Cerebellar projections to the macaque midbrain tegmentum: Possible near response connections

Since most gaze shifts are to targets that lie at a different distance from the viewer than the current target, gaze changes commonly require a change in the angle between the eyes. As part of this response, lens curvature must also be adjusted with respect to target distance by the ciliary muscle. It has been suggested that projections by the cerebellar fastigial and posterior interposed nuclei to the supraoculomotor area (SOA), which lies immediately dorsal to the oculomotor nucleus and contains near response neurons, support this behavior. However, the SOA also contains motoneurons that supply multiply innervated muscle fibers (MIFs) and the dendrites of levator palpebrae superioris motoneurons. To better determine the targets of the fastigial nucleus in the SOA, we placed an anterograde tracer into this cerebellar nucleus in Macaca fascicularis monkeys and a retrograde tracer into their contralateral medial rectus, superior rectus, and levator palpebrae muscles. We only observed close associations between anterogradely labeled boutons and the dendrites of medial rectus MIF and levator palpebrae motoneurons. However, relatively few of these associations were present, suggesting these are not the main cerebellar targets. In contrast, labeled boutons in SOA, and in the adjacent central mesencephalic reticular formation (cMRF), densely innervated a subpopulation of neurons. Based on their location, these cells may represent premotor near response neurons that supply medial rectus and preganglionic Edinger–Westphal motoneurons. We also identified lens accommodation-related cerebellar afferent neurons via retrograde trans-synaptic transport of the N2c rabies virus from the ciliary muscle. They were found bilaterally in the fastigial and posterior interposed nuclei, in a distribution which mirrored that of neurons retrogradely labeled from the SOA and cMRF. Our results suggest these cerebellar neurons coordinate elements of the near response during symmetric vergence and disjunctive saccades by targeting cMRF and SOA premotor neurons.

Intrinsic Well-Demarcated Midline Brainstem Lesion Successfully Resected through a Midline Pontine Splitting Approach

<b><i>Introduction:</i></b> Surgical approaches to intrinsic pontine lesions are technically difficult and prone to complications. The surgical approach to the brainstem through midline pontine splitting is regarded as safe since there are no crossing vital fibers in the midline between the abducens nuclei at the facial colliculi in the pons and the oculomotor nucleus in the midbrain, although its actual utilization has not been reported previously. <b><i>Case Presentation:</i></b> A 6-year-old boy presented with a large intrinsic cystic lesion in the pons. We successfully achieved gross total removal via the median sulcus of the fourth ventricle. The fixation in adduction and limitation of abduction were newly observed in the left eye after surgery. <b><i>Discussion:</i></b> The advantage of the surgical approach through the median sulcus is the longer line of dissection in an axial direction and the gain of a wider operative view. On the other hand, the disadvantage of this approach is the limited orientation and view toward lateral side and a possible impairment of the medial longitudinal fasciculi and paramedian pontine reticular formation, which are located lateral to the midline sulcus bilaterally and are easily affected via the median sulcus of the fourth ventricular floor. Ongoing developments in intraoperative neuro-monitoring and navigation systems are expected to enhance this promising approach, resulting in a safer and less complicated procedure in the future. <b><i>Conclusion:</i></b> The surgical approach through midline pontine splitting is suitable for midline and deep locations of relatively large pontine lesions that necessitate a wider surgical window.

Apoptotic Markers in the Midbrain of the Human Neonate After Perinatal Hypoxic/Ischemic Injury

Our previous postmortem studies on neonates with neuropathological injury of perinatal hypoxia/ischemia (PHI) showed a dramatic reduction of tyrosine hydroxylase expression (dopamine synthesis enzyme) in substantia nigra (SN) neurons, with reduction of their cellular size. In order to investigate if the above observations represent an early stage of SN degeneration, we immunohistochemically studied the expression of cleaved caspase-3 (CCP3), apoptosis inducing factor (AIF), and DNA fragmentation by using terminal deoxynucleotidyltransferase-mediated dUTP-biotin 3′-end-labeling (TUNEL) technique in the SN of 22 autopsied neonates (corrected age ranging from 34 to 46.5 gestational weeks), in relation to the severity/duration of PHI injury, as estimated by neuropathological criteria. No CCP3-immunoreactive neurons and a limited number of apoptotic TUNEL-positive neurons with pyknotic characteristics were found in the SN. Nuclear AIF staining was revealed only in few SN neurons, indicating the presence of early signs of AIF-mediated degeneration. By contrast, motor neurons of the oculomotor nucleus showed higher cytoplasmic AIF expression and nuclear translocation, possibly attributed to the combined effect of developmental processes and increased oxidative stress induced by antemortem and postmortem factors. Our study indicates the activation of AIF, but not CCP3, in the SN and oculomotor nucleus of the human neonate in the developmentally critical perinatal period.

Response of supraoculomotor area neurons during combined saccade-vergence movements

Combined saccade-vergence movements allow humans and other primates to align their eyes with objects of interest in three-dimensions. In the absence of saccades, vergence movements are typically slow, symmetrical movements of the two eyes in opposite directions. However, combined saccade-vergence movements produce vergence velocities that exceed values observed during vergence alone. This phenomenon is often called “vergence enhancement”, or “saccade-facilitated vergence,” though it is important to consider that rapid vergence changes, known as “vergence transients,” are also observed during conjugate saccades. We developed a visual target array that allows monkeys to make saccades in all directions between targets spaced at distances that correspond to ~1° intervals of vergence angle relative to the monkey. We recorded the activity of vergence-sensitive neurons in the supra-oculomotor area (SOA), located dorsal and lateral to the oculomotor nucleus while monkeys made saccades with vergence amplitudes ranging from 0 to 10°. The primary focus of this study was to test the hypothesis that neurons in the SOA fire a high frequency burst of spikes during saccades that could generate the enhanced vergence. We found that individual neurons encode vergence velocity during both saccadic and non-saccadic vergence, yet firing rates were insufficient to produce the observed enhancement of vergence velocity. Our results are consistent with the hypothesis that slow vergence changes are encoded by the SOA while fast vergence movements require an additional contribution from the saccadic system. NEW & NOTEWORTHY Research into combined saccade-vergence movements has so far focused on exploring the saccadic neural circuitry, leading to diverging hypotheses regarding the role of the vergence system in this behavior. In this study, we report the first quantitative analysis of the discharge of individual neurons that encode vergence velocity in the monkey brain stem during combined saccade-vergence movements.

A Case of Progressive Stroke on Posterior Circulation with Transient Bilateral Oculomotor Palsy

Infarction located in the midbrain and pons presents various ophthalmic symptoms, because of the damage of the nuclei that control the movement of internal and external ocular and palpebral muscles. We experienced a case which presented with rare ocular symptoms and course. A 61-year-old man presented with left hemiparesis and dysarthria, bilateral ptosis, and bilateral impaired eyeball movement: right eyeball movement was totally impaired and left could only perform slight adduction. MRI showed fresh stroke in the right thalamus, cerebral crus, and posterior lobe and cuneate lesion on bilateral paramedian portion of the midbrain. MRA showed occlusion in the P1 area of the posterior cerebral artery (PCA). Transesophageal echocardiography (TEE) showed findings of a patent foramen ovale (PFO). These findings suggested cardioembolic stroke as a cause of PCA occlusion and we prescribed rivaroxaban. The patient’s eyeball and eyelid movement, only on the left side, was improved imperfectly 2 weeks later. We thought that neurological findings and course of this case may have arisen from dysfunction of the oculomotor nucleus and oculomotor fascicles, and MLF results from the presence of the lesion in paramedian midbrain and pons.