Interrogating basal ganglia circuit function in people with Parkinson’s disease and dystonia

Srdjan Sumarac; Kiah A Spencer; Leon A Steiner; Conor Fearon; Emily A Haniff; Andrea A Kühn; Mojgan Hodaie; Suneil K Kalia; Andres Lozano; Alfonso Fasano; William Duncan Hutchison; Luka Milosevic

doi:10.7554/eLife.90454

eLife (Aug 2024)

Interrogating basal ganglia circuit function in people with Parkinson’s disease and dystonia

Srdjan Sumarac,
Kiah A Spencer,
Leon A Steiner,
Conor Fearon,
Emily A Haniff,
Andrea A Kühn,
Mojgan Hodaie,
Suneil K Kalia,
Andres Lozano,
Alfonso Fasano,
William Duncan Hutchison,
Luka Milosevic

Affiliations

Srdjan Sumarac: ORCiD; Institute of Biomedical Engineering, University of Toronto, Toronto, Canada; Krembil Brain Institute, University Health Network, Toronto, Canada
Kiah A Spencer: Institute of Biomedical Engineering, University of Toronto, Toronto, Canada; Krembil Brain Institute, University Health Network, Toronto, Canada
Leon A Steiner: Krembil Brain Institute, University Health Network, Toronto, Canada; Department of Neurology and Experimental Neurology, Charité-Universitätsmedizin Berlin, Berlin, Germany; Berlin Institute of Health (BIH), Berlin, Germany
Conor Fearon: Krembil Brain Institute, University Health Network, Toronto, Canada; Edmond J. Safra Program in Parkinson's Disease, Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, Toronto, Canada; Department of Neurology, University of Toronto, Toronto, Canada
Emily A Haniff: Krembil Brain Institute, University Health Network, Toronto, Canada
Andrea A Kühn: Department of Neurology and Experimental Neurology, Charité-Universitätsmedizin Berlin, Berlin, Germany
Mojgan Hodaie: Krembil Brain Institute, University Health Network, Toronto, Canada; Institute of Medical Sciences, University of Toronto, Toronto, Canada; Center for Advancing Neurotechnological Innovation to Application (CRANIA), Toronto, Canada; Department of Surgery, University of Toronto, Toronto, Canada
Suneil K Kalia: Krembil Brain Institute, University Health Network, Toronto, Canada; Center for Advancing Neurotechnological Innovation to Application (CRANIA), Toronto, Canada; Department of Surgery, University of Toronto, Toronto, Canada; KITE, University Health Network, Toronto, Canada
Andres Lozano: Krembil Brain Institute, University Health Network, Toronto, Canada; Institute of Medical Sciences, University of Toronto, Toronto, Canada; Center for Advancing Neurotechnological Innovation to Application (CRANIA), Toronto, Canada; Department of Surgery, University of Toronto, Toronto, Canada
Alfonso Fasano: Krembil Brain Institute, University Health Network, Toronto, Canada; Edmond J. Safra Program in Parkinson's Disease, Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, Toronto, Canada; Department of Neurology, University of Toronto, Toronto, Canada; Institute of Medical Sciences, University of Toronto, Toronto, Canada; Center for Advancing Neurotechnological Innovation to Application (CRANIA), Toronto, Canada
William Duncan Hutchison: ORCiD; Krembil Brain Institute, University Health Network, Toronto, Canada; Center for Advancing Neurotechnological Innovation to Application (CRANIA), Toronto, Canada; Department of Surgery, University of Toronto, Toronto, Canada; Department of Physiology, University of Toronto, Toronto, Canada
Luka Milosevic: ORCiD; Institute of Biomedical Engineering, University of Toronto, Toronto, Canada; Krembil Brain Institute, University Health Network, Toronto, Canada; Institute of Medical Sciences, University of Toronto, Toronto, Canada; Center for Advancing Neurotechnological Innovation to Application (CRANIA), Toronto, Canada; KITE, University Health Network, Toronto, Canada

DOI: https://doi.org/10.7554/eLife.90454
Journal volume & issue: Vol. 12

Abstract

Read online

Background: The dichotomy between the hypo- versus hyperkinetic nature of Parkinson’s disease (PD) and dystonia, respectively, is thought to be reflected in the underlying basal ganglia pathophysiology. In this study, we investigated differences in globus pallidus internus (GPi) neuronal activity, and short- and long-term plasticity of direct pathway projections. Methods: Using microelectrode recording data collected from the GPi during deep brain stimulation surgery, we compared neuronal spiketrain features between people with PD and those with dystonia, as well as correlated neuronal features with respective clinical scores. Additionally, we characterized and compared readouts of short- and long-term synaptic plasticity using measures of inhibitory evoked field potentials. Results: GPi neurons were slower, burstier, and less regular in dystonia. In PD, symptom severity positively correlated with the power of low-beta frequency spiketrain oscillations. In dystonia, symptom severity negatively correlated with firing rate and positively correlated with neuronal variability and the power of theta frequency spiketrain oscillations. Dystonia was moreover associated with less long-term plasticity and slower synaptic depression. Conclusions: We substantiated claims of hyper- versus hypofunctional GPi output in PD versus dystonia, and provided cellular-level validation of the pathological nature of theta and low-beta oscillations in respective disorders. Such circuit changes may be underlain by disease-related differences in plasticity of striato-pallidal synapses. Funding: This project was made possible with the financial support of Health Canada through the Canada Brain Research Fund, an innovative partnership between the Government of Canada (through Health Canada) and Brain Canada, and of the Azrieli Foundation (LM), as well as a grant from the Banting Research Foundation in partnership with the Dystonia Medical Research Foundation (LM).

Published in eLife

ISSN: 2050-084X (Online)
Publisher: eLife Sciences Publications Ltd
Country of publisher: United Kingdom
LCC subjects: Medicine; Science: Biology (General)
Website: https://elifesciences.org

About the journal

Abstract

Keywords