The integrative role of the pedunculopontine nucleus in human gait

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.

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

“…Another series of 5 patients was reported with bilateral PPN DBS administered in tandem with DBS in the caudal zona incerta (cZI) [10]. A recent study which included a double-blind randomized study protocol applied bilateral DBS to the anterior PPN [11,12]. …”

“…Paris, France [12]. The PPN was targeted using an MRI and a 3D histological atlas of the basal ganglia that were deformed to the preoperative T1-weighted MRI.…”

“…The report from the Paris group, however, reported 2 severe complications [11,12]. Symptomatic bleeding occurred in 1 patient, who developed a midbrain hematoma, followed by impairment of consciousness.…”

Participation of the pedunculopontine tegmental nucleus in arousal-demanding functions

“…With regard to the motor nature of the PPTg, this is supported by the PPTg being part of most of the mesencephalic locomotor region, by its connections with subcortical and cortical motor structures, by its fibers innervating lower brainstem and reticulospinal neurons, by its activation in locomotor imagery tasks, by its neurons that discharge in relation to limb movements and, finally, by improvements of motor disabilities induced by its continuous electrical stimulation in PD patients [29,[33][34][35]169,[179][180][181][182][183][184].…”

Where and what is the PPN and what is its role in locomotion?

“…For example, FOG is accentuated when approaching doorways and can be alleviated by the availability of targets for stepping. In this issue of Brain, Lau et al (2015) explore the effects of deep brain stimulation on performance of a locomotor imagery task in patients with Parkinson's disease, and reveal distinct roles for the STN and a second structure, the pedunculopontine nucleus (PPN), in the control of gait.…”