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Imagined gait modulates neuronal network dynamics in the human pedunculopontine nucleus

Abstract

The pedunculopontine nucleus (PPN) is a part of the mesencephalic locomotor region and is thought to be important for the initiation and maintenance of gait. Lesions of the PPN induce gait deficits, and the PPN has therefore emerged as a target for deep brain stimulation for the control of gait and postural disability. However, the role of the PPN in gait control is not understood. Using extracellular single-unit recordings in awake patients, we found that neurons in the PPN discharged as synchronous functional networks whose activity was phase locked to alpha oscillations. Neurons in the PPN responded to limb movement and imagined gait by dynamically changing network activity and decreasing alpha phase locking. Our results indicate that different synchronous networks are activated during initial motor planning and actual motion, and suggest that changes in gait initiation in Parkinson's disease may result from disrupted network activity in the PPN.

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Figure 1: Single units in the human PPN respond to both passive movement and imagined gait.
Figure 2: Distinct networks of neurons in the PPN are engaged during movement and imagined gait.
Figure 3: LFP oscillation is more prevalent in caudal PPN and phase locks neural activity.

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Acknowledgements

We are grateful to all of the patients for agreeing to participate in this study. We thank R. Tweedale and P. Martin for comments on the manuscript. This work was supported by grants from the Australian National Health and Medical Research Council and Australian Research Council.

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Authors and Affiliations

Authors

Contributions

T.J.C. and R.C. performed all of the surgical procedures. P.A.S. and P. Silberstein recruited patients and chose targets for recording, and performed all of the intraoperative clinical assessment. T.L.T. collected and analyzed data and wrote the manuscript. F.W. collected and analyzed data. P.G.S. helped to analyze the data. P. Sah analyzed the data and wrote the manuscript.

Corresponding author

Correspondence to Pankaj Sah.

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The authors declare no competing financial interests.

Integrated supplementary information

Supplementary Figure 1 Units in the pedunculopontine nucleus form two populations based on spike width.

a, Autocorrelograms of two exemplar units accepted for analysis, showing refractory period greater than 1 ms. b, Example of a single unit with spike width indicated. The panel on the right shows the histogram of spike widths for all well-isolated units in the PPN. The overall distribution of spike widths was best fit with two Gaussians with means of 168 ± 17 and 226 ± 48 µs (red curves). These two distributions had significant overlap and we separated units into those with narrow-spikes (spike duration < 225 μs) and those with wide-spikes (spike duration > 225 μs).

Supplementary Figure 2 Both narrow and wide units can respond to passive movement and imagined gait.

Pie charts depict numbers of wide and narrow units for which the firing rate either increased (black), decreased (white) or showed no change (grey). In total, 76 narrow, and 10 wide-spike neurons were tested during passive limb movement. For narrow-spike units, 13 (17%) responded with an increase in discharge while 36 (47%) were inhibited. For wide-spike units, only 1 (10 %) responded with increase in discharge while 4 (40%) showed a decrease in discharge. During imagined gait we tested 80 narrow-spike units and 14 wide-spike units. For narrow-spike units 14 (18%) responded with an increase in firing rate, while 44 (55%) had a decrease in firing during imagined gait. For wide-spike neurons 2/14 (14%) increased their discharge during imagined gait and 7/14 (50%) were inhibited during imagined gait.

Supplementary Figure 3 Imagined gait has no associated movement.

a, Rectified EMG activity is shown from quadriceps muscles in the lower limb during rest, imagined gait, voluntary movement and return to rest. EMG power is shown in (b). It can be seen that EMG power does not change during imagined gait but increases during movement of the limb.

Supplementary Figure 4 Neurons in the PPN discharge in networks.

a, Recording from the caudal PPN in which five units were isolated. b, Correlated activity between two of the pairs (units 2 and 3; units 2 and 4) is shown by cross-correlations analysis. c, Network diagram showing the presence of correlated unit activity between 4 neurons in the network of the 5 neurons shown in (a). Wide-spiking neurons are indicated by red circles, and narrow-spiking neurons by blue circles.

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Tattersall, T., Stratton, P., Coyne, T. et al. Imagined gait modulates neuronal network dynamics in the human pedunculopontine nucleus. Nat Neurosci 17, 449–454 (2014). https://doi.org/10.1038/nn.3642

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