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
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
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
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).
