title: Stimulation through electrodes implanted near the subthalamic nucleus activates projections to motor areas of cerebral cortex in patients with Parkinson's disease.
abstract: High-frequency electrical stimulation through electrodes implanted in the subthalamic nucleus (STN) has been shown to reduce significantly the cardinal symptoms of Parkinson's disease (PD). Despite the success of this treatment, the mechanisms of action of stimulation are poorly understood. To elucidate further the mechanisms of action of deep brain stimulation and its effects on cortical activity, we recorded electroencephalographic potentials from 61 scalp-surface electrodes during low-frequency (5-10 Hz) bipolar stimulation in 11 patients with advanced PD (14 implanted electrodes were tested). In all electrodes tested, stimulation through at least one of the four contacts produced a medium-latency waveform with an average onset of 14 +/- 3 ms and peak at 23 +/- 4 ms. This potential typically increased in magnitude across contacts from ventral to dorsal. Within-subject comparisons of median nerve somatosensory evoked potentials demonstrated that the generator of the medium-latency potential was within the primary sensorimotor cortex or lateral premotor cortex ipsilateral to stimulation. The timing and topography of this potential were consistent with indirect activation of the cortex by excitation of pallido-thalamic axons that traverse the dorsal aspect of the STN. The potential evoked by stimulation through the contact used for optimal clinical effect was highly variable across electrodes and frequently different from the medium-latency potential described above, suggesting that the neuronal elements mediating the medium-latency potential were different from those that mediate the clinical effects.
authors.affiliation: Department of Physical Therapy and Human Movement Sciences, Feinberg School of Medicine, Northwestern University, 645 North Michigan Avenue, Suite 1100, Chicago, IL 60611, USA. c-mackinnon@northwestern.edu
authors.forename: Colum D
authors.initials: CD
authors.lastname: MacKinnon
authors.forename: Ruth M
authors.initials: RM
authors.lastname: Webb
authors.forename: Paul
authors.initials: P
authors.lastname: Silberstein
authors.forename: Steven
authors.initials: S
authors.lastname: Tisch
authors.forename: Peter
authors.initials: P
authors.lastname: Asselman
authors.forename: Patricia
authors.initials: P
authors.lastname: Limousin
authors.forename: John C
authors.initials: JC
authors.lastname: Rothwell
mesh_terms: D000328:Adult; D000344:Afferent Pathways / Q000503:physiopathology / Q000528:radiation effects*; D000368:Aged; D001931:Brain Mapping; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation / Q000379:methods*; D004567:Electrodes, Implanted; D004569:Electroencephalography / Q000379:methods; D005073:Evoked Potentials, Somatosensory / Q000502:physiology / Q000528:radiation effects; D005260:Female; D007839:Functional Laterality; D006801:Humans; D008297:Male; D008475:Median Nerve / Q000528:radiation effects; D008875:Middle Aged; D009044:Motor Cortex / Q000503:physiopathology / Q000528:radiation effects*; D010300:Parkinson Disease / Q000503:physiopathology* / Q000628:therapy; D011930:Reaction Time / Q000502:physiology / Q000528:radiation effects; D013057:Spectrum Analysis; D020531:Subthalamic Nucleus / Q000528:radiation effects*; D013997:Time Factors