied 12 patients undergoing VIM stimulation for debilitating tremor. We initiated noninvasive diffusion tractography from tremor-suppressive VIM electrode contacts. Moreover, we tested for the contribution of primary motor projections in this structural correlate of a functional tremor network, comparing the connectivity of effective DBS contacts with those of adjacent, but clinically ineffective, stimulation sites.
  
  
  RESULTS
  VIM stimulation resulted in decrease of tremor and improvement in quality of life. Tractography initiated from the effective stimulation site reconstructed a highly reproducible network of structural connectivity comprising motor cortical, subcortical, and cerebellar sites and the brainstem, forming the anatomic basis for remote effects of VIM stimulation. This network is congruent with functional imaging studies in humans and with thalamic projections found in the animal literature. Connectivity to the primary motor cortex seemed to play a key role in successful stimulation.
  
  
  CONCLUSIONS
  Patients undergoing DBS provide a unique opportunity to assess an electrophysiologically defined seed region in human thalamus, a technique that is usually restricted to animal research. In the future, preoperative tractography could aid with stereotactic planning of individual subcortical target points for stimulation in tremor and in other disease entities.
authors.affiliation: Department of Neurology, Goethe-University Frankfurt, Frankfurt Germany. klein@med.uni-frankfurt.de
authors.forename: J C
authors.initials: JC
authors.lastname: Klein
authors.forename: M T
authors.initials: MT
authors.lastname: Barbe
authors.forename: C
authors.initials: C
authors.lastname: Seifried
authors.forename: S
authors.initials: S
authors.lastname: Baudrexel
authors.forename: M
authors.initials: M
authors.lastname: Runge
authors.forename: M
authors.initials: M
authors.lastname: Maarouf
authors.forename: T
authors.initials: T
authors.lastname: Gasser
authors.forename: E
authors.initials: E
authors.lastname: Hattingen
authors.forename: T
authors.initials: T
authors.lastname: Liebig
authors.forename: R
authors.initials: R
authors.lastname: Deichmann
authors.forename: L
authors.initials: L
authors.lastname: Timmermann
authors.forename: L
authors.initials: L
authors.lastname: Weise
authors.forename: R
authors.initials: R
authors.lastname: Hilker
mesh_terms: D000328:Adult; D000368:Aged; D003627:Data Interpretation, Statistical; D046690:Deep Brain Stimulation / Q000379:methods*; D056324:Diffusion Tensor Imaging; D004567:Electrodes, Implanted; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D009415:Nerve Net / Q000473:pathology*; D009434:Neural Pathways / Q000502:physiology; D014202:Tremor / Q000473:pathology / Q000628:therapy*; D020651:Ventral Thalamic Nuclei / Q000502:physiology*