title: Anatomical targets associated with abrupt versus gradual washout of subthalamic deep brain stimulation effects on bradykinesia.
abstract: The subthalamic nucleus (STN) is a common anatomical target for deep brain stimulation (DBS) for the treatment of Parkinson's disease. However, the effects of stimulation may spread beyond the STN. Ongoing research aims to identify nearby anatomical structures where DBS-induced effects could be associated with therapeutic improvement or side effects. We previously found that DBS lead location determines the rate--abrupt vs. gradual--with which therapeutic effect washes out after stimulation is stopped. Those results suggested that electrical current spreads from the electrodes to two spatially distinct stimulation targets associated with different washout rates. In order to identify these targets we used computational models to predict the volumes of tissue activated during DBS in 14 Parkinson's patients from that study. We then coregistered each patient with a stereotaxic atlas and generated a probabilistic stimulation atlas to obtain a 3-dimensional representation of regions where stimulation was associated with abrupt vs. gradual washout. We found that the therapeutic effect which washed out gradually was associated with stimulation of the zona incerta and fields of Forel, whereas abruptly-disappearing therapeutic effect was associated with stimulation of STN itself. This supports the idea that multiple DBS targets exist and that current spread from one electrode may activate more than one of them in a given patient, producing a combination of effects which vary according to electrode location and stimulation settings.
authors.affiliation: Cleveland Clinic, Center for Neurological Restoration, Cleveland, Ohio, United States of America.
authors.forename: Scott E
authors.initials: SE
authors.lastname: Cooper
authors.affiliation: Medical College of Wisconsin, Departments of Neurology & Neurosurgery, Biotechnology and Bioengineering Center, Milwaukee, Wisconsin, United States of America.
authors.forename: Klaus G
authors.initials: KG
authors.lastname: Driesslein
authors.affiliation: Case Western Reserve University, Department of Biomedical Engineering, Cleveland, Ohio, United States of America.
authors.forename: Angela M
authors.initials: AM
authors.lastname: Noecker
authors.affiliation: Case Western Reserve University, Department of Biomedical Engineering, Cleveland, Ohio, United States of America.
authors.forename: Cameron C
authors.initials: CC
authors.lastname: McIntyre
authors.affiliation: Cleveland Clinic, Center for Neurological Restoration, Cleveland, Ohio, United States of America.
authors.forename: Andre M
authors.initials: AM
authors.lastname: Machado
authors.affiliation: Medical College of Wisconsin, Departments of Neurology & Neurosurgery, Biotechnology and Bioengineering Center, Milwaukee, Wisconsin, United States of America.
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Butson
mesh_terms: D000368:Aged; D046690:Deep Brain Stimulation; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D018476:Hypokinesia / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D020531:Subthalamic Nucleus / Q000473:pathology / Q000503:physiopathology
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