Angelique Van Ombergen

Cortical reorganization in an astronaut's brain after long-duration spaceflight

To date, hampered physiological function after exposure to microgravity has been primarily attributed to deprived peripheral neuro-sensory systems. For the first time, this study elucidates alterations in human brain function after long-duration spaceflight. More specifically, we found significant differences in resting-state functional connectivity between motor cortex and cerebellum, as well as changes within the default mode network. In addition, the cosmonaut showed changes in the supplementary motor areas during a motor imagery task. These results highlight the underlying neural basis for the observed physiological deconditioning due to spaceflight and are relevant for future interplanetary missions and vestibular patients.To date, hampered physiological function after exposure to microgravity has been primarily attributed to deprived peripheral neuro-sensory systems. For the first time, this study elucidates alterations in human brain function after long-duration spaceflight. More specifically, we found significant differences in resting-state functional connectivity between motor cortex and cerebellum, as well as changes within the default mode network. In addition, the cosmonaut showed changes in the supplementary motor areas during a motor imagery task. These results highlight the underlying neural basis for the observed physiological deconditioning due to spaceflight and are relevant for future interplanetary missions and vestibular patients.

Vestibular migraine in an otolaryngology clinic: prevalence, associated symptoms, and prophylactic medication effectiveness.

Objective To assess the prevalence of vestibular migraine (VM) in patients consulting to an otolaryngology clinic, the neuro-otological associated symptoms, and the effect of prophylactic antimigrainous medication on VM symptom improvement. Study Design Retrospective chart review. Setting Tertiary referral otolaryngology clinic. Subjects and Methods We used the diagnostic criteria from the Bárány Society and the International Headache Society to allocate patients to a subgroup: VM, possible VM, and atypical VM. Main Outcome Measure The prevalence of VM, percentages of associated neurotological symptoms, and percentages of effectiveness of prophylactic medication. Results Sixty-five (16%) patients were selected from the total patient population (n = 407) from which 4.2% were assigned to the definite VM group, 5.7% to the probable VM group, and 6.1% to the atypical VM group. We found a significantly different distribution between the groups for photophobia (p = 0.035), ear pressure (p = 0.023), and scotoma (p = 0.015). Thirty patients were administered with flunarizine and 68% responded with an improvement in VM symptoms (p < 0.001). For propranolol, 31 patients were treated and there was an improvement of symptoms in 73% (p < 0.001). Remarkable was the fact that these percentages were not significantly different between the subgroups. Conclusion VM is a common disorder presenting in a dizziness clinic, and detailed history taking is important to assess VM-associated symptoms and thus to prevent underdiagnosis. The latter is very important because our study shows that the majority of patients, regardless of VM subtype, can benefit from a prophylactic treatment, but further prospective studies are necessary.

Mal de debarquement syndrome: a systematic review

Mal de debarquement (MdD) is a subjective perception of self-motion after exposure to passive motion, in most cases sea travel, hence the name. Mal de debarquement occurs quite frequently in otherwise healthy individuals for a short period of time (several hours). However, in some people symptoms remain for a longer period of time or even persist and this is then called mal de debarquement syndrome (MdDS). The underlying pathogenesis is poorly understood and therefore, treatment options are limited. In general, limited studies have focused on the topic, but the past few years more and more interest has been attributed to MdDS and its facets, which is reflected by an increasing number of papers. Till date, some interesting reviews on the topic have been published, but a systematic review of the literature is lacking and could help to address the shortcomings and flaws of the current literature. We here present a systematic review of MdD(S) based on a systematic search of medical databases employing predefined criteria, using the terms “mal de debarquement” and “sea legs”. Based on this, we suggest a list of criteria that could aid healthcare professionals in the diagnosis of MdDS. Further research needs to address the blank gaps by addressing how prevalent MdD(S) really is, by digging deeper into the underlying pathophysiology and setting up prospective, randomized placebo-controlled studies to evaluate the effectiveness of possible treatment strategies.

Decreased otolith-mediated vestibular response in 25 astronauts induced by long-duration spaceflight.

The information coming from the vestibular otolith organs is important for the brain when reflexively making appropriate visual and spinal corrections to maintain balance. Symptoms related to failed balance control and navigation are commonly observed in astronauts returning from space. To investigate the effect of microgravity exposure on the otoliths, we studied the otolith-mediated responses elicited by centrifugation in a group of 25 astronauts before and after 6 mo of spaceflight. Ocular counterrolling (OCR) is an otolith-driven reflex that is sensitive to head tilt with regard to gravity and tilts of the gravito-inertial acceleration vector during centrifugation. When comparing pre- and postflight OCR, we found a statistically significant decrease of the OCR response upon return. Nine days after return, the OCR was back at preflight level, indicating a full recovery. Our large study sample allows for more general physiological conclusions about the effect of prolonged microgravity on the otolith system. A deconditioned otolith system is thought to be the cause of several of the negative effects seen in returning astronauts, such as spatial disorientation and orthostatic intolerance. This knowledge should be taken into account for future long-term space missions.

Altered functional brain connectivity in patients with visually induced dizziness

Background Vestibular patients occasionally report aggravation or triggering of their symptoms by visual stimuli, which is called visually induced dizziness (VID). These patients therefore experience dizziness, discomfort, disorientation and postural unsteadiness. The underlying pathophysiology of VID is still poorly understood. Objective The aim of the current explorative study was to gain a first insight in the underlying neural aspects of VID. Methods We included 10 VID patients and 10 healthy matched controls, all of which underwent a resting state fMRI scan session. Changes in functional connectivity were explored by means of the intrinsic connectivity contrast (ICC). Seed-based analysis was subsequently performed in visual and vestibular seeds. Results We found a decreased functional connectivity in the right central operculum (superior temporal gyrus), as well as increased functional connectivity in the occipital pole in VID patients as compared to controls in a hypothesis-free analysis. A weaker functional connectivity between the thalamus and most of the right putamen was measured in VID patients in comparison to controls in a seed-based analysis. Furthermore, also by means of a seed-based analysis, a decreased functional connectivity between the visual associative area and the left parahippocampal gyrus was found in VID patients. Additionally, we found increased functional connectivity between thalamus and occipital and cerebellar areas in the VID patients, as well as between the associative visual cortex and both middle frontal gyrus and precuneus. Conclusions We found alterations in the visual and vestibular cortical network in VID patients that could underlie the typical VID symptoms such as a worsening of their vestibular symptoms when being exposed to challenging visual stimuli. These preliminary findings provide the first insights into the underlying functional brain connectivity in VID patients. Future studies should extend these findings by employing larger sample sizes, by investigating specific task-based paradigms in these patients and by exploring the implications for treatment.

The effect of spaceflight and microgravity on the human brain

Microgravity, confinement, isolation, and immobilization are just some of the features astronauts have to cope with during space missions. Consequently, long-duration space travel can have detrimental effects on human physiology. Although research has focused on the cardiovascular and musculoskeletal system in particular, the exact impact of spaceflight on the human central nervous system remains to be determined. Previous studies have reported psychological problems, cephalic fluid shifts, neurovestibular problems, and cognitive alterations, but there is paucity in the knowledge of the underlying neural substrates. Previous space analogue studies and preliminary spaceflight studies have shown an involvement of the cerebellum, cortical sensorimotor, and somatosensory areas and the vestibular pathways. Extending this knowledge is crucial, especially in view of long-duration interplanetary missions (e.g., Mars missions) and space tourism. In addition, the acquired insight could be relevant for vestibular patients, patients with neurodegenerative disorders, as well as the elderly population, coping with multisensory deficit syndromes, immobilization, and inactivity.

Intranasal scopolamine affects the semicircular canals centrally and peripherally

Space motion sickness (SMS), a condition caused by an intravestibular conflict, remains an important obstacle that astronauts encounter during the first days in space. Promethazine is currently the standard treatment of SMS, but scopolamine is used by some astronauts to prevent SMS. However, the oral and transdermal routes of administration of scopolamine are known to have substantial drawbacks. Intranasal administration of scopolamine ensures a fast absorption and rapid onset of therapeutic effect, which might prove to be suitable for use during spaceflights. The aim of this study was to evaluate the effects of intranasally administered scopolamine (0.4 mg) on the semicircular canals (SCCs) and the otoliths. This double-blind, placebo-controlled study was performed on 19 healthy male subjects. The function of the horizontal SCC and the vestibulo-ocular reflex, as well as the saccular function and utricular function, were evaluated. Scopolamine turned out to affect mainly the SCCs centrally and peripherally but also the utricles to a lesser extent. Centrally, the most probable site of action is the medial vestibular nucleus, where the highest density of muscarinic receptors has been demonstrated and afferent fibers from the SCCs and utricles synapse. Furthermore, our results suggest the presence of muscarinic receptors in the peripheral vestibular system on which scopolamine has a suppressive effect. Given the depressant actions on the SCCs, it is suggested that the pharmacodynamic effect of scopolamine may be attributed to the obliteration of intravestibular conflict that arises during (S)MS.

Spaceflight-induced neuroplasticity in humans as measured by MRI: what do we know so far?

Space travel poses an enormous challenge on the human body; microgravity, ionizing radiation, absence of circadian rhythm, confinement and isolation are just some of the features associated with it. Obviously, all of the latter can have an impact on human physiology and even induce detrimental changes. Some organ systems have been studied thoroughly under space conditions, however, not much is known on the functional and morphological effects of spaceflight on the human central nervous system. Previous studies have already shown that central nervous system changes occur during and after spaceflight in the form of neurovestibular problems, alterations in cognitive function and sensory perception, cephalic fluid shifts and psychological disturbances. However, little is known about the underlying neural substrates. In this review, we discuss the current limited knowledge on neuroplastic changes in the human central nervous system associated with spaceflight (actual or simulated) as measured by magnetic resonance imaging-based techniques. Furthermore, we discuss these findings as well as their future perspectives, since this can encourage future research into this delicate and intriguing aspect of spaceflight. Currently, the literature suffers from heterogeneous experimental set-ups and therefore, the lack of comparability of findings among studies. However, the cerebellum, cortical sensorimotor and somatosensory areas and vestibular-related pathways seem to be involved across different studies, suggesting that these brain regions are most affected by (simulated) spaceflight. Extending this knowledge is crucial, especially with the eye on long-duration interplanetary missions (e.g. Mars) and space tourism.

The Effect of Optokinetic Stimulation on Perceptual and Postural Symptoms in Visual Vestibular Mismatch Patients

Background Vestibular patients occasionally report aggravation or triggering of their symptoms by visual stimuli, which is called visual vestibular mismatch (VVM). These patients therefore experience discomfort, disorientation, dizziness and postural unsteadiness. Objective Firstly, we aimed to get a better insight in the underlying mechanism of VVM by examining perceptual and postural symptoms. Secondly, we wanted to investigate whether roll-motion is a necessary trait to evoke these symptoms or whether a complex but stationary visual pattern equally provokes them. Methods Nine VVM patients and healthy matched control group were examined by exposing both groups to a stationary stimulus as well as an optokinetic stimulus rotating around the naso-occipital axis for a prolonged period of time. Subjective visual vertical (SVV) measurements, posturography and relevant questionnaires were assessed. Results No significant differences between both groups were found for SVV measurements. Patients always swayed more and reported more symptoms than healthy controls. Prolonged exposure to roll-motion caused in patients and controls an increase in postural sway and symptoms. However, only VVM patients reported significantly more symptoms after prolonged exposure to the optokinetic stimulus compared to scores after exposure to a stationary stimulus. Conclusions VVM patients differ from healthy controls in postural and subjective symptoms and motion is a crucial factor in provoking these symptoms. A possible explanation could be a central visual-vestibular integration deficit, which has implications for diagnostics and clinical rehabilitation purposes. Future research should focus on the underlying central mechanism of VVM and the effectiveness of optokinetic stimulation in resolving it.

Letter to the Editor: comment and erratum to "Mal de debarquement syndrome: a systematic review".

In the recent Journal of Neurology publication ‘‘Mal de debarquement syndrome: a systematic review’’, Van Ombergen et al. carried out a systematic review of studies on mal de debarquement syndrome (MdDS) [1]. However, additional comments are necessary to clarify some views stated in the paper and to correct some unfortunate errors. We are coauthoring this erratum with Dr. Yoon-Hee Cha who brought the errors to our attention after the initial publication. Errors in the text as well as in the two Tables are corrected here. Whereas the paper equated MdDS to ‘sea legs,’ we wish to clarify that getting ‘sea legs’ is the process of adapting to passive motion conditions, whereas the terms ‘MdD,’ or ‘MdDS’ should be specifically used to refer to the postadaptation syndrome. Therefore, most people who develop ‘sea legs’ do not necessarily develop MdD or MdDS. Thus, our referencing of Gibbs et al. as an example of MdD(S) was not appropriate as this study addressed the formation of ‘sea legs’ but not the phenomenon of MdD(S). We indicated that stress and hormonal changes were possible triggers for MdDS several times in the paper but we’d like to clarify that these are aggravating factors of MdDS symptoms, not actual triggers. Furthermore, in the original publication, the authors stated that there was no data on the prevalence of MdDS in the general population. Indeed, no studies have yet addressed this issue directly, but in 2012 Cha reported that MdDS was diagnosed in 1.3 % of the patients of a well-established neuro-otology clinic [2]. Future epidemiological studies should investigate the prevalence in the general population, however. In our summarization of the current knowledge on the pathophysiology of MdDS, we stated that decreased brain metabolism was found in ‘‘diffusely spread cortical areas’’ in reference to a 2012 paper by Cha and colleagues [3]. However, this is not accurate since the hypometabolism was specifically seen in the left prefrontal, left temporal, right amygdala and right insula. We also need to correct an additional error stating that this paper stated that there was relatively higher brain metabolism in the left dorsolateral prefrontal cortex (DLPFC) in participants with MdDS compared to healthy controls [3], whereas it should have said that MdDS patients presented with lower brain metabolism in the left DLPFC. Furthermore, an important study by Ding et al. on the modulation effects of repetitive transcranial magnetic stimulation (rTMS) on MdDS symptoms [4] should have been more explicitly addressed. This group found that when MdDS participants reported an alleviation of MdDS symptoms after rTMS stimulation, the degree of independent component phase coherence (ICPC) went down. ICPC is a measure of the synchronicity between two cortical regions and therefore, a measure of neural connectivity. The fact that ICPC levels always decreased in parallel to a decrease in MdDS symptoms suggested that a higher state of neural synchronicity could be linked to MdDS symptoms. In addition, the regions in which the ICPC changed were predominantly in sensory processing areas in the posterior parietal and occipital cortices with an important connection to the prefrontal cortex, the region that was stimulated during the rTMS treatment. These results suggest a mechanism by which rTMS could be beneficial for & Angelique Van Ombergen angelique.vanombergen@uantwerpen.be