Vestibular loss promotes procedural response during a spatial task in rats.

Declarative memory refers to a spatial strategy using numerous sources of sensory input information in which visual and vestibular inputs are assimilated in the hippocampus. In contrast, procedural memory refers to a response strategy based on motor skills and familiar gestures and involves the striatum. Even if vestibular loss impairs hippocampal activity and spatial memory, vestibular-lesioned rats remain able to find food rewards during complex spatial memory task. Since hippocampal lesions induce a switch from declarative memory to procedural memory, we hypothesize that vestibular-lesioned rats use a strategy other than that of hippocampal spatial response to complete the task and to counterbalance the loss of vestibular information. We test, in a reverse T-maze paradigm, the types of strategy vestibular-lesioned rats preferentially uses in a spatial task. We clearly demonstrate that all vestibular-lesioned rats shift to a response strategy to solve the spatial task, while control rats use spatial and response strategies equally. We conclude that the loss of vestibular informations leading to spatial learning impairments is not offset at the hippocampus level by integration process of other sense mainly visual informations; but favors a response strategy through procedural memory most likely involving the striatum, cerebellum, and motor learning.

Navigation strategies in patients with vestibular loss tested in a virtual reality T-maze.

During navigation, humans mainly rely on egocentric and allocentric spatial strategies, two different frames of reference working together to build a coherent representation of the environment. Spatial memory deficits during navigation have been repeatedly reported in patients with vestibular disorders. However, little is known about how vestibular disorders can change the use of spatial navigation strategies. Here, we used a new reverse T-maze paradigm in virtual reality to explore whether vestibular loss specifically modifies the use of egocentric or allocentric spatial strategies in patients with unilateral (n = 23) and bilateral (n = 23) vestibular loss compared to healthy volunteers (n = 23) matched for age, sex and education level. Results showed that the odds of selecting and using a specific strategy in the T-maze were significantly reduced in both unilateral and bilateral vestibular loss. An exploratory analysis suggests that only right vestibular loss decreased the odds of adopting a spatial strategy, indicating an asymmetry of vestibular functions. When considering patients who used strategies to navigate, we observed that a bilateral vestibular loss reduced the odds to use an allocentric strategy, whereas a unilateral vestibular loss decreased the odds to use an egocentric strategy. Age was significantly associated with an overall lower chance to adopt a navigation strategy and, more specifically, with a decrease in the odds of using an allocentric strategy. We did not observe any sex difference in the ability to select and use a specific navigation strategy. Findings are discussed in light of previous studies on visuo-spatial abilities and studies of vestibulo-hippocampal interactions in peripheral vestibular disorders. We discuss the potential impact of the history of the disease (chronic stage in patients with a bilateral vestibulopathy vs. subacute stage in patients with a unilateral vestibular loss), of hearing impairment and non-specific attentional deficits in patients with vestibular disorders.

Impaired Attentional Processing During Parabolic Flight.

Previous studies suggest that altered gravity levels during parabolic flight maneuvers affect spatial updating. Little is known about the impact of the experimental setting and psychological stressors associated with parabolic flight experiments on attentional processes. To address this gap, we investigated the level of alertness, selective and sustained attention in 1 and 0 g using a Go/No-Go Continuous Performance Task. We also identified several parameters associated with the experimental set-up of a parabolic flight that could be expected to affect attentional processing. These included the use of scopolamine, sleep quality prior to the flight day, participant's stress level as well as mood and anxiety state before and after the parabolic flight. We observed a deterioration in attentional processing prior to the first parabola that was further aggravated in weightlessness and returned to baseline after the last parabola. Reaction Time, Hit and False Alarm Rate were moderately correlated with self-reported anxiety state, but not cortisol levels or emotional states. The use of scopolamine had minor effects on Reaction Time. Our results confirm previous studies reporting impairments of cognitive performance in 0 g, and highlight important aspects that should be considered for the design of behavioral research experiments in future parabolic flight campaigns.

Cooperation of the vestibular and cerebellar networks in anxiety disorders and depression.

The discipline of affective neuroscience is concerned with the neural bases of emotion and mood. The past decades have witnessed an explosion of research in affective neuroscience, increasing our knowledge of the brain areas involved in fear and anxiety. Besides the brain areas that are classically associated with emotional reactivity, accumulating evidence indicates that both the vestibular and cerebellar systems are involved not only in motor coordination but also influence both cognition and emotional regulation in humans and animal models. The cerebellar and the vestibular systems show the reciprocal connection with a myriad of anxiety and fear brain areas. Perception anticipation and action are also major centers of interest in cognitive neurosciences. The cerebellum is crucial for the development of an internal model of action and the vestibular system is relevant for perception, gravity-related balance, navigation and motor decision-making. Furthermore, there are close relationships between these two systems. With regard to the cooperation between the vestibular and cerebellar systems for the elaboration and the coordination of emotional cognitive and visceral responses, we propose that altering the function of one of the systems could provoke internal model disturbances and, as a result, anxiety disorders followed potentially with depressive states.

The balance of sleep: Role of the vestibular sensory system.

The vestibular system encodes linear and angular head motion supporting numerous functions from gaze stabilization and postural control, to high-level cortical functions involving spatial cognition, including self-body perception, verticality perception, orientation, navigation and spatial memory. At the brainstem and mesencephalic levels, the vestibular organs also influence postural blood pressure regulation, bone density and muscle composition via specific vestibulo-sympathetic efferences and have been shown to act as a powerful synchronizer of circadian rhythms. Here, we review the evidence that sleep deprivation and sleep apnea syndrome alter vestibular-related oculo-motor and postural control, and that, in turn, vestibular pathologies induce sleep disturbances. We suggest that sleep-related neuroplasticity might serve the adaptation and compensation processes following vestibular lesions in patients. Interestingly, a reciprocal neuroanatomical route between the vestibular nuclei and the orexinergic neurons has been reported. While orexinergic modulation of the vestibular nuclei related to postural control has been suggested, we postulate that vestibular inputs might in turn influence the sleep-wake state switch, informing the brain about the daily quantity of motion.

Differential regulation of NMDA receptor-expressing neurons in the rat hippocampus and striatum following bilateral vestibular loss demonstrated using flow cytometry.

There is substantial evidence that loss of vestibular function impairs spatial learning and memory related to hippocampal (HPC) function, as well as increasing evidence that striatal (Str) plasticity is also implicated. Since the N-methyl-d-aspartate (NMDA) subtype of glutamate receptor is considered essential to spatial memory, previous studies have investigated whether the expression of HPC NMDA receptors changes following vestibular loss; however, the results have been contradictory. Here we used a novel flow cytometric method to quantify the number of neurons expressing NMDA receptors in the HPC and Str following bilateral vestibular loss (BVL) in rats. At 7 and 30 days post-op., there was a significant increase in the number of HPC neurons expressing NMDA receptors in the BVL animals, compared to sham controls (P ≤ 0.004 and P ≤ 0.0001, respectively). By contrast, in the Str, at 7 days there was a significant reduction in the number of neurons expressing NMDA receptors in the BVL group (P ≤ 0.05); however, this difference had disappeared by 30 days post-op. These results suggest that BVL causes differential changes in the number of neurons expressing NMDA receptors in the HPC and Str, which may be related to its long-term impairment of spatial memory.

Critical Flicker Fusion Frequency: A Marker of Cerebral Arousal During Modified Gravitational Conditions Related to Parabolic Flights.

In situ evaluation of human brain performance and arousal remains challenging during operational circumstances, hence the need for a rapid, reliable and reproducible tool. Here we hypothesized that the Critical flicker fusion frequency (CFFF) reflecting/requiring visual integration, visuo-motor skills and decision-taking process might be a powerful, fast and simple tool in modified gravity environments. Therefore 11 male healthy volunteers were assessed for higher cognitive functions with CFFF during parabolic flights. They were assessed at different time points: upon arrival to the base, 30 min after subcutaneous scopolamine administration, before parabolas, during hypergravity and microgravity at break time (between the 16th and the 17th parabola), on the return flight and on the ground after landing. First, a stable, and consistent measurement of CFFF could be obtained within 12 s. Second, under modified gravitational conditions, the perceptual ability of participants is significantly modified. Compared to the baseline, evolution is characterized by a significant increase of CFFF when in microgravity (0g: 106.9 ± 5.5%), and a significant decrease of CFFF while in hypergravity (2g: 94.5 ± 3.8%). Other time-points were not statistically different from the baseline value. Although the underlying mechanism is still debated, we suggest that the CFFF test is a global marker of cerebral arousal as the result of visuo-motor and decision taking testing based on a simple visual stimulus with an uncomplicated set up that could be used under various environmental conditions. The authors express an opinion that it would be advisable to introduce CFFF measurement during spaceflights as it allows individual longitudinal assessment of individual ability even under conditions of incomplete physiological compensation, as shown here during parabolic flights.

Effects of acute altered gravity during parabolic flight and/or vestibular loss on cell proliferation in the rat dentate gyrus.

Both parabolic flight, i.e. a condition of altered gravity, and loss of vestibular function, have been suggested to affect spatial learning and memory, which is known to be influenced by neurogenesis in the hippocampus. In this study we investigated whether short alternated micro- and hyper-gravity stimulations during parabolic flight and/or loss of vestibular function, would alter cell proliferation in the hippocampal dentate gyrus of rats, by measuring the number of bromodeoxyuridine (BrdU)-incorporated cells. Rats were randomly allocated to the following experimental groups: (1) sham transtympanic saline injection only (n=5); (2) bilateral vestibular deafferentation (BVD) by sodium arsanilate transtympanic injection only (n=5); (3) sham treatment and parabolic flight (n=5); (4) BVD and parabolic flight (n=6). Forty-two days following transtympanic injection, the animals were subjected to parabolic flight in an awake restrained condition after habituation. A modified Airbus A300 aircraft was flown on a parabolic path, creating 20s of 1.8G during both climbing and descending and 22s of 0G at the apex of each parabola. The no flight animals were subjected to the same housing for the same duration. Immediately after the parabolic flight or control ground condition, animals were injected with BrdU (300mg/kg, i.p). Twenty-four hs after BrdU injection, rats were sacrificed. BrdU immunolabelling was performed and the number of BrdU+ve cells in the dentate gyrus of the hippocampus was quantified using a modified fractionator method. BVD caused a large and significant reduction in the number of BrdU-positive cells compared to sham animals (P≤0.0001); however, flight and all interactions were non-significant. These results indicate that BVD significantly decreased cell proliferation irrespective of the short exposure to altered/modified gravity.