Modern Magnetic Resonance Imaging Modalities to Advance Neuroimaging in Astronauts.

INTRODUCTION: The rapid development of the space industry requires a deeper understanding of spaceflight's impact on the brain. MRI research reports brain volume changes following spaceflight in astronauts, potentially affecting cognition. Recently, we have demonstrated that this evidence of volumetric changes, as measured by typical T1-weighted sequences (e.g., magnetization-prepared rapid gradient echo sequence; MPRAGE), is error-prone due to the microgravity-related redistribution of cerebrospinal fluid in the brain. More modern neuroimaging methods, particularly dual-echo MPRAGE (DEMPRAGE) and magnetization-prepared rapid gradient echo sequence utilizing two inversion pulses (MP2RAGE), have been suggested to be resilient to this error. Here, we tested if these imaging modalities offered consistent segmentation performance improvements in some commonly employed neuroimaging software packages.METHODS: We conducted manual gray matter tissue segmentation in traditional T1w MRI images to utilize for comparison. Automated tissue segmentation was performed for traditional T1w imaging, as well as on DEMPRAGE and MP2RAGE images from the same subjects. Statistical analysis involved a comparison of total gray matter volumes for each modality, and the extent of tissue segmentation agreement was assessed using a test of similarity (Dice coefficient).RESULTS: Neither DEMPRAGE nor MP2RAGE exhibited consistent segmentation performance across all toolboxes tested.DISCUSSION: This research indicates that customized data collection and processing methods are necessary for reliable and valid structural MRI segmentation in astronauts, as current methods provide erroneous classification and hence inaccurate claims of neuroplastic brain changes in the astronaut population.Berger L, Burles F, Jaswal T, Williams R, Iaria G. Modern magnetic resonance imaging modalities to advance neuroimaging in astronauts. Aerosp Med Hum Perform. 2024; 95(5):245-253.

Functional brain networks in Developmental Topographical Disorientation.

Despite a decade-long study on Developmental Topographical Disorientation, the underlying mechanism behind this neurological condition remains unknown. This lifelong selective inability in orientation, which causes these individuals to get lost even in familiar surroundings, is present in the absence of any other neurological disorder or acquired brain damage. Herein, we report an analysis of the functional brain network of individuals with Developmental Topographical Disorientation ($n = 19$) compared against that of healthy controls ($n = 21$), all of whom underwent resting-state functional magnetic resonance imaging, to identify if and how their underlying functional brain network is altered. While the established resting-state networks (RSNs) are confirmed in both groups, there is, on average, a greater connectivity and connectivity strength, in addition to increased global and local efficiency in the overall functional network of the Developmental Topographical Disorientation group. In particular, there is an enhanced connectivity between some RSNs facilitated through indirect functional paths. We identify a handful of nodes that encode part of these differences. Overall, our findings provide strong evidence that the brain networks of individuals suffering from Developmental Topographical Disorientation are modified by compensatory mechanisms, which might open the door for new diagnostic tools.

Medial positioning of the hippocampus and hippocampal fissure volume in developmental topographical disorientation.

Developmental topographical disorientation (DTD) refers to the lifelong inability to orient by means of cognitive maps in familiar surroundings despite otherwise well-preserved general cognitive functions, and the absence of any acquired brain injury or neurological condition. While reduced functional connectivity between the hippocampus and other brain regions has been reported in DTD individuals, no structural differences in gray matter tissue for the whole brain neither for the hippocampus were detected. Considering that the human hippocampus is the main structure associated with cognitive map-based navigation, here, we investigated differences in morphological and morphometric hippocampal features between individuals affected by DTD (N = 20) and healthy controls (N = 238). Specifically, we focused on a developmental anomaly of the hippocampus that is characterized by the incomplete infolding of hippocampal subfields during fetal development, giving the hippocampus a more round or pyramidal shape, called incomplete hippocampal inversion (IHI). We rated IHI according to standard criteria and extracted hippocampal subfield volumes after FreeSurfer's automatic segmentation. We observed similar IHI prevalence in the group of individuals with DTD with respect to the control population. Neither differences in whole hippocampal nor major hippocampal subfield volumes have been observed between groups. However, when assessing the IHI independent criteria, we observed that the hippocampus in the DTD group is more medially positioned comparing to the control group. In addition, we observed bigger hippocampal fissure volume for the DTD comparing to the control group. Both of these findings were stronger for the right hippocampus comparing to the left. Our results provide new insights regarding the hippocampal morphology of individuals affected by DTD, highlighting the role of structural anomalies during early prenatal development in line with the developmental nature of the spatial disorientation deficit.

Anxiety and Depressive Traits in the Healthy Population Does Not Affect Spatial Orientation and Navigation.

The ability to navigate and orient in spatial surroundings is critical for effective daily functioning. Such ability is perturbed in clinically diagnosed mood and anxiety disorders, with patients exhibiting poor navigational skills. Here, we investigated the effects of depression and anxiety traits (not the clinical manifestation of the disorders) on the healthy population and hypothesized that greater levels of depression and anxiety traits would manifest in poorer spatial orientation skills and, in particular, with a poor ability to form mental representations of the environment, i.e., cognitive maps. We asked 1237 participants to perform a battery of spatial orientation tasks and complete two questionnaires assessing their anxiety and depression traits. Contrary to our hypothesis, we did not find any correlation between participants' anxiety and depression traits and their ability to form cognitive maps. These findings may imply a significant difference between the clinical and non-clinical manifestations of anxiety and depression as affecting spatial orientation and navigational abilities.

Neurocognitive Adaptations for Spatial Orientation and Navigation in Astronauts.

Astronauts often face orientation challenges while on orbit, which can lead to operator errors in demanding spatial tasks. In this study, we investigated the impact of long-duration spaceflight on the neural processes supporting astronauts' spatial orientation skills. Using functional magnetic resonance imaging (fMRI), we collected data from 16 astronauts six months before and two weeks after their International Space Station (ISS) missions while performing a spatial orientation task that requires generating a mental representation of one's surroundings. During this task, astronauts exhibited a general reduction in neural activity evoked from spatial-processing brain regions after spaceflight. The neural activity evoked in the precuneus was most saliently reduced following spaceflight, along with less powerful effects observed in the angular gyrus and retrosplenial regions of the brain. Importantly, the reduction in precuneus activity we identified was not accounted for by changes in behavioral performance or changes in grey matter concentration. These findings overall show less engagement of explicitly spatial neurological processes at postflight, suggesting astronauts make use of complementary strategies to perform some spatial tasks as an adaptation to spaceflight. These preliminary findings highlight the need for developing countermeasures or procedures that minimize the detrimental effects of spaceflight on spatial cognition, especially in light of planned long-distance future missions.

Sex and menstrual cycle influence human spatial navigation strategies and performance.

Which facets of human spatial navigation do sex and menstrual cycle influence? To answer this question, a cross-sectional online study of reproductive age women and men was conducted in which participants were asked to demonstrate and self-report their spatial navigation skills and strategies. Participants self-reported their sex and current menstrual phase [early follicular (EF), late follicular/periovulatory (PO), and mid/late luteal (ML)], and completed a series of questionnaires and tasks measuring self-reported navigation strategy use, topographical memory, cognitive map formation, face recognition, and path integration. We found that sex influenced self-reported use of cognitive map- and scene-based strategies, face recognition, and path integration. Menstrual phase moderated the influence of sex: compared to men, women had better face recognition and worse path integration, but only during the PO phase; PO women were also better at path integration in the presence of a landmark compared to EF + ML women and men. These findings provide evidence that human spatial navigation varies with the menstrual cycle and suggest that sensitivity of the entorhinal cortex and longitudinal axis of the hippocampus to differential hormonal effects may account for this variation.

The Unresolved Methodological Challenge of Detecting Neuroplastic Changes in Astronauts.

After completing a spaceflight, astronauts display a salient upward shift in the position of the brain within the skull, accompanied by a redistribution of cerebrospinal fluid. Magnetic resonance imaging studies have also reported local changes in brain volume following a spaceflight, which have been cautiously interpreted as a neuroplastic response to spaceflight. Here, we provide evidence that the grey matter volume changes seen in astronauts following spaceflight are contaminated by preprocessing errors exacerbated by the upwards shift of the brain within the skull. While it is expected that an astronaut's brain undergoes some neuroplastic adaptations during spaceflight, our findings suggest that the brain volume changes detected using standard processing pipelines for neuroimaging analyses could be contaminated by errors in identifying different tissue types (i.e., tissue segmentation). These errors may undermine the interpretation of such analyses as direct evidence of neuroplastic adaptation, and novel or alternate preprocessing or experimental paradigms are needed in order to resolve this important issue in space health research.

Rare diseases and space health: optimizing synergies from scientific questions to care.

Knowledge transfer among research disciplines can lead to substantial research progress. At first glance, astronaut health and rare diseases may be seen as having little common ground for such an exchange. However, deleterious health conditions linked to human space exploration may well be considered as a narrow sub-category of rare diseases. Here, we compare and contrast research and healthcare in the contexts of rare diseases and space health and identify common barriers and avenues of improvement. The prevalent genetic basis of most rare disorders contrasts sharply with the occupational considerations required to sustain human health in space. Nevertheless small sample sizes and large knowledge gaps in natural history are examples of the parallel challenges for research and clinical care in the context of both rare diseases and space health. The two areas also face the simultaneous challenges of evidence scarcity and the pressure to deliver therapeutic solutions, mandating expeditious translation of research knowledge into clinical care. Sharing best practices between these fields, including increasing participant involvement in all stages of research and ethical sharing of standardized data, has the potential to contribute to humankind's efforts to explore ever further into space while caring for people on Earth in a more inclusive fashion.

COVID-19 in a pregnant kidney transplant recipient - what we need to know: A case report.

BACKGROUND: In the era of the coronavirus disease 2019 (COVID-19) pandemic, kidney tran splant recipients are more susceptible to severe acute respiratory syndrome co ronavirus (SARS-CoV-2) infection, developing severe morbidity and graft im pairment. Pregnant women are also more likely to develop severe COVID-19 di sease, causing pregnancy complications such as preterm births and acute kidney injury. CASE SUMMARY: Herein, we report the case of a pregnant woman with a third kidney tran splantation who developed COVID-19 disease. The reduction of immunosuppressive drugs and strict monitoring of trough blood levels were needed to avoid severe SARS-CoV-2-related complications, and permitted to continue a healthy pregnancy and maintain good graft function. In such a complex scenario, the con comitance of COVID-19-related morbidity, the risk of acute rejection in the hype rimmune recipient, graft dysfunction and pregnancy complications make the management of immunosuppression a very difficult task and clinicians must be aware. CONCLUSION: Tailoring the immunosuppressive regimen is a key factor affecting both the graft outcome and pregnancy safety.

Evaluation of APOE ɛ2/ɛ3/ɛ4 Alleles in a Cohort of Individuals Affected by Developmental Topographical Disorientation.

The three common alleles of the APOE gene, ɛ2/ɛ3/ɛ4, have been linked to human spatial orientation. We investigated the genetic role of APOE in developmental topographical disorientation (DTD), a lifelong condition that results in topographical disorientation. We genotyped the APOE ɛ2/ɛ3/ɛ4 alleles in a cohort of 20 unrelated DTD probands, and found allele frequencies not statistically different from the those seen in the population as a whole. Therefore, we found no evidence that DTD occurs preferentially on a genetic background containing any particular APOE allele, making it unlikely that these APOE alleles are contributing to the development of DTD.

How Does Dementia Begin to Manifest in Bipolar Disorder? A Description of Prodromal Clinical and Cognitive Changes.

BACKGROUND: Older adults with bipolar disorder (BD) have increased dementia risk, but signs of dementia are difficult to detect in the context of pre-existing deficits inherent to BD. OBJECTIVE: To identify the emergence of indicators of early dementia in BD. METHODS: One hundred and fifty-nine non-demented adults with BD from the National Alzheimer's Coordinating Center (NACC) data repository underwent annual neuropsychological assessment up to 14 years (54.0 months average follow-up). Cognitive performance was examined longitudinally with linear mixed-effects models, and yearly differences between incident dementia cases and controls were examined in the six years prior to diagnosis. RESULTS: Forty participants (25.2%) developed dementia over the follow-up period ('incident dementia cases'). Alzheimer's disease was the most common presumed etiology, though this was likely a result of sampling biases within NACC. Incident dementia cases showed declining trajectories in memory, language, and speeded attention two years prior to dementia onset. CONCLUSION: In a sample of BD patients enriched for Alzheimer's type dementia, prodromal dementia in BD can be detected up to two years before onset using the same cognitive tests used in psychiatrically-healthy older adults (i.e., measures of verbal recall and fluency). Cognition in the natural course of BD is generally stable, and impairment or marked decline on measures of verbal episodic memory or semantic retrieval may indicate an early neurodegenerative process.

The relationship between mental and physical space and its impact on topographical disorientation.

We generate mental representations of space to facilitate our ability to remember things and navigate our environment. Many studies implicitly assume that these representations simply reflect the environments that they represent without considering other factors that influence the extent to which this is the case. Here, we bring together findings from cognitive psychology, environmental psychology, geography, urban planning, and neuroscience to discuss how internalizing the environment involves a complex interplay between bottom-up and top-down mental processes and depends on key characteristics of the physical environment itself. We describe how mental space is structured, the ways in which mental and physical space converge and diverge, and the disparate but complementary techniques used to assess these relationships. Finally, we contextualize this knowledge in the clinical populations affected by acquired and developmental topographical disorientation, exploring mechanisms that cause these patients to get lost in familiar surroundings.

The hamletic dilemma of patients waiting for kidney transplantation during the COVID-19 pandemic: To accept or not to accept (an organ offer)?

The outbreak of COVID-19 led to a reduction in the number of organ transplant interventions in most Countries. In April 2020, at the Tor Vergata University in Rome, Italy, two patients on the waiting list for kidney transplantation (KT) declined a deceased donor's kidney offer. Therefore, between April 20 and 25, 2020, we conducted a telephone survey among our 247 KT waitlist patients. Our aim was to explore: (a) the COVID-19 diffusion among them and (b) their current willingness to be transplanted in case of a kidney offer from a deceased donor. Two hundred and forty-three patients participated in a phone interview. One patient had died from COVID-19. Eighty-five (35%) KT candidates would decline any kidney offer, in most cases until the end of the COVID-19 pandemic. Upon a multivariate analysis, female gender (OR = 2.25, 95% CI = 1.26-4.03, P = .006), high cardiovascular risk (OR = 2.33, 95% CI = 1.06-5.08, P = .034), a waiting list time <3 years (OR = 0.375, 95% CI = 0.15-0.95, P = .04), and the need to be transferred to another hospital for HD (OR = 2.56, 95% CI = 1.10-5.9, P = .03) were associated with such refusal. The COVID-19 pandemic led to a fear of transplantation in a third of the KT candidates. Proactive educational webinars could be a useful tool to remove, or at least lessen, any doubts on the part of KT candidates and to avoid losing the opportunity to quit dialysis.

Egocentric Navigation Abilities Predict Episodic Memory Performance.

The medial temporal lobe supports both navigation and declarative memory. On this basis, a theory of phylogenetic continuity has been proposed according to which episodic and semantic memories have evolved from egocentric (e.g., path integration) and allocentric (e.g., map-based) navigation in the physical world, respectively. Here, we explored the behavioral significance of this neurophysiological model by investigating the relationship between the performance of healthy individuals on a path integration and an episodic memory task. We investigated the path integration performance through a proprioceptive Triangle Completion Task and assessed episodic memory through a picture recognition task. We evaluated the specificity of the association between performance in these two tasks by including in the study design a verbal semantic memory task. We also controlled for the effect of attention and working memory and tested the robustness of the results by including alternative versions of the path integration and semantic memory tasks. We found a significant positive correlation between the performance on the path integration the episodic, but not semantic, memory tasks. This pattern of correlation was not explained by general cognitive abilities and persisted also when considering a visual path integration task and a non-verbal semantic memory task. Importantly, a cross-validation analysis showed that participants' egocentric navigation abilities reliably predicted episodic memory performance. Altogether, our findings support the hypothesis of a phylogenetic continuity between egocentric navigation and episodic memory and pave the way for future research on the potential causal role of egocentric navigation on multiple forms of episodic memory.

Behavioural and cognitive mechanisms of Developmental Topographical Disorientation.

Individuals affected by Developmental Topographical Disorientation (DTD) get lost on a daily basis, even in the most familiar of surroundings such as their neighbourhood, the building where they have worked for many years, and, in extreme cases, even in their own homes. Individuals with DTD report a lifelong selective inability to orient despite otherwise well-preserved general cognitive functions, and the absence of any acquired brain injury or neurological condition, with general intelligence reported to be within the normal range. To date, the mechanisms underlying such a selective developmental condition remain unknown. Here, we report the findings of a 10-year-long study investigating the behavioural and cognitive mechanisms of DTD in a large sample of 1211 cases. We describe the demographics, heritability pattern, self-reported and objective spatial abilities, and some personality traits of individuals with DTD as compared to a sample of 1624 healthy controls; importantly, we test the specific hypothesis that the presence of DTD is significantly related to the inability of the individuals to form a mental representation of the spatial surroundings (i.e., a cognitive map). We found that individuals with DTD reported relatively greater levels of neuroticism and negative affect, and rated themselves more poorly on self-report measures of memory and imagery skills related to objects, faces, and places. While performing interactive tasks, as a group, the individuals with DTD performed slightly worse on a scene-based perspective-taking task, and, notably struggled to solve tasks that demand the generation and use of a cognitive map. These novel findings help define the phenotype of DTD, and lay the foundation for future studies of the neurological and genetic mechanisms of this lifelong condition.

Awareness and Impact of Non-pharmaceutical Interventions During Coronavirus Disease 2019 Pandemic in Renal Transplant Recipients.

The concerns generated by coronavirus disease 2019 (COVID-19) pandemic are having profound impact on solid organ transplantation (SOT). Non-pharmaceutical interventions (NPI) are currently the only measures available to contain COVID-19 in the general population and in more vulnerable recipients of any organ transplant. In this cross-sectional case control study from a patient survey undertaken in 2 transplant centers (TxC) in the Kingdom of Saudi Arabia and Italy, we aimed to appraise awareness of the NPI implemented by respective these governments. We have also evaluated the impact of COVID-19 on our kidney transplant (KT) recipients and a control group of kidney living donors (KLD). In our series, there were zero cases of COVID-19 among 111 KT recipients and 70 KLD of the control group. Demography, transplant type, immunosuppression regimes, and, importantly, the different COVID-19 prevalence in the 2 regions of the TxC did not appear to influence incidence of COVID-19 in our KT recipients. The absence of COVID-19 cases in our series was unexpected. Our findings suggest that awareness of NPI is associated with a successful containment of COVID-19 in vulnerable, immunosuppressed KT recipients.

Body illusion and affordances: the influence of body representation on a walking imagery task in virtual reality.

It is well known that our body works as a fundamental reference when we perform visuo-perceptual judgements in spatial surroundings, and that body illusions can modify our perception of size and distance of objects in space. To date, however, few studies have evaluated whether or not a body illusion could have a significant impact on the way individuals perceive to move within the environment. Here, we used a full-body illusion paradigm to verify the hypothesis that an altered representation of the legs of the individuals influences their time-to-walk estimation while imaging to reach objects in a virtual environment. To do so, we asked a group of young healthy volunteers to perform a task in which they were required to imagine walking towards a previously seen target location in a virtual environment, soon after receiving the body illusion; we required participants to use a response button to time their imagined walk from start to end. We found that participants imagined walking faster following the illusion elicited by the vision of longer legs presented from an anatomical perspective, as compared to when experiencing standard legs in the same position.This difference in imagined walking distance decreased when the object to reach was displayed farther, suggesting a fading effect. Furthermore, taking into consideration the baseline error in walking time estimation in VR, we noticed a specific influence of the long anatomical legs in reducing the perceived time needed to reach an object and a general increase in the percentage of error when the same legs are presented in a non-anatomical orientation. These findings provide evidence that body illusions could influence the way individuals perceive their locomotion in the spatial surrounding.

A pilot study evaluating the effects of concussion on the ability to form cognitive maps for spatial orientation in adolescent hockey players.

OBJECTIVE: In this pilot study, we investigated the impact of a sport-related concussion (SRC) on the ability to form cognitive maps, mental representations of the environment that are critical for spatial orientation and navigation. PARTICIPANTS: We recruited 18 adolescent hockey players suffering from a SRC, and 19 age, sex and handedness-matched hockey players with no history of concussion. MAIN MEASURE: We asked participants to perform the Spatial Configuration Task (SCT), a computerized tool used to quantitatively measure the ability of the individuals to form cognitive maps. RESULTS: We found that athletes with a concussion performed significantly worse than controls on the SCT (F(1,34) = 5.82, p =.021, [Formula: see text] = -0.72), confirming a negative effect of a SRC on the ability to form cognitive maps. We found no significant difference between groups in average response time, and no significant correlation between participants' performance at the SCT and reported symptoms of concussion as rated on the Sport Concussion Assessment Tool (SCAT5). CONCLUSIONS: Consistent with the integrity of extended neural networks required for effective spatial orientation and navigation, the findings of our pilot study provide preliminary evidence suggesting that a SRC may affect the ability to familiarize with a spatial surrounding and orient within it.

A Novel Training Program to Improve Human Spatial Orientation: Preliminary Findings.

The ability to form a mental representation of the surroundings is a critical skill for spatial navigation and orientation in humans. Such a mental representation is known as a "cognitive map" and is formed as individuals familiarize themselves with the surrounding, providing detailed information about salient environmental landmarks and their spatial relationships. Despite evidence of the malleability and potential for training spatial orientation skills in humans, it remains unknown if the specific ability to form cognitive maps can be improved by an appositely developed training program. Here, we present a newly developed computerized 12-days training program in a virtual environment designed specifically to stimulate the acquisition of this important skill. We asked 15 healthy volunteers to complete the training program and perform a comprehensive spatial behavioral assessment before and after the training. We asked participants to become familiar with the environment by navigating a small area before slowly building them up to navigate within the larger and more complex environment; we asked them to travel back and forth between environmental landmarks until they had built an understanding of where those landmarks resided with respect to one another. This process repeated until participants had visited every landmark in the virtual town and had learned where each landmark resided with respect to the others. The results of this study confirmed the feasibility of the training program and suggested an improvement in the ability of participants to form mental representations of the spatial surrounding. This study provides preliminary findings on the feasibility of a 12-days program in training spatial orientation skills. We discuss the utility and potential impact of this training program in the lives of the many individuals affected by topographical disorientation as a result of an acquired or developmental condition.