Physiological identification of the human pedunculopontine nucleus

Abstract

Background: The pedunculopontine nucleus (PPN) is a brainstem structure with widespread connections to the basal ganglia. Despite the recent introduction of PPN deep brain stimulation (DBS) for the treatment of gait disorders, little is known about its physiology in humans.

Methods: Single unit discharge characteristics of neurons in the PPN region were analysed in four patients and PPN local field potentials (LFP) in one patient, recorded during the course of DBS implantation. Two patients had Parkinson disease, and two had non-sinemet responsive parkinsonism. Cell locations were plotted in the coordinate system of a human brainstem atlas.

Results: Fifty-six units in the PPN region were studied, of which 32 mapped to within PPN boundaries. The mean (SD) discharge rate of neurons in the PPN was 23.2 (15.6) Hz. Spontaneous neuronal firing rate and burst discharge rate were significantly different between neurons in the region dorsal to PPN and those in the PPN. Responses to passive movement of contralateral and ipsilateral limbs were found. Theta and beta band oscillations were present in the PPN LFP.

Conclusion: PPN discharge characteristics may prove useful in the electrophysiological identification of PPN during DBS implantation surgery.

Figure 1

Determination of electrode tip location in the coordinates system of the Paxinos Atlas of the Human Brainstem. (A) Post-operative sagittal plane MRI from case 4, reformatted in Paxinos atlas coordinates. The origin (0,0,0) is at the obex. (B) Same MRI as (A), reformatted in the axial plane 33 mm dorsal to the obex, showing DBS lead location at this axial level. (C) Drawing of the corresponding slice from the Paxinos Atlas of the Human Brainstem with lead location marked (*). The PPN and major surrounding structures have been traced from the Paxinos atlas.

Figure 2

Examples of single unit recordings obtained at various distances above and within the pedunculopontine nucleus from case 1. (A) Average electrode trajectory superimposed on parasagittal section from the Schaltenbrand and Warren human brain atlas, 6.5 mm from midline. Circles along the trajectory indicate microelectrode recording location for the example recordings. (B–E) Examples of neuronal recordings. One second of data is shown on the left, with an expanded timescale (2 ms) trace of a single action potential at right. (B) Obex +39.5 mm. (C) Obex +35.6 mm. (D) Obex +33.7 mm. (E) Obex +32.2 mm. RN, red nucleus; SNr, substantia nigra pars reticulata.

Figure 3

Spontaneous neuronal discharge rate of all cells, plotted as a function of their normalised distances from the obex. The boundaries of the pedunculopontine nucleus, based on the Paxinos Atlas of the Human Brainstem, are indicated by dotted lines. Open circles, narrow action potential (AP) widths; closed circles, wide action potential widths.

Figure 4

Distribution of oscillatory frequencies in spontaneous discharge. (A) Dorsal to PPN. (B) Within PPN.

Figure 5

Examples of neuronal responses to passive joint movements and eye opening in the region of the PPN. (A) Perimovement spike density function illustrating a brief, phasic response to joint displacement (39.6 mm dorsal to obex). The initial accelerometer deflection occurred at time zero. Responses to 10 movement repetitions were averaged. Horizontal dotted lines represent threshold of significance. (B) Perimovement spike density function illustrating a prolonged response to joint displacement (38.8 mm dorsal to obex). Responses to 12 movement repetitions were averaged. (C) Raster plot of neuronal discharge (dorsal to pedunculopontine nucleus) showing a dramatic increase in activity with eye opening (40.7 mm dorsal to obex). The solid line above the raster marks the epochs when the eyes were open.

Figure 6

Power spectral density of the local field potential recorded in the region of the pedunculopontine nucleus (PPN) in subject 4, during alternating rest and voluntary contralateral elbow movement (solid line=rest, dotted line=movement). (A) Recording at depth of 37.8 mm in the Paxinos atlas coordinates (above the PPN). (B) Recording at depth 33.6 mm in the Paxinos atlas coordinates (in the PPN). (C, D) Percentage of power in theta-alpha, low beta, high beta, low gamma and high gamma frequency bands recorded dorsal to PPN (same data as in (A)) or within the PPN (same data as in (B)). Solid bar, rest; grey bar, movement.