Giuseppe Iaria

Background/Objectives: The glymphatic system is a recently characterized glial-dependent waste clearance pathway in the brain, which makes use of perivascular spaces for cerebrospinal fluid exchange. Diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) offers a non-invasive method for estimating perivascular flow, but its biological specificity and susceptibility to methodological variation, particularly head position during MRI acquisition, remain as threats to the validity of this technique. This study aimed to assess the prevalence of current DTI-ALPS practices, evaluate the impact of head orientation on ALPS index calculation, and propose a novel computational approach to improve measurement validity. Methods: We briefly reviewed DTI-ALPS literature to determine the use of head-orientation correction strategies. We then analyzed diffusion MRI data from 172 participants in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) to quantify the influence of head orientation on ALPS indices computed using the conventional Unrotated-ALPS, a vecrec-corrected ALPS, and the new LD-ALPS method proposed within. Results: A majority of studies employed Unrotated-ALPS, which does not correct for head orientation. In our sample, Unrotated-ALPS values were significantly associated with absolute head pitch (r₁₆₉ = −0.513, p < 0.001), indicating systematic bias. This relationship was eliminated using either vecreg or LD-ALPS. Additionally, LD-ALPS showed more sensitivity to cognitive status as measured by Mini-Mental State Examination scores. Conclusions: Correcting for head orientation is essential in DTI-ALPS studies. The LD-ALPS method, while computationally more demanding, improves the reliability and sensitivity of perivascular fluid estimates, supporting its use in future research on aging and neurodegeneration.

(1) Background: Evidence from non-human animal and spaceflight analog studies have suggested that traveling to outer space could have a significant impact on the structural properties of the hippocampus, a brain region within the medial temporal lobe that is critical for learning and memory. Here, we tested this hypothesis in a group of astronauts who participated in a six-month mission in the International Space Station (ISS). (2) Methods: We collected magnetic resonance imaging (MRI) scans from a sample of 17 (9 males, 8 females) astronauts before and after the ISS mission, and calculated percent gray matter volume changes in the whole hippocampus and its (anterior, body, and posterior) subregions in both hemispheres. (3) Following the six-month mission in the ISS, we found a significantly decreased volume in the whole left hippocampus; in addition, when looking at subregions separately, we detected a significantly decreased volume in the anterior subregion of the left hippocampus and the body subregion of the right hippocampus. We also found a significantly decreased volume in the whole right hippocampus of male astronauts as compared to female astronauts. (4) Conclusions: This study, providing the very first evidence of hippocampal volumetric changes in astronauts following a six-month mission to the ISS, could have significant implications for cognitive performance during future long-duration spaceflights.

Background/Objectives: Developmental Topographical Disorientation (DTD) refers to a condition in which individuals report getting lost in very familiar surroundings, since childhood, with no other cognitive complaints, and no brain injuries or neurological disorders. While the cognitive and neurological mechanisms underlying DTD are being investigated, to date, there is no tool available to the public and health practitioners for identifying this lifelong condition. Methods: Here, we used a decade of data (N = 3794) collected in healthy and DTD individuals to produce a short and reliable measure of self-reported sense of direction that could point to the presence of DTD. Results: We adopted a measure of internal consistency (Cronbach’s alpha) and identified four items of the well-known Santa Barbara Sense of Direction (SBSOD) Scale that retain its original strong internal consistency. These four items remain sensitive to the well-known effects of sex on spatial orientation and, importantly, to the presence of DTD, while maintaining the same pattern of association with a cognitive battery of computerized tasks measuring different spatial abilities. Conclusions: This four-item measure could be of practical use to obtain a rapid assessment of an individual’s self-reported sense of direction and help to identify the presence of DTD in the general population.

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.

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.

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.

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.