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PubMed1998

Dissociation of mnemonic and perceptual processes during spatial and nonspatial working memory using fMRI.

Neuroimaging studies in humans have consistently found robust activation of frontal, parietal, and temporal regions during working memory tasks. Whether these activations represent functional networks segregated by perceptual domain is still at issue. Two functional magnetic resonance imaging experiments were conducted, both of which used multiple-cycle, alternating task designs. Experiment 1 compared spatial and object working memory tasks to identify cortical regions differentially activated by these perceptual domains. Experiment 2 compared working memory and perceptual control tasks within each of the spatial and object domains to determine whether the regions identified in experiment 1 were driven primarily by the perceptual or mnemonic demands of the tasks, and to identify common brain regions activated by working memory in both perceptual domains. Domain-specific activation occurred in the inferior parietal cortex for spatial tasks, and in the inferior occipitotemporal cortex for object tasks, particularly in the left hemisphere. However, neither area was strongly influenced by task demands, being nearly equally activated by the working memory and perceptual control tasks. In contrast, activation of the dorsolateral prefrontal cortex and the intraparietal sulcus (IPS) was strongly task-related. Spatial working memory primarily activated the right middle frontal gyrus (MFG) and the IPS. Object working memory activated the MFG bilaterally, the left inferior frontal gyrus, and the IPS, particularly in the left hemisphere. Finally, activation of midline posterior regions, including the cingulate gyrus, occurred at the offset of the working memory tasks, particularly the shape task. These results support a prominent role of the prefrontal and parietal cortices in working memory, and indicate that spatial and object working memory tasks recruit differential hemispheric networks. The results also affirm the distinction between spatial and object perceptual processing in dorsal and ventral visual pathways.

Adult↗
PubMed2026

Spatial Total RNA Sequencing of Formalin-Fixed Paraffin-Embedded Tissue by spRandom-seq.

The molecular pathogenesis of infectious diseases and cancer is orchestrated by nanoscale of host and microbial RNA transcripts within the tissue microenvironment. Nevertheless, spatially resolving the comprehensive transcriptional landscape within complex clinical tissues, like formalin-fixed paraffin-embedded (FFPE) specimens, still poses a formidable challenge. Here, we present spRandom-seq, a random primer-based spatial total RNA sequencing technology designed to spatially resolve complete transcriptomes from host, bacteria, and even nanoscale viruses in FFPE tissues. Capitalizing on the random primer design, our technology not only facilitated the discovery of specific lncRNAs and alternative splicing events in mouse brain and olfactory bulb, but also delineated pronounced spatial heterogeneity in clinical FFPE sections-across distinct tumor regions in breast cancer and microbial infection sites in Klebsiella pneumoniae-infected tissues. Importantly, integrated analysis of host and viral RNAs in FFPE samples from hepatitis B virus (HBV)‑positive hepatocellular carcinoma (HCC) demonstrated that complement and coagulation pathways were specifically activated across expansive HBV‑infected tumor areas, which also exhibited an increased burden of copy number variations (CNVs). Owing to its compatibility with existing spatial transcriptomics platforms and minimal operational complexity, spRandom-seq represents a practical and scalable approach for clinical pathology applications and infection diagnostics.

Paraffin Embedding↗
PubMed2026

GenOT: generative optimal transport enables spatiotemporal interpolation and generation in cross-platform spatial transcriptomics.

Spatial transcriptomics technologies have revolutionized the analysis of spatial gene expression, yet integrating spatial information and generating data across heterogeneous samples remain challenging. We present GenOT, a generative framework combining multi-scale graph self-supervised contrastive learning with optimal transport barycenter theory for efficient cross-slice and cross-platform spatiotemporal interpolation. The core innovation of GenOT lies in introducing an optimal transport barycenter-based interpolation algorithm, which mathematically models spatial distribution differences across heterogeneous samples to reconstruct spatiotemporal gene expression dynamics. Extensive evaluations demonstrate that GenOT consistently outperforms existing approaches in spatial domain identification, cross-platform interpolation, and developmental trajectory reconstruction.

Spatial Transcriptomics↗
PubMed2026

Single-section multiplex spatial proteomics of immune microenvironments in kidney transplantation.

Characterizing kidney disease is challenged by marked cellular heterogeneity and limited tissue availability from renal biopsies. Conventional diagnostic workflows rely on multiple serial sections for parallel staining, increasing tissue consumption, sampling bias, and loss of spatial information, thereby constraining molecular characterization within intact tissue architecture. High-plex spatial proteomics may overcome these limitations by enabling comprehensive molecular profiling on a single section. Here, we present and evaluate a high-plex cyclic immunofluorescence imaging workflow (MACSima™, Miltenyi Biotec) applied to kidney transplant biopsies, including BK virus nephropathy (BKVN) and focal segmental glomerulosclerosis (FSGS), to characterize spatial immune organization with a focus on complement system components. Feasibility and subcellular resolution were first assessed in a lupus nephritis section, demonstrating compatibility with diagnostic immune panels and preservation of tissue morphology. A 48-marker multiplex panel interrogating immunity, oxidative stress, senescence, and fibrosis was then applied to BKVN samples, including paired pre- and post-treatment biopsies, revealing distinct proteomic patterns and dynamic changes following therapy. In FSGS, a glomerulus-focused panel identified spatially resolved innate and adaptive immune signatures, including complement-related patterns supporting exploratory analysis of glomerular immune architecture. Structural, nuclear, membrane, and phosphorylated signaling markers enabled precise delineation of renal compartments and assessment of cellular states such as proliferation, DNA damage, and pathway activation. The workflow also supported detection of extracellular vesicles in cultured renal cells, highlighting its versatility. Overall, this approach provides a robust, tissue-sparing platform for integrated spatial and molecular profiling of renal biopsies, reducing sampling bias while enabling discovery-level phenotyping from a single section. This unified strategy is particularly suited to kidney transplantation, where diagnosis, therapeutic decision-making, and longitudinal monitoring are closely interconnected.

Kidney Transplantation↗
PubMed1988

Urbanization and spatial development in the Asian and Pacific region: trends and issues.

"This article reviews the trends and patterns of urbanization and spatial development since 1960 in selected Asian and Pacific developing countries and discusses the main forces underlying the trends. It examines issues such as the speed of urbanization, spatial concentration and appropriate measures to deal with them; the effects of income and differences in sectoral productivity and of population growth; the relative effectiveness of spatial policies; and urban problems and measures to cope with them. It then attempts to preview the likely urbanization trends to the year 2000, highlighting problems associated with rapid urban growth and excessive spatial concentration. Finally, it discusses the various policy approaches to spatial and urban issues."

Asia↗
PubMed1997

Exposure to chronic psychosocial stress and corticosterone in the rat: effects on spatial discrimination learning and hippocampal protein kinase Cgamma immunoreactivity.

Previous reports have demonstrated a striking increase of the immunoreactivity of the gamma-isoform of protein kinase C (PKCgamma-ir) in Ammon's horn and dentate gyrus (DG) of rodent hippocampus after training in a spatial orientation task. In the present study, we investigated how 8 days of psychosocial stress affects spatial discrimination learning in a hole board and influences PKCgamma-ir in the hippocampal formation. The acquisition of both reference memory and working memory was significantly delayed in the stressed animals during the entire training period. With respect to cellular plasticity, the training experience in both nonstressed and stressed groups yielded enhanced PKCgamma-ir in the CA1 and CA3 regions of the posterior hippocampus but not in subfields of the anterior hippocampus. Stress enhanced PKCgamma-ir in the DG and CA3 pyramidal cells of the anterior hippocampus. In stressed animals that were subsequently trained, the PKCgamma-ir was increased in the posterior CA1 region to the same level as that found in nonstressed trained animals. Stress apparently abrogated the PKCgamma-ir training response in the CA3 region. In a second experiment, the elevation of plasma corticosterone levels to values that are found during stress did not significantly influence reference memory scores but slightly and temporarily affected working memory. The training-induced enhancement of PKCgamma-ir in the CA1 region was similar in trained and corticosterone-treated trained animals, but the learning-induced PKCgamma-ir response in the posterior CA3 area was absent after corticosterone pretreatment. These results reveal that prolonged psychosocial stress causes spatial learning deficits, whereas artificial elevation of corticosterone levels to the levels that occur during stress only mildly affects spatial memory performance. The spatial learning deficits following stress are reflected only in part in the redistribution of hippocampal PKCgamma-ir following training.

Adrenal Glands↗
PubMed2002

Hippocampal expression of c-fos is not essential for spatial learning.

The formation of long-term memory is thought to involve underlying changes in synaptic strength. Many studies have focused on the mechanisms of spatial learning behavior in mammals that is critically dependent on the proper function of the hippocampus. Because of the enduring nature of long-term memory, it is thought that gene expression is involved in this process. The immediate early gene (IEG) c-fos encodes a transcription factor. The c-Fos proteins form heterodimeric proteins with the c-Jun family proteins and the resulting AP-1 transcription complex plays a key role in coupling short-term events elicited by stimuli received at the cell membrane to long-term neuroplastic changes by regulating gene expression. c-fos is induced in the hippocampus after spatial learning. Despite this knowledge, the precise role of c-fos in memory formation and the underlying mechanisms remain unknown. To start investigating the role of c-fos in learning and memory and underlying mechanisms, we evaluated spatial learning capabilities using mice carrying a hippocampal region-specific mutation of c-fos. We found that the c-fos mutant mice exhibit normal spatial learning behaviors in both the Morris water maze and the Barnes maze tests compared to control mice. Our results suggest that hippocampal c-fos expression is not essential for spatial learning.

Animals↗
PubMed2002

The effects of aging and dorsal hippocampal lesions: performance on spatial and nonspatial comparable versions of the water maze.

Aged intact and young hippocampal-lesioned rats show similar deficits on the spatial water maze. However, this does not necessitate that the source of these deficits in the aged animals is due to hippocampal damage. These water maze deficits may arise from other aging factors such as changes in thermoregulation, muscle fatigue, swim ability, and response to stress. Consequently, it is imperative to examine the performance of aged rats on a comparable nonhippocampal version of this task. Past attempts to develop a hippocampus-independent version of the water maze were confounded because these tasks were easier (i.e., the rats spent much less time swimming in the water) than the spatial versions of the task. The current study examined performance on a hippocampus-independent task comparable in difficulty to the spatial water one. Middle-aged (16-m) and old (25-m) male F344 rats were given sham or dorsal hippocampus lesions and tested on both a spatial and a nonspatial water maze. The middle-aged rats with hippocampal lesions were impaired on the spatial task but not on the nonspatial task. Conversely, aged animals showed a similar impairment on both types of water maze tasks. Additionally, hippocampal lesions exacerbated the age-related impairment on both tasks. These findings indicate that caution must be used when interpreting the results of water maze tasks for aged animals.

Aging↗
PubMed1996

Ocular exploration of space as a function of neck proprioceptive and vestibular input--observations in normal subjects and patients with spatial neglect after parietal lesions.

We recently argued that the specific compensation of spatial neglect by manipulating neck proprioceptive and vestibular input is due to a central "correction" of the disturbed neural transformation process converting the afferent input coordinates from the peripheral sensory organs into a central representation of egocentric space. Both types of stimulation were proposed to induce a reorientation of the deviated or distorted egocentric spatial reference frame. The aim of the present study was to observe this process of reorientation under a condition in which no visual stimulus can attract the subject's attention and thus influence exploration behaviour from outside. We recorded eye movements of normal subjects and of three patients with spatial neglect after right parietal lesions while searching for a non-existent target in complete darkness. It was assumed that the area of the outer space that subjects spontaneously explore under this condition is a direct function of the subject's representation of egocentric space. Ocular space exploration was biased and confined almost entirely to the right side of the midsagittal plane in patients with neglect. This spatial distribution of exploratory eye movements changed remarkably with left-sided neck muscle vibration as well as with left-sided vestibular stimulation using ice water calorics. The spatial area of exploration was significantly enlarged to the contralesional side and the exploration maximum shifted in the same direction. Whereas with both types of stimulation space exploration of patients with neglect was similar to that of normal subjects when not being stimulated, neck proprioceptive and vestibular stimulation in normal subjects induced a quasi neglect-like exploration pattern, i.e. a bias to one side of the objective midsagittal plane. If ocular space exploration was, however, related to the subjectively perceived position of the midsagittal plane in space, eye movements were symmetrically distributed and carried out to both sides of subjective "straight ahead" in all experimental conditions, in normal subjects as well as in patients with neglect. The present results support the above hypothesis and indicate that neck proprioceptive as well as vestibular input directly contribute to the computation of the subject's central representation of egocentric space used for localizing body orientation and for guiding motor behaviour in space.

Adult↗
PubMed2003

Refining the critical period for methamphetamine-induced spatial deficits in the Morris water maze.

RATIONALE: Neonatal administration of methamphetamine (MA) to rats from postnatal day (P) 11 to 20, but not from P1 to P10, produces lasting deficits in spatial learning and memory. The preweaning period of development in the rat corresponds to human third trimester hippocampal development and because of the increased use of MA in women of childbearing age, there is a greater likelihood that fetuses will be exposed to this drug. Development of the hippocampus is dependent upon many factors, including an optimal level of corticosterone (CORT). We have demonstrated that the CORT response of animals on P11 to MA is protracted relative to administration on P15 or P20. Interestingly, the P11 animals are still in the stress hyporesponsive period. OBJECTIVES: We postulated that because of the prolonged CORT response on P11, the effects of MA on spatial learning and memory may be confined to a shorter period of exposure. METHODS: Neonatal rats were administered MA (10 mg/kg) 4 times daily from either P11 to P15 or from P16 to P20, raised to adulthood and tested against animals only administered saline (SAL) from P11 to P20 for anxiety, swimming ability, and spatial learning and memory. RESULTS: Animals exposed to MA, regardless of exposure period, tended to be less anxious in the Zero maze relative to SAL animals. No differences were noted for swimming ability. Only animals exposed to MA from P11 to P15 demonstrated deficits in spatial learning and memory during acquisition as well as during a shifted platform phase where learning a new position was required. CONCLUSIONS: The results demonstrate that spatial learning and memory deficits produced by MA administration are dependent upon when the exposure of the animal occurs and appears to be during the period of development in the rat when the response to threatening environments, stressors, is greatly reduced.

Animals↗
PubMed1998

Effects of drugs of abuse and scopolamine on memory in rats: delayed spatial alternation and matching to position.

Drugs of abuse produce amnestic effects in humans and laboratory animals in a variety of tasks. Generally, only a few compounds have been examined in any particular procedure. It was the goal of the present studies to examine drugs of abuse of different pharmacological classes in rats responding under two behavioral schedules historically employed as experimental models of memory: spatial alternation and matching to position. One group of rats responded under a single-response spatial-alternation baseline with a 10-s delay and another group responded under a matching-to-position baseline with delay values of 3, 10 and 30 s. Performance under the spatial-alternation baseline was characterized by low variability and >90% accuracy. Under the matching-to-position baseline, saline control percent accuracy was >95% at 3 s, >85% at 10 s and >70% at 30 s. Under spatial alternation cocaine, d-amphetamine, pentobarbital, diazepam, phencyclidine, scopolamine and methscopolamine produced significant (P<0.05) effects on accuracy, whereas only cocaine, d-amphetamine, pentobarbital and phencyclidine disrupted accuracy under the matching-to-position baseline. These results suggest that spatial alternation may be a more sensitive baseline for determining drug effects on working memory in the rat.

Animals↗
PubMed2004

Obstructive jaundice in rats: cause of spatial memory deficits with recovery after biliary decompression.

Children with end-stage liver disease have been found to have cognitive deficits. The aim of this study was to examine whether cholestatic jaundice causes spatial deficits in rats and if these cognitive deficits are reversed by biliary drainage. Rats were randomly divided into three groups. In the first group, the bile duct was ligated for 3 weeks (BDL group); in the second group, the proximal bile duct was ligated with a Broviac CV catheter for 2 weeks followed by a tube bilioduodenostomy (TBD group); in the third group, a sham operation was performed (SHAM group). All the surviving rats were assessed for spatial learning and memory (a major cognitive function in rats) by the Morris water maze task about 3 weeks after the first operation. Blood was aspirated by cardiocentesis and assayed for total bilirubin, albumin, ammonia, and hemoglobin levels on the day following the water maze task. During the four consecutive acquisition trial days of the Morris water maze, jaundiced rats (BDL group) had a significant longer latency to escape than the SHAM group ( p < 0.05). Rats that underwent biliary decompression for 1 week (TBD group) showed improved status of the spatial deficit, as they required less time to reach the escape platform, approaching the performance of the SHAM group. The BDL group had a significantly higher serum ammonia level, higher bilirubin level, and lower hemoglobin level than the other two groups. After biliary decompression for 1 week, the serum albumin concentration in the TBD group still did not return to the level of the SHAM group. The results of this study suggest that long-term cholestasis results in spatial memory deficits in rats that correlate with anemia and hyperbilirubinemia encephalopathy. Early biliary decompression of obstructive jaundice improves spatial memory deficits, possibly related to the recovery of the serum ammonia and hemoglobin levels.

Analysis of Variance↗
PubMed2000

Spatial cognition and neuro-mimetic navigation: a model of hippocampal place cell activity.

A computational model of hippocampal activity during spatial cognition and navigation tasks is presented. The spatial representation in our model of the rat hippocampus is built on-line during exploration via two processing streams. An allothetic vision-based representation is built by unsupervised Hebbian learning extracting spatio-temporal properties of the environment from visual input. An idiothetic representation is learned based on internal movement-related information provided by path integration. On the level of the hippocampus, allothetic and idiothetic representations are integrated to yield a stable representation of the environment by a population of localized overlapping CA3-CA1 place fields. The hippocampal spatial representation is used as a basis for goal-oriented spatial behavior. We focus on the neural pathway connecting the hippocampus to the nucleus accumbens. Place cells drive a population of locomotor action neurons in the nucleus accumbens. Reward-based learning is applied to map place cell activity into action cell activity. The ensemble action cell activity provides navigational maps to support spatial behavior. We present experimental results obtained with a mobile Khepera robot.

Animals↗
PubMed2006

The role of body-based sensory information in the acquisition of enduring spatial representations.

Although many previous studies have shown that body-based sensory modalities such as vestibular, kinesthetic, and efferent information are useful for acquiring spatial information about one's immediate environment, relatively little work has examined how these modalities affect the acquisition of long-term spatial memory. Three groups of participants learned locations along a 146 m indoor route, and subsequently pointed to these locations, estimated distances between them, and constructed maps of the environment. One group had access to visual, proprioceptive, and inertial information, another had access to matched visual and matched inertial information, and another had access only to matched visual information. In contrast to previous findings examining transient, online spatial representations, our results showed very few differences among groups in the accuracy of the spatial memories acquired. The only difference was the improved pointing accuracy of participants who had access to proprioceptive information relative to that of participants in the other conditions. Results are discussed in terms of differential sensory contributions to transient and enduring spatial representations.

Adult↗
PubMed2004

Spatial aggregation across ephemeral resource patches in insect communities: an adaptive response to natural enemies?

Although an increase in competition is a common cost associated with intraspecific crowding, spatial aggregation across food-limited resource patches is a widespread phenomenon in many insect communities. Because intraspecific aggregation of competing insect larvae across, e.show $132#g. fruits, dung, mushrooms etc., is an important means by which many species can coexist (aggregation model of species coexistence), there is a strong need to explore the mechanisms that contribute to the maintenance of this kind of spatial resource exploitation. In the present study, by using Drosophila-parasitoid interactions as a model system, we tested the hypothesis whether intraspecific aggregation reflects an adaptive response to natural enemies. Most of the studies that have hitherto been carried out on Drosophila-parasitoid interactions used an almost two-dimensional artificial host environment, where host larvae could not escape from parasitoid attacks, and have demonstrated positive density-dependent parasitism risk. To test whether these studies captured the essence of such interactions, we used natural breeding substrates (decaying fruits). In a first step, we analysed the parasitism risk of Drosophila larvae on a three-dimensional substrate in natural fly communities in the field, and found that the risk of parasitism decreased with increasing host larval density (inverse density dependence). In a second step, we analysed the parasitism risk of Drosophila subobscura larvae on three breeding substrate types exposed to the larval parasitoids Asobara tabida and Leptopilina heterotoma. We found direct density-dependent parasitism on decaying sloes, inverse density dependence on plums, and a hump-shaped relationship between fly larval density and parasitism risk on crab apples. On crab apples and plums, fly larvae benefited from a density-dependent refuge against the parasitoids. While the proportion of larvae feeding within the fruit tissues increased with larval density, larvae within the fruit tissues were increasingly less likely to become victims of parasitoids than those exposed at the fruit surface. This suggests a facilitating effect of group-feeding larvae on reaching the spatial refuge. We conclude that spatial aggregation in Drosophila communities can at least in part be explained as a predator avoidance strategy, whereby natural enemies act as selective agents maintaining spatial patterns of resource utilisation in their host communities.

Adaptation, Biological↗
PubMed2005

Using animal movement paths to measure response to spatial scale.

Animals live in an environment that is patchy and hierarchical. I present a method of detecting the scales at which animals perceive their world. The hierarchical nature of habitat causes movement path structure to vary with spatial scale, and the patchy nature of habitat causes movement path structure to vary throughout space. These responses can be measured by a combination of path tortuousity (measured with fractal dimension) versus spatial scale, the variation in tortuousity of small path segments along the movement path, and the correlation between tortuousities of adjacent path segments. These statistics were tested using simulated animal movements. When movement paths contained no spatial heterogeneity, then fractal D and variance continuously increased with scale, and correlation was zero at all scales. When movement paths contained spatial heterogeneity, then fractal D sometimes showed a discontinuity at transitions between domains of scale, variation showed peaks at transitions, and correlations showed a statistically significant positive value at scales smaller than patch size, decreasing to below zero at scales greater than patch size. I illustrated these techniques with movement paths from deer mice and red-backed voles. These new analyses should help understand how animals perceive and react to their landscape structure at various spatial scales, and to answer questions about how habitat structure affects animal movement patterns.

Animals↗
PubMed2003

Training in tasks with different visual-spatial components does not improve virtual arthroscopy performance.

BACKGROUND: We earlier showed that training in the Procedicus KSA Simulator improves the performance of tasks done later in the same simulator. However, it is still unclear how performance in a specific visual-spatial simulator context may change after training in other simulators with different visual-spatial components. In particular, the aim of this study was to test whether performance in the Procedicus Virtual Arthroscopy (VA) Knee Simulator would remain unchanged after a training session in three other simulators with different visual-spatial components. METHODS: Twenty-eight medical students participated in a quasi-transfer study. They were randomly allocated to an experimental group ( n = 14) and a control group ( n = 14). RESULTS: Performance in the Procedicus VA Knee Simulator did not improve after training in other simulators with different visual-spatial components ( t-test p = NS). No significant correlation was found between the Procedicus VA Knee and the Minimally Invasive Surgical Trainer (MIST) simulators. CONCLUSION: One hour of training in different visual-spatial contexts was not enough to improve the performance in virtual arthroscopy tasks. It cannot be excluded, however, that experienced trainees could improve their performance, because perceived similarity between different situations is influenced by many psychological factors, such as the knowledge or expertise of the person performing the transfer task.

Adult↗
PubMed1986

Sex role and spatial ability: an EEG study.

The purpose of this study was to examine the relationship between sex role and spatial ability using both performance and electrocortical (EEG) measures. Two hundred and fifty four subjects were given the Differential Aptitudes Space Relations Test and a short form of the Personal Attributes Questionnaire (PAQ) which gives an indication of sex role. From this initial group, 40 males and females were chosen based on sex role scores. These subjects were asked to solve additional visuo-spatial problems. Bilateral EEG measures were taken from the frontal and parietal areas. The results indicate that frontal EEG measures are related to the sex role orientation of the subjects whereas parietal EEG measures are associated with performance on the visuo-spatial task for males but not females. These results suggest that frontal and parietal EEG measures reflect different processes. Counter to the traditional hypothesis, performance on the visuo-spatial task was negatively related to masculine sex-role orientation suggesting that factors which influence spatial processing go beyond biological sex.

Brain↗