Chronic, Mild Vestibulopathy Leads to Deficits in Spatial Tasks that Rely on Vestibular Input While Leaving Other Cognitive Functions and Brain Volumes Intact

Objectives: In this study, based on the known vestibulo-hippocampal connections, we asked whether mild chronic vestibulopathy leads only to vestibular-related deficits or whether there are effects on hippocampal function, structure, and cognition in general. In more detail, we assessed whether chronic vestibulopathy leads to (a) deficits in vestibular tasks without cognitive demand (balancing), (b) deficits in spatial cognitive tasks that require vestibular input (path integration, rotational memory), (c) deficits in spatial cognitive tasks that do not rely on vestibular input, (d) deficits in general cognitive function, and (e) atrophy in the brain. Methods: A total of 15 patients with chronic uni- or bilateral vestibulopathy (56.8 ± 10.1 years; 4 females) were included in this study and were age- and gender-matched by the control participants (57.6 ± 10.5) in a pairwise manner. Given their clinical symptoms and their deficits of the vestibulo-ocular reflex (VOR) the patients could be classified as being mildly affected. All participants of the underwent the following tests: clinical balance (CBT), triangle completion (TCT) for path integration, rotational memory (RM), the visuo-spatial subset of the Berlin intelligence structure test (BIS-4) and d2-R for attention and concentration, and a structural MRI for gray matter analysis using voxel-based morphometry (VBM). Results: Compared to the healthy controls, the vestibulopathy patients performed significantly worse in terms of CBT, TCT, and RM but showed no differences in terms of the BIS-4 and d2-R. There were also no significant volumetric gray matter differences between the two groups. Conclusions: This study provides evidence that both non-cognitive and cognitive functions that rely on vestibular input (balancing, path integration, rotational memory) are impaired, even in mild chronic vestibulopathy, while other cognitive functions, which rely on visual input (visuo-spatial memory, attention), are unimpaired in this condition, together with an overall intact brain structure. These findings may reflect a segregation between vestibular- and visual-dependent processes in the medial temporal lobe on the one hand and a structure–function dissociation on the other.

Developing Proprioceptive Countermeasures to Mitigate Postural and Locomotor Control Deficits After Long-Duration Spaceflight

Astronauts experience post-flight disturbances in postural and locomotor control due to sensorimotor adaptations during spaceflight. These alterations may have adverse consequences if a rapid egress is required after landing. Although current exercise protocols can effectively mitigate cardiovascular and muscular deconditioning, the benefits to post-flight sensorimotor dysfunction are limited. Furthermore, some exercise capabilities like treadmill running are currently not feasible on exploration spaceflight vehicles. Thus, new in-flight operational countermeasures are needed to mitigate postural and locomotor control deficits after exploration missions. Data from spaceflight and from analog studies collectively suggest that body unloading decreases the utilization of proprioceptive input, and this adaptation strongly contributes to balance dysfunction after spaceflight. For example, on return to Earth, an astronaut’s vestibular input may be compromised by adaptation to microgravity, but their proprioceptive input is compromised by body unloading. Since proprioceptive and tactile input are important for maintaining postural control, keeping these systems tuned to respond to upright balance challenges during flight may improve functional task performance after flight through dynamic reweighting of sensory input. Novel approaches are needed to compensate for the challenges of balance training in microgravity and must be tested in a body unloading environment such as head down bed rest. Here, we review insights from the literature and provide observations from our laboratory that could inform the development of an in-flight proprioceptive countermeasure.

Nociceptin/orphanin FQ peptide receptor mediates inhibition of N-type calcium currents in vestibular afferent neurons of the rat

Our results show that in primary vestibular afferent neurons, activation of the nociceptin/orphanin FQ peptide receptor inhibits the N-type calcium current by a mechanism mediated by G proteins. We propose that calcium current inhibition modulates neurotransmitter release from vestibular afferents, producing a presynaptic modulation of vestibular input to vestibular nuclei, thus contributing to gain control in the vestibular afferent input.

Linking vestibular function and sub-cortical grey matter volume changes in a longitudinal study of aging adults

Emerging evidence suggests a relationship between impairments of the vestibular (inner ear balance) system and decline in visuospatial cognitive performance in older adults. However, it is unclear whether age-related vestibular loss is associated with volume loss in brain regions known to receive vestibular input. To address this gap, we investigated the association between vestibular function and the volumes of four structures that process vestibular information (the hippocampus, entorhinal cortex, thalamus, and basal ganglia) in a longitudinal study of 97 healthy, older participants from the Baltimore Longitudinal Study of Aging. Vestibular testing included cervical vestibular-evoked myogenic potentials (cVEMP) to measure saccular function, ocular VEMP (oVEMP) to measure utricular function, and video head-impulse tests to measure the horizontal semi-circular canal vestibulo-ocular reflex (VOR). Participants in the sample had vestibular and brain MRI data for a total of 1 (18.6%), 2 (49.5%) and 3 (32.0%) visits. Linear mixed-effects regression was used to model regional volume over time as a function of vestibular physiological function, correcting for age, sex, intracranial volume, and inter-subject random variation in the baseline levels of and rates of change of volume over time. We found that poorer saccular function, characterized by lower cVEMP amplitude, is associated with reduced bilateral volumes of the thalamus and basal ganglia at each time point, demonstrated by a 0.0714 cm3 ± 0.0344 (p=0.038; 95% CI: 0.00397-0.139) lower bilateral-mean volume of the basal ganglia and a 0.0440 cm3 ± 0.0221 (p=0.046; 95% CI: 0.000727-0.0873) lower bilateral-mean volume of the thalamus for each 1 unit lower cVEMP amplitude. There were no significant associations between volume and oVEMP or mean VOR gain. These findings provide insight into the potential neural substrates for the observed link between age-related vestibular loss and spatial cognition.Comprehensive SummaryHumans rely on their vestibular, or inner ear balance, system to manage everyday life. In addition to sensing head motion and head position with respect to gravity, the vestibular system helps to maintain balance and gaze stability. Furthermore, the evidence is mounting that vestibular function is linked to spatial cognition: the capacity to mentally represent the world and navigate through it. Yet, the exact processes by which vestibular function enables spatial cognition are unclear. One promising mechanism is through changes of the sizes and shapes of the brain anatomies that support spatial cognitive function. The intuition is that, as vestibular function declines with aging, less vestibular information is distributed throughout the brain, leading to a loss of neurons in areas that receive those inputs. In support of this putative mechanism, recent discoveries underscore the association of vestibular impairment with spatial cognitive declines and with atrophy of brain areas that support spatial cognition, the hippocampus and entorhinal cortex, in older adults. This work investigates the extent over time to which age-related vestibular loss contributes to the atrophy of four brain regions that receive vestibular input and subserve spatial cognition: the hippocampus, entorhinal cortex, thalamus, and basal ganglia. Using data from a cohort of healthy, older adults between 2013 and 2017 from the Baltimore Longitudinal Study of Aging, we assessed regional brain volume as a function of vestibular function, while accounting for common confounds of brain volume change (e.g. age, sex, head size). We found that poor vestibular function is associated with significantly reduced volumes of the thalamus and basal ganglia. Notably, this study is one of the first to demonstrate relationships between age-related vestibular loss and brain atrophy in brain regions that receive vestibular input and promote spatial cognition. But more research is needed to understand the observed connection between vestibular function, neuroanatomy, and spatial cognition. Which brain areas suffer from age-related vestibular loss? How and in what sequence are they affected? As the world’s aging population—and likely the prevalence of age-related vestibular impairment—increases, answering questions like these becomes increasingly important. One day, these answers will provide targets for preemptive interventions, like physical or cognitive pre-habilitation, to stave off malignant cognitive changes before they occur and progress into clinical significance.

Sensory conflict alters visual perception of action capabilities during crossing of a closing gap in virtual reality

The somatosensory, vestibular, and visual systems contribute to multisensory integration, which facilitates locomotion around obstacles in the environment. The joystick-controlled virtual reality (VR) locomotion interface does not preserve congruent sensory input like real-walking, yet is commonly used in human behaviour research. Our purpose was to determine if collision avoidance behaviours were affected during an aperture crossing task when somatosensory and vestibular input were incongruent, and only vision was accurate. Participants included 36 young adults who completed a closing gap aperture crossing task in VR using real-walking and joystick-controlled locomotion. Participants successfully completed the task using both interfaces. Switch point between passable and impassable apertures was larger for joystick-controlled locomotion compared with real-walking, but time-to-contact (TTC) was lower for real-walking than joystick-controlled locomotion. Increased joystick-controlled locomotion switch point may be attributed to incongruency between visual and non-visual information, causing underestimation of distance travelled towards the aperture. Performance on future VR applications incorporating dynamically changing gaps can be considered successful using joystick-controlled locomotion, while taking into account a potential behaviour difference. Differences in TTC may be explained by the requirement of gait termination in real-walking but not in joystick-controlled locomotion. Future VR studies would benefit from programming acceleration and deceleration into joystick-controlled locomotion interfaces.

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.

Antero-posterior versus lateral vestibular input processing in human visual cortex

Visuo-vestibular integration is crucial for locomotion, yet cortical mechanisms involved remain poorly understood. We combined binaural monopolar galvanic vestibular stimulation (GVS) and functional magnetic resonance imaging (fMRI) to characterize the cortical networks activated during antero-posterior and lateral stimulations in humans. We focused on functional areas that selectively respond to egomotion-consistent optic flow patterns: the human middle temporal complex (hMT+), V6, the ventral intraparietal (VIP) area, the cingulate sulcus visual (CSv) area and the posterior insular cortex (PIC). Areas hMT+, CSv, and PIC were equivalently responsive during lateral and antero-posterior GVS while areas VIP and V6 were highly activated during antero-posterior GVS but remained silent during lateral GVS. Using psychophysiological interaction (PPI) analyses, we confirmed that a cortical network including areas V6 and VIP is engaged during antero-posterior GVS. Our results suggest that V6 and VIP play a specific role in processing multisensory signals specific to locomotion during navigation.