Pedunculopontine nucleus deep brain stimulation in Parkinson’s disease

Tykocki, Tomasz; Mandat, Tomasz; Nauman, Paweł

doi:10.5114/aoms.2011.24119

Cited by 27 publications

(17 citation statements)

References 72 publications

(77 reference statements)

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“…In rats, low-frequency stimulation of the PPN leads to decreased firing in the STN (Alam et al, 2012) and as such, impairments in the effectiveness of this signaling pathway could potentially lead to an increase in the influence of the STN over the basal ganglia. These concepts are supported by the functional improvements experienced by patients with freezing following DBS of the PPN nucleus (Stefani et al, 2007; Strafella et al, 2008; Ferraye et al, 2010; Hamani et al, 2011; Tykocki et al, 2011; Follett and Torres-Russotto, 2012; Khan et al, 2012), along with increases in regional cerebral blood flow observed during stimulation of the PPN (Strafella et al, 2008; Ballanger et al, 2009). In addition, this interpretation is consistent with the finding that the PPN lacks appropriate white matter connectivity with the cerebellum in patients with FOG and PD (Tessitore et al, 2012b; Fling et al, 2013), however, this finding could also be explained as the by-product of decreased firing within the PPN as a result of overwhelming inhibition from the basal ganglia (Lewis and Barker, 2009), suggesting that the primary pathology in freezing may not reside in the PPN.…”

Section: Insights Into Potential Pathological Processesmentioning

confidence: 92%

The role of frontostriatal impairment in freezing of gait in Parkinson's disease

Shine

Moustafa

Matar³

et al. 2013

Front. Syst. Neurosci.

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Freezing of gait (FOG) is a disabling symptom of advanced Parkinson's disease (PD) that leads to an increased risk of falls and nursing home placement. Interestingly, multiple lines of evidence suggest that the manifestation of FOG is related to specific deficits in cognition, such as set shifting and the ability to process conflict-related signals. These findings are consistent with the specific patterns of abnormal cortical processing seen during functional neuroimaging experiments of FOG, implicating increased neural activation within cortical structures underlying cognition, such as the Cognitive Control Network. In addition, these studies show that freezing episodes are associated with abnormalities in the BOLD response within key structures of the basal ganglia, such as the striatum and the subthalamic nucleus. In this article, we discuss the implications of these findings on current models of freezing behavior and propose an updated model of basal ganglia impairment during FOG episodes that integrates the neural substrates of freezing from the cortex and the basal ganglia to the cognitive dysfunctions inherent in the condition.

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Section: Insights Into Potential Pathological Processesmentioning

confidence: 92%

The role of frontostriatal impairment in freezing of gait in Parkinson's disease

Shine

Moustafa

Matar³

et al. 2013

Front. Syst. Neurosci.

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“…Notably, the PPN is directly innervated by the STN (Nauta and Cole 1974;Parent and Smith 1987). We record from the rat PPTg since this area is homologous to the human PPN (Ballanger et al 2009;Hammond et al 1983;Ichinohe et al 2000;Jackson and Crossman 1983;Ruggiero et al 1997;Takakusaki et al 1997;Winn 2006), the PPTg directly receives STN neuronal efferents in rats (Hammond et al 1983), this area can modulate pontine nuclei activity which give rise to cerebellar mossy fibers (Tsutsumi et al 2007) and imaging studies (Aravamuthan et al 2007;Ballanger et al 2009;Fling et al 2013;Schweder et al 2010;Tykocki et al 2011) or retrograde tract tracing study (Newman and Ginsberg 1992) report signaling between the PPTg and cerebellum. We chose to focus our analysis on Purkinje cells since they are the main output cells of the cerebellar cortex and are easy to identify electrophysiologically.…”

Section: Acute In Vivo Electrophysiological Recordingsmentioning

confidence: 98%

Stimulation of the subthalamic nucleus engages the cerebellum for motor function in parkinsonian rats

et al. 2014

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Deep brain stimulation (DBS) is effective in managing motor symptoms of Parkinson's disease in well-selected individuals. Recently, research has shown that DBS in the basal ganglia (BG) can alter neural circuits beyond the traditional basal ganglia-thalamus-cortical (BG-TH-CX) loop. For instance, functional imaging showed alterations in cerebellar activity with DBS in the subthalamic nucleus (STN). However, these imaging studies revealed very little about how cell-specific cerebellar activity responds to STN stimulation or if these changes contribute to its efficacy. In this study, we assess whether STN-DBS provides efficacy in managing motor symptoms in Parkinson's disease by recruiting cerebellar activity. We do this by applying STN-DBS in hemiparkinsonian rats and simultaneously recording neuronal activity from the STN, brainstem and cerebellum. We found that STN neurons decreased spiking activity by 55% during DBS (P = 0.038), which coincided with a decrease in most pedunculopontine tegmental nucleus and Purkinje neurons by 29% (P < 0.001) and 28% (P = 0.003), respectively. In contrast, spike activity in the deep cerebellar nuclei increased 45% during DBS (P < 0.001), which was likely from reduced afferent activity of Purkinje cells. Then, we applied STN-DBS at sub-therapeutic current along with stimulation of the deep cerebellar nuclei and found similar improvement in forelimb akinesia as with therapeutic STN-DBS alone. This suggests that STN-DBS can engage cerebellar activity to improve parkinsonian motor symptoms. Our study is the first to describe how STN-DBS in Parkinson's disease alters cerebellar activity using electrophysiology in vivo and reveal a potential for stimulating the cerebellum to potentiate deep brain stimulation of the subthalamic nucleus.

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“…The major components of the mesencephalic locomotor region are the PPN and the cuneiform nucleus (Garcia-Rill, 1991). In the context of different outcomes of STN-DBS and PPN-DBS, PPN dysfunction likely contributes to PIGD in PD (Tykocki et al, 2011). The PPN receives direct inputs from the pre-SMA and the basal ganglion to modulate muscle tone by directly exciting pontine reticular formation (Burn, 2013).…”

Section: Introductionmentioning

confidence: 99%

Rapid Alleviation of Parkinson’s Disease Symptoms via Electrostimulation of Intrinsic Auricular Muscle Zones

Çakmak

Apaydın

Kızıltan

et al. 2017

Front. Hum. Neurosci.

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Background: Deep brain stimulation of the subthalamic nucleus (STN-DBS) and the pedunculopontine nucleus (PPN) significantly improve cardinal motor symptoms and postural instability and gait difficulty, respectively, in Parkinson’s disease (PD).Objective and Hypothesis: Intrinsic auricular muscle zones (IAMZs) allow the potential to simultaneously stimulate the C2 spinal nerve, the trigeminal nerve, the facial nerve, and sympathetic and parasympathetic nerves in addition to providing muscle feedback and control areas including the STN, the PPN and mesencephalic locomotor regions. Our aim was to observe the clinical responses to IAMZ stimulation in PD patients.Method: Unilateral stimulation of an IAMZ, which includes muscle fibers for proprioception, the facial nerve, and C2, trigeminal and autonomic nerve fibers, at 130 Hz was performed in a placebo- and sham-controlled, double-blinded, within design, two-armed study of 24 PD patients.Results: The results of the first arm (10 patients) of the present study demonstrated a substantial improvement in Unified Parkinson’s Disease Ratings Scale (UPDRS) motor scores due to 10 min of IAMZ electrostimulation (p = 0.0003, power: 0.99) compared to the placebo control (p = 0.130). A moderate to large clinical difference in the improvement in UPDRS motor scores was observed in the IAMZ electrostimulation group. The results of the second arm (14 patients) demonstrated significant improvements with dry needling (p = 0.011) and electrostimulation of the IAMZ (p < 0.001) but not with sham electrostimulation (p = 0.748). In addition, there was a significantly greater improvement in UPDRS motor scores in the IAMZ electrostimulation group compared to the IAMZ dry needling group (p < 0.001) and the sham electrostimulation (p < 0.001) groups. The improvement in UPDRS motor scores of the IAMZ electrostimulation group (ΔUPDRS = 5.29) reached moderate to high clinical significance, which was not the case for the dry needling group (ΔUPDRS = 1.54). In addition, both arms of the study demonstrated bilateral improvements in motor symptoms in response to unilateral IAMZ electrostimulation.Conclusion: The present study is the first demonstration of a potential role of IAMZ electrical stimulation in improving the clinical motor symptoms of PD patients in the short term.

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Pedunculopontine nucleus deep brain stimulation in Parkinson’s disease

Cited by 27 publications

References 72 publications

The role of frontostriatal impairment in freezing of gait in Parkinson's disease

The role of frontostriatal impairment in freezing of gait in Parkinson's disease

Stimulation of the subthalamic nucleus engages the cerebellum for motor function in parkinsonian rats

Rapid Alleviation of Parkinson’s Disease Symptoms via Electrostimulation of Intrinsic Auricular Muscle Zones

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