Physiological identification of the human pedunculopontine nucleus

Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA.
Journal of neurology, neurosurgery, and psychiatry (Impact Factor: 5.58). 10/2009; 81(1):80-6. DOI: 10.1136/jnnp.2009.179069
Source: PubMed

ABSTRACT The pedunculopontine nucleus (PPN) is a brainstem structure with widespread connections to the basal ganglia. Despite the recent introduction of PPN deep brain stimulation (DBS) for the treatment of gait disorders, little is known about its physiology in humans.
Single unit discharge characteristics of neurons in the PPN region were analysed in four patients and PPN local field potentials (LFP) in one patient, recorded during the course of DBS implantation. Two patients had Parkinson disease, and two had non-sinemet responsive parkinsonism. Cell locations were plotted in the coordinate system of a human brainstem atlas.
Fifty-six units in the PPN region were studied, of which 32 mapped to within PPN boundaries. The mean (SD) discharge rate of neurons in the PPN was 23.2 (15.6) Hz. Spontaneous neuronal firing rate and burst discharge rate were significantly different between neurons in the region dorsal to PPN and those in the PPN. Responses to passive movement of contralateral and ipsilateral limbs were found. Theta and beta band oscillations were present in the PPN LFP.
PPN discharge characteristics may prove useful in the electrophysiological identification of PPN during DBS implantation surgery.

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    • "nses appeared distinct from 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 . "
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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 · 10.23 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 · 2.87 Impact Factor
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    • "Nowadays, stereotactically placed electrodes with therapeutic aims such as deep brain stimulation (DBS), offer the possibility to reach structures that could not be otherwise targeted in humans and investigate further physiological aspects of brain circuits. For these purposes, authors have used the DBS electrodes inserted either in the nucleus ventralis intermedius of the thalamus (Vim), the globus pallidus internus (GPi), the subthalamic nucleus (STN), the pedunculopontine nucleus (PPN) or others in which the results of research are still scarce (Weinberger et al., 2008; Galati et al., 2008; Shimamoto et al., 2010; Alessandro et al., 2010). The information brought by these studies has already shed some light on the functioning of some central nervous system circuits. "
    Diagnostics and Rehabilitation of Parkinson's Disease, 12/2011; , ISBN: 978-953-307-791-8