title: Reduced paired pulse depression in the basal ganglia of dystonia patients.
abstract: Decreased inhibition and aberrant plasticity are key features in the pathophysiology of dystonia. Impaired short interval cortical inhibition and resultant increased excitability have been described for various forms of dystonia using paired pulse methods with transcranial magnetic stimulation of motor cortex. It is hypothesized that, in addition to cortical abnormalities, impairments in basal ganglia function may lead to dystonia but a deficit of inhibition within the basal ganglia has not been demonstrated to date. To examine the possibility that impaired inhibition and synaptic plasticity within the basal ganglia play a role in dystonia, the present study used a pair of microelectrodes to test paired pulse inhibition in the globus pallidus interna (GPi) and substantia nigra pars reticulata (SNr) of dystonia and PD patients undergoing implantation of deep brain stimulating (DBS) electrodes. We found that there was less paired pulse depression of local field evoked potentials in the basal ganglia output nuclei of dystonia patients compared with Parkinson's disease patients on dopaminergic medication. Paired pulse depression could be restored following focal high frequency stimulation (HFS). These findings suggest that abnormalities exist in synaptic function of striatopallidal and/or striatonigral terminals in dystonia patients and that these abnormalities may contribute to the pathophysiology of dystonia, either independent of, or in addition to the increased excitability and plasticity observed in cortical areas in dystonia patients. These findings also suggest that HFS is capable of enhancing striatopallidal and striatonigral GABA release in basal ganglia output nuclei, indicating a possible mechanism for the therapeutic benefits of DBS in the GPi of dystonia patients.
authors.affiliation: Department of Physiology, University of Toronto, Canada.
authors.forename: I A
authors.initials: IA
authors.lastname: Prescott
authors.forename: J O
authors.initials: JO
authors.lastname: Dostrovsky
authors.forename: E
authors.initials: E
authors.lastname: Moro
authors.forename: M
authors.initials: M
authors.lastname: Hodaie
authors.forename: A M
authors.initials: AM
authors.lastname: Lozano
authors.forename: W D
authors.initials: WD
authors.lastname: Hutchison
mesh_terms: D000328:Adult; D000368:Aged; D001479:Basal Ganglia / Q000503:physiopathology*; D004421:Dystonia / Q000503:physiopathology*; D005071:Evoked Potentials / Q000502:physiology; D005260:Female; D006801:Humans; D036881:Long-Term Synaptic Depression / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D055815:Young Adult