title: The Cognitive Role of the Globus Pallidus interna; Insights from Disease States.
abstract: The motor symptoms of both Parkinson's disease and focal dystonia arise from dysfunction of the basal ganglia, and are improved by pallidotomy or deep brain stimulation of the Globus Pallidus interna (GPi). However, Parkinson's disease is associated with a greater degree of basal ganglia-dependent learning impairment than dystonia. We attempt to understand this observation in terms of a comparison of the electrophysiology of the output of the basal ganglia between the two conditions. We use the natural experiment offered by Deep Brain Stimulation to compare GPi local field potential responses in subjects with Parkinson's disease compared to subjects with dystonia performing a forced-choice decision-making task with sensory feedback. In dystonic subjects, we found that auditory feedback was associated with the presence of high gamma oscillations nestled on a negative deflection, morphologically similar to sharp wave ripple complexes described in human rhinal cortex. These were not present in Parkinson's disease subjects. The temporal properties of the high gamma burst were modified by incorrect trial performance compared to correct trial performance. Both groups exhibited a robust low frequency response to 'incorrect' trial performance in dominant GPi but not non-dominant GPi at theta frequency. Our results suggest that cellular processes associated with striatum-dependent memory function may be selectively impaired in Parkinson's disease even if dopaminergic drugs are administered, but that error detection mechanisms are preserved.
authors.affiliation: Nuffield Department of Surgical Sciences, West Wing, John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DU, UK.
authors.forename: M J
authors.initials: MJ
authors.lastname: Gillies
authors.affiliation: Nuffield Department of Surgical Sciences, West Wing, John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DU, UK.|Victor Horsley Department of Neurosurgery, Institute of Neurology, Queen Square, UCL, London, UK.
authors.forename: J A
authors.initials: JA
authors.lastname: Hyam
authors.affiliation: Nuffield Department of Surgical Sciences, West Wing, John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DU, UK.
authors.forename: A R
authors.initials: AR
authors.lastname: Weiss
authors.affiliation: Nuffield Department of Clinical Neuroscience, West Wing, John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DU, UK.
authors.forename: C A
authors.initials: CA
authors.lastname: Antoniades
authors.affiliation: Nuffield Department of Clinical Neuroscience, West Wing, John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DU, UK.
authors.forename: R
authors.initials: R
authors.lastname: Bogacz
authors.affiliation: Nuffield Department of Surgical Sciences, West Wing, John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DU, UK.|Nuffield Department of Clinical Neuroscience, West Wing, John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DU, UK.|Department of Neurosurgery, West Wing Level 3, John Radcliffe Hospital, Oxford, OX3 9DU, UK.
authors.forename: J J
authors.initials: JJ
authors.lastname: Fitzgerald
authors.affiliation: Nuffield Department of Surgical Sciences, West Wing, John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DU, UK.|Nuffield Department of Clinical Neuroscience, West Wing, John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DU, UK.
authors.forename: T Z
authors.initials: TZ
authors.lastname: Aziz
authors.affiliation: Hull York Medical School, University of York, Heslington, York, YO10 5DD, UK.
authors.forename: M A
authors.initials: MA
authors.lastname: Whittington
authors.affiliation: Nuffield Department of Surgical Sciences, West Wing, John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DU, UK. alex.green@nds.ox.ac.uk.|Nuffield Department of Clinical Neuroscience, West Wing, John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DU, UK. alex.green@nds.ox.ac.uk.|Department of Neurosurgery, West Wing Level 3, John Radcliffe Hospital, Oxford, OX3 9DU, UK. alex.green@nds.ox.ac.uk.
authors.forename: Alexander L
authors.identifier: 0000-0002-7262-7297
authors.initials: AL
authors.lastname: Green
mesh_terms: D000328:Adult; D000368:Aged; D003071:Cognition / Q000502:physiology*; D046690:Deep Brain Stimulation / Q000379:methods*; D020821:Dystonic Disorders / Q000000981:diagnostic imaging / Q000628:therapy*; D005071:Evoked Potentials / Q000502:physiology; D005260:Female; D005917:Globus Pallidus / Q000000981:diagnostic imaging / Q000502:physiology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010300:Parkinson Disease / Q000000981:diagnostic imaging / Q000628:therapy*; D010812:Physical Stimulation; D011930:Reaction Time / Q000502:physiology; D015898:Tomography Scanners, X-Ray Computed; D055815:Young Adult
keywords: Cognition; Deep brain stimulation; Dystonia; Globus Pallidus; Parkinson’s disease