Implantation of human pedunculopontine nucleus: a safe and clinically relevant target in Parkinson's disease

Abstract

The peduncolopontine nucleus modulates locomotor activity and dysfunction in this nucleus may be responsible for the gait and postural impairments seen in Parkinson's disease and other movement disorders. We report the first surgical exploration and implantation of deep brain stimulating electrodes of the peduncolopontine nucleus area in two Parkinson's disease patients to examine the safety and the potential benefit of chronic electrical stimulation at this site. Under local anesthesia, the peduncolopontine nucleus was approached from a coronal burr hole using a trajectory that was 78-80 degrees and 62-64 degrees on the coronal and sagittal planes. Microrecordings helped to identify neurons in peduncolopontine nucleus and the adjacent substantia nigra pars reticulata. Chronic deep brain stimulating electrodes were implanted within the peduncolopontine nucleus in a manner similar to that practiced with deep brain stimulating surgery at other targets. Peduncolopontine nucleus neurons were characterized by small and broad multiunits (230 muV, 2.5 ms, 14.6 Hz). Caudal to this area, neurons firing at higher frequency, approximately 70 Hz, characteristic of nigral neuronal discharges, were encountered, followed by 2 mm of cells similar to those recorded in the dorsal peduncolopontine nucleus area. After deep brain stimulating electrodes implantation, acute intraoperative stimulation (up to 3 V) was performed with two stimulation frequencies in each session. Stimulation at 80 Hz has little discernable effect. On the other hand, stimulation at 10 Hz fostered a subjective feeling of 'well-being' and a time-locked amelioration of the clinical scores. These findings demonstrate that the stereotactic approach of peduncolopontine nucleus is safe. The target may reliably be identified by microrecordings. Low-frequency stimulation may produce acute improvements in motor function.

Deep Brain Stimulation for Movement Disorders of Basal Ganglia Origin: Restoring Function or Functionality?

“…Vim receives strong inputs from the cerebellum, and the effectiveness of tremor control with DBS at this location is a strong argument in favor of cerebellar involvement in the pathophysiology of tremor. PPN DBS [226][227][228][229][230][231][232][233][234][235][236][237][238][239], alone or in combination with STN or GPi DBS, is currently under study for patients with advanced PD who develop levodopaunresponsive freezing of gait, balance impairments, and falls. DBS of the PPN has been shown to be most effective at low stimulation frequencies [240].…”

Imagined gait modulates neuronal network dynamics in the human pedunculopontine nucleus

“…A high filter order (1000) was used to isolate narrow sub-bands of the LFP in order to distinguish, for example, high alpha oscillations (10-12 Hz) from low beta oscillations (12)(13)(14)(15)(16)(17)(18)(19)(20). The filtered signal was Hilbert transformed to extract the signal phase, and then the spike phase distribution (i.e.…”

“…Within the MLR, the pedunculopontine nucleus (PPN), that is extensively connected with the basal ganglia 11 , has a central role in the initiation and maintenance of gait [12][13][14] and lesions of the PPN induce gait deficits 14 . Gait and postural disturbances in PD are accompanied by cell loss within the PPN [14][15][16] , but are partially relieved by deep brain stimulation (DBS) in the PPN [17][18][19] , supporting the central role of the PPN in locomotion.Much is understood about the development and function of spinal cord CPGs 20 . However, while CPG function is controlled by afferent projections from the MLR 9, 10 , little is understood about activity within the MLR, and its response to movement.…”

Mechanisms of Deep Brain Stimulation in Movement Disorders as Revealed by Changes in Stimulus Frequency

“…First, while the effects of PPN DBS on PPN activity are unknown, firing rates in the PPN of a single PD subject (range, 8 -29 Hz in 27 multiunit recordings) suggest the presence of low-rate intrinsic activity of the PPN in subjects with PD. 83 Furthermore, cytochrome oxidase subunit I, choline acetyl transferase, and substance P mRNA expression de- creased significantly in the PPN of MPTP monkeys as compared with healthy monkeys, 84 suggesting that the pathological activity in the PPN has a low intrinsic frequency. Second, although the average rate of GPi neuronal firing is approximately the same in PD and HD, (mean rate Ϯ standard error of the mean ϭ 89.9 Ϯ 3 Hz in PD and 81.8 Ϯ 4.3 Hz in HD), intrinsic neuronal activity in PD includes more bursting and irregular spiking.…”