The pedunculopontine region and breathing in Parkinson's disease

Hyam, Jonathan A.; Wang, Shouyan; Roy, Holly; Moosavi, Shakeeb H.; Martin, Sean; Brittain, John-Stuart; Coyne, Terry; Silburn, Peter A.; Aziz, Tipu Z.; Green, Alexander L.

doi:10.1002/acn3.752

Cited by 9 publications

(4 citation statements)

References 38 publications

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“…Furthermore, the coupling between neural activity and respiration may facilitate our understanding of brain disease. Hyam et al stimulated the pedunculopontine region (PPNr) and observed improvement in upper airway function in Parkinson’s patients ( Hyam et al, 2019 ). Loss of neurons in the preBötzinger complex was found to cause sleep-disordered breathing ( McKay et al, 2005 ).…”

Section: Discussionmentioning

confidence: 99%

Neural underpinning of a respiration-associated resting-state fMRI network

Zhang

2022

eLife

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Respiration can induce motion and CO2 fluctuation during resting-state fMRI (rsfMRI) scans, which will lead to non-neural artifacts in the rsfMRI signal. In the meantime, as a crucial physiologic process, respiration that can directly drive neural activity change in the brain, and may thereby modulate the rsfMRI signal. Nonetheless, this potential neural component in the respiration-fMRI relationship is largely unexplored. To elucidate this issue, here we simultaneously recorded the electrophysiology, rsfMRI and respiration signals in rats. Our data show that respiration is indeed associated with neural activity changes, evidenced by a phase-locking relationship between slow respiration variations and the gamma-band power of the electrophysiologic signal recorded in the anterior cingulate cortex. Intriguingly, slow respiration variations are also linked to a characteristic rsfMRI network, which is mediated by gamma-band neural activity. In addition, this respiration-related brain network disappears when brain-wide neural activity is silenced at an iso-electrical state, while the respiration is maintained, further confirming the necessary role of neural activity in this network. Taken together, this study identifies a respiration-related brain network underpinned by neural activity, which represents a novel component in the respiration-rsfMRI relationship that is distinct from respiration-related rsfMRI artifacts. It opens a new avenue for investigating the interactions between respiration, neural activity and resting-state brain networks in both healthy and diseased conditions.

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Section: Discussionmentioning

confidence: 99%

Neural underpinning of a respiration-associated resting-state fMRI network

Zhang

2022

eLife

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“…They were implanted with 1.5 mm-spaced St. Jude Medical Infinity directional DBS electrodes (Abbott, Plano,TX) as part of a clinical trial examining autonomic and motor function in MSA (STAG-MSA NCT03593512). We have previously described our surgical approach and technique 29 . Electrode placement was clinically confirmed after implantation by the fusion of preoperative magnetic resonance imaging (MRI) and postoperative computed tomography (CT) scans.…”

Section: Participantsmentioning

confidence: 99%

Tailoring Human Sleep: selective alteration through Brainstem Arousal Circuit Stimulation

Deli

Duchet

et al. 2023

Preprint

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Brainstem nuclei, such as the pedunculopontine nucleus, send activating projections to cortex, modulating states of sleep, wakefulness and arousal levels. Surgical modulation of subcortical activity using deep brain stimulation (DBS) is utilised in the management of pain and movement disorders. DBS of brainstem arousal circuits in a state-dependent manner could offer an attractive alternative in severe pharmacoresistant cases of hypersomnia and in disorders of consciousness, where behavioural activation is desired. We wanted to investigate if we can selectively induce wakefulness and/or alter sleep state through DBS of the PPN region (PPNR). To this end, we used the opportunity of implanted PPNR electrodes in stimulation-naive patients with multiple systems atrophy. PPNR activity was recorded during both slow wave sleep (SWS) and quiet wakefulness with simultaneous cortical EEG, in order to identify differences in brainstem oscillatory patterns during different states of excitability. PPNR DBS in two gamma frequency protocols (40Hz and 100Hz) was delivered during SWS of the same sleep stage and with comparable pre-trial levels of slow wave activity. Additionally, SHAM trials were used as a control where no stimulation was applied. We examined changes in cortical oscillatory power, changes in functional connectivity (coherence and causality) from pre- to post- stimulation and phase-locking of cortical oscillations with DBS frequencies and their sub-harmonics during stimulation. We also evaluated connectivity changes induced by DBS and corresponding differences in circuit dynamics between SWS and wakefulness. Beta and gamma PPNR oscillatory power increased when wake was compared to sleep. We saw clear PPNR power modulation by the phase of EEG slow wave, with significant increase in gamma compared to beta power during the excitable part of the slow-wave cycle. Gamma PPNR DBS induced transitions to wakefulness and REM, while it truncated sleep time compared to baseline. The 40Hz stimulation protocol was more efficient in reducing slow wave activity and increasing cortical beta power, compared to PPNR DBS at 100Hz. Furthermore, intrinsic cortical rhythms phase-locked with 40 Hz PPNR DBS to a significantly higher degree compared to the 100Hz protocol, with regional differences in phase-locking, suggesting a complex biological phenomenon. Finally, functional connectivity changes induced by PPNR DBS were consistent with differences in circuit dynamics between SWS and wakefulness. Overall, these results highlight the possibility of using DBS of brainstem arousal circuits to promote arousal and wakefulness, which opens new perspectives for using closed-loop approaches to modulate vigilance states in humans for therapeutic benefit.

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“…A recent study has confirmed beneficial effects of low-frequency PPN-DBS on the upper airways function, also showing a significant correlation between the increase of oscillatory α-band activity and forced respiratory manoeuvres [85]; this effect was particularly marked when the rostral PPN was stimulated, as a part of the "mesencephalic locomotor region" (MLR); in animal studies, the MLR has been shown to project directly to a medullary respiratory generator and plays a key role in changes in respiration linked to motion [86].…”

Section: Deep Brain Stimulation and Respiratory Failurementioning

confidence: 74%

Respiratory dysfunction in Parkinson's disease: a narrative review

et al. 2020

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The presence of respiratory symptoms in Parkinson's disease (PD) has been known since the first description of the disease, even though the prevalence and incidence of these disturbances are not well defined. Several causes have been reported, comprising obstructive and restrictive pulmonary disease and changes in the central ventilatory control, and different pathogenetic mechanisms have been postulated accordingly. In our review, we encompass the current knowledge about respiratory abnormalities in PD, as well as the impact of anti-Parkinsonian drugs as either risk or protective factors. A description of putative pathogenetic mechanisms is also provided, and possible treatments are discussed, focusing on the importance of recognising and treating respiratory symptoms as a key manifestation of the disease itself. A brief description of respiratory dysfunctions in atypical Parkinsonism, especially α-synucleinopathies, is also provided.

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The pedunculopontine region and breathing in Parkinson's disease

Cited by 9 publications

References 38 publications

Neural underpinning of a respiration-associated resting-state fMRI network

Neural underpinning of a respiration-associated resting-state fMRI network

Tailoring Human Sleep: selective alteration through Brainstem Arousal Circuit Stimulation

Respiratory dysfunction in Parkinson's disease: a narrative review

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