Involvement of the human pedunculopontine nucleus region in voluntary movements

Division of Brain Imaging & Behaviour Systems-Neuroscience, Toronto Western Hospital, McLaughlin Pavilion, Toronto, Ontario M5T 2S8, Canada.
Neurology (Impact Factor: 8.29). 09/2010; 75(11):950-9. DOI: 10.1212/WNL.0b013e3181f25b35
Source: PubMed


The pedunculopontine nucleus region (PPNR) is being investigated as a target for deep brain stimulation (DBS) in Parkinson disease (PD), particularly for gait and postural impairment. A greater understanding of how PPNR activities and oscillations are modulated with voluntary movements is crucial to the development of neuromodulation strategies.
We studied 7 patients with PD who underwent DBS electrode implantations in the PPNR. PPNR local field potential and EEG were recorded while patients performed self-paced wrist and ankle movements.
Back-averaging of the PPNR recording showed movement-related potentials before electromyography onset. Frequency analysis showed 2 discrete movement-related frequency bands in the theta (6- to 10-Hz) and beta (14- to 30-Hz) ranges. The PPNR theta band showed greater event-related desynchronization with movements in the ON than in the OFF medication state and was coupled with the sensorimotor cortices in the ON state only. Beta event-related desynchronization was observed in the PPNR during the premovement and movement execution phases in the OFF state. In contrast, premovement PPNR beta event-related synchronization occurred in the ON state. Moreover, beta band coherence between the PPNR and the midline prefrontal region was observed during movement preparation in the ON but not the OFF state.
Activities of PPNR change during movement preparation and execution in patients with PD. Dopaminergic medications modulate PPNR activities and promote the interactions between the cortex and PPNR. Beta oscillations may have different functions in the basal ganglia and PPNR, and may be prokinetic rather than antikinetic in the PPNR.

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Available from: Andres M Lozano, Oct 10, 2015
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    • " overt motor modulations , which we also observed in spiking activity and local field potentials during button pressing , in agreement with observations that PPN neurons can be modulated during movements outside of any locomotor context ( Matsumura et al . , 1997 ; Weinberger et al . , 2008 ; Okada and Kobayashi , 2009 ; Shimamoto et al . , 2010 ; Tsang et al . , 2010 ; Thompson and Felsen , 2013 ; Hong and Hikosaka , 2014 ; Tattersall et al . , 2014 ) . PPN visual activity may play a role in increasing alertness or attention to visual stimuli relevant for task performance by influencing cortical processing via ascending projections ( Steriade and McCarley , 1990 ; Lee et al . , 2014 ) . These ascend"
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    ABSTRACT: The brainstem pedunculopontine nucleus has a likely, although unclear, role in gait control, and is a potential deep brain stimulation target for treating resistant gait disorders. These disorders are a major therapeutic challenge for the ageing population, especially in Parkinson's disease where gait and balance disorders can become resistant to both dopaminergic medication and subthalamic nucleus stimulation. Here, we present electrophysiological evidence that the pedunculopontine and subthalamic nuclei are involved in distinct aspects of gait using a locomotor imagery task in 14 patients with Parkinson's disease undergoing surgery for the implantation of pedunculopontine or subthalamic nuclei deep brain stimulation electrodes. We performed electrophysiological recordings in two phases, once during surgery, and again several days after surgery in a subset of patients. The majority of pedunculopontine nucleus neurons (57%) recorded intrasurgically exhibited changes in activity related to different task components, with 29% modulated during visual stimulation, 41% modulated during voluntary hand movement, and 49% modulated during imaginary gait. Pedunculopontine nucleus local field potentials recorded post-surgically were modulated in the beta and gamma bands during visual and motor events, and we observed alpha and beta band synchronization that was sustained for the duration of imaginary gait and spatially localized within the pedunculopontine nucleus. In contrast, significantly fewer subthalamic nucleus neurons (27%) recorded intrasurgically were modulated during the locomotor imagery, with most increasing or decreasing activity phasically during the hand movement that initiated or terminated imaginary gait. Our data support the hypothesis that the pedunculopontine nucleus influences gait control in manners extending beyond simply driving pattern generation. In contrast, the subthalamic nucleus seems to control movement execution that is not likely to be gait-specific. These data highlight the crucial role of these two nuclei in motor control and shed light on the complex functions of the lateral mesencephalus in humans.
    Brain 05/2015; 138(5):1284-1296. DOI:10.1093/brain/awv047 · 9.20 Impact Factor
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    • "Local field potentials of spontaneous activity increase to the beta range as recording electrodes enter the PPN in the human (Shimamoto et al. 2010; Weinberger et al. 2008). While activity in the absence of stimulation or movement is most abundant in the alpha range in the human PPN, higher frequency activity in the beta range is evident in relation to passive and self-paced movements (Shimamoto et al. 2010; Tsang et al. 2010; Weinberger et al. 2008). "
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    ABSTRACT: This brief review resolves a number of persistent conflicts regarding the location and characteristics of the mesencephalic locomotor region, which has in the past been described as not locomotion-specific and is more likely the pedunculopontine nucleus (PPN). The parameters of stimulation used to elicit changes in posture and locomotion we now know are ideally suited to match the intrinsic membrane properties of PPN neurons. The physiology of these cells is important not only because it is a major element of the reticular activating system, but also because it is a novel target for the treatment of gait and postural deficits in Parkinson's disease (PD). The discussion explains many of the effects reported following deep brain stimulation (DBS) of the PPN by different groups and provides guidelines for the determination of long-term assessment and effects of PPN DBS. A greater understanding of the physiology of the target nuclei within the brainstem and basal ganglia, amassed over the past decades, has enabled increasingly better patient outcomes from DBS for movement disorders. Despite these improvements, there remains a great opportunity for further understanding of the mechanisms through which DBS has its effects and for further development of appropriate technology to effect these treatments. We review the scientific basis for one of the newest targets, the PPN, in the treatment of PD and other movement disorders, and address the needs for further investigation.
    Journal of Neural Transmission 06/2014; 122(2). DOI:10.1007/s00702-014-1243-x · 2.40 Impact Factor
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    • "One limitation to this study is the number of patients included, which does not afford a strong power to the statistical analyses. However, PPN surgery currently remains experimental and our sample size is comparable to, or even greater than, that of other groups [16], [19], [20], [29]. "
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    ABSTRACT: The pedunculopontine area (PPNa) including the pedunculopontine and cuneiform nuclei, belongs to the mesencephalic locomotor region. Little is known about the oscillatory mechanisms underlying the function of this region in postural and gait control. We examined the modulations of the oscillatory activity of the PPNa and cortex during stepping, a surrogate of gait, and stance in seven Parkinson's disease patients who received bilateral PPNa implantation for disabling freezing of gait (FOG). In the days following the surgery, we recorded behavioural data together with the local field potentials of the PPNa during sitting, standing and stepping-in-place, under two dopaminergic medication conditions (OFF and ON levodopa). Our results showed that OFF levodopa, all subjects had FOG during step-in-place trials, while ON levodopa, stepping was effective (mean duration of FOG decreasing from 61.7±36.1% to 7.3±10.1% of trial duration). ON levodopa, there was an increase in PPNa alpha (5-12 Hz) oscillatory activity and a decrease in beta (13-35 Hz) and gamma (65-90 Hz) bands activity. PPNa activity was not modulated during quiet standing and sitting. Our results confirm the role of the PPNa in the regulation of gait and suggest that, in Parkinson disease, gait difficulties could be related to an imbalance between low and higher frequencies.
    PLoS ONE 12/2013; 8(12):e83919. DOI:10.1371/journal.pone.0083919 · 3.23 Impact Factor
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