Deep Brain Stimulation of Different Pedunculopontine Targets in a Novel Rodent Model of Parkinsonism

Gut, Nadine K.; Winn, Philip

doi:10.1523/jneurosci.3646-14.2015

Cited by 65 publications

(64 citation statements)

References 80 publications

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“…A recent study on an animal model of PD showed that stimulation of the anterior PPN induced freezing and worsened gait, but gait was improved by posterior PPN stimulation [21]. …”

Section: Stereotactic Targetingmentioning

confidence: 99%

Pedunculopontine Nucleus Region Deep Brain Stimulation in Parkinson Disease: Surgical Techniques, Side Effects, and Postoperative Imaging

Hamani

Lozano

Mazzone

et al. 2016

Stereotact Funct Neurosurg

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The pedunculopontine nucleus (PPN) region has received considerable attention in clinical studies as a target for deep brain stimulation (DBS) in Parkinson disease. These studies have yielded variable results with an overall impression of improvement in falls and freezing in many but not all patients treated. We evaluated the available data on the surgical anatomy and terminology of the PPN region in a companion paper. Here we focus on issues concerning surgical technique, imaging, and early side effects of surgery. The aim of this paper was to gain more insight into the reasoning for choosing specific techniques and to discuss shortcomings of available studies. Our data demonstrate the wide range in almost all fields which were investigated. There are a number of important challenges to be resolved, such as identification of the optimal target, the choice of the surgical approach to optimize electrode placement, the impact on the outcome of specific surgical techniques, the reliability of intraoperative confirmation of the target, and methodological differences in postoperative validation of the electrode position. There is considerable variability both within and across groups, the overall experience with PPN DBS is still limited, and there is a lack of controlled trials. Despite these challenges, the procedure seems to provide benefit to selected patients and appears to be relatively safe. One important limitation in comparing studies from different centers and analyzing outcomes is the great variability in targeting and surgical techniques, as shown in our paper. The challenges we identified will be of relevance when designing future studies to better address several controversial issues. We hope that the data we accumulated may facilitate the development of surgical protocols for PPN DBS.

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“…A recent study on an animal model of PD showed that stimulation of the anterior PPN induced freezing and worsened gait, but gait was improved by posterior PPN stimulation [21]. …”

Section: Stereotactic Targetingmentioning

confidence: 99%

Pedunculopontine Nucleus Region Deep Brain Stimulation in Parkinson Disease: Surgical Techniques, Side Effects, and Postoperative Imaging

Hamani

Lozano

Mazzone

et al. 2016

Stereotact Funct Neurosurg

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“…In that respect, the influence of PPN DBS on cortical structures (and in fine on the cortico-striatal activity) is also to be considered (Gut and Winn 2015) just as an modulatory effect on BG and thalamus regarding the dense projection from the MRF to the thalamic nuclei (Paré et al 1988; Van der Werf et al 2002;Benarroch 2008;Galvan and Smith 2011) and the different components of the BG (Lavoie and Parent 1994b;Mena-Segovia et al 2004;Martinez-Gonzalez et al 2011;Dautan et al 2014).…”

Section: Implication For Dbsmentioning

confidence: 99%

The primate pedunculopontine nucleus region: towards a dual role in locomotion and waking state

et al. 2016

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The mesencephalic reticular formation (MRF) mainly composed by the pedunculopontine and the cuneiform nuclei is involved in the control of several fundamental brain functions such as locomotion, rapid eye movement sleep and waking state. On the one hand, the role of MRF neurons in locomotion has been investigated for decades in different animal models, including in behaving nonhuman primate (NHP) using extracellular recordings. On the other hand, MRF neurons involved in the control of waking state have been consistently shown to constitute the cholinergic component of the reticular ascending system. However, a dual control of the locomotion and waking state by the same groups of neurons in NHP has never been demonstrated in NHP. Here, using microelectrode recordings in behaving NHP, we recorded 38 neurons in the MRF that were followed during transition between wakefulness (TWS) and sleep, i.e., until the emergence of sleep episodes characterized by typical cortical slow wave activity (SWA). We found that the MRF neurons, mainly located in the pedunculopontine nucleus region, modulated their activity during TWS with a decrease in firing rate during SWA. Of interest, we could follow some MRF neurons from locomotion to SWA and found that they also modulated their firing rate during locomotion and TWS. These new findings confirm the role of MRF neurons in both functions. They suggest that the MRF is an integration center that potentially allows to fine tune waking state and locomotor signals in order to establish an efficient locomotion.

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“…Other workers have challenged the importance of the PPN as a component of the MLR since PPN lesions do not alter locomotor capability (Winn, 2006; Hernández-Chan et al, 2011; MacLaren et al, 2014; Gut and Winn, 2015, 2016). Moreover, neurons activated during locomotion (indicated by the presence of the activity-dependent marker Fos) are found in the CnF and other nearby areas, including the deep mesencephalic nucleus (DpMe; Jordan, 1998; Vianna et al, 2003; Heise and Mitrofanis, 2006), but not in the PPN.…”

Section: Introductionmentioning

confidence: 99%

LFP Oscillations in the Mesencephalic Locomotor Region during Voluntary Locomotion

Noga

Sánchez

Villamil

et al. 2017

Front. Neural Circuits

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Oscillatory rhythms in local field potentials (LFPs) are thought to coherently bind cooperating neuronal ensembles to produce behaviors, including locomotion. LFPs recorded from sites that trigger locomotion have been used as a basis for identification of appropriate targets for deep brain stimulation (DBS) to enhance locomotor recovery in patients with gait disorders. Theta band activity (6–12 Hz) is associated with locomotor activity in locomotion-inducing sites in the hypothalamus and in the hippocampus, but the LFPs that occur in the functionally defined mesencephalic locomotor region (MLR) during locomotion have not been determined. Here we record the oscillatory activity during treadmill locomotion in MLR sites effective for inducing locomotion with electrical stimulation in rats. The results show the presence of oscillatory theta rhythms in the LFPs recorded from the most effective MLR stimulus sites (at threshold ≤60 μA). Theta activity increased at the onset of locomotion, and its power was correlated with the speed of locomotion. In animals with higher thresholds (>60 μA), the correlation between locomotor speed and theta LFP oscillations was less robust. Changes in the gamma band (previously recorded in vitro in the pedunculopontine nucleus (PPN), thought to be a part of the MLR) were relatively small. Controlled locomotion was best achieved at 10–20 Hz frequencies of MLR stimulation. Our results indicate that theta and not delta or gamma band oscillation is a suitable biomarker for identifying the functional MLR sites.

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Deep Brain Stimulation of Different Pedunculopontine Targets in a Novel Rodent Model of Parkinsonism

Cited by 65 publications

References 80 publications

Pedunculopontine Nucleus Region Deep Brain Stimulation in Parkinson Disease: Surgical Techniques, Side Effects, and Postoperative Imaging

Pedunculopontine Nucleus Region Deep Brain Stimulation in Parkinson Disease: Surgical Techniques, Side Effects, and Postoperative Imaging

The primate pedunculopontine nucleus region: towards a dual role in locomotion and waking state

LFP Oscillations in the Mesencephalic Locomotor Region during Voluntary Locomotion

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