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.

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.

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.

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.

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.

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.

Sleep quality and its association with the insular cortex in emotional empathy.

The human ability to vicariously share someone else's emotions (i.e., emotional empathy) relies on an extended neural network including regions in the anterior cingulate and insular cortex. Here, we tested the hypothesis that good sleep quality is associated with increased activation in the brain areas underlying emotional empathy. To this aim, we assessed subjective sleep quality in a large sample of healthy young volunteers, and asked participants to complete a computerized emotional empathy task. Then, we asked 16 participants to complete the same task while undergoing functional Magnetic Resonance Imaging (fMRI). After confirming the behavioral relationship between quality of sleep and emotional empathy in the large sample, we conducted a Region of Interest (ROI) analysis on selected ROIs involved in emotional empathy, and measured Blood Oxygen Level Dependent (BOLD) signal change in participants who performed the emotional empathy task in the MRI scanner; additionally, we assessed how the BOLD signal in different brain areas temporally correlated with performance throughout the task (i.e., task-based functional connectivity). We found increased BOLD signal change in a selective region within the left insula for individuals with better subjective sleep quality. These findings provide the very first evidence that individuals' sleep quality relates to emotional empathic responses through increased neural activation of a specific area within the insular cortex.

Environmental layout complexity affects neural activity during navigation in humans.

Navigating large-scale surroundings is a fundamental ability. In humans, it is commonly assumed that navigational performance is affected by individual differences, such as age, sex, and cognitive strategies adopted for orientation. We recently showed that the layout of the environment itself also influences how well people are able to find their way within it, yet it remains unclear whether differences in environmental complexity are associated with changes in brain activity during navigation. We used functional magnetic resonance imaging to investigate how the brain responds to a change in environmental complexity by asking participants to perform a navigation task in two large-scale virtual environments that differed solely in interconnection density, a measure of complexity defined as the average number of directional choices at decision points. The results showed that navigation in the simpler, less interconnected environment was faster and more accurate relative to the complex environment, and such performance was associated with increased activity in a number of brain areas (i.e. precuneus, retrosplenial cortex, and hippocampus) known to be involved in mental imagery, navigation, and memory. These findings provide novel evidence that environmental complexity not only affects navigational behaviour, but also modulates activity in brain regions that are important for successful orientation and navigation.

Familial aggregation in developmental topographical disorientation (DTD).

A variety of brain lesions may affect the ability to orient, resulting in what is termed "acquired topographical disorientation". In some individuals, however, topographical disorientation is present from childhood, with no apparent brain abnormalities and otherwise intact general cognitive abilities, a condition referred to as "developmental topographical disorientation" (DTD). Individuals affected by DTD often report relatives experiencing the same lifelong orientation difficulties. Here, we sought to assess the familial aggregation of DTD by investigating its occurrence in the families of DTD probands, and in the families of control probands who did not experience topographical disorientation. We found that DTD appears to cluster in the DTD families, with tested relatives displaying the trait, whereas in the control families we did not detect any individuals with DTD. These findings provide the very first evidence for the familial clustering of DTD and motivate further work investigating the genetic factors producing this clustering.

Intraparietal sulcus activity and functional connectivity supporting spatial working memory manipulation.

The intraparietal sulcus (IPS) is recruited during tasks requiring attention, maintenance and manipulation of information in working memory (WM). While WM tasks often show broad bilateral engagement along the IPS, topographic maps of contralateral (CL) visual space have been identified along the IPS, similar to retinotopic maps in visual cortex. In the present study, we asked how these visuotopic IPS regions are differentially involved in the maintenance and manipulation of spatial information in WM. Visuotopic mapping was performed in 26 participants to define regions of interest along the IPS, corresponding to previously described IPS0-4. In a separate task, we showed that while maintaining the location of a briefly flashed target in WM preferentially engaged CL IPS, manipulation of spatial information by mentally rotating the target around a circle engaged bilateral IPS, peaking in IPS1 in most participants. Functional connectivity analyses showed increased interaction between the IPS and prefrontal regions during manipulation, as well as interhemispheric interactions. Two control tasks demonstrated that covert attention shifts, and nonspatial manipulation (arithmetic), engaged patterns of IPS activation and connectivity that were distinct from WM manipulation. These findings add to our understanding of the role of IPS in spatial WM maintenance and manipulation.

[Sleep disturbances and spatial memory deficits in post-traumatic stress disorder: the case of L'Aquila (Central Italy)]. / Disturbi del sonno e della memoria spaziale nel disturbo post-traumatico da stress: il caso dell'Aquila.

Altered sleep is a common and central symptom of post-traumatic stress disorder (PTSD). In fact, sleep disturbances are included in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnostic criteria for PTSD. However, it has been hypothesized that sleep disturbances are crucially involved in the aetiology of PTSD, rather than being solely a symptom arising secondarily from this disorder. Therefore, knowing the long-term effects of a trauma can be essential to establish the need of specific interventions for the prevention and treatment of mental disorders that may persist years after a traumatic experience. In one study we showed, for the first time, that even after a period of two years people exposed to a catastrophic disaster such as the L'Aquila earthquake continue to suffer from a reduced sleep quality. Moreover, we observed that sleep quality scores decreased as a function of the proximity to the epicentre, suggesting that the psychological effects of an earthquake may be pervasive and long-lasting. It has been widely shown that disruption of sleep by acute stress may lead to deterioration in memory processing. In fact, in a recent study we observed alterations in spatial memory in PTSD subjects. Our findings indicated that PTSD is accompanied by an impressive deficit in forming a cognitive map of the environment, as well as in sleep-dependent memory consolidation. The fact that this deterioration was correlated to the subjective sleep disturbances in our PTSD group demonstrates the existence of an intimate relationship between sleep, memory consolidation, and stress.

Spatial and temporal functional connectivity changes between resting and attentive states.

Remote brain regions show correlated spontaneous activity at rest within well described intrinsic connectivity networks (ICNs). Meta-analytic coactivation studies have uncovered networks similar to resting ICNs, suggesting that in task states connectivity modulations may occur principally within ICNs. However, it has also been suggested that specific "hub" regions dynamically link networks under different task conditions. Here, we used functional magnetic resonance imaging at rest and a continuous visual attention task in 16 participants to investigate whether a shift from rest to attention was reflected by within-network connectivity modulation, or changes in network topography. Our analyses revealed evidence for both modulation of connectivity within the default-mode (DMN) and dorsal attention networks (DAN) between conditions, and identified a set of regions including the temporoparietal junction (TPJ) and posterior middle frontal gyrus (MFG) that switched between the DMN and DAN depending on the task. We further investigated the temporal nonstationarity of flexible (TPJ and MFG) regions during both attention and rest. This showed that moment-to-moment differences in connectivity at rest mirrored the variation in connectivity between tasks. Task-dependent changes in functional connectivity of flexible regions may, therefore, be understood as shifts in the proportion of time specific connections are engaged, rather than a switch between networks per se. This ability of specific regions to dynamically link ICNs under different task conditions may play an important role in behavioral flexibility.

Neural network configuration and efficiency underlies individual differences in spatial orientation ability.

Spatial orientation is a complex cognitive process requiring the integration of information processed in a distributed system of brain regions. Current models on the neural basis of spatial orientation are based primarily on the functional role of single brain regions, with limited understanding of how interaction among these brain regions relates to behavior. In this study, we investigated two sources of variability in the neural networks that support spatial orientation--network configuration and efficiency--and assessed whether variability in these topological properties relates to individual differences in orientation accuracy. Participants with higher accuracy were shown to express greater activity in the right supramarginal gyrus, the right precentral cortex, and the left hippocampus, over and above a core network engaged by the whole group. Additionally, high-performing individuals had increased levels of global efficiency within a resting-state network composed of brain regions engaged during orientation and increased levels of node centrality in the right supramarginal gyrus, the right primary motor cortex, and the left hippocampus. These results indicate that individual differences in the configuration of task-related networks and their efficiency measured at rest relate to the ability to spatially orient. Our findings advance systems neuroscience models of orientation and navigation by providing insight into the role of functional integration in shaping orientation behavior.

Developmental topographical disorientation and decreased hippocampal functional connectivity.

Developmental topographical disorientation (DTD) is a newly discovered cognitive disorder in which individuals experience a lifelong history of getting lost in both novel and familiar surroundings. Recent studies have shown that such a selective orientation defect relies primarily on the inability of the individuals to form cognitive maps, i.e., mental representations of the surrounding that allow individuals to get anywhere from any location in the environment, although other orientation skills are additionally affected. To date, the neural correlates of this developmental condition are unknown. Here, we tested the hypothesis that DTD may be related to ineffective functional connectivity between the hippocampus (HC; known to be critical for cognitive maps) and other brain regions critical for spatial orientation. A group of individuals with DTD and a group of control subjects underwent a resting-state functional magnetic resonance imaging (rsfMRI) scan. In addition, we performed voxel-based morphometry to investigate potential structural differences between individuals with DTD and controls. The results of the rsfMRI study revealed a decreased functional connectivity between the right HC and the prefrontal cortex (PFC) in individuals with DTD. No structural differences were detected between groups. These findings provide evidence that ineffective functional connectivity between HC and PFC may affect the monitoring and processing of spatial information while moving within an environment, resulting in the lifelong selective inability of individuals with DTD to form cognitive maps that are critical for orienting in both familiar and unfamiliar surroundings.

Hippocampal slow EEG frequencies during NREM sleep are involved in spatial memory consolidation in humans.

The hypothesis that sleep is instrumental in the process of memory consolidation is currently largely accepted. Hippocampal formation is involved in the acquisition of declarative memories and particularly of spatial memories. Nevertheless, although largely investigated in rodents, the relations between spatial memory and hippocampal EEG activity have been scarcely studied in humans. Aimed to evaluate the effects of spatial learning on human hippocampal sleep EEG activity, we recorded hippocampal Stereo-EEG (SEEG) in a group of refractory epilepsy patients undergoing presurgical clinical evaluation, after a training on a spatial navigation task. We observed that hippocampal high-delta (2-4 Hz range) activity increases during the first NREM episode after learning compared to the baseline night. Moreover, the amount of hippocampal NREM high-delta power was correlated with task performance at retest. The effect involved only the hippocampal EEG frequencies inasmuch no differences were observed at the neocortical electrodes and in the traditional polysomnographic measures. The present findings support the crucial role of hippocampal slow EEG frequencies during sleep in the memory consolidation processes. More generally, together with previous results, they suggest that slow frequency rhythms are a fundamental characteristic of human hippocampal EEG during both sleep and wakefulness, and are related to the consolidation of different types of memories.

The effects of sleep deprivation on emotional empathy.

Previous studies have shown that sleep loss has a detrimental effect on the ability of the individuals to process emotional information. In this study, we tested the hypothesis that this negative effect extends to the ability of experiencing emotions while observing other individuals, i.e. emotional empathy. To test this hypothesis, we assessed emotional empathy in 37 healthy volunteers who were assigned randomly to one of three experimental groups: one group was tested before and after a night of total sleep deprivation (sleep deprivation group), a second group was tested before and after a usual night of sleep spent at home (sleep group) and the third group was tested twice during the same day (day group). Emotional empathy was assessed by using two parallel versions of a computerized test measuring direct (i.e. explicit evaluation of empathic concern) and indirect (i.e. the observer's reported physiological arousal) emotional empathy. The results revealed that the post measurements of both direct and indirect emotional empathy of participants in the sleep deprivation group were significantly lower than those of the sleep and day groups; post measurement scores of participants in the day and sleep groups did not differ significantly for either direct or indirect emotional empathy. These data are consistent with previous studies showing the negative effect of sleep deprivation on the processing of emotional information, and extend these effects to emotional empathy. The findings reported in our study are relevant to healthy individuals with poor sleep habits, as well as clinical populations suffering from sleep disturbances.

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.

Structural connectivity of visuotopic intraparietal sulcus.

The intraparietal sulcus (IPS) contains topographically organized regions, similar to retinotopic maps in visual cortex. These regions, referred to as IPS1-4, show similar functional responses to the mapping tasks used to define them, yet differing responses to tests of other posterior parietal cortex (PPC) functions such as short-term memory, eye movements and object viewing, suggesting that they may have distinct patterns of structural connectivity to other parts of the brain. The present study combined functional magnetic resonance imaging (fMRI) mapping with diffusion tensor imaging (DTI) to describe white matter connections of visuotopic regions along the IPS, in 25 neurotypical young-adult participants. We found that posterior IPS more likely connects to retinotopically defined visual regions, and superior temporal gyrus, relative to anterior IPS. Anterior IPS regions 3 and 4 had higher connection probabilities to prefrontal regions, relative to posterior IPS. All four IPS regions showed inter-hemispheric connections to analogous regions in the opposite hemisphere, as well as consistent connections to the thalamus and regions of the striatum. Multivariate pattern classification at the group level reliably distinguished IPS regions from one another on the basis of connectivity patterns, especially for the most distal pairs of regions; occipital and prefrontal regions provided the most discriminating information. These findings advance our understanding of the structure of visuotopic IPS, with implications for functional differences between regions, and possible homologies between humans and macaques. Visuospatial functions dependent on the parietal cortex are frequently impaired in individuals with developmental disorders and those afflicted by cerebrovascular disease; the findings described here can be used as a basis for comparing connectivity differences in these populations.