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.
Highlights
There is sufficient history in the application of deep brain stimulation (DBS) to be confident that implanted electrodes at such sites as the subthalamic region (STN), internal pallidum, and the pedunculopontine nucleus (PPN) have salutary effects on some of the symptoms of Parkinson’s disease (PD) and related disorders
These results demonstrate that PPN neurons are mainly active during high frequency EEG states such as waking and rapid eye movement (REM) sleep
We suggest that a more thorough assessment of the parameters used in PD patients is needed, in responses to various frequencies of frequencies of neuronal PPN activity are in the 10 Hz and 20–60 Hz ranges
Summary
There is sufficient history in the application of deep brain stimulation (DBS) to be confident that implanted electrodes at such sites as the subthalamic region (STN), internal pallidum (iGP), and the pedunculopontine nucleus (PPN) have salutary effects on some of the symptoms of Parkinson’s disease (PD) and related disorders. The problem is that physicians adjust the frequency of stimulation, the duration of pulses applied, and the polarity of the leads activated on an empirical–clinical basis That is, it appears as if every medical center settles on their individual parameters depending on the response of each patient, without systematic testing across variations in the parameters. This review provides background information on the anatomy and physiology of the PPN that might explain some of the effects of particular parameters being applied to this region. Such information is essential in formulating a set of effective and replicable parameters. Very little work on similar morphological and physiological properties of the STN and iGP is available
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