Local and Relayed Effects of Deep Brain Stimulation of the Pedunculopontine Nucleus

Abstract

Our discovery of low-threshold stimulation-induced locomotion in the pedunculopontine nucleus (PPN) led to the clinical use of deep brain stimulation (DBS) for the treatment of disorders such as Parkinson’s disease (PD) that manifest gait and postural disorders. Three additional major discoveries on the properties of PPN neurons have opened new areas of research for the treatment of motor and arousal disorders. The description of (a) electrical coupling, (b) intrinsic gamma oscillations, and (c) gene regulation in the PPN has identified a number of novel therapeutic targets and methods for the treatment of a number of neurological and psychiatric disorders. We first delve into the circuit, cellular, intracellular, and molecular organization of the PPN, and then consider the clinical results to date on PPN DBS. This comprehensive review will provide valuable information to explain the network effects of PPN DBS, point to new directions for treatment, and highlight a number of issues related to PPN DBS.

Subthalamic nucleus oscillations correlate with vulnerability to freezing of gait in patients with Parkinson's disease

“…The PPN comprises part of the so-called MLR in the brain stem and is the final output of the cortico-subcortical loops that regulate gait initiation and adaptation (Garcia-Rill et al, 2015). More recent studies have suggested that low frequency stimulation (40–60 Hz) effectively activates the PPN, whereas high frequency stimulation (> 80 Hz) inactivates the same structure (Garcia-Rill et al, 2019).…”

“…PPN stimulation can reduce FOG in some patients (Moro et al, 2010; Thevathasan et al, 2011). In animal models, rostral PPN neurons are strongly interconnected with the basal ganglia, including the STN and globus pallidus interna (Garcia-Rill et al, 2019). Cortical regions, such as supplementary motor area (SMA), may also be involved (Shine et al, 2013a; Snijders et al, 2016).…”

Review of the Midbrain Ascending Arousal Network Nuclei and Implications for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), Gulf War Illness (GWI) and Postexertional Malaise (PEM)

“…Reduced activity of the locus coeruleus (LC) in PTSD may lead to reduced adrenergic inhibition of the PTN that permits an increase in anxiety, hyperarousal, and drive for rapid eye movement (REM) sleep with nightmares and traumatic memories (flashbacks). The PTN also participates in the regulation of posture and locomotion, gait instability, falling, and voluntary movement [ 123 ].…”

Deep Brain Stimulation of the Pedunculopontine Tegmental Nucleus Renders Neuroprotection through the Suppression of Hippocampal Apoptosis: An Experimental Animal Study

“…It is capable of influencing and regulating all levels of basal ganglia and corticostriatal activity other than being a vital component of brainstem reticular and motor control circuitry. Besides this, PPTg has served as a pivotal target area for DBS for the treatment of several neurodegenerative disorders [11]. The PPTg primarily consists of a subpopulation of coleogenic, glutamergic, and GABAergic neurons in the brain stem [12], and it has been mainly involved in hippocampus formation and theta rhythm.…”