Abstract

BACKGROUND: Animal studies have demonstrated that the pedunculopontine nucleus (PPN) is involved in the control of posture and gait, and that it is also a key structure in controlling basic non-motor functions such as sleep, attention and arousal. In this systematic review we aimed to evaluate all available studies assessing the role of PPN on cognition, nocturnal sleep and alertness in humans. Finally, we attempted to define a model in which PPN acts as an interface structure between motor control and behavior. METHODS: A systematic search of the computerized databases MEDLINE and PubMed was conducted to identify papers on PPN and cognitive functions, sleep and alertness. Key search terms included: 'PPN', 'arousal', 'sleep', 'cognition', 'memory', 'language', 'attention', 'alertness', 'PPN-DBS', 'Parkinson's and PPN', 'Parkinson's and PPN-DBS'. RESULTS: Twelve studies met our inclusion criteria and were included. All of them involved PD patients implanted with unilateral or bilateral PPN-DBS, most patients had concomitant DBS of another anatomical structure (subthalamic nucleus or Zona incerta). There is a lack of consistent evidences confirming the effect of PPN-DBS on specific cognitive functions, alertness or sleep in PD. There is heterogeneity between and within surgical centres of study protocols especially regarding DBS targeting, parameters of stimulation and experimental methods. Moreover, the available studies are limited by the small sample size and the short follow-up time. It has been suggested that low frequency stimulation (25 Hz) has a better effect compared to the high frequency one (60-80 Hz) on alertness, however this needs to be confirmed in further studies. CONCLUSIONS: PPN-DBS is a promising but yet an experimental procedure. PD represents an encouraging pathological model for future studies aiming to shade light on the role of PPN in cognition, attention and alertness in humans.