14. Vestibular modulation of theta band oscillations in human pedunculopontine nucleus

Abstract

Background and aims: The pedunculopontine nucleus (PPN) is a new deep brain stimulation (DBS) target, thought to be particularly for useful in ameliorating gait disturbance in Parkinson’s disease. Recent evidence shows a prominent theta (4–7 Hz) rhythm in the PPN (Tsang et al., Neurology, 2010; Simon et al., J. Neurophysiol., 2010; Shimamoto et al., JNNP, 2010). Given that theta activity is modulated by vestibular signals elsewhere in the brain, e.g. hippocampus, (Shin, Synapse, 2010; Chen et al., Neuroimage, 2010), we assessed whether vestibular signals modulate PPN theta activity. Methods: We recorded local field potentials (LFPs) in three patients with implanted bilateral subthalamic nucleus (STN) and PPN DBS electrodes at 2000 Hz and filtered at 0.5–500 Hz at rest and during passive, yaw-plane whole body rotations (i.e., vestibular stimulation) at 0.2 and 0.4 Hz with eyes closed and then open with manifest vestibular ocular reflex activation (i.e., nystagmus) and then with VOR suppression (VORS). Frequency power spectra and the average power across a 1–1000 Hz frequency range were obtained. Results: PPN LFPs showed significant modulation during vestibular activation (rotations) compared to rest with power changes ca. four times larger than those found in the STN. The PPN LFP was dominated by theta (4–7 Hz) activity which was enhanced during all tasks compared to rest (including eyes open vs. closed at rest) except for VORS where there was a clear reduction in theta activity and this was more prominent for ‘fast’ (i.e., 0.4 Hz rotations) rotations. The pattern of theta activity was the same for right and left PPN including task-dependent modulation. To rule out the possibility that this theta activity was purely driven by nystagmus, we recorded LFPs during optokinetic nystagmus (OKN). OKN was associated with a decrease of theta power compared to rest. Conclusions: This is the first demonstration of vestibular modulation of PPN activity (in either animals or humans). Human PPN activity is increased during vestibular activation with a relative suppression of theta during VORS. This pattern of a reduction of activity during VORS compared to VOR is seen in the vestibular nuclei. Thus, the PPN may represent an important component of vestibular processing within the brainstem. We speculate that given the role of the vestibular system in balance and posture, PPN DBS may be work to improve gait and balance control via vestibular circuits.