Publication

Distinct roles of the human cuneiform and pedunculopontine nuclei in gait initiation and freezing of gait

2026

Abstract

Freezing of gait (FOG) in Parkinson’s disease (PD) is a major cause of disability, often resistant to dopaminergic therapy and deep brain stimulation (DBS). Its underlying neural mechanisms remain unclear. The mesencephalic locomotor region (MLR) is a critical hub for gait control and a therapeutic target for DBS, but the respective functional roles of its two main nuclei, i.e. the cuneiform nucleus (CuN) and the pedunculopontine nucleus (PPN), remain unclear in human gait.

Here, we combined local field potential recordings from both the CuN and PPN with detailed biomechanical analyses of gait initiation in four PD patients suffering from dopa-resistant FOG. Neural activity was aligned to anticipatory postural adjustments (APA) and step execution to characterize the temporal organization of MLR dynamics during gait initiation and to identify alterations preceding freezing episodes. We also examined the effects of CuN, PPN and sham stimulation on gait initiation.

During gait initiation, the CuN and PPN exhibited distinct temporal and spectral neuronal activity patterns associated with different phases of gait initiation. Alpha-band activity in the CuN increased prior to APA and correlated with stepping rhythm, whereas the PPN showed prominent beta-band desynchronization during postural adjustments followed by alpha modulation during step execution. When FOG occurred after gait initiation (FOG + trials, n = 38), we observed a breakdown of this spatiotemporal organization. Specifically, freezing was preceded by exaggerated and mistimed alpha-band synchronization across the MLR and abnormal modulation of PPN beta activity compared with non-freezing trials (FOG− trials, n = 115, p

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2026

Abstract

Official source

Related concepts (32)

Neural oscillation

Neural oscillations, or brainwaves, are rhythmic or repetitive patterns of neural activity in the central nervous system. Neural tissue can generate oscillatory activity in many ways, driven either by mechanisms within individual neurons or by interactions between neurons. In individual neurons, oscillations can appear either as oscillations in membrane potential or as rhythmic patterns of action potentials, which then produce oscillatory activation of post-synaptic neurons.

Pedunculopontine nucleus

The pedunculopontine nucleus (PPN) or pedunculopontine tegmental nucleus (PPT or PPTg) is a collection of neurons located in the upper pons in the brainstem. It lies caudal to the substantia nigra and adjacent to the superior cerebellar peduncle. It has two divisions of subnuclei; the pars compacta containing mainly cholinergic neurons, and the pars dissipata containing mainly glutamatergic neurons and some non-cholinergic neurons. The pedunculopontine nucleus is one of the main components of the reticular activating system.

Gait (human)

A gait is a manner of limb movements made during locomotion. Human gaits are the various ways in which humans can move, either naturally or as a result of specialized training. Human gait is defined as bipedal forward propulsion of the center of gravity of the human body, in which there are sinuous movements of different segments of the body with little energy spent. Varied gaits are characterized by differences such as limb movement patterns, overall velocity, forces, kinetic and potential energy cycles, and changes in contact with the ground.

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Distinct roles of the human cuneiform and pedunculopontine nuclei in gait initiation and freezing of gait

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