Cytochrome P450 26b1-mediated specification of vestibular striola and central zones is required for transient responses in linear acceleration

ABSTRACTEach vestibular sensory epithelia of the inner ear is divided into two zones, the striola and extrastriola in maculae of otolith organs and the central and peripheral zones in cristae of semicircular canals, that differ in morphology and physiology. We found that formation of striolar/central zones during embryogenesis requires Cytochrome P450 26b1 (Cyp26b1)-mediated degradation of retinoic acid (RA). In Cyp26b1 conditional knockout mice, the identities of the striolar/central zones were compromised, including abnormal innervating neurons and otoconia in otolith organs. Vestibular evoked potentials (VsEP) in response to jerk stimuli were largely absent. Vestibulo-ocular reflexes and standard motor performances such as forced swimming were unaffected, but mutants had head tremors and deficits in balance beam tests that were consistent with abnormal vestibular input. Thus, degradation of RA during embryogenesis is required for patterning highly specialized regions of the vestibular sensory epithelia that may provide acute feedback about head motion.

Visual and vestibular functioning, and age and surgery effects on postural control in healthy children with vertical strabismus

Purpose: To describe visual and vestibular functioning and the effects of age and surgery effects on postural control in healthy children with vertical strabismus. Design: This is a comparative case series. Methods: We evaluated participants at the Scientific Institute Eugenio Medea during routine clinical activities. We enrolled 30 consecutive children/adolescents (age range 4–13 years) with isolated vertical strabismus, with and without corrective surgery. Participants were split into four subgroups according to age (4–8 years versus 9–13 years) and ocular surgery (surgery versus no surgery). The clinical protocol included ophthalmological, orthoptic, neurological, physiatrical, otolaryngological, and vestibular evaluations, and the instrumental protocol included ocular cyclotorsions assessment, posturography, and vestibular myogenic-evoked potentials. Main outcome measures of the study were the prevalence of study-relevant orthopedic, ocular, vestibular, and posturographic abnormalities. Results: Among the overall largely variable findings across patients’ groups, we found some interesting trends: larger binocular vision and convergence disorders in younger children, smaller prevalence of asymmetric vestibular-evoked potentials in operated children, less posturographic abnormalities in younger children. No clear-cut beneficial effect of surgery was found on all clinical and instrumental parameters considered, despite good re-alignment of the eyes. Conclusion: The pathophysiology of postural control in vertical strabismus is extremely complex and above the potential of this study design and should be specifically addressed in deeper experimental studies.

The inion response revisited: evidence for a possible cerebellar contribution to vestibular-evoked potentials produced by air-conducted sound stimulation

This study investigated the effect of eye gaze and head position on vestibular-evoked potentials (VsEPs). Head position would be expected to affect myogenic sources, and eye position is known to affect ocular myogenic responses (ocular vestibular-evoked myogenic potentials), whereas a neurogenic source should behave otherwise. Eleven healthy subjects were recruited, and VsEPs, using 72-channel EEG, were recorded at a fixed intensity above the vestibular threshold. Three eye gaze and three head positions were tested (−20°, 0°, and +20° to the horizontal). Short-latency potentials showed that in addition to the expected effect of gaze on infraocular (IO′) leads, where up-gaze gives a maximum response, significant changes in amplitude were also observed in electrodes remote from the eyes and in particular, from contralateral parietal-occipital (PO) and neck (CB′) leads. Short-latency potentials of similar latency were observed (p10/n17 and n10/p17, respectively). The pattern of change with gaze in the PO leads was distinct from that observed for the IO′ leads. For the PO leads, the maximum response was obtained with neutral gaze, and this was also distinct from that observed for CB′ electrodes, where a maximal response was observed with head flexion in the second wave but not the first. Evidence of modulation of N42 and N1 potentials with both eye and head position was also observed. Head- and eye-position manipulation thus suggests that the inion response consists of an early neurogenic component, as well as myogenic responses. The p10/n17 at PO, in particular, may be an indicator of vestibulocerebellar projections. NEW & NOTEWORTHY Loud sounds were used to activate vestibular receptors in human volunteers and the effects of head and eye position studied for short-latency responses. A potential (p10/n17) recorded in the parieto-occipital leads showed behavior not expected for a response with a myogenic origin. Source modeling suggested a possible origin from the cerebellum. It may represent a new indicator of human vestibulocerebellar function.