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This article is part of the Research Topic Cognition and Sleep in Parkinson’s disease (PD)

Hypothesis & Theory ARTICLE

Front. Neurol., 05 June 2013 |

The serendipity case of the pedunculopontine nucleus low-frequency brain stimulation: chasing a gait response, finding sleep, and cognition improvement

Alessandro Stefani1,2*, Antonella Peppe2, Salvatore Galati3, Mario Stampanoni Bassi1, Vincenza D’Angelo1 and Mariangela Pierantozzi1
  • 1Department of Neuroscience, “Tor Vergata” University, Rome, Italy
  • 2IRCCS, Fondazione Santa Lucia, Rome, Italy
  • 3Neurocenter of Southern Switzerland, Lugano, Switzerland

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an efficacious therapy for Parkinson’s disease (PD) but its effects on non-motor facets may be detrimental. The low-frequency stimulation (LFS) of the pedunculopontine nucleus (PPN or the nucleus tegmenti pedunculopontini – PPTg-) opened new perspectives. In our hands, PPTg-LFS revealed a modest influence on gait but increased sleep quality and degree of attentiveness. At odds with potential adverse events following STN-DBS, executive functions, under PPTg-ON, ameliorated. A recent study comparing both targets found that only PPTg-LFS improved night-time sleep and daytime sleepiness. Chances are that different neurosurgical groups influence either the PPN sub-portion identified as pars dissipata (more interconnected with GPi/STN) or the caudal PPN region known as pars compacta, preferentially targeting intralaminar and associative nucleus of the thalamus. Yet, the wide electrical field delivered affects a plethora of en passant circuits, and a fine distinction on the specific pathways involved is elusive. This review explores our angle of vision, by which PPTg-LFS activates cholinergic and glutamatergic ascending fibers, influencing non-motor behaviors.

Keywords: deep brain stimulation, Parkinson disease, neuromodulation, executive function, sleep structure

Citation: Stefani A, Peppe A, Galati S, Stampanoni Bassi M, D’Angelo V and Pierantozzi M (2013) The serendipity case of the pedunculopontine nucleus low-frequency brain stimulation: chasing a gait response, finding sleep, and cognition improvement. Front. Neurol. 4:68. doi: 10.3389/fneur.2013.00068

Received: 16 August 2012; Accepted: 22 May 2013;
Published online: 05 June 2013.

Edited by:

Giovanni Albani, Istituto Auxologico Italiano, Italy

Reviewed by:

Alberto Albanese, Università Cattolica del Sacro Cuore, Italy
Mário M. Rosa, Universidade de Lisboa, Portugal
Josep Valls-Sole, Hospital Clinic, Spain

Copyright: © 2013 Stefani, Peppe, Galati, Stampanoni Bassi, D’Angelo and Pierantozzi. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.

*Correspondence: Alessandro Stefani, Movement Disorder Center, Department of System Medicine, “Tor Vergata” University, Viale Montpellier 1, Rome 00133, Italy e-mail: