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The subcortical anatomy of human spatial neglect: putamen, caudate nucleus and pulvinar.

Various studies have documented that right hemispheric lesions restricted to the basal ganglia or to the thalamus may evoke spatial neglect. However, for methodological reasons, the exact anatomical correlate of spatial neglect within these two subcortical structures still remained uncertain. The present study identified these locations by comparing the anatomy of subcortical lesions to the basal ganglia or thalamus between neglect and control patients. Analysis revealed that the putamen, the pulvinar and, to a smaller degree, the caudate nucleus are the subcortical structures typically associated with spatial neglect in humans. All these structures have direct anatomical connections to the superior temporal gyrus (STG), which recently has been identified as the neural correlate of spatial neglect in the human cortex. Therefore, it is assumed that the right putamen, caudate nucleus, pulvinar and STG form a coherent corticosubcortical anatomical network in the genesis of spatial neglect in humans.

Adult↗

Computer-assisted shock-reinforced Y-maze training: a method for studying spatial alternation behaviour.

Y-mazes are widely used for discrimination learning and spatial alternation tasks. We present here a computer-assisted Y-maze model for spatial alternation learning via footshock reinforcement. No intramaze cues are provided and handling between trials is no longer required. Pretraining application of scopolamine (1 mg kg-1) and D-AP5 (2-amino-5-phosphonopentanoate; 0.016 mg) clearly impairs acquisition and retention (tested 24 h after acquisition) of spatial alternation. These effects are not due to state-dependent changes caused by drug treatment. Similar results were reported by others in food-motivated spatial alternation tasks as well as spontaneous alternation paradigms. The data support our model as a useful tool for studying spatial alternation in the Y-maze.

2-Amino-5-phosphonovalerate↗

Olfactory based spatial learning in neonatal mice and its dependence on CaMKII.

Spatial learning and memory involves the ability to encode geometric relationships between perceived cues and depends critically on the hippocampus. Visually guided spatial learning has been demonstrated in adult animals. As infant animals rely heavily on olfaction, olfactory based spatial learning was assessed in infant mice. When 12-day-old pups were displaced from their nest, they learned within a few training trials to use the spatial pattern of odor cues to move back to the nest. However, mouse pups that over-expressed Ca2+/calmodulin-dependent protein kinase (CaMKII) in hippocampal neurons were impaired in olfactory based spatial learning.

Age Factors↗

Spatially explicit analyses unveil density dependence.

Density-dependent processes are fundamental in the understanding of species population dynamics. Whereas the benefits of considering the spatial dimension in population biology are widely acknowledged, the implications of doing so for the statistical detection of spatial density dependence have not been examined. The outcome of traditional tests may therefore differ from those that include ecologically relevant locational information on both the prey species and natural enemy. Here, we explicitly incorporate spatial information on individual counts when testing for density dependence between an insect herbivore and its parasitoids. The spatially explicit approach used identified significant density dependence more frequently and in different instances than traditional methods. The form of density dependence detected also differed between methods. These results demonstrate that the explicit consideration of patch location in density-dependence analyses is likely to significantly alter current understanding of the prevalence and form of spatial density dependence in natural populations.

Animals↗

Mechanistic home range models capture spatial patterns and dynamics of coyote territories in Yellowstone.

Patterns of space-use by individuals are fundamental to the ecology of animal populations influencing their social organization, mating systems, demography and the spatial distribution of prey and competitors. To date, the principal method used to analyse the underlying determinants of animal home range patterns has been resource selection analysis (RSA), a spatially implicit approach that examines the relative frequencies of animal relocations in relation to landscape attributes. In this analysis, we adopt an alternative approach, using a series of mechanistic home range models to analyse observed patterns of territorial space-use by coyote packs in the heterogeneous landscape of Yellowstone National Park. Unlike RSAs, mechanistic home range models are derived from underlying correlated random walk models of individual movement behaviour, and yield spatially explicit predictions for patterns of space-use by individuals. As we show here, mechanistic home range models can be used to determine the underlying determinants of animal home range patterns, incorporating both movement responses to underlying landscape heterogeneities and the effects of behavioural interactions between individuals. Our analysis indicates that the spatial arrangement of coyote territories in Yellowstone is determined by the spatial distribution of prey resources and an avoidance response to the presence of neighbouring packs. We then show how the fitted mechanistic home range model can be used to correctly predict observed shifts in the patterns of coyote space-use in response to perturbation.

Animals↗

Designing smart spatial omics experiments with S2Omics.

Spatial omics technologies have transformed biomedical research by enabling high-resolution molecular profiling while preserving the native tissue architecture. These advances provide unprecedented insights into tissue structure and function. However, the high cost and time-intensive nature of spatial omics experiments necessitate careful experimental design, particularly in selecting regions of interest (ROIs) from large tissue sections. Currently, ROI selection is performed manually, which introduces subjectivity, inconsistency, and a lack of reproducibility. Previous studies have shown strong correlations between spatial molecular patterns and histological features, suggesting that readily available and cost-effective histology images can be leveraged to guide spatial omics experiments. Here, we present S2Omics, an end-to-end workflow that automatically selects ROIs from histology images with the goal of maximizing molecular information content in the ROIs. Through comprehensive evaluations across multiple spatial omics platforms and tissue types, we demonstrate that S2Omics enables systematic and reproducible ROI selection and enhances the robustness and impact of downstream biological discovery.

digital pathology↗

Seizures in the developing brain cause adverse long-term effects on spatial learning and anxiety.

PURPOSE: Seizures in the developing brain cause less macroscopic structural damage than do seizures in adulthood, but accumulating evidence shows that seizures early in life can be associated with persistent behavioral and cognitive impairments. We previously showed that long-term spatial memory in the eight-arm radial-arm maze was impaired in rats that experienced a single episode of kainic acid (KA)-induced status epilepticus during early development (postnatal days (P) 1-14). Here we extend those findings by using a set of behavioral paradigms that are sensitive to additional aspects of learning and behavior. METHODS: On P1, P7, P14, or P24, rats underwent status epilepticus induced by intraperitoneal injections of age-specific doses of KA. In adulthood (P90-P100), the behavioral performance of these rats was compared with that of control rats that did not receive KA. A modified version of the radial-arm maze was used to assess short-term spatial memory; the Morris water maze was used to evaluate long-term spatial memory and retrieval; and the elevated plus maze was used to determine anxiety. RESULTS: Compared with controls, rats with KA seizures at each tested age had impaired short-term spatial memory in the radial-arm maze (longer latency to criterion and more reference errors), deficient long-term spatial learning and retrieval in the water maze (longer escape latencies and memory for platform location), and a greater degree of anxiety in the elevated plus maze (greater time spent in open arms). CONCLUSIONS: These findings provide additional support for the concept that seizures early in life may be followed by life-long impairment of certain cognitive and behavioral functions. These results may have clinical implications, favoring early and aggressive control of seizures during development.

Animals↗

Spatial aggregation and association in different resource-patch distributions: experimental analysis with Drosophila.

1. Laboratory experiments using homogeneous resources were conducted to examine intra- and interspecific spatial egg distribution of D. simulans, D. auraria and D. immigrans in three different resource-patch distribution patterns: patchy, even and clustered. 2. Individuals of each species were introduced separately or simultaneously into the cage, into which artificial substrates were placed and allowed to oviposit for 24 h. Spatial analyses were performed with indices of intraspecific aggregation (J), interspecific association (C) and L-function based on Ripley's K-function. 3. Eggs were always spatially aggregated irrespective of species and the resource-patch distribution patterns. Spatial egg aggregation was influenced significantly by the resource-patch distribution pattern and tended to be weaker in the clustered resource-patch distribution than in the patchy or even resource-patch distribution. 4. Spatial extent of egg aggregation was always beyond the single resource patch scale, indicating aggregation of ovipositing females. 5. Interspecific association of egg distribution was absent or very weak. Thus, these results present experimental evidence of independent egg aggregation among drosophilids.

Adaptation, Physiological↗

Transient spatial deficit associated with bilateral lesions of the lateral mammillary nuclei.

The mammillary bodies have long been implicated in spatial memory, and lesions of this structure in rats can impair some spatial memory tasks. The mammillary bodies, however, comprise two main nuclei that have different electrophysiological and anatomical properties. It is therefore possible that they have different functions. The present study determined whether selective lesions of one of these components, the lateral mammillary nucleus, are sufficient to induce spatial memory deficits. While selective lateral mammillary nuclei lesions induced deficits on a working memory task in the water maze, this impairment was milder and not as persistent as that seen with complete mammillary body lesions. Furthermore, lateral mammillary nuclei lesions did not impair T-maze alternation, which is sensitive to complete mammillary body lesions. From these results it appears that lesions confined to the lateral mammillary nuclei are sufficient to produce mild impairments when rapid, new spatial learning is at a premium. At the same time, the remaining mammillary nuclei also contribute to spatial learning, though this may be in a qualitatively different manner.

Animals↗

Testosterone and photoperiod interact to affect spatial learning and memory in adult male white-footed mice (Peromyscus leucopus).

Gonadal hormones affect spatial learning and memory in mammals and circulating gonadal hormone concentrations fluctuate by season. Most nontropical rodents are spring/summer breeders and males display higher testosterone concentrations during the breeding season compared with the nonbreeding season (fall/winter). Seasonal patterns of testosterone concentration (as well as many other seasonal modifications of physiology, morphology, and behaviour) are induced by manipulation of photoperiod (day length; i.e. short or long days) in the laboratory. Coincident with reducing testosterone concentration, short days also impair spatial learning and memory performance in male white-footed mice (Peromyscus leucopus) compared with long days. We hypothesized that short-day-induced reduction of testosterone concentrations inhibits spatial learning and memory performance compared with long days. Adult male white-footed mice were maintained in long (16 h light/day) or short (8 h light/day) days for 14 weeks following sham-castration, castration plus saline implant, or castration plus testosterone implant treatment. Spatial learning and memory was assessed using a water maze, and photoperiod-evoked changes in gene expression of sex steroid receptors within the hippocampus were also examined. Castrated, short-day mice with testosterone replacement displayed enhanced water maze performance compared with other short-day mice, but no differences among testosterone treatments were observed in long-day mice. Photoperiod did not affect hippocampal androgen, oestrogen alpha, or oestrogen beta receptor gene expression. These results suggest that photoperiod modulates the effects of testosterone on spatial learning performance by mechanisms indirect of the hippocampus.

Animals↗

Impaired spatial learning in the APPSwe + PSEN1DeltaE9 bigenic mouse model of Alzheimer's disease.

Mice co-expressing the Swedish amyloid precursor protein mutation (APP(Swe)) and exon 9 deletion (DeltaE9) of the PSEN1 gene begin to develop amyloid plaques at 6-7 months of age. We demonstrate here a spatial learning deficit in 7-month-old APP(Swe) + PSEN1DeltaE9 bigenic mice using an adaptation of the Barnes maze. Mice were first trained on a cued target followed by a hidden-target condition. Although bigenic mice quickly learned the cued-target version of the task, they were significantly impaired when switched to the hidden-target version. In contrast, a separate group of double-transgenic mice trained first on the spatial hidden-target version of the task were unimpaired relative to wild-type controls. We propose that processes such as general rule learning, context learning and exploratory habituation exert a greater influence when the testing environment is novel and overshadow the spatial memory deficit in naive bigenic mice. However, when cued-target training is conducted first, these processes habituate and the spatial learning deficit is unmasked. Seven-month-old APP(Swe) + PSEN1DeltaE9 mice were unimpaired on tests of memory that did not involve learning the rules governing spatial associations.

Alzheimer Disease↗

Spatial learning induces predominant downregulation of cytosolic proteins in the rat hippocampus.

Spatial learning is known to depend on protein synthesis in the hippocampus. Whereas the role of the hippocampus in spatial memory is established, the biochemical and molecular mechanisms underlying this process are poorly understood. To comprehend the complex pattern of protein expression induced by spatial learning, we analyzed alterations in the rat hippocampus proteome after 7 days of spatial learning in the Morris water maze. Forty Wistar rats were randomized into two groups. Animals of group A learned to localize a hidden platform in the water maze. Animals of group B served as controls and spent exactly the same time in the water maze as animals of group A. However, no platform was used in this test and the rats could not learn to localize the target. After the last trial, hydrophilic proteins from the hippocampus were isolated. A proteome-wide study was performed, based on two-dimensional gel electrophoresis and mass spectrometry. Compared with non-learning animals, 53 (70%) proteins were downregulated and 23 (30%) proteins were upregulated after 7 days in rats with spatial learning. The overall changes in protein expression, as quantified by the induction factor, ranged from -1.62 (downregulation to 62%) to 2.10 (upregulation by 110%) compared with controls (100%). Most identified proteins exhibit known functions in vesicle transport, cytoskeletal architecture, and metabolism as well as neurogenesis. These findings indicate that learning in the Morris water maze has a morphological correlate on the proteome level in the hippocampus.

Animals↗

Optokinetic stimulation influences the disturbed perception of body orientation in spatial neglect.

The effect of optokinetic stimulation on the disturbed perception of body orientation in three patients with right brain damage and spatial neglect was examined. The patients were asked to direct a laser point to the position which they felt lay exactly "straight ahead" of their bodies' orientation. Without stimulation they localised the body's sagittal midplane markedly to the right of the objective orientation. The patients' horizontal displacement of the sagittal midplane was reduced by a movement of the surround to the left and worsened by a movement to the right. The findings are consistent with those found in patients with spatial neglect using vestibular and neck proprioceptive stimulation. They show that visual input, together with vestibular and neck proprioceptive input, is used for computing a central representation of egocentric space. In spatial neglect this coordinate transformation works with a systematic error and deviation of the spatial reference frame to the ipsilesional side. The positive effect of optokinetic stimulation in patients with spatial neglect is interpreted with a "correction" of the neural coordinate transformation process by producing asymmetric input at the sensory organs of the contributing channels.

Adult↗

New Frontiers in the Study of Dispersal and Spatial Analysis of Epidemics Caused by Species in the Genus Phytophthora.

Diseases caused by species in the genus Phytophthora are responsible for significant economic losses on a wide range of host plants. Spatial pattern is one of the most characteristic ecological properties of a species, and reflects environmental and genetic heterogeneity and reproductive population growth acting on the processes of reproduction, dispersal, and mortality. Species of Phytophthora can be dispersed either in soil, via surface water movement down rows, from rain splash dispersal, by air, or via movement by humans or invertebrate activity. Dispersal results in patchiness in patterns of disease or inoculum in soil. In this chapter we discuss the mechanisms of dispersal of members of this important genus and describe several methods that can be used to statistically analyze data for which spatial coordinates are known. The methods include testing spatial autocorrelation for binary data or continuous data, semivariograms, and regression models for spatial data. The goal of spatial pattern analysis is to gain an understanding of the mechanisms of dispersal of propagules and to sort out the physical and biological factors that are important for spread of plant pathogens and ultimately, for disease management.

Phytophthora diseases↗

Information about spatial view in an ensemble of primate hippocampal cells.

Hippocampal function was analyzed by making recordings from hippocampal neurons in monkeys actively walking in the laboratory. "Spatial view" cells, which respond when the monkey looks at a part of the environment, were analyzed. To assess quantitatively the information about the spatial environment represented by these cells, we applied information theoretic techniques to their responses. The average information provided by these cells about which location the monkey was looking at was 0.32 bits, and the mean across cells of the maximum information conveyed about which location was being looked at was 1.19 bits, measured in a period of 0.5 s. There were 16 locations for this analysis, each being one-quarter of one of the walls of the room. It also was shown that the mean spontaneous rate of firing of the neurons was 0.1 spikes/s, that the mean firing rate in the center of the spatial field of the neurons was 13.2 spikes/s, and that the mean sparseness of the representation measured in a 25-ms period was 0.04 and in a 500-ms time period was 0.19. (The sparseness is approximately equivalent to the proportion of the 25- or 500-ms periods in which the neurons showed one or more spikes.) Next it was shown that the mean size of the view fields of the neurons was 0.9 of a wall. In an approach to the issue of how an ensemble of neurons might together provide more precise information about spatial location than a single neuron, it was shown that in general the neurons had different centers for their view fields. It then was shown that the information from an ensemble of these cells about where in space is being looked at increases approximately linearly with the number of cells in the ensemble. This indicates that the number of places that can be represented increases approximately exponentially with the number of cells in the population. It is concluded that there is an accurate representation of space "out there" in the primate hippocampus. This representation of space out there would be an appropriate part of a primate memory system involved in memories of where in an environment an object was seen, and more generally in the memory of particular events or episodes, for which a spatial component normally provides part of the context.

Algorithms↗

A 6-year study of cognition and spatial function in the demented and non-demented elderly: the Sydney Older Persons Study.

BACKGROUND: Spatial function has been suggested to be disproportionately worse in people with dementia with Lewy bodies (DLB) than other dementia groups, and poor performance on the Mini-Mental State Examination pentagon copying (PC) task has been proposed as adequate for assessing this. We aimed to establish the prevalence of poor PC in the non-demented elderly; determine the validity of the use of PC as a spatial function test, and determine if poor PC is more common in DLB than non-DLB dementias. METHODS: In a population-based sample of 299 participants, 126 were rated as being cognitively normal (clinical rating scale [CDR] = 0), 95 mildly cognitively impaired (CDR = 0.5), and 78 met criteria for dementia, 19 of whom met criteria for probable DLB (pDLB) and 25 with none of the core features of DLB (non-DLB). The accuracy of PC performance was determined across CDR groups, and the relationship of PC to performance on a broad range of cognitive tests was evaluated. The dementia groups were compared cross-sectionally to determine differences in PC and other cognitive test performance, as well as 3 and 6 years earlier to determine cognitive differences at initial stages of cognitive decline. RESULTS: Poor PC was common in the non-demented elderly (39% CDR = 0; 43% CDR = 0.5). In this non-demented group, PC was selectively related to tests of spatial function. Poor PC was not significantly different in the pDLB and non-DLB groups at any assessment time, however it became more prevalent as dementia severity increased. Memory function and verbal fluency were more impaired in the pDLB group in the early stages of the disorder. COMMENT: PC appears to be a good measure of spatial function in the elderly. However, in contrast to other findings of poor spatial skills in DLB when dementia is in the mild to moderate stages, poor PC performance has not been shown to be a good early marker of DLB and its clinical correlates are yet to be determined.

Aged↗

Auditory spatial tuning in late-onset blindness in humans.

Blind individuals who lost their sight as older children or adults were compared with normally sighted controls in their ability to focus auditory spatial attention and to localize sounds in a noisy acoustic environment. Event-related potentials (ERPs) were recorded while participants attended to sounds presented in free field from either central or peripheral arrays of speakers with the task of detecting infrequent targets at the attended location. When attending to the central array of speakers, the two groups detected targets equally well, and their spatial tuning curves for both ERPs and target detections were highly similar. By contrast, late blind participants were significantly more accurate than sighted participants at localizing sounds in the periphery. For both groups, the early N1 amplitude to peripheral standard stimuli displayed no significant spatial tuning. In contrast, the amplitude of the later P3 elicited by targets/deviants displayed a more sharply tuned spatial gradient during peripheral attention in the late blind than in the sighted group. These findings were compared with those of a previous study of congenitally blind individuals in the same task [Röder, B., Teder-Sälejärvi, W., Sterr, A., Rösler, F., Hillyard, S. A., & Neville, H. J. Improved auditory spatial tuning in blind humans. Nature, 400, 162-166, 1999]. It was concluded that both late blind and congenitally blind individuals demonstrate an enhanced capability for focusing auditory attention in the periphery, but they do so via different mechanisms: whereas congenitally blind persons demonstrate a more sharply tuned early attentional filtering, manifested in the N1, late blind individuals show superiority in a later stage of target discrimination and recognition, indexed by the P3.

Acoustic Stimulation↗

Spatial ability and land navigation under degraded visual conditions.

Land navigation tasks require the use of visual cues. When these cues are degraded by the loss of resolution, navigators suffer varying degrees of performance decrements. We tested the hypothesis that these decrements are less severe for people of high spatial ability than they are for people of low spatial ability. We tested 108 noncommissioned officers on a task that required them to determine if two woodland photographs taken from different directions (N, NE, E ... NW) were of the same location; spatial ability was assessed using the Cognitive Laterality Battery. Spatial ability was related to the ability to do this task. Furthermore, there was a significant interaction between spatial ability and visual resolution on recognition performance. This article discusses the implications of these results for teleoperations and land navigation.

Cognition↗