The pedunculopontine region and breathing in Parkinson's disease

Ann Clin Transl Neurol. 2019 May 1;6(5):837-847. doi: 10.1002/acn3.752. eCollection 2019 May.

Abstract

Objective: Respiratory abnormalities such as upper airway obstruction are common in Parkinson's disease (PD) and are an important cause of mortality and morbidity. We tested the effect of pedunculopontine region (PPNr) stimulation on respiratory maneuvers in human participants with PD, and separately recorded PPNr neural activity reflected in the local field potential (LFP) during these maneuvers.

Methods: Nine patients with deep brain stimulation electrodes in PPNr, and seven in globus pallidus interna (GPi) were studied during trials of maximal inspiration followed by forced expiration with stimulation OFF and ON. Local field potentials (LFPs) were recorded in the unstimulated condition.

Results: PEFR increased from 6.41 ± 0.63 L/sec in the OFF stimulation state to 7.5 L ± 0.65 L/sec in the ON stimulation state (z = -2.666, df = 8, P = 0.024). Percentage improvement in PEFR was strongly correlated with proximity of the stimulated electrode contact to the mesencephalic locomotor region in the rostral PPN (r = 0.814, n = 9, P = 0.008). Mean PPNr LFP power increased within the alpha band (7-11 Hz) during forced respiratory maneuvers (1.63 ± 0.16 μV2/Hz) compared to resting breathing (0.77 ± 0.16 μV2/Hz; z = -2.197, df = 6, P = 0.028). No changes in alpha activity or spirometric indices were seen with GPi recording or stimulation. Percentage improvement in PEFR was strongly positively correlated with increase in alpha power (r = 0.653, n = 14 (7 PPNr patients recorded bilaterally), P = 0.0096).

Interpretation: PPNr stimulation in PD improves indices of upper airway function. Increased alpha-band activity is seen within the PPNr during forced respiratory maneuvers. Our findings suggest a link between the PPNr and respiratory performance in PD.

MeSH terms

  • Aged
  • Airway Obstruction / therapy*
  • Deep Brain Stimulation / methods
  • Electric Stimulation
  • Female
  • Globus Pallidus / physiology*
  • Humans
  • Lung
  • Male
  • Middle Aged
  • Parkinson Disease / complications*
  • Parkinson Disease / physiopathology*
  • Pedunculopontine Tegmental Nucleus / physiology*
  • Respiration

Grants and funding

This work was funded by Medtronic grant ; Oxford Biomedical Research Centre grant ; Norman Collisson Foundation grant ; Wolfson Charitable Trust grant ; National Health and Medical Research Council (Australia) grant .