SEARCH · Search PubMed

Results for “spatial”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,027 records · Page 57Linked to original sources

PubMed1997

Spatial frames of reference and somatosensory processing: a neuropsychological perspective.

In patients with lesions in the right hemisphere, frequently involving the posterior parietal regions, left-sided somatosensory (and visual and motor) deficits not only reflect a disorder of primary sensory processes, but also have a higher-order component related to a defective spatial representation of the body. This additional factor, related to right brain damage, is clinically relevant: contralesional hemianaesthesia (and hemianopia and hemiplegia) is more frequent in right brain-damaged patients than in patients with damage to the left side of the brain. Three main lines of investigation suggest the existence of this higher-order pathological factor. (i) Right brain-damaged patients with left hemineglect may show physiological evidence of preserved processing of somatosensory stimuli, of which they are not aware. Similar results have been obtained in the visual domain. (ii) Direction-specific vestibular, visual optokinetic and somatosensory or proprioceptive stimulations may displace spatial frames of reference in right brain-damaged patients with left hemineglect, reducing or increasing the extent of the patients' ipsilesional rightward directional error, and bring about similar directional effects in normal subjects. These stimulations, which may improve or worsen a number of manifestations of the neglect syndrome (such as extrapersonal and personal hemineglect), have similar effects on the severity of left somatosensory deficits (defective detection of tactile stimuli, position sense disorders). However, visuospatial hemineglect and the somatosensory deficits improved by these stimulations are independent, albeit related, disorders. (iii) The severity of left somatosensory deficits is affected by the spatial position of body segments, with reference to the midsagittal plane of the trunk. A general implication of these observations is that spatial (non-somatotopic) levels of representation contribute to corporeal awareness. The neural basis of these spatial frames includes the posterior parietal and the premotor frontal regions. These spatial representations could provide perceptual-premotor interfaces for the organization of movements (e.g. pointing, locomotion) directed towards targets in personal and extrapersonal space. In line with this view, there is evidence that the sensory stimulations that modulate left somatosensory deficits affect left motor disorders in a similar, direction-specific, fashion.

Brain Diseases↗

PubMed2006

Hippocampal CA1 kindling but not long-term potentiation disrupts spatial memory performance.

Long-term synaptic enhancement in the hippocampus has been suggested to cause deficits in spatial performance. Synaptic enhancement has been reported after hippocampal kindling that induced repeated electrographic seizures or afterdischarges (ADs) and after long-term potentiation (LTP) defined as synaptic enhancement without ADs. We studied whether repeated stimulations that gave LTP or ADs resulted in spatial performance deficits on the radial arm maze (RAM) and investigated the minimal number of ADs required for such deficits. Three experimental groups were run as follows: (1) 5 hippocampal ADs in 1 d (5-AD group), (2) 10 hippocampal ADs in 2 d (10-AD group), and (3) 12 -frequency primed-burst stimulations (PBSs) in 2 d in order to induce LTP without ADs (LTP group). Each experimental group was run together with a control group during the same time period. Rats were first trained in a spatial task on a radial arm maze with four of the eight arms baited, then given control or experimental treatment, and maze performance was tested in the first week (1-4 d) and fourth week (22-25 d) after treatment. Basal dendritic population excitatory postsynaptic potentials (pEPSPs) and medial perforant path (MPP)-evoked dentate gyrus population spike and polysynaptic CA1 excitation were recorded before and after experimental and control treatment. Spatial memory errors, in particular reference memory errors, were significantly higher in the 10-AD kindled group than any other group on the first and fourth week after treatment. Spatial memory errors were not significantly different in the 5-AD and LTP groups as compared with any control groups at any time. Basal dendritic pEPSP in CA1 was enhanced for about 1 wk after 12 PBSs, 10 ADs, or 5 ADs, while the dentate gyrus population spike and CA1 polysynaptic excitation evoked by MPP was increased for up to 4 wk after 10 ADs, but not 12 PBSs. Thus, distributed alteration of multiple synaptic transmission in the entorhinal-hippocampal circuit, but not LTP at the basal dendritic synapses in CA1, may disrupt spatial performance after 10 hippocampal ADs.

Animals↗

PubMed2005

A study on the role of the dorsal striatum and the nucleus accumbens in allocentric and egocentric spatial memory consolidation.

There is now accumulating evidence that the striatal complex in its two major components, the dorsal striatum and the nucleus accumbens, contributes to spatial memory. However, the possibility that different striatal subregions might modulate specific aspects of spatial navigation has not been completely elucidated. Therefore, in this study, two different learning procedures were used to determine whether the two striatal components could be distinguished on the basis of their involvement in spatial learning using different frames of reference: allocentric and egocentric. The task used involved the detection of a spatial change in the configuration of four objects placed in an arena, after the mice had had the opportunity to experience the objects in a constant position for three previous sessions. In the first part of the study we investigated whether changes in the place where the animals were introduced into the arena during habituation and testing could induce a preferential use of an egocentric or an allocentric frame of reference. In the second part of the study we performed focal injections of the N-methyl-d-aspartate (NMDA) receptors' antagonist, AP-5, within the two subregions immediately after training. The results indicate that using the two behavioral procedures, the animals rely on an egocentric and an allocentric spatial frame of reference. Furthermore, they demonstrate that AP-5 (37.5, 75, and 150 ng/side) injections into the dorsal striatum selectively impaired consolidation of spatial information in the egocentric but not in the allocentric procedure. Intra-accumbens AP-5 administration, instead, impaired animals trained using both procedures.

Analysis of Variance↗

PubMed2026

Cell Type-Resolved Causal Inference and Spatial Transcriptomic Integration Reveal Immune-Specific Genetic Drivers of Autoimmune and Malignant Thyroid Disease.

BACKGROUND: Thyroid diseases, including autoimmune thyroid disease (AITD) and thyroid cancer, are characterized by immune dysregulation, yet the cell type-specific genetic mechanisms underlying these conditions remain poorly understood. Most genome-wide association studies (GWAS) have relied on bulk tissue expression quantitative trait loci (eQTL), which cannot resolve the heterogeneity of immune cell populations. METHODS: We performed two-sample Mendelian randomization (MR) analyses using single-cell cis-eQTLs from 14 immune cell subtypes (OneK1K cohort) as instrumental variables against GWAS summary statistics for four thyroid outcomes: autoimmune hyperthyroidism, autoimmune hypothyroidism, thyroid cancer and autoimmune thyroiditis. Causal associations were validated through Bayesian colocalization, phenome-wide association analysis (PheWAS) and multi-layered transcriptomic validation encompassing spatial transcriptomics of AITD tissue (GSE248205), bulk RNA-seq of thyroid cancer (GSE3678) and single-cell RNA-seq of thyroid tumours (GSE250521). gsMap spatial LD score regression was applied to map disease heritability onto spatial tissue architecture. RESULTS: We identified six Bonferroni-significant causal gene-cell type pairs for autoimmune hyperthyroidism, including protective effects of ABHD16A in naïve/immature B cells (OR = 0.440), HIST1H3H in CD8 NC T cells (OR = 0.324), HMGN4 in NK recruiting cells (OR = 0.556) and ZKSCAN4 in CD8 S100B T cells (OR = 0.427), with five pairs showing strong colocalization (PP.H4 ≥ 86%). Three pairs reached significance for autoimmune hypothyroidism, including a risk association of HLA-F in CD4 NC T cells (OR = 1.139). For autoimmune thyroiditis, FAM134B/RETREG1 showed consistent suggestive protective associations across both CD4 and CD8 NC T cells (PP.H4 ≥ 90% for both), suggesting a possible involvement of ER phagy regulation in thyroiditis susceptibility. Thyroid cancer showed a suggestive association with HLA-G in classical monocytes (OR = 1.899, PP.H4 = 53%). Spatial transcriptomic validation demonstrated progressive immune infiltration from control tissue to Graves' disease to Hashimoto's thyroiditis (7.7%-15.7%, 46.1%-54.1%, respectively) and strong spatial correlation between target gene expression and corresponding cell type enrichment (e.g., plasma cell-HLA-DQB1: r = 0.491, p < 10-300). HLA-G was independently validated in thyroid cancer bulk (log2fc = 0.542, p = 9.51 × 10-3, AUC = 0.857) and single-cell datasets. PheWAS revealed no significant associations detected for the core candidates. gsMap identified significant enrichment of autoimmune hypothyroidism heritability in gastrointestinal tract, adrenal gland and adipose tissue (all Bonferroni p < 0.002). CONCLUSIONS: This study establishes a multi-scale analytical framework integrating cell type-resolved genetic inference with spatial tissue validation, revealing distinct immunogenetic architectures underlying autoimmune versus malignant thyroid disease. Protective genetic programs in autoimmune hyperthyroidism converge on chromatin remodelling (HIST1H3H, HMGN4, ZKSCAN4) and lipid metabolism (ABHD16A) across lymphocyte subsets, whereas thyroid cancer risk involves immune escape mediated by HLA-G in myeloid cells. The ER-phagy receptor RETREG1 represents a candidate pathway warranting further investigation in autoimmune thyroiditis. These findings provide genetically supported, cell type-specific therapeutic targets and demonstrate a generalizable strategy for dissecting the immune-mediated mechanisms of complex thyroid diseases.

Mendelian randomization↗

PubMed1996

Hippocampal lesions cause forgetting in a spatial response task.

UNLABELLED: Monkeys with lesions to the hippocampus and overlying cortex were impaired in making a spatially selective response on the basis of a spatial cue. Their impairment was even more severe on a task in which they were required to make spatial responses on the basis of cues which are not spatially distinct. A second experiment showed that once lesioned monkeys had been trained on a task with spatially distinct stimuli, they were initially able to perform accurately if the aspatial distinctiveness of the cue was reduced. However, their performance declined to chance over four to six trials. These results suggest that lesions to the hippocampus and overlying cortex may cause impairments in memory for the arrangement of visual scenes, including the spatial location of responses. KEYWORDS: spiny neurons, direct pathway, indirect pathways, rat neostriatum

Animals↗

PubMed2005

Genetic ablation of the mammillary bodies in the Foxb1 mutant mouse leads to selective deficit of spatial working memory.

Mammillary bodies and the mammillothalamic tract are parts of a classic neural circuitry that has been implicated in severe memory disturbances accompanying Korsakoff's syndrome. However, the specific role of mammillary bodies in memory functions remains controversial, often being considered as just an extension of the hippocampal memory system. To study this issue we used mutant mice with a targeted mutation in the transcription factor gene Foxb1. These mice suffer perinatal degeneration of the medial and most of the lateral mammillary nuclei, as well as of the mammillothalamic bundle. Foxb1 mutant mice showed no deficits in such hippocampal-dependent tasks as contextual fear conditioning and social transmission of food preference. They were also not impaired in the spatial reference memory test in the radial arm maze. However, Foxb1 mutants showed deficits in the task for spatial navigation within the Barnes maze. Furthermore, they showed impairments in spatial working memory tasks such as the spontaneous alternation and the working memory test in the radial arm maze. Thus, our behavioural analysis of Foxb1 mutants suggests that the medial mammillary nuclei and mammillothalamic tract play a role in a specific subset of spatial tasks, which require combined use of both spatial and working memory functions. Therefore, the mammillary bodies and the mammillothalamic tract may form an important route through which the working memory circuitry receives spatial information from the hippocampus.

Animals↗

PubMed2003

Spatial tuning to virtual sounds in the inferior colliculus of the guinea pig.

How do neurons in the inferior colliculus (IC) encode the spatial location of sound? We have addressed this question using a virtual auditory environment. For this purpose, the individual head-related transfer functions (HRTFs) of 18 guinea pigs were measured under free-field conditions for 122 locations covering the upper hemisphere. From 257 neurons, 94% responded to the short (50-ms) white noise stimulus at 70 dB sound pressure level (SPL). Out of these neurons, 80% were spatially tuned with a receptive field that is smaller than a hemifield (at 70 dB). The remainder responded omnidirectionally or showed fractured receptive fields. The majority of the neurons preferred directions in the contralateral hemisphere. However, preference for front or rear positions and high elevations occurred frequently. For stimulation at 70 dB SPL, the average diameter of the receptive fields, based on half-maximal response, was less than a quarter of the upper hemisphere. Neurons that preferred frontal directions responded weakly or showed no response to posterior directions and vice versa. Hence, front/back discrimination is present at the single-neuron level in the IC. When nonindividual HRTFs were used to create the stimuli, the spatial receptive fields of most neurons became larger, split into several parts, changed position, or the response became omnidirectional. Variation of absolute sound intensity had little effect on the preferred directions of the neurons over a range of 20 to 40 dB above threshold. With increasing intensity, most receptive fields remained constant or expanded. Furthermore, we tested the influence of binaural decorrelation and stimulus bandwidth on spatial tuning. The vast majority of neurons with a low characteristic frequency (<2.5 kHz) lost spatial tuning under stimulation with binaurally uncorrelated noise, whereas high-frequency units were mostly unaffected. Most neurons that showed spatial tuning under broadband stimulation (white noise and 1 octave wide noise) turned omnidirectional when stimulated with 1/3 octave wide noise.

Acoustic Stimulation↗

PubMedDate not supplied

Intraretrosplenial cortical grafts of fetal cholinergic neurons and the restoration of spatial memory function.

The retrosplenial cortex (RSC) receives cholinergic afferent fibers from the medial septal nucleus and diagonal band of Broca (DBB) by way of the cingulate bundle and the fornix. Bilateral lesions of both the cingulate and fornix pathways result in a complete depletion of cholinergic input to the RSC. In the present study we have examined the effects of transplanting cholinergic neurons from fetal rat pups to the RSC of adult rats following lesions of the cingulate bundle and fornix. The animals with lesions exhibited severe spatial memory impairments with a complete loss of extrinsic cholinergic afferents to the RSC. Animals with intraretrosplenial cortical transplants exhibited significant improvements in learning and memory performance as revealed by decreased escape latencies in spatial reference memory tests, increased numbers of platform crossings in spatial navigation tests, and a higher percentage of correct choices in a spatial working memory task. These improvements appeared to be cholinergically mediated because atropine administration significantly disrupted spatial navigation performance. The survival of the transplanted cholinergic neurons and their innervation of the RSC were characterized using a monoclonal antibody to choline acetyltransferase (ChAT). The staining of graft-derived ChAT-positive fibers also revealed a pattern of innervation that mimicked that of the cholinergic input in normal animals. These results indicate that intraretrosplenial cortical transplants of cholinergic neurons can rectify spatial memory deficits produced by the loss of intrinsic cholinergic afferents from the medial septal nucleus.

Animals↗

PubMed2002

Spatial cognition in young children with spinal muscular atrophy.

Success in visuospatial tasks has often been demonstrated in teenagers with spinal muscular atrophy (SMA). However, what has been tested in these studies, with the Wechsler Intelligence Scale for Children-Revised (Wechsler, 1974) performance scale, does not deal with the spatial capacities that co-occur with the advent of self-produced locomotion. Indeed, various studies have shown that occurrence of locomotion in infancy is correlated with the development of visuospatial cognitive competencies, suggesting that locomotor experience might play a central role in spatial development, especially in the realm of manual search for hidden objects. It is thus of interest to assess spatial search skills in SMA young children suffering total deprivation of locomotor experience. Twelve Type-2 SMA children with a mean age of 30 months were compared with controls with respect to their spatial search skills in a memory-for-locations task. In this search task, hiding containers were rotated 180 degrees before search was permitted. The performance obtained with the SMA group did not differ from that obtained in the healthy control group. SMA patients searched correctly for a hidden object in the 3-choice search task. Locomotor impairment does not appear to be a key risk factor for dramatic slowing down or deviation in the development of spatial search skills, as assumed by some authors. Further research is needed to identify the alternative pathways to normal spatial development that are used by SMA young children.

Case-Control Studies↗

PubMed1999

Goal-specific influences on the representation of spatial perspective.

In two experiments, subjects learned an unfamiliar campus environment, either by studying a map or by navigating. During acquisition, the subjects had one of two spatial goals: to learn the layout of the building (survey goal) or to learn the fastest routes between locations (route goal). Spatial memory was tested with several tasks, some assessing survey perspective processing and some assessing route perspective processing. Results indicate multiple influences on the representation of spatial perspective. Learning condition influenced performance. Individuals studying maps gave more accurate responses to some survey perspective tasks, whereas individuals navigating gave more accurate responses to some route perspective tasks. Spatial goals also influenced performance. Having a route goal enhanced performance on route perspective tasks; having a survey goal enhanced performance on survey perspective tasks. These findings are discussed in the context of research indicating flexibility when processing spatial perspective. Individuals can use spatial information from different perspectives, often doing so in a goal-directed manner.

Goals↗

PubMed1999

A partial agonist at strychnine-insensitive glycine sites facilitates spatial learning in aged rats.

1-Aminocyclopropanecarboxylic acid (ACPC) is a high affinity ligand at strychnine-insensitive glycine sites of the N-methyl-D-aspartate (NMDA) channels and exhibits partial agonist properties in both biochemical and electrophysiological measures. While ACPC was reported active in animal models used to evaluate potential antidepressants and anxiolytics, its effects on learning and memory are unknown. In the present study we investigated the effects of ACPC on spatial learning in the Morris water maze. On a schedule of 12 learning trials, one trial per day, mature male Wistar rats (3 months of age) rapidly acquired the task. Electroconvulsive shocks applied after each of the learning trials markedly inhibited the consolidation of spatial memory. Administration of either a muscarinic agonist, arecoline (1 mg/kg) or ACPC (250 or 400 mg/kg) 20 min before each of the learning trials did not affect the acquisition of spatial learning. Aged (16 months old) male Wistar rats demonstrated difficulties in the acquisition of spatial learning task. In these subjects, ACPC administered 20 min before each of the learning trials at a dose of 400, but not 250 mg/kg, facilitated the acquisition of spatial memory as indicated on trials 3-5. ACPC did not affect the strength of spatial memory as assessed at the end of conditioning, by measuring swimming behavior of rats in the pool with platform removed. It is suggested that ACPC may alleviate learning deficits observed in the elderly.

Age Factors↗

PubMed2004

[Effects of febrile seizures on motor, behavior, spatial learning and memory in rats].

OBJECTIVE: Febrile seizure is a very common emergency in children. Although researchers home and abroad constantly pay close attention to studies on brain damage and lesion possibly caused by febrile seizure, studies of effects on motor, behavior, spatial learning and memory are relatively seldom. In our study, Sprague-Dawley rats were utilized for the purpose of the exploration of effects of febrile seizures on their motor, behavior, spatial learning and memory. METHODS: Sixty 21-day-old male Sprague-Dawley rats, weighing (50 +/- 5) g were divided randomly and equally into febrile seizure group (FS), febrile control group (FG) and normal control group (NG). Febrile seizure animal model was induced by hyperthermal bath with 45 degrees C water. Febrile seizure was induced twice a day, thus ten times within five days in FS group. Rats of FG group were immersed in the same hyperthermal water for 2 minutes. Nothing special was performed on NG group. The abilities of motor and behavior of every rat in these 3 groups were tested in inclined plane test (IPT), overhanging test (OHT) and open field test (OFT) to show their varieties. Furthermore, Morris water maze was applied to evaluate the effects by febrile seizure on spatial learning and memory in rats during the place navigation test and spatial probe test. RESULTS: In the present experiments, febrile seizures were altogether induced 192 times with the mean latency being (4.25 +/- 0.98) minutes and the mean duration being (1.06 +/- 0.59) minutes. The experiments confirmed that multiple febrile seizures could lead to decreases of abilities in all tests in which analysis of variance indicated that there were significant differences between febrile seizure group and the other two (P < 0.01). In inclined plane test, the turning ability of the rats was weakened. The mean turning time was (9.1 +/- 2.6) seconds for FS, (5.3 +/- 2.1) seconds for FG and (5.3 +/- 2.0) seconds for NG. In overhanging test, the overhanging time was shortened: (33.4 +/- 18.1) seconds for FS, (50.1 +/- 20.3) seconds for FG and (59.0 +/- 20.7) seconds for NG. In the open field test, the rats became less active with the scores (5.1 +/- 2.0) for FS, (10.4 +/- 3.0) for FG and (13.2 +/- 2.3) for NG. Meanwhile, the authors discovered the decreases of the abilities of spatial learning and memory in rats caused by febrile seizures many times. In the place navigation test, the mean escape latency for the rats' looking for hidden platform was prolonged; the efficiency of their search strategy decreased; the swimming time the animals spent in platform region decreased [(44.02 +/- 5.25) seconds for FS, (51.75 +/- 5.28) seconds for FG and (57.07 +/- 5.36) seconds for NG; analysis of variance, P < 0.01.]; the number of times they crossed the platform area decreased [(6.07 +/- 1.77) times for FS, (9.25 +/- 2.07) times for FG and (11.34 +/- 2.37) times for NG; analysis of variance, P < 0.01]; the percentage of their swimming time fell (36.68% for FS, 43.13% for FG and 47.56% for NG). CONCLUSION: The experiments confirmed that multiple febrile seizures could result in damage and lesion of motor, behavior, spatial learning and memory in rats.

Animals↗

PubMed2006

[Changes of NMDA receptor expression in rat hippocampal formation after establishment of spatial memory by different training modes].

There is no unambiguous report so far on whether short reinforcing training could establish stable spatial long-term memory and how the NMDA/NR1 expression in the hippocampal formation changes after establishment of short- and long-term memory. In the present study, three spatial memory training modes of Morris water maze were used: spatial long-term memory training mode (LT group), spatial short-term memory training mode (ST group) and short reinforcing training mode (SRT group). The characteristics of those memories established by different training modes were compared. The immunofluorescence histochemical staining technique was used to observe the changes of NMDA/NR1 expression in the hippocampal formation in the three groups. The results showed that, during Morris water maze training, no significant difference was found in the mean latency and the strategies to the target between the LT and SRT groups. The examination of the memories following different trainings indicated that the mean latency and the strategies to the target as well as the times crossing the target in LT group were not significantly different from those in SRT group, except that the mean time remaining in the platform quadrant in LT group was significantly longer than that in SRT group. In addition, no significant difference in the intensity of NMDA/NR1 immunoreactivity in CA1, CA3 and dentate gyrus of the hippocampal formation was observed between the control and ST groups or between LT and SRT groups. However, the intensity of NMDA/NR1 immunoreactivity in CA1 area and dentate gyrus in both LT and SRT groups was significantly increased as compared with that in ST or the control groups. These results suggest that the short reinforcing training mode can establish long-term spatial memory, which is almost the same as that established by the long-term training mode, and that the increase of NMDA/NR1 expression in CA1 area and dentate gyrus of the hippocampal formation may be one of the mechanisms of spatial long-term memory formation.

Animals↗

PubMed1988

Apparent contrast of spatially and temporally sampled gratings.

We have measured the apparent contrast of spatially and temporally sampled gratings having the spatial frequency of 2, 4 and 8 c/deg. A contrast matching task was used in two different sampling conditions which allowed us to stimulate selectively the sustained and transient mechanisms in spatial and temporal vision. The results demonstrate the visual interpolation characteristics in the two domains and suggest a better response linearity for spatial than for temporal interpolation. The strongest nonlinear responses were obtained for temporally sampled medium spatial frequency gratings, suggesting separate temporal processing mechanisms for medium and high spatial frequencies

Humans↗

PubMed2026

Spatially defined microenvironmental niches are associated with clinical outcome and tumor ecosystem diversity in head and neck cancer.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) exhibits substantial biological heterogeneity that is not fully explained by human papillomavirus (HPV) status. The spatial organization of tumor, immune, and stromal cell populations and its relationship to clinical outcome remain incompletely understood. METHODS: We performed single-cell spatial transcriptomic and proteomic profiling of 44 primary HNSCC tumors, generating a spatial atlas of 19,471,501 cells across whole-slide tissue sections. Spatial niches and ecosystem states were identified through integrated computational analyses and evaluated for associations with tumor programs, clinicopathologic features, and patient outcomes. FINDINGS: HPV-negative tumors were enriched for fibroblast-rich, immune-poor niches associated with epithelial-mesenchymal transition and hypometabolic tumor programs, whereas HPV-positive tumors displayed more diverse immune, stromal, and vascular niche combinations and were enriched for immunogenic ecosystem states. Approximately 20% of HPV-positive tumors exhibited fibroblast-rich ecosystem architectures resembling HPV-negative disease and were associated with less favorable outcomes than other HPV-positive tumors of similar stage. In patient-derived co-culture models, extracellular matrix-associated fibroblasts were associated with epithelial-mesenchymal transition (EMT)-like tumor states, CD8+ T cell dysfunction, and chemotherapy resistance-associated phenotypes. CONCLUSIONS: Spatial ecosystem architecture is associated with clinically relevant heterogeneity beyond conventional HPV-based classification. Fibroblast-rich, immune-poor ecosystem states characterize a high-risk subset of HPV-positive tumors and may provide a framework for improved biological classification and risk stratification in HNSCC. FUNDING: This work was supported by the National Institutes of Health (R01CA291607 and R21CA267527-01) and the Feldstein Medical Foundation.

Humans↗

PubMed1999

Spatial view cells and the representation of place in the primate hippocampus.

The information represented in the primate hippocampus is being analysed by making recordings in monkeys actively walking in the laboratory. In a sample of 352 cells recorded in this situation, no "place" cells have so far been found. Instead, we have found a considerable population of "spatial view" cells tuned to respond when the monkey looks at small parts of the environment. We have been able to demonstrate (1) that these hippocampal neurons respond to a view of space "out there," not to the place where the monkey is; (2) that the responses depend on where the monkey is looking, by measuring eye position; (3) that the responses in some cases (e.g., CA1 but not CA3) still occur if the view details are obscured with curtains; (4) that the cells (in, e.g., CA1) retain part of their "space" tuning even in complete darkness, for several minutes; and (5) that the spatial representation is allocentric. The spatial representation is, thus, different from that in the rat hippocampus, in which place cells respond based on where the rat is located. The representation is also different from that described in the parietal cortex, where neurons respond in egocentric coordinates. This representation of space "out there" provided by primate spatial view cells would be an appropriate part of a memory system involved in memories of particular events or episodes, for example, of where in an environment an object was seen. Spatial view cells (in conjunction with whole body motion cells in the primate hippocampus, and head direction cells in the primate presubiculum) would also be useful as part of a spatial navigation system, for which they would provide a memory component.

Animals↗

PubMed1999

Resolution enhancement in single-shot imaging using simultaneous acquisition of spatial harmonics (SMASH).

Spatial resolution in single-shot imaging is limited by signal attenuation due to relaxation of transverse magnetization. This effect can be reduced by minimizing acquisition times through the use of short interecho spacings. However, the minimum interecho spacing is constrained by limits on gradient switching rates, radiofrequency (RF) power deposition and RF pulse length. Recently, simultaneous acquisition of spatial harmonics (SMASH) has been introduced as a method to acquire magnetic resonance images at increased speeds using a reduced number of phase-encoding gradient steps by extracting spatial information contained in an RF coil array. In this study, it is shown that SMASH can be used to reduce the effects of relaxation, resulting in single-shot images with increased spatial resolution without increasing imaging time. After a brief theoretical discussion, two strategies to reduce signal attenuation and increase spatial resolution in single-shot imaging are introduced and their performance is evaluated in phantom studies. In vivo single-shot echoplanar imaging (EPI), BURST, and half-Fourier single-shot turbo spin-echo (HASTE) images are then presented demonstrating the practical implementation of these resolution enhancement strategies. Images acquired with SMASH show increased spatial resolution and improved image quality when compared with images obtained with the conventional acquisitions. The general principles presented for imaging with SMASH can also be applied to other partially parallel imaging techniques.

Computer Simulation↗

PubMed1977

The function of septo-hippocampal connections in spatially organized behaviour.

The role of septo-hippocampal connections in spatial behaviour is examined in lesion and stimulation experiments in rats. Destruction of septo-hippocampal connections produces a severe and enduring deficit in the ability to perform a spatial memory task. Furthermore, crossed unilateral lesions of the entorhinal area and fimbria-fornix produce the same deficit as bilateral lesions in either the entorhinal area or the fimbria-fornix, as predicted from a disconnection analysis of hippocampal lesions. Evidence also suggests that septo-hippocampal damage produces a greater deficit in spatial behaviours when a flexible response is required than when a consistent response is required, although this difference is a relative one rather than an absolute one. Finally, disruptive stimulation of the hippocampus while rats are performing a spatial memory task produces retrograde amnesia but not proactive interference. Taken together, these data indicate an important role of the septo-hippocampal system in spatial behaviour, and in the maintenance of spatial memories.

Animals↗