Preliminary evidence of high prevalence of cerebral microbleeds in astronauts with spaceflight experience.

Long-duration spaceflight poses a variety of health risks to astronauts, largely resulting from extended exposure to microgravity and radiation. Here, we assessed the prevalence and incidence of cerebral microbleeds in sixteen astronauts before and after a typical 6-month mission on board the International Space Station Cerebral microbleeds are microhemorrhages in the brain, which are typically interpreted as early evidence of small vessel disease and have been associated with cognitive impairment. We identified evidence of higher-than-expected microbleed prevalence in astronauts with prior spaceflight experience. However, we did not identify a statistically significant increase in microbleed burden up to 7 months after spaceflight. Altogether, these preliminary findings suggest that spaceflight exposure may increase microbleed burden, but this influence may be indirect or occur over time courses that exceed 1 year. For health monitoring purposes, it may be valuable to acquire neuroimaging data that are able to detect the occurrence of microbleeds in astronauts following their spaceflight missions.

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.

Sex differences in the relationship between age, performance, and BOLD signal variability during spatial context memory processing.

Recent work suggests that the relationship between age and memory-related brain activity are different for men and women. We sought to extend this work by examining sex differences in the association between age, memory performance, and brain signal variability during context memory tasks in neurotypical adults (aged 19-76 years; N = 128, 87 women). We measured blood oxygen level-dependent standard deviation (BOLD SD) during encoding and retrieval in easy and difficult spatial context memory tasks and investigated sex-specific, age- and performance-associated BOLD SD patterns. Behavioral analysis revealed age-related decreases in memory retrieval, but no sex differences nor an age-by-sex interaction. Imaging results indicated that both sexes showed a negative correlation between BOLD SD and retrieval accuracy in memory-related regions. We also identified significant sex differences: women exhibited age-associated increases in BOLD SD which were negatively associated with performance. Men exhibited both age-associated decreases and increases, which were not related to performance. Our results revealed sex differences in the relationship between age and BOLD SD during high-demand episodic memory tasks.

The structure of prior knowledge enhances memory in experts by reducing interference.

The influence of prior knowledge on memory is ubiquitous, making the specific mechanisms of this relationship difficult to disentangle. Here, we show that expert knowledge produces a fundamental shift in the way that interitem similarity (i.e., the perceived resemblance between items in a set) biases episodic recognition. Within a group of expert birdwatchers and matched controls, we characterized the psychological similarity space for a set of well-known local species and a set of less familiar, nonlocal species. In experts, interitem similarity was influenced most strongly by taxonomic features, whereas in controls, similarity judgments reflected bird color. In controls, perceived episodic oldness during a recognition memory task increased along with measures of global similarity between items, consistent with classic models of episodic recognition. Surprisingly, for experts, high global similarity did not drive oldness signals. Instead, for local birds memory tracked the availability of species-level name knowledge, whereas for nonlocal birds, it was mediated by the organization of generalized conceptual space. These findings demonstrate that episodic memory in experts can benefit from detailed subcategory knowledge, or, lacking that, from the overall relational structure of concepts. Expertise reshapes psychological similarity space, helping to resolve mnemonic separation challenges arising from high interitem overlap. Thus, even in the absence of knowledge about item-specific details or labels, the presence of generalized knowledge appears to support episodic recognition in domains of expertise by altering the typical relationship between psychological similarity and memory.

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.

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.

Aerobic Fitness Unrelated to Acquisition of Spatial Relational Memory in College-Aged Adults.

While compelling evidence indicates that poorer aerobic fitness relates to impairments in retrieving information from hippocampal-dependent memory, there is a paucity of research on how aerobic fitness relates to the acquisition of such relational information. Accordingly, the present investigation examined the association between aerobic fitness and the rate of encoding spatial relational memory-assessed using a maximal oxygen consumption test and a spatial configuration task-in a sample of 152 college-aged adults. The findings from this investigation revealed no association between aerobic fitness and the acquisition of spatial relational memory. These findings have implications for how aerobic fitness is characterized with regard to memory, such that aerobic fitness does not appear to relate to the rate of learning spatial-relational information; however, given previously reported evidence, aerobic fitness may be associated with a greater ability to recall relational information from memory.

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.

The Emergence of Cognitive Maps for Spatial Navigation in 7- to 10-Year-Old Children.

Although much is known about adults' ability to orient by means of cognitive maps (mental representations of the environment), it is less clear when this important ability emerges in development. In the present study, 97 seven- to 10-year-olds and 26 adults played a video game designed to investigate the ability to orient using cognitive maps. The game required participants to reach target locations as quickly as possible, necessitating the identification and use of novel shortcuts. Seven- and 8-year-olds were less effective than older children and adults in using shortcuts. These findings provide clear evidence of a distinct developmental change around 9 years of age when children begin to proficiently orient and navigate using cognitive maps.

Revisiting mental rotation with stereoscopic disparity: A new spin for a classic paradigm.

To understand how the presence of stereoscopic disparity influences cognitive and neural processing, we recorded participants' behavior and scalp electrical activity while they performed a mental rotation task. Participants wore active shutter 3D goggles, allowing us to present stimuli with or without stereoscopic disparity on a trial-by-trial basis. Participants were more accurate and faster when stimuli were presented with stereoscopic disparity. This improvement in performance was accompanied by changes in neural activity recorded from scalp electrodes at parietal and occipital regions; stereoscopic disparity produced earlier P2 peaks, larger N2 amplitudes, and earlier, smaller P300 peak amplitudes. The presence of stereoscopic disparity also produced greater neural entropy at occipital electrode sites, and lower entropy at frontal sites. These findings suggest that the nature of the benefit afforded by stereoscopic disparity occurs at both low-level perceptual processing and higher-level cognitive processing, and results in more accurate and rapid performance.