Vestibular responses in the macaque pedunculopontine nucleus and central mesencephalic reticular formation.

The pedunculopontine nucleus (PPN) and central mesencephalic reticular formation (cMRF) both send projections and receive input from areas with known vestibular responses. Noting their connections with the basal ganglia, the locomotor disturbances that occur following lesions of the PPN or cMRF, and the encouraging results of PPN deep brain stimulation in Parkinson's disease patients, both the PPN and cMRF have been linked to motor control. In order to determine the existence of and characterize vestibular responses in the PPN and cMRF, we recorded single neurons from both structures during vertical and horizontal rotation, translation, and visual pursuit stimuli. The majority of PPN cells (72.5%) were vestibular-only (VO) cells that responded exclusively to rotation and translation stimuli but not visual pursuit. Visual pursuit responses were much more prevalent in the cMRF (57.1%) though close to half of cMRF cells were VO cells (41.1%). Directional preferences also differed between the PPN, which was preferentially modulated during nose-down pitch, and cMRF, which was preferentially modulated during ipsilateral yaw rotation. Finally, amplitude responses were similar between the PPN and cMRF during rotation and pursuit stimuli, but PPN responses to translation were of higher amplitude than cMRF responses. Taken together with their connections to the vestibular circuit, these results implicate the PPN and cMRF in the processing of vestibular stimuli and suggest important roles for both in responding to motion perturbations like falls and turns.

The anatomy and localization of the pedunculopontine nucleus determined using probabilistic diffusion tractography [corrected].

Deep brain stimulation (DBS) of the pedunculopontine nucleus (PPN) has recently been shown to effectively ameliorate medically intractable axial symptoms of Parkinson's disease (PD). The effects of DBS are not limited to the targeted structure, but will affect the distributed anatomical networks to which the target structure belongs. Therefore, understanding the anatomical connections of the PPN will help elucidate treatment effects. Furthermore, establishing the topography of cortical and sub-cortical connections of the PPN in the human brain could aid accurate targeting of critical pathways in DBS. This article summarizes the connections of the PPN and the distribution of these connections within this nucleus (topography) as previously determined using diffusion tensor imaging (DTI) in healthy human volunteers and in a primate Macaca mulatta brain. These findings highlight DTI as a useful tool for surgical targeting for DBS of the PPN, and also show that DTI can be used to accurately probe the anatomy of the human and monkey brain in vivo.

Topography of cortical and subcortical connections of the human pedunculopontine and subthalamic nuclei.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is the most common surgical therapy for Parkinson' s disease (PD). DBS of the pedunculopontine nucleus (PPN) is emerging as a promising surgical therapy for PD as well. In order to better characterize these nuclei in humans, we determined the anatomical connections of the PPN and STN and the topography of these connections using probabilistic diffusion tractography. Diffusion tractography was carried out in eight healthy adult subjects using diffusion data acquired at 1.5 T MRI (60 directions, b=1000 s/mm(2), 2 x 2 x 2 mm(3) voxels). The major connections that we identified from single seed voxels within STN or PPN were present in at least half the subjects and the topography of these connections within a 36-voxel region surrounding the initial seed voxel was then examined. Both the PPN and STN showed connections with the cortex, basal ganglia, cerebellum, and down the spinal cord, largely matching connections demonstrated in primates. The topography of motor and associative brain areas in the human STN was strikingly similar to that shown in animals. PPN Topography has not been extensively demonstrated in animals, but we showed significant topography of cortical and subcortical connections in the human PPN. In addition to demonstrating the usefulness of PDT in determining the connections and topography of small grey matter structures in vivo, these results allow for inference of optimal DBS target locations and add to our understanding of the role of these nuclei in PD.