Human Pedunculopontine Nucleus Research Articles

Direct localization and delineation of human pedunculopontine nucleus based on a self-supervised magnetic resonance image super-resolution method.

The pedunculopontine nucleus (PPN) is a small brainstem structure and has attracted attention as a potentially effective deep brain stimulation (DBS) target for the treatment of Parkinson's disease (PD). However, the in vivo location of PPN remains poorly described and barely visible on conventional structural magnetic resonance (MR) images due to a lack of high spatial resolution and tissue contrast. This study aims to delineate the PPN on a high-resolution (HR) atlas and investigate the visibility of the PPN in individual quantitative susceptibility mapping (QSM) images. We combine a recently constructed Montreal Neurological Institute (MNI) space unbiased QSM atlas (MuSus-100), with an implicit representation-based self-supervised image super-resolution (SR) technique to achieve an atlas with improved spatial resolution. Then guided by a myelin staining histology human brain atlas, we localize and delineate PPN on the atlas with improved resolution. Furthermore, we examine the feasibility of directly identifying the approximate PPN location on the 3.0-T individual QSM MR images. The proposed SR network produces atlas images with four times the higher spatial resolution (from 1 to 0.25 mm isotropic) without a training dataset. The SR process also reduces artifacts and keeps superb image contrast for further delineating small deep brain nuclei, such as PPN. Using the myelin staining histological atlas as guidance, we first identify and annotate the location of PPN on the T1-weighted (T1w)-QSM hybrid MR atlas with improved resolution in the MNI space. Then, we relocate and validate that the optimal targeting site for PPN-DBS is at the middle-to-caudal part of PPN on our atlas. Furthermore, we confirm that the PPN region can be identified in a set of individual QSM images of 10 patients with PD and 10 healthy young adults. The contrast ratios of the PPN to its adjacent structure, namely the medial lemniscus, on images of different modalities indicate that QSM substantially improves the visibility of the PPN both in the atlas and individual images. Our findings indicate that the proposed SR network is an efficient tool for small-size brain nucleus identification. HR QSM is promising for improving the visibility of the PPN. The PPN can be directly identified on the individual QSM images acquired at the 3.0-T MR scanners, facilitating a direct targeting of PPN for DBS surgery.

Closed-Loop Deep Brain Stimulation to Treat Medication-Refractory Freezing of Gait in Parkinson's Disease.

Background: Treating medication-refractory freezing of gait (FoG) in Parkinson’s disease (PD) remains challenging despite several trials reporting improvements in motor symptoms using subthalamic nucleus or globus pallidus internus (GPi) deep brain stimulation (DBS). Pedunculopontine nucleus (PPN) region DBS has been used for medication-refractory FoG, with mixed findings. FoG, as a paroxysmal phenomenon, provides an ideal framework for the possibility of closed-loop DBS (CL-DBS).Methods: In this clinical trial (NCT02318927), five subjects with medication-refractory FoG underwent bilateral GPi DBS implantation to address levodopa-responsive PD symptoms with open-loop stimulation. Additionally, PPN DBS leads were implanted for CL-DBS to treat FoG. The primary outcome of the study was a 40% improvement in medication-refractory FoG in 60% of subjects at 6 months when “on” PPN CL-DBS. Secondary outcomes included device feasibility to gauge the recruitment potential of this four-lead DBS approach for a potentially larger clinical trial. Safety was judged based on adverse events and explantation rate.Findings: The feasibility of this approach was demonstrated as we recruited five subjects with both “on” and “off” medication freezing. The safety for this population of patients receiving four DBS leads was suboptimal and associated with a high explantation rate of 40%. The primary clinical outcome in three of the five subjects was achieved at 6 months. However, the group analysis of the primary clinical outcome did not reveal any benefit.Interpretation: This study of a human PPN CL-DBS trial in medication-refractory FoG showed feasibility in recruitment, suboptimal safety, and a heterogeneous clinical effect in FoG outcomes.

Neurophysiological Correlates of Gait in the Human Basal Ganglia and the PPN Region in Parkinson's Disease.

This study aimed to characterize the neurophysiological correlates of gait in the human pedunculopontine nucleus (PPN) region and the globus pallidus internus (GPi) in Parkinson’s disease (PD) cohort. Though much is known about the PPN region through animal studies, there are limited physiological recordings from ambulatory humans. The PPN has recently garnered interest as a potential deep brain stimulation (DBS) target for improving gait and freezing of gait (FoG) in PD. We used bidirectional neurostimulators to record from the human PPN region and GPi in a small cohort of severely affected PD subjects with FoG despite optimized dopaminergic medications. Five subjects, with confirmed on-dopaminergic medication FoG, were implanted with bilateral GPi and bilateral PPN region DBS electrodes. Electrophysiological recordings were obtained during various gait tasks for 5 months postoperatively in both the off- and on-medication conditions (obtained during the no stimulation condition). The results revealed suppression of low beta power in the GPi and a 1–8 Hz modulation in the PPN region which correlated with human gait. The PPN feature correlated with walking speed. GPi beta desynchronization and PPN low-frequency synchronization were observed as subjects progressed from rest to ambulatory tasks. Our findings add to our understanding of the neurophysiology underpinning gait and will likely contribute to the development of novel therapies for abnormal gait in PD.Clinical Trial Registration: Clinicaltrials.gov identifier; NCT02318927.

A Review of the Pedunculopontine Nucleus in Parkinson's Disease.

The pedunculopontine nucleus (PPN) is situated in the upper pons in the dorsolateral portion of the ponto-mesencephalic tegmentum. Its main mass is positioned at the trochlear nucleus level, and is part of the mesenphalic locomotor region (MLR) in the upper brainstem. The human PPN is divided into two subnuclei, the pars compacta (PPNc) and pars dissipatus (PPNd), and constitutes both cholinergic and non-cholinergic neurons with afferent and efferent projections to the cerebral cortex, thalamus, basal ganglia (BG), cerebellum, and spinal cord. The BG controls locomotion and posture via GABAergic output of the substantia nigra pars reticulate (SNr). In PD patients, GABAergic BG output levels are abnormally increased, and gait disturbances are produced via abnormal increases in SNr-induced inhibition of the MLR. Since the PPN is vastly connected with the BG and the brainstem, dysfunction within these systems lead to advanced symptomatic progression in Parkinson's disease (PD), including sleep and cognitive issues. To date, the best treatment is to perform deep brain stimulation (DBS) on PD patients as outcomes have shown positive effects in ameliorating the debilitating symptoms of this disease by treating pathological circuitries within the parkinsonian brain. It is therefore important to address the challenges and develop this procedure to improve the quality of life of PD patients.

Direct localisation of the human pedunculopontine nucleus using MRI: a coordinate and fibre-tracking study.

To image the pedunculopontine tegmental nucleus (PPN), a deep brain stimulation (DBS) target for Parkinson disease, using MRI with validated results. This study used the MP2RAGE sequence with high resolution and enhanced grey-white matter contrast on a 7-T ultra-high-field MRI system to image the PPN as well as a diffusion spectrum imaging method on a 3-T MRI system to reconstruct the main fibre systems surrounding the PPN. The coordinates of the rostral and caudal PPN poles of both sides were measured in relation to the third and fourth ventricular landmarks on the 7-T image. The boundary of the PPN was delineated, and showed morphology consistent with previous histological works. The main fibres around the PPN were reconstructed. The pole coordinate results combined with the fibre spatial relationships validate the imaging results. A practical protocol is provided to directly localise the PPN using MRI; the position and morphology of the PPN can be obtained and validated by locating its poles relative to two ventricular landmarks and by inspecting its spatial relationship with the surrounding fibre systems. This technique can be potentially used in clinics to define the boundary of the PPN before DBS surgery for treatment of Parkinson disease in a more precise and reliable manner. • Combined information helps localise the PPN as a DBS target for PD patients • Scan the PPN at 7 T and measure its coordinates against different ventricular landmarks • Reconstruct the main fibres around the PPN using diffusion spectrum imaging.

Dopamine and the Brainstem Locomotor Networks: From Lamprey to Human

In vertebrates, dopamine neurons are classically known to modulate locomotion via their ascending projections to the basal ganglia that project to brainstem locomotor networks. An increased dopaminergic tone is associated with increase in locomotor activity. In pathological conditions where dopamine cells are lost, such as in Parkinson's disease, locomotor deficits are traditionally associated with the reduced ascending dopaminergic input to the basal ganglia. However, a descending dopaminergic pathway originating from the substantia nigra pars compacta was recently discovered. It innervates the mesencephalic locomotor region (MLR) from basal vertebrates to mammals. This pathway was shown to increase locomotor output in lampreys, and could very well play an important role in mammals. Here, we provide a detailed account on the newly found dopaminergic pathway in lamprey, salamander, rat, monkey, and human. In lampreys and salamanders, dopamine release in the MLR is associated with the activation of reticulospinal neurons that carry the locomotor command to the spinal cord. Dopamine release in the MLR potentiates locomotor movements through a D1-receptor mechanism in lampreys. In rats, stimulation of the substantia nigra pars compacta elicited dopamine release in the pedunculopontine nucleus, a known part of the MLR. In a monkey model of Parkinson's disease, a reduced dopaminergic innervation of the brainstem locomotor networks was reported. Dopaminergic fibers are also present in human pedunculopontine nucleus. We discuss the conserved locomotor role of this pathway from lamprey to mammals, and the hypothesis that this pathway could play a role in the locomotor deficits reported in Parkinson's disease.

24. Dorsal column nuclei evoked activity recorded from the human Pedunculopontine nucleus

This study aimed to verify the hypothesis that somatosensory activity recorded from the Pedunculopontine nucleus (PPTg) comes from the dorsal column nuclei (DCN) (Insola et al., 2015). In one parkinsonian patient implanted in the PPTg for DBS, both tibial and median nerve SEPs were recorded from the PPTg electrode. The finding obtained from this patient was compared with that issued from another patient implanted with an epidural electrode at Cv2 level for pain relief. The triphasic waform and HFOs recorded from the PPTg after tibial nerve stimulation were very similar to the low- and high-frequency components recorded from the Cv2 epidural electrode, known to be generated in the DCN (Insola et al., 2010). Therefore, the present results suggest that both the low-frequency triphasic waveform and the HFOs recorded from the PPTg are generated from the DCN.

A descending dopamine pathway conserved from basal vertebrates to mammals

Dopamine neurons are classically known to modulate locomotion indirectly through ascending projections to the basal ganglia that project down to brainstem locomotor networks. Their loss in Parkinson's disease is devastating. In lampreys, we recently showed that brainstem networks also receive direct descending dopaminergic inputs that potentiate locomotor output. Here, we provide evidence that this descending dopaminergic pathway is conserved to higher vertebrates, including mammals. In salamanders, dopamine neurons projecting to the striatum or brainstem locomotor networks were partly intermingled. Stimulation of the dopaminergic region evoked dopamine release in brainstem locomotor networks and concurrent reticulospinal activity. In rats, some dopamine neurons projecting to the striatum also innervated the pedunculopontine nucleus, a known locomotor center, and stimulation of the dopaminergic region evoked pedunculopontine dopamine release in vivo. Finally, we found dopaminergic fibers in the human pedunculopontine nucleus. The conservation of a descending dopaminergic pathway across vertebrates warrants re-evaluating dopamine's role in locomotion.

Understanding the human pedunculopontine nucleus in Parkinson's disease.

This paper presents the Brisbane experience of pedunculopontine nucleus (PPN) deep brain stimulation (DBS) in Parkinson's disease (PD). Clinical outcomes along with studies of the mechanisms and neurophysiology of PPN in PD patients with severe freezing of gait (FoG) and postural imbalance (PI) are summarised and presented. Our results indicate that PPN DBS improves FoG and falls in the relatively uncommon group of PD patients who respond well to medication other than for continuing on time FoG and falls. Our studies indicate that bilateral DBS is more beneficial than unilateral DBS, and that the more caudal region of the PPN seems preferable for stimulation. There is evidence that rapid-release programs for initiation and correction of gait and posture are modulated by the PPN, possibly to some extent independently of the cerebral cortex. These functions were found to be impaired in PD patients with severe FoG/PI, but to some extent corrected by bilateral PPN DBS.

Pharmacogenetic stimulation of cholinergic pedunculopontine neurons reverses motor deficits in a rat model of Parkinson's disease.

BackgroundPatients with advanced Parkinson's disease (PD) often present with axial symptoms, including postural- and gait difficulties that respond poorly to dopaminergic agents. Although deep brain stimulation (DBS) of a highly heterogeneous brain structure, the pedunculopontine nucleus (PPN), improves such symptoms, the underlying neuronal substrate responsible for the clinical benefits remains largely unknown, thus hampering optimization of DBS interventions. Choline acetyltransferase (ChAT)::Cre+ transgenic rats were sham-lesioned or rendered parkinsonian through intranigral, unihemispheric stereotaxic administration of the ubiquitin-proteasomal system inhibitor, lactacystin, combined with designer receptors exclusively activated by designer drugs (DREADD), to activate the cholinergic neurons of the nucleus tegmenti pedunculopontine (PPTg), the rat equivalent of the human PPN. We have previously shown that the lactacystin rat model accurately reflects aspects of PD, including a partial loss of PPTg cholinergic neurons, similar to what is seen in the post-mortem brains of advanced PD patients.ResultsIn this manuscript, we show that transient activation of the remaining PPTg cholinergic neurons in the lactacystin rat model of PD, via peripheral administration of the cognate DREADD ligand, clozapine-N-oxide (CNO), dramatically improved motor symptoms, as was assessed by behavioral tests that measured postural instability, gait, sensorimotor integration, forelimb akinesia and general motor activity. In vivo electrophysiological recordings revealed increased spiking activity of PPTg putative cholinergic neurons during CNO-induced activation. c-Fos expression in DREADD overexpressed ChAT-immunopositive (ChAT+) neurons of the PPTg was also increased by CNO administration, consistent with upregulated neuronal activation in this defined neuronal population.ConclusionsOverall, these findings provide evidence that functional modulation of PPN cholinergic neurons alleviates parkinsonian motor symptoms.Electronic supplementary materialThe online version of this article (doi:10.1186/s13024-015-0044-5) contains supplementary material, which is available to authorized users.

P839: Low and high-frequency somatosensory evoked potentials recorded from the human pedunculopontine nucleus

P839: Low and high-frequency somatosensory evoked potentials recorded from the human pedunculopontine nucleus

Imagined gait modulates neuronal network dynamics in the human pedunculopontine nucleus

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.

Low and high-frequency somatosensory evoked potentials recorded from the human pedunculopontine nucleus

ObjectiveTo investigate the generators of the somatosensory evoked potential (SEP) components recorded from the Pedunculopontine Tegmental nucleus (PPTg). MethodsTwenty-two patients, suffering from Parkinson’s disease (PD), underwent electrode implantation in the PPTg area for deep brain stimulation (DBS). SEPs were recorded from the DBS electrode contacts to median nerve stimulation. ResultsSEPs recorded from the PPTg electrode contacts could be classified in 3 types, according to their waveforms. (1) The biphasic potential showed a positive peak (P16) whose latency (16.05±0.61ms) shifted of 0.18±0.07ms from the lower to the upper contact of the electrode. (2) The triphasic potential showed an initial positive peak (P15) whose latency (15.4±0.2ms) did not change across the DBS electrode contacts. (3) In the last SEP configuration (mixed biphasic and triphasic waveform), the positive peak was bifid including both the P15 and P16 potentials. ConclusionWhile the P16 potential is probably generated by the somatosensory volley travelling along the medial lemniscus, the P15 response represents a far-field potential probably generated at the cuneate nucleus level. SignificanceOur results show the physiological meaning of the somatosensory responses recorded from the PPTg nucleus area.

14. Vestibular modulation of theta band oscillations in human pedunculopontine nucleus

Background and aims: The pedunculopontine nucleus (PPN) is a new deep brain stimulation (DBS) target, thought to be particularly for useful in ameliorating gait disturbance in Parkinson’s disease. Recent evidence shows a prominent theta (4–7 Hz) rhythm in the PPN (Tsang et al., Neurology, 2010; Simon et al., J. Neurophysiol., 2010; Shimamoto et al., JNNP, 2010). Given that theta activity is modulated by vestibular signals elsewhere in the brain, e.g. hippocampus, (Shin, Synapse, 2010; Chen et al., Neuroimage, 2010), we assessed whether vestibular signals modulate PPN theta activity. Methods: We recorded local field potentials (LFPs) in three patients with implanted bilateral subthalamic nucleus (STN) and PPN DBS electrodes at 2000 Hz and filtered at 0.5–500 Hz at rest and during passive, yaw-plane whole body rotations (i.e., vestibular stimulation) at 0.2 and 0.4 Hz with eyes closed and then open with manifest vestibular ocular reflex activation (i.e., nystagmus) and then with VOR suppression (VORS). Frequency power spectra and the average power across a 1–1000 Hz frequency range were obtained. Results: PPN LFPs showed significant modulation during vestibular activation (rotations) compared to rest with power changes ca. four times larger than those found in the STN. The PPN LFP was dominated by theta (4–7 Hz) activity which was enhanced during all tasks compared to rest (including eyes open vs. closed at rest) except for VORS where there was a clear reduction in theta activity and this was more prominent for ‘fast’ (i.e., 0.4 Hz rotations) rotations. The pattern of theta activity was the same for right and left PPN including task-dependent modulation. To rule out the possibility that this theta activity was purely driven by nystagmus, we recorded LFPs during optokinetic nystagmus (OKN). OKN was associated with a decrease of theta power compared to rest. Conclusions: This is the first demonstration of vestibular modulation of PPN activity (in either animals or humans). Human PPN activity is increased during vestibular activation with a relative suppression of theta during VORS. This pattern of a reduction of activity during VORS compared to VOR is seen in the vestibular nuclei. Thus, the PPN may represent an important component of vestibular processing within the brainstem. We speculate that given the role of the vestibular system in balance and posture, PPN DBS may be work to improve gait and balance control via vestibular circuits.

15. Functional mapping of monaural auditory brainstem responses

Background and aims: The pedunculopontine nucleus (PPN) is a new deep brain stimulation (DBS) target, thought to be particularly for useful in ameliorating gait disturbance in Parkinson’s disease. Recent evidence shows a prominent theta (4–7 Hz) rhythm in the PPN (Tsang et al., Neurology, 2010; Simon et al., J. Neurophysiol., 2010; Shimamoto et al., JNNP, 2010). Given that theta activity is modulated by vestibular signals elsewhere in the brain, e.g. hippocampus, (Shin, Synapse, 2010; Chen et al., Neuroimage, 2010), we assessed whether vestibular signals modulate PPN theta activity. Methods: We recorded local field potentials (LFPs) in three patients with implanted bilateral subthalamic nucleus (STN) and PPN DBS electrodes at 2000 Hz and filtered at 0.5–500 Hz at rest and during passive, yaw-plane whole body rotations (i.e., vestibular stimulation) at 0.2 and 0.4 Hz with eyes closed and then open with manifest vestibular ocular reflex activation (i.e., nystagmus) and then with VOR suppression (VORS). Frequency power spectra and the average power across a 1–1000 Hz frequency range were obtained. Results: PPN LFPs showed significant modulation during vestibular activation (rotations) compared to rest with power changes ca. four times larger than those found in the STN. The PPN LFP was dominated by theta (4–7 Hz) activity which was enhanced during all tasks compared to rest (including eyes open vs. closed at rest) except for VORS where there was a clear reduction in theta activity and this was more prominent for ‘fast’ (i.e., 0.4 Hz rotations) rotations. The pattern of theta activity was the same for right and left PPN including task-dependent modulation. To rule out the possibility that this theta activity was purely driven by nystagmus, we recorded LFPs during optokinetic nystagmus (OKN). OKN was associated with a decrease of theta power compared to rest. Conclusions: This is the first demonstration of vestibular modulation of PPN activity (in either animals or humans). Human PPN activity is increased during vestibular activation with a relative suppression of theta during VORS. This pattern of a reduction of activity during VORS compared to VOR is seen in the vestibular nuclei. Thus, the PPN may represent an important component of vestibular processing within the brainstem. We speculate that given the role of the vestibular system in balance and posture, PPN DBS may be work to improve gait and balance control via vestibular circuits.

C-Fos expression after deep brain stimulation of the pedunculopontine tegmental nucleus in the rat 6-hydroxydopamine Parkinson model

Deep brain stimulation (DBS) is used to alleviate motor dysfunction in Parkinson's disease (PD). The pedunculopontine nucleus (PPN) may be a potential target for severe freezing and postural instability with 25 Hz stimulation being considered more effective than 130 Hz stimulation. Here we evaluated the expression of c-Fos after 25 Hz and 130 Hz DBS of the pedunculopontine tegmental nucleus (PPTg, i.e., the rodent equivalent to the human PPN) in the rat 6-hydroxydopamine (6-OHDA) PD model. Anaesthetized male Sprague Dawley rats with unilateral 6-OHDA-induced nigrostriatal lesions were stimulated with 25 Hz, 130 Hz, or 0 Hz sham-stimulation for 4 h by electrodes implanted into the ipsilateral PPTg. Thereafter the distribution and number of neurons expressing the immediate early gene c-Fos, a marker for acute neuronal activity, was assessed. DBS of the PPTg induced strong ipsilateral c-Fos expression at the stimulation site, with 25 Hz having a more marked impact than 130 Hz. Additionally, c-Fos was strongly expressed in the central gray. In the dorsal part expression was stronger after 25 Hz stimulation, while in the medial and ventral part there was no difference between 25 Hz and 130 Hz stimulation. Expression in the basal ganglia was negligible. In the rat 6-OHDA PD model stimulation of the PPTg did not affect c-Fos expression in the basal ganglia, but had a strong impact on other functional circuitries. PPN stimulation in humans might therefore also have an impact on other systems than the motor system.

Action control related local field potentials in the human pedunculopontine nuclei: a single case report

Event Abstract Back to Event Action control related local field potentials in the human pedunculopontine nuclei: a single case report Marcus Heldmann1*, Tino Zaehle2, Imke Galazky3, Thomas Münte1, Jürgen Voges4, Hans-Jochen Heinze3 and Hermann Hinrichs3 1 Dep. Neurology, University Medical Center SH, Germany 2 German Centre for Neurodegenerative Diseases (DZNE) Magdeburg, Germany 3 University Department of Neurology, Magdeburg, Germany 4 Department of Stereotactic Neurosurgery, Germany The pedunculopontine nucleus (PPN) is a rostral midbrain structure and an essential part of the reticular activation system and the mesencephalic locomotor region. Anatomically, the PPN is characterized by its reciprocal cholinergic and non-cholinergic connections to the basal ganglia, the thalamus and the spinal cord. It is known from the animal literature that the PPN is not only involved in sleep behavior and the control of movement, but also supports cognitive functions like attention, reward processing and learning. The PPN has recently been identified as a target for deep brain stimulation (DBS) to treat Parkinson Disease and related movement disorders such as progressive supranuclear palsy (PSP) in particular for freezing of gait and postural instability. Thus, the impact of DBS in the PPN on executive functions and the control of motor behavior in humans can be investigated. First behavioral studies reported faster reaction times and improved executive functions under active DBS, indicating an involvement of the PPN in these functions in humans. In the present single case report we recorded local field potentials from the PPN in a 71 years old PSP patient, while he performed two simple motor (tapping/task-switching) paradigms. Results clearly demonstrate an association of intracranially recoded local field potentials in the (left) PPN and the given feedback information that indicated to switch or not to switch the task set. We will discuss this finding as first direct evidence for an involvement of the human PPN in action monitoring mechanisms. Keywords: Intra-cranial Electrophysiology, PPN Conference: XI International Conference on Cognitive Neuroscience (ICON XI), Palma, Mallorca, Spain, 25 Sep - 29 Sep, 2011. Presentation Type: Poster Presentation Topic: Abstracts Citation: Heldmann M, Zaehle T, Galazky I, Münte T, Voges J, Heinze H and Hinrichs H (2011). Action control related local field potentials in the human pedunculopontine nuclei: a single case report. Conference Abstract: XI International Conference on Cognitive Neuroscience (ICON XI). doi: 10.3389/conf.fnhum.2011.207.00072 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 16 Nov 2011; Published Online: 25 Nov 2011. * Correspondence: Dr. Marcus Heldmann, Dep. Neurology, University Medical Center SH, Lübeck, Germany, marcus.heldmann@neuro.uni-luebeck.de Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Marcus Heldmann Tino Zaehle Imke Galazky Thomas Münte Jürgen Voges Hans-Jochen Heinze Hermann Hinrichs Google Marcus Heldmann Tino Zaehle Imke Galazky Thomas Münte Jürgen Voges Hans-Jochen Heinze Hermann Hinrichs Google Scholar Marcus Heldmann Tino Zaehle Imke Galazky Thomas Münte Jürgen Voges Hans-Jochen Heinze Hermann Hinrichs PubMed Marcus Heldmann Tino Zaehle Imke Galazky Thomas Münte Jürgen Voges Hans-Jochen Heinze Hermann Hinrichs Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

POD06 Human pedunculopontine nucleus displays vestibular reactivity

We recorded local field potentials (LFPs) in a patient with implanted bilateral subthalamic nucleus (STN) and pedunculopontine nucleus (PPN) deep brain stimulation (DBS) electrodes at 2 kHz and filtered at...

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### Involvement of the human pedunculopontine nucleus region in voluntary movements This paper investigated 7 patients with Parkinson disease who underwent deep brain stimulation electrode implantations in the pedunculopontine nucleus (PPN) region. Recordings showed that dopaminergic medications promote cortical and PPN interactions. Beta oscillations in the PPN have different functions and may explain why different frequencies are used for therapeutic stimulation of these structures. See p. 950; Editorial, p. 944 ### Aortic stiffness and pulse wave reflection in young subjects with migraine: A case-control study This case-control study showed that 60 patients with migraine had increased aortic stiffness and enhanced peripheral pressure wave reflection compared with 60 age-, sex-, and blood pressure-matched …

Involvement of the human pedunculopontine nucleus region in voluntary movements

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.