Abstract
The pedunculopontine nucleus (PPN) is a reticular collection of neurons at the junction of the midbrain and pons, playing an important role in modulating posture and locomotion. Deep brain stimulation of the PPN has been proposed as an emerging treatment for patients with Parkinson's disease (PD) or multiple system atrophy (MSA) who have gait-related atypical parkinsonian syndromes. In this study, we investigated PPN activities during gait to better understand its functional role in locomotion. Specifically, we investigated whether PPN activity is rhythmically modulated by gait cycles during locomotion. PPN local field potential (LFP) activities were recorded from PD or MSA patients with gait difficulties during stepping in place or free walking. Simultaneous measurements from force plates or accelerometers were used to determine the phase within each gait cycle at each time point. Our results showed that activities in the alpha and beta frequency bands in the PPN LFPs were rhythmically modulated by the gait phase within gait cycles, with a higher modulation index when the stepping rhythm was more regular. Meanwhile, the PPN–cortical coherence was most prominent in the alpha band. Both gait phase-related modulation in the alpha/beta power and the PPN–cortical coherence in the alpha frequency band were spatially specific to the PPN and did not extend to surrounding regions. These results suggest that alternating PPN modulation may support gait control. Whether enhancing alternating PPN modulation by stimulating in an alternating fashion could positively affect gait control remains to be tested.
| Original language | English |
|---|---|
| Pages (from-to) | 8390-8402 |
| Number of pages | 13 |
| Journal | Journal of Neuroscience |
| Volume | 41 |
| Issue number | 40 |
| Early online date | 19 Aug 2021 |
| DOIs | |
| Publication status | Published - 6 Oct 2021 |
Bibliographical note
Funding Information:Received Apr. 6, 2021; revised June 21, 2021; accepted Aug. 4, 2021. Author contributions: P.F., P.B., and H.T. designed research; S.H., A.D., P.F., Y.H., S.M., T.Z.A., A.L.G., and H.T. performed research; S.H. contributed unpublished reagents/analytic tools; S.H., A.D., C.W., and S.K. analyzed data; S.H., A.D., P.F., C.W., Y.H., S.M., S.K., T.Z.A., A.L.G., P.B., and H.T. wrote the paper. This work was supported by the MRC (Grants MR/P012272/1 and MC_UU_00003/2), the National Institute for Health Research (Oxford Biomedical Research Center), and the Rosetrees Trust. P.B. is a consultant for Medtronic. The authors declare no other competing financial interests. Correspondence should be addressed to Huiling Tan at [email protected]. https://doi.org/10.1523/JNEUROSCI.0770-21.2021 Copyright © 2021 He et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
Publisher Copyright:
© 2021 He et al.