Assessing rapid spatial working memory in community-living older adults in a virtual adaptation of the rodent water maze paradigm.

Aging often leads to a decline in various cognitive domains, potentially contributing to spatial navigation challenges among older individuals. While the Morris water maze is a common tool in rodents research for evaluating allocentric spatial memory function, its translation to studying aging in humans, particularly its association with hippocampal dysfunction, has predominantly focused on spatial reference memory assessments. This study expanded the adaptation of the Morris water maze for older adults to assess flexible, rapid, one-trial working memory. This adaptation involved a spatial search task guided by allocentric cues within a 3-D virtual reality (VR) environment. The sensitivity of this approach to aging was examined in 146 community-living adults from three Chinese cities, categorized into three age groups. Significant performance deficits were observed in participants over 60 years old compared to younger adults aged between 18 and 43. However, interpreting these findings was complicated by factors such as psychomotor slowness and potential variations in task engagement, except during the probe tests. Notably, the transition from the 60 s to the 70 s was not associated with a substantial deterioration of performance. A distinction only emerged when the pattern of spatial search over the entire maze was examined in the probe tests when the target location was never revealed. The VR task's sensitivity to overall cognitive function in older adults was reinforced by the correlation between Montreal Cognitive Assessment (MoCA) scores and probe test performance, demonstrating up to 17 % shared variance beyond that predicted by chronological age alone. In conclusion, while implementing a VR-based adaptation of rodent water maze paradigms in older adults was feasible, our experience highlighted specific interpretative challenges that must be addressed before such a test can effectively supplement traditional cognitive assessment tools in evaluating age-related cognitive decline.

Integration of auditory and visual cues in spatial navigation under normal and impaired viewing conditions.

Auditory landmarks can contribute to spatial updating during navigation with vision. Whereas large inter-individual differences have been identified in how navigators combine auditory and visual landmarks, it is still unclear under what circumstances audition is used. Further, whether or not individuals optimally combine auditory cues with visual cues to decrease the amount of perceptual uncertainty, or variability, has not been well-documented. Here, we test audiovisual integration during spatial updating in a virtual navigation task. In Experiment 1, 24 individuals with normal sensory acuity completed a triangular homing task with either visual landmarks, auditory landmarks, or both. In addition, participants experienced a fourth condition with a covert spatial conflict where auditory landmarks were rotated relative to visual landmarks. Participants generally relied more on visual landmarks than auditory landmarks and were no more accurate with multisensory cues than with vision alone. In Experiment 2, a new group of 24 individuals completed the same task, but with simulated low vision in the form of a blur filter to increase visual uncertainty. Again, participants relied more on visual landmarks than auditory ones and no multisensory benefit occurred. Participants navigating with blur did not rely more on their hearing compared with the group that navigated with normal vision. These results support previous research showing that one sensory modality at a time may be sufficient for spatial updating, even under impaired viewing conditions. Future research could investigate task- and participant-specific factors that lead to different strategies of multisensory cue combination with auditory and visual cues.

Connectomic reconstruction predicts visual features used for navigation.

Many animals use visual information to navigate1-4, but how such information is encoded and integrated by the navigation system remains incompletely understood. In Drosophila melanogaster, EPG neurons in the central complex compute the heading direction5 by integrating visual input from ER neurons6-12, which are part of the anterior visual pathway (AVP)10,13-16. Here we densely reconstruct all neurons in the AVP using electron-microscopy data17. The AVP comprises four neuropils, sequentially linked by three major classes of neurons: MeTu neurons10,14,15, which connect the medulla in the optic lobe to the small unit of the anterior optic tubercle (AOTUsu) in the central brain; TuBu neurons9,16, which connect the AOTUsu to the bulb neuropil; and ER neurons6-12, which connect the bulb to the EPG neurons. On the basis of morphologies, connectivity between neural classes and the locations of synapses, we identify distinct information channels that originate from four types of MeTu neurons, and we further divide these into ten subtypes according to the presynaptic connections in the medulla and the postsynaptic connections in the AOTUsu. Using the connectivity of the entire AVP and the dendritic fields of the MeTu neurons in the optic lobes, we infer potential visual features and the visual area from which any ER neuron receives input. We confirm some of these predictions physiologically. These results provide a strong foundation for understanding how distinct sensory features can be extracted and transformed across multiple processing stages to construct higher-order cognitive representations.

Noninvasive modulation of the hippocampal-entorhinal complex during spatial navigation in humans.

Because of the depth of the hippocampal-entorhinal complex (HC-EC) in the brain, understanding of its role in spatial navigation via neuromodulation was limited in humans. Here, we aimed to better elucidate this relationship in healthy volunteers, using transcranial temporal interference electric stimulation (tTIS), a noninvasive technique allowing to selectively neuromodulate deep brain structures. We applied tTIS to the right HC-EC in either continuous or intermittent theta-burst stimulation patterns (cTBS or iTBS), compared to a control condition, during a virtual reality-based spatial navigation task and concomitant functional magnetic resonance imaging. iTBS improved spatial navigation performance, correlated with hippocampal activity modulation, and decreased grid cell-like activity in EC. Collectively, these data provide the evidence that human HC-EC activity can be directly and noninvasively modulated leading to changes of spatial navigation behavior. These findings suggest promising perspectives for patients suffering from cognitive impairment such as following traumatic brain injury or dementia.

Olfactory navigation in fluctuating environments.

We humans move around in the world, guided largely by light and sound. Many cohabitants of our planet, however, predominantly use their chemical senses to navigate a rich landscape. Light and sound propagate with predictable geometric precision, and animals in particular have evolved ways to exploit these physical principles. Odors, on the other hand, are at the mercy of the carrier medium, air or water, for long distance transport, which can quickly become turbulent and unpredictable. Nevertheless, animals have found ways to navigate these fickle features to chase mates, find food or return home. Understanding the physics of odor transport can help rationalize the strategies animals use for navigation and guide studies of how the corresponding algorithms are implemented by their brains and bodies.

Path Integration Detects Prodromal Alzheimer's Disease and Predicts Cognitive Decline.

Background: The entorhinal cortex is the very earliest involvement of Alzheimer's disease (AD). Grid cells in the medial entorhinal cortex form part of the spatial navigation system. Objective: We aimed to determine whether path integration performance can be used to detect patients with mild cognitive impairment (MCI) at high risk of developing AD, and whether it can predict cognitive decline. Methods: Path integration performance was assessed in 71 patients with early MCI (EMCI) and late MCI (LMCI) using a recently developed 3D virtual reality navigation task. Patients with LMCI were further divided into those displaying characteristic brain imaging features of AD, including medial temporal lobe atrophy on magnetic resonance imaging and posterior hypoperfusion on single-photon emission tomography (LMCI+), and those not displaying such features (LMCI-). Results: Path integration performance was significantly lower in patients with LMCI+than in those with EMCI and LMCI-. A significantly lower performance was observed in patients who showed progression of MCI during 12 months, than in those with stable MCI. Path integration performance distinguished patients with progressive MCI from those with stable MCI, with a high classification accuracy (a sensitivity of 0.88 and a specificity of 0.70). Conclusions: Our results suggest that the 3D virtual reality navigation task detects prodromal AD patients and predicts cognitive decline after 12 months. Our navigation task, which is simple, short (12-15 minutes), noninvasive, and inexpensive, may be a screening tool for therapeutic choice of disease-modifiers in individuals with prodromal AD.

Adult zebrafish can learn Morris water maze-like tasks in a two-dimensional virtual reality system.

Virtual reality (VR) has emerged as a powerful tool for investigating neural mechanisms of decision-making, spatial cognition, and navigation. In many head-fixed VRs for rodents, animals locomote on spherical treadmills that provide rotation information in two axes to calculate two-dimensional (2D) movement. On the other hand, zebrafish in a submerged head-fixed VR can move their tail to enable movement in 2D VR environment. This motivated us to create a VR system for adult zebrafish to enable 2D movement consisting of forward translation and rotations calculated from tail movement. Besides presenting the VR system, we show that zebrafish can learn a virtual Morris water maze-like (VMWM) task in which finding an invisible safe zone was necessary for the zebrafish to avoid an aversive periodic mild electric shock. Results show high potential for our VR system to be combined with optical imaging for future studies to investigate spatial learning and navigation.

Landmark knowledge overrides optic flow in honeybee waggle dance distance estimation.

Honeybees encode in their waggle dances the vector (distance and direction) of an outbound flight to a food source or a new nest site. Optic flow has been identified as the major source of information in the distance estimation. Additional components of distance estimation were also identified, e.g. the sequence of experienced landmarks. Here, we address the question of whether bees also use the landscape memory developed during exploratory orientation flights to estimate distance. We took advantage of the fact that flights in a narrow tunnel lead to further distance measures as a result of higher optic flow. We found that this effect was lost when bees had explored the area in which the tunnel was located and when they had somewhat restricted visual access to the surrounding environment through the mesh on top of the tunnel. These data are interpreted in the context of other findings about the structure of navigational memory in bees that develops during exploratory orientation flights. In particular, the data suggest that bees embed distance measures into a representation of navigational space that stores previously experienced landscape features.

Accuracy, rationality and specialization in a generalized model of collective navigation.

Animal navigation is a key behavioural process, from localized foraging to global migration. Within groups, individuals may improve their navigational accuracy by following those with more experience or knowledge, by pooling information from many directional estimates ('many wrongs') or some combination of these strategies. Previous agent-based simulations have highlighted that homogeneous leaderless groups can improve their collective navigation accuracy when individuals preferentially copy the movement directions of their neighbours while giving a low weighting to their own navigational knowledge. Meanwhile, other studies have demonstrated how specialized leaders may emerge, and that a small number of such individuals can improve group-level navigation performance. However, in general, these earlier results either lack a full mathematical grounding or do not fully consider the effect of individual self-interest. Here we derive and analyse a mathematically tractable model of collective navigation. We demonstrate that collective navigation is compromised when individuals seek to optimize their own accuracy in both homogeneous groups and those with differing navigational abilities. We further demonstrate how heterogeneous navigational strategies (specialized leaders and followers) may evolve within the model. Our results thus unify different lines of research in collective navigation and highlight the importance of individual selection in determining group composition and performance.

Experience of Euclidean geometry sculpts the development and dynamics of rodent hippocampal sequential cell assemblies.

Euclidean space is the fabric of the world we live in. Whether and how geometric experience shapes our spatial-temporal representations of the world remained unknown. We deprived male rats of experience with crucial features of Euclidean geometry by rearing them inside spheres, and compared activity of large hippocampal neuronal ensembles during navigation and sleep with that of cuboid cage-reared controls. Sphere-rearing from birth permitted emergence of accurate neuronal ensemble spatial codes and preconfigured and plastic time-compressed neuronal sequences. However, sphere-rearing led to diminished individual place cell tuning, more similar neuronal mapping of different track ends/corners, and impaired pattern separation and plasticity of multiple linear tracks, coupled with reduced preconfigured sleep network repertoires. Subsequent experience with multiple linear environments over four days largely reversed these effects. Thus, early-life experience with Euclidean geometry enriches the hippocampal repertoire of preconfigured neuronal patterns selected toward unique representation and discrimination of multiple linear environments.

Protocol to investigate the gradual selection and deployment of goal-oriented search strategies during unsupervised navigation in mice.

The ability of rodents to effectively navigate in an environment is based on trial-and-error learning and flexible decision-making and can be analyzed via navigational trajectories. We present a protocol for studying the deployment of search strategies in mice using the Morris water maze. We describe steps for assigning mice to different maze variations and procedures for post-training tracking and analysis. This protocol represents an effective behavioral readout to probe brain networks involved in strategy deployment and goal-oriented behavior. For complete details on the use and execution of this protocol, please refer to Parrini et al.1.

Persistent Impact of Prior Experience on Spatial Learning.

Learning to solve a new problem involves identifying the operating rules, which can be accelerated if known rules generalize in the new context. We ask how prior experience affects learning a new rule that is distinct from known rules. We examined how rats learned a new spatial navigation task after having previously learned tasks with different navigation rules. The new task differed from the previous tasks in spatial layout and navigation rule. We found that experience history did not impact overall performance. However, by examining navigation choice sequences in the new task, we found experience-dependent differences in exploration patterns during early stages of learning, as well as differences in the types of errors made during stable performance. The differences were consistent with the animals adopting experience-dependent memory strategies to discover and implement the new rule. Our results indicate prior experience shapes the strategies for solving novel problems, and the impact of prior experience remains persistent.

FOS mapping reveals two complementary circuits for spatial navigation in mouse.

Here, we show that during continuous navigation in a dynamic external environment, mice are capable of developing a foraging strategy based exclusively on changing distal (allothetic) information and that this process may involve two alternative components of the spatial memory circuit: the hippocampus and retrosplenial cortex. To this end, we designed a novel custom apparatus and implemented a behavioral protocol based on the figure-8-maze paradigm with two goal locations associated with distinct contexts. We assessed whether mice are able to learn to retrieve a sequence of rewards guided exclusively by the changing context. We found out that training mice in the apparatus leads to change in strategy from the internal tendency to alternate into navigation based exclusively on visual information. This effect could be achieved using two different training protocols: prolonged alternation training, or a flexible protocol with unpredictable turn succession. Based on the c-FOS mapping we also provide evidence of opposing levels of engagement of hippocampus and retrosplenial cortex after training of mice in these two different regimens. This supports the hypothesis of the existence of parallel circuits guiding spatial navigation, one based on the well-described hippocampal representation, and another, RSC-dependent.

Navigation performance in glaucoma: virtual-reality-based assessment of path integration.

Navigation is essential for moving between locations in our daily lives. We investigated the relationship between visual impairment in glaucoma and path-integration-based navigation. Fourteen glaucoma and 15 controls underwent ophthalmological examination (including visual acuity (logMAR), visual field sensitivity (MD: mean deviation from matched reference cohort), and peripapillary retinal nerve fiber layer (pRNFL)). Both groups navigated physically in virtual reality (VR) environments during daylight and dawn conditions. Briefly, the participants traversed a path marked by three targets, subsequently pointing back to the path's origin. Outcome measures included (i) travel-time, (ii) pointing-time, and (iii) Euclidian-distance error between indicated and starting position. Robust linear regression was conducted between visual function outcomes of the better eye and VR outcome measures. Glaucoma patients showed increase in travel-time (by 8.2 ± 1.7 s; p = 0.002) and in pointing-time (by 5.3 ± 1.6 s; p = 0.016). Predictors were MD for all outcome measures (p < 0.01) and pRNFL for travel-time (p < 0.01). The results suggest that the effect of glaucoma on the elapsed time depends on disease progression, i.e. people with stronger visual impairment need more time. This uncertainty during everyday navigation tasks may adversely affect their quality of life.

[Three-dimensional positioning and trajectory tracking of pigeons in large indoor spaces].

Animal localization and trajectory tracking are of great value for the study of brain spatial cognition and navigation neural mechanisms. However, traditional optical lens video positioning techniques are limited in their scope due to factors such as camera perspective. For pigeons with excellent spatial cognition and navigation abilities, based on the beacon positioning technology, a three-dimensional (3D) trajectory positioning and tracking method suitable for large indoor spaces was proposed, and the corresponding positioning principle and hardware structure were provided. The results of in vitro and in vivo experiments showed that the system could achieve centimeter-level positioning and trajectory tracking of pigeons in a space of 360 cm × 200 cm × 245 cm. Compared with traditional optical lens video positioning techniques, this system has the advantages of large space, high precision, and high response speed. It not only helps to study the neural mechanisms of pigeon 3D spatial cognition and navigation, but also has high reference value for trajectory tracking of other animals.

Animal navigation: Jellyfish dodge the drift.

Orientation in the ocean can be challenging because of a lack of landmarks. Evidence is accumulating that jellyfish, once considered to be passive drifters, can also show directional swimming to avoid stranding ashore, using ocean waves for orientation, just like hatchling turtles.

Spatial dissociation between recognition and navigation in the primate hippocampus.

The primate hippocampus, crucial for both episodic memory and spatial navigation, remains an enigma regarding whether these functions share the same neural substrates. We investigated how identical hippocampal neurons in macaque monkeys dynamically shifted their representations between tasks. In a recognition memory task, a notable fraction of hippocampal neurons showed that rate modulation strongly correlated with recognition performance. During free navigation in an open arena, spatial view, rather than position, predominantly influenced the spatial selectivity of hippocampal neurons. Neurons selective for recognition memory displayed minimal spatial tuning, while spatially tuned neurons exhibited limited memory-related activity. These neural correlates of recognition memory and space were more pronounced in the anterior and posterior portions of the hippocampus, respectively. These opposing gradients extended further into the anterior and posterior neocortices. Overall, our findings suggest the presence of orthogonal long-axis gradients between recognition memory and spatial navigation in the hippocampal-neocortical networks of macaque monkeys.

Adaptive closed-loop modulation of cortical theta oscillations: Insights into the neural dynamics of navigational decision-making.

Navigational decision-making tasks, such as spatial working memory (SWM), rely highly on information integration from several cortical and sub-cortical regions. Performance in SWM tasks is associated with theta rhythm, including low-frequency oscillations related to movement and memory. The interaction of the ventral hippocampus (vHPC) and medial prefrontal cortex (mPFC), reflected in theta synchrony, is essential in various steps of information processing during SWM. We used a closed-loop neurofeedback (CLNF) system to upregulate theta power in the mPFC and investigate its effects on circuit dynamics and behavior in animal models. Specifically, we hypothesized that enhancing the power of the theta rhythm in the mPFC might improve SWM performance. Animals were divided into three groups: closed-loop (CL), random-loop (RL), and OFF (without stimulation). We recorded local field potential (LFP) in the mPFC while electrical reward stimulation contingent on cortical theta activity was delivered to the lateral hypothalamus (LH), which is considered one of the central reward-associated regions. We also recorded LFP in the vHPC to evaluate the related subcortical neural changes. Results revealed a sustained increase in the theta power in both mPFC and vHPC for the CL group. Our analysis also revealed an increase in mPFC-vHPC synchronization in the theta range over the stimulation sessions in the CL group, as measured by coherence and cross-correlation in the theta frequency band. The reinforcement of this circuit improved spatial decision-making performance in the subsequent behavioral results. Our findings provide direct evidence of the relationship between specific theta upregulation and SWM performance and suggest that theta oscillations are integral to cognitive processes. Overall, this study highlights the potential of adaptive CLNF systems in investigating neural dynamics in various brain circuits.

Investigating Egocentric Tuning in Hippocampal CA1 Neurons.

Navigation requires integrating sensory information with a stable schema to create a dynamic map of an animal's position using egocentric and allocentric coordinate systems. In the hippocampus, place cells encode allocentric space, but their firing rates may also exhibit directional tuning within egocentric or allocentric reference frames. We compared experimental and simulated data to assess the prevalence of tuning to egocentric bearing (EB) among hippocampal cells in rats foraging in an open field. Using established procedures, we confirmed egocentric modulation of place cell activity in recorded data; however, simulated data revealed a high false-positive rate (FPR). When we accounted for false positives by comparing with shuffled data that retain correlations between the animal's direction and position, only a very low number of hippocampal neurons appeared modulated by EB. Our study highlights biases affecting FPRs and provides insights into the challenges of identifying egocentric modulation in hippocampal neurons.

Thermal infrared directs host-seeking behaviour in Aedes aegypti mosquitoes.

Mosquito-borne diseases affect hundreds of millions of people annually and disproportionately impact the developing world1,2. One mosquito species, Aedes aegypti, is a primary vector of viruses that cause dengue, yellow fever and Zika. The attraction of Ae. aegypti female mosquitos to humans requires integrating multiple cues, including CO2 from breath, organic odours from skin and visual cues, all sensed at mid and long ranges, and other cues sensed at very close range3-6. Here we identify a cue that Ae. aegypti use as part of their sensory arsenal to find humans. We demonstrate that Ae. aegypti sense the infrared (IR) radiation emanating from their targets and use this information in combination with other cues for highly effective mid-range navigation. Detection of thermal IR requires the heat-activated channel TRPA1, which is expressed in neurons at the tip of the antenna. Two opsins are co-expressed with TRPA1 in these neurons and promote the detection of lower IR intensities. We propose that radiant energy causes local heating at the end of the antenna, thereby activating temperature-sensitive receptors in thermosensory neurons. The realization that thermal IR radiation is an outstanding mid-range directional cue expands our understanding as to how mosquitoes are exquisitely effective in locating hosts.