Abstract
The pedunculopontine nucleus (PPN) is engaged in posture and gait control, and neuronal degeneration in the PPN has been associated with Parkinsonian disorders. Clinical outcomes of deep brain stimulation of the PPN in idiopathic Parkinson’s disease (IPD) and progressive supranuclear palsy (PSP) differ, and we investigated whether the PPN is differentially affected in these conditions. We had the rare opportunity to record continuous electrophysiological data intraoperatively in 30 s blocks from single microelectrode contacts implanted in the PPN in six PSP patients and three IPD patients during rest, passive movement, and active movement. Neuronal spikes were sorted according to shape using a wavelet-based clustering approach to enable comparisons between individual neuronal firing rates in the two disease states. The action potential widths showed a bimodal distribution consistent with previous findings, suggesting spikes from noncholinergic (likely glutamatergic) and cholinergic neurons. A higher PPN spiking rate of narrow action potentials was observed in the PSP than in the IPD patients when pooled across all three conditions (Wilcoxon rank sum test: p = 0.0141). No correlation was found between firing rate and disease severity or duration. The firing rates were higher during passive movement than rest and active movement in both groups, but the differences between conditions were not significant. PSP and IPD are believed to represent distinct disease processes, and our findings that the neuronal firing rates differ according to disease state support the proposal that pathological processes directly involving the PPN may be more pronounced in PSP than IPD.
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IG: conceived of and designed the study and recorded the electrophysiological data; JV: surgically implanted the electrodes; IG, JK, and JV: localized the electrodes using imaging; CMSR: designed and performed the electrophysiological data analysis; IG and CMSR interpreted the data analysis, drafted the manuscript, and revised it critically; JK, JV, HH, and HJH: critically revised the manuscript. All the authors approved the final version of the manuscript.
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The study was approved by the Local Ethics Committee of the Otto-von-Guericke University, Magdeburg, Germany and was performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. All participants gave their informed written consent prior to their inclusion in the study.
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Galazky, I., Kaufmann, J., Voges, J. et al. Neuronal spiking in the pedunculopontine nucleus in progressive supranuclear palsy and in idiopathic Parkinson’s disease. J Neurol 266, 2244–2251 (2019). https://doi.org/10.1007/s00415-019-09396-9
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DOI: https://doi.org/10.1007/s00415-019-09396-9