Bilateral effects of concurrent verbal and spatial rehearsal on complex motor sequencing.
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Dominance, Cerebral↗
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Results for “spatial sequencing”
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Topographic segmentation of waking EEG in medication-free schizophrenic patients.
Lehmann has demonstrated that EEG topography can be used to segment EEG map series into a sequence of spatially stationary segments characterized by location of potential maxima and minima. We employed topographic segmentation techniques to study 9 channel EEGs recorded from 11 medication-free schizophrenic patients and 10 normal controls during resting and active task conditions, retesting 8 patients after neuroleptic treatment. To define EEG segments, average reference potential maps corresponding to global field power peaks in theta, alpha, and low beta activity were classified according to locations of extreme minimum and maximum values. Normals and schizophrenics did not differ in the number or types of switches between segments, or the frequency of hemisphere crossing of potential extrema. However, EEGs of normal subjects were characterized by significantly more (P less than 0.003) unused theta segment types (of a theoretically possible 36). Moreover, medication significantly (P less than 0.02) increased the number of unused theta segment types in EEGs of schizophrenics. We interpret these findings as evidence of increased spatial variability of brain electrical activity in schizophrenics and discuss their functional implications.
Adult↗
MR imaging of fat-containing tissues: valuation of two quantitative imaging techniques in comparison with localized proton spectroscopy.
Since lipid protons, consisting mainly of triacylglycerols (TAG), are rather mobile, magnetic resonance imaging (MRI) is ideally suited for the examination of fat-containing tissues such as bone marrow. In contrast to water protons, however, lipid protons are chemically distinct and give rise to at least eight resonance peaks with different T1 and T2 relaxation times in the 1H spectrum. This is why the characterization of fat-containing tissues by quantitative MRI is much more difficult than that of most other tissues. In our study we wanted to examine the accuracy and the potential of a 1H chemical shift imaging (CSI) technique and a multiple spin-echo imaging (MSEI) technique. A stimulated-echo (STEAM) sequence for spatially localized proton spectroscopy was used as the reference method. In the first part of this paper, we describe quantitative imaging experiments which were performed to assess the accuracy of the fat-water separation according to the Dixon method and the bi-exponential decomposition of the MSEI data. For that purpose, we used a two-compartment phantom filled with either an aqueous Gd-DTPA solution and vegetable oil or with two different aqueous Gd-DTPA solutions, respectively. The analysis of the 1H CSI data revealed that the presence of non-methylen protons in neutral fats leads to a slight under-estimation (of about 15%) of the relative fat fraction. The error is described theoretically and verified quantitatively by STEAM measurements. The bi-exponential analysis of the transverse relaxation data, on the other hand, yields reliable T2 values if the relative proton density of both components is higher than 15%. IN the second part of our investigation, the same techniques were applied to acquire data from the subcutaneous fatty tissue, the femoral head, and the lumbar vertebrae of three healthy volunteers. In the bone marrow spectra, only two broad resonances could be resolved; they were superpositions of diverse molecular groups with different T1 and T2 relaxation times. In these cases, localized proton spectroscopy does not provide additional information with respect to 1H CSI. The MSEI data of the three examined fat containing tissue regions were adequately fitted by a bi-exponential function despite the fact that there were much more chemically distinct protons present in fatty tissues.
Adipose Tissue↗
Sequencing-free whole-genome spatial transcriptomics at single-molecule resolution.
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Published Erratum↗
Three-dimensional phase contrast velocity mapping acquisition improves wall shear stress estimation in vivo.
The purpose of this study was to evaluate and apply high-resolution three-dimensional phase contrast mapping for estimation of wall shear stress in vivo. A silicon pipe of 8 mm diameter with a 8.3 ml/s steady flow and the entrance of the carotid bifurcation in 10 young healthy volunteers aged 23.6 +/- 3.1 years was studied. Very high resolution three-dimensional and two-dimensional phase contrast mapping sequences with spatial resolutions of 0.31 x 0.31 x 1.5 mm(3) and 0.31 x 0.31 x 3 mm(3), respectively, were compared in vivo and in vitro. Wall shear stress was calculated using multi-sectored, three-dimensional paraboloid fitting. In comparison to the two-dimensional measurements, the three-dimensional method with only half the slice thickness gave higher signal-to-noise ratio and velocity-to-noise ratios both in vivo and in vitro. Wall shear stress derived from the three-dimensional velocity measurements did not differ from the two-dimensional velocity measurements either in vitro or in vivo. Mean wall shear stress was lowest and oscillatory shear index was highest at the outer wall, towards the carotid bifurcation. Three-dimensional velocity mapping increases resolution and image quality and allows estimation of wall shear stress patterns circumferentially and longitudinally in human arteries.
Adult↗
Comparison of high-resolution MRI, optical microscopy and SEM for quantitation of trabecular architecture in the rat femur.
Magnetic resonance imaging (MRI) has been used to analyze trabecular bone architecture in femur heads taken from adult Wistar rats. The aim of this study was to validate the use of MRI in assessing trabecular structure and morphology by comparing standard measures of bone morphology in the rat femur obtained from high resolution MRI with those obtained by conventional optical microscopy and by scanning electron microscopy (SEM). MR images were obtained on a Bruker 4.7 T micro-imaging system using a three-dimensional spin echo sequence with spatial resolution of 23 microm in-plane and a slice thickness of 39 microm. Optical images were obtained by de-calcifying the bone in EDTA and then sectioning 5-microm-thick slices. SEM images were obtained from bone embedded in epoxy resin with surface preparation by diamond polishing. Values of standard bone morphological parameters were compared and correlation coefficients between the MRI and the optical- and SEM-derived measures of morphology were calculated. Partial volume effects in MRI were minimized in this study by the use of very thin slices, yielding better agreement with optical- and SEM-derived measures of trabecular bone morphology than have been obtained in previous studies. Correlations between the MRI and optical data were significantly lower than those between the MRI and SEM data. Effects of de-calcification were also investigated. The results indicate that comparison of MRI with thin (de-calcified) optical images may be inherently flawed due to the destructive de-calcification and sectioning process used to prepare samples for the optical imaging.
Animals↗
Altered GABAergic function accompanies hippocampal degeneration in mice lacking ClC-3 voltage-gated chloride channels.
Mice lacking ClC-3 chloride channels, encoded by the Clcn3 gene, undergo neurodegeneration of the hippocampal formation and retina [Neuron, 29 (2001) 185-196; Genes Cells, 7 (2002) 597-605]. We independently created a mouse lacking the Clcn3 gene which demonstrated similar central nervous system abnormalities, including early postnatal degeneration of retinal photoreceptors. However, we observed a characteristic spatial-temporal sequence of hippocampal neurodegeneration that differs from the pattern previously reported. Anterior-to-posterior degeneration and astrogliosis of the dentate gyrus and hippocampus progressed over months. Sequential loss of hippocampal neuronal subpopulations began in the dentate gyrus and progressed to CA3, followed by CA1 neurons. Projection neurons of the entorhinal cortex degenerated, secondary to the loss of their synaptic targets within the hippocampal formation. Other characteristics of the Clcn3(-/-) mice included an abnormal gait, kyphosis, and absence of hindlimb escape extension upon tail elevation. Spontaneous seizures were observed in four adult Clcn3(-/-) mice, and one mouse died during the event. We hypothesized that neuronal injury may be related to recurrent seizures. Clcn3(-/-) mice had normal serum electrolytes and pH, and exhibited neither hyperglycemia nor rebound hypoglycemia following a glucose load. They displayed a greatly reduced susceptibility to pentylenetetrazole-induced seizures and an abnormally prolonged sedation to benzodiazepines. There was no change in vulnerability to kainic acid-induced seizures. Immunostaining revealed a progressive loss of GABA synthesizing cells in the dentate gyrus. The death of these cells was preceded by increased GABA(A) receptor immunoreactivity. These data suggest that GABA(A) inhibitory neurotransmission is altered in Clcn3(-/-) mice. The increase in GABA(A) receptor density may represent a compensatory response either to chronic excessive excitatory stimuli or reduced inhibitory input from local GABAergic interneurons within the dentate gyrus.
Animals↗
Visualizing the spatial relationships between defined DNA sequences and the axial region of extracted metaphase chromosomes.
Using fluorescence in situ hybridization to extracted metaphase chromosomes, we present visual evidence that specific human DNA sequences occupy distinctive positions with respect to the axial region of chromosomes and that the DNA is organized into loops emanating from this region. In a stretch of unique DNA on chromosome 11, large loops of DNA can be traced and one specific region associated with the axial region of the chromosome. Within rDNA, nontranscribed spacer sequences are more closely apposed to the chromosome axis than are rRNA genes. Heterochromatic and euchromatic DNAs appear to be organized into loops of similar size. We could not detect loops at centromeres; most alphoid DNA appears to remain close to the axial region.
Centromere↗
Phosphorylation of tau, Abeta-formation, and apoptosis after in vivo inhibition of PP-1 and PP-2A.
Chronic inhibition of protein phosphatases 1 and 2A in vivo was induced by infusion of okadaic acid into lateral ventricles of rat brain for up to 4 months. Cytoskeletal pathology, alterations of the amyloid precursor protein, and apoptotic cell death induced by this treatment followed a certain sequence and spatial distribution. Changes in the expression, phosphorylation, and subcellular distribution of neurofilament proteins and tau, as well as first signs of apoptotic cell death, occurred already after about 2 weeks. The distribution of apoptotic cells, however, was different from those revealing a high accumulation of hyperphosphorylated tau, indicating that those cytoskeletal pathology had no obvious sequelae for the viability of these neurones. A continuation of treatment for longer than 2 weeks induced diffuse deposits of both hyperphosphorylated tau and A beta-amyloid-immunoreactive material in white matter areas that increased in size and number over time. Because tau-phosphorylation is a regulator of the dynamic stability of microtubules, the pathology observed in the present experimental paradigm in the white matter might be viewed as an indication of a disturbed axonal transport. It is hypothesized that perturbations of the axonal transport might also be critically involved in the formation of paired helical filaments and amyloid deposits in Alzheimer's disease.
Amyloid beta-Peptides↗
Memory for faces dissociates from memory for location following anterior temporal lobectomy.
It has been suggested that the right and left mesial temporal lobes are specialized for processing different types of information for long-term memory (LTM). Although findings have been consistent in regard to the dominant role of the left mesial temporal lobe (MTL) in verbal memory, the role of the right MTL in non-verbal memory remains debatable. Given the existence of two cortical pathways specialized for processing different types of visuospatial information, we examined whether memory processing for these two types of information might also be differentially localized. The effect of unilateral anterior temporal lobectomy (ATL) was compared for memory for unfamiliar faces and a novel sequence of spatial locations in 86 ATL patients (left ATL (LATL) = 35; right ATL (RATL) = 51) pre- and post-surgery to examine the contributions of right and left MTL structures to LTM for pattern and spatial information. Memory for spatial location was not related to side of ATL or time of testing. On the facial memory task, RATL patients showed impairments relative to LATL patients prior to surgery, which became magnified after surgery. These results extend the proposed dissociation between an occipitotemporal and an occipitoparietal pathway for processing visuospatial information by demonstrating dissociations in LTM systems for these two types of information. Lesions in the right MTL, adjacent to the cortical structures believed to be specialized for facial recognition, specifically impair the memory encoding of new faces, but not spatial locations.
Adult↗
The latest in ultrasound: three-dimensional imaging. Part II.
INTRODUCTION: The three-dimensional (3D) reconstruction of ultrasound images has become a widespread option in ultrasound equipment. Specific softwares have become available and 3D reconstruction feasible since the early 1990s, particularly since 1994. POSSIBLE CLINICAL APPLICATIONS: Several clinical applications are feasible in all parenchymatous organs (mainly the liver and prostate), hollow viscera (e.g. the bladder and gallbladder), peripheral vessels (supra-aortic trunks and limb vessels) and central (the aorta and iliac arteries) or cerebral vessels. Moreover, tumoral vessels in parenchymatous organs can be reconstructed, and even the fetus in the uterine cavity, with excellent detailing. The recent introduction of echocontrast agents and second harmonic imaging has permitted to study normal and abnormal peripheral, central and parenchymatous vessels, with similar patterns to those obtained with digital angiography. The spatial relationships between the vascular structures of the liver, kidney and placenta were studied with 3D ultrasound angiograms. The applications of this new technique include the analysis of vascular anatomy and the potential assessment of organ perfusion. THE LATEST APPLICATIONS--INTRAVASCULAR STUDIES: Some catheters with an ultrasound transducer in the tip have been tested for intravascular studies. Just like conventional transducers, they provide two-dimensional (2D) images which are then postprocessed into longitudinal 3D or volume reconstructions. The former resemble angiographic images and can be viewed 3D rotating the image along its longitudinal axis. Volume images, which are more complex and slower to obtain, can be rotated on any spatial plane and provide rich detailing of the internal vascular lumen. The clinical importance of intravascular ultrasound with 3D volume reconstructions lies in the diagnosis of vascular conditions and the assessment and monitoring of intravascular interventional procedures--e.g. to detect inaccurate deployment of intravascular stents and endoluminal grafts during the maneuver. Three-dimensional reconstructions involve geometric data assembly and volumetric interpolation of a spatially related sequence of tomographic cross sections generated by an ultrasound catheter withdrawn at a constant rate through a vascular segment of interest, resulting in the display of a straight segment. Therefore particular care is needed and there are some useful hints to avoid mistakes. CONCLUSIONS: Three dimensional reconstructions of B-mode and color Doppler images are no longer a work in progress and their clinical importance and possible applications are both established and ever-increasing. On the other hand, independent of the different types of energy used, also computed tomography and magnetic resonance 3D reconstructions are very useful from a clinical viewpoint and they have become an established routine technique for both these methods. It is very likely that 3D volume reconstructions in ultrasound will find numerous applications in the near future. They may help to increase the diagnostic confidence and to facilitate diagnosis, intraprocedure monitoring in interventional radiology and follow-up and also to reduce the number of invasive examinations with iodinated contrast agents. This could result in cutting the cost and duration of the most expensive examinations. New, although invasive, applications can be hypothesized for intravascular or intraluminal catheters with an ultrasound transducer inside.
Blood Vessels↗
Dynamic brain topography of somatosensory evoked potentials and equivalent dipoles in response to graded painful skin and muscle stimulation.
The differential effects of painful stimulation of skin vs. muscle on the cerebral electrophysiology have been poorly described. This study examined the somatosensory evoked potentials (SEPs) and the associated dipole models of non-painful and graded painful electrical stimulation applied to the skin and muscle in 20 healthy subjects. With the psychophysical stimulus-response functions determined, the skin stimulation showed a steeper slope than muscle stimulation. For both types of stimulation, the SEPs indicated a similar temporo-spatial activation sequence: F4/N90-P4/P95, Fc2/N135, Cz/P250, Cz/P300, and Cz/N460. The SEP amplitudes increased significantly with the stimulus intensities in these components. The peak SEP latencies of skin stimulation were in general shorter than that of muscle stimulation. The SEP amplitudes to skin stimulation were significantly larger than those caused by muscle stimulation at every stimulus intensity level, except the early mid-latency component. In this case, muscle stimulation caused higher amplitudes over the contralateral parietal-frontal sites. For both types of stimulation, the topographic maps were quite similar. Equivalent dipole modeling revealed identical site parameters (<1.0 cm) between skin and muscle stimulation. However, the electrical skin stimulation did not correlate with the pain intensity. Pain intensity, in contrast, was uniquely associated with the Cz/P250 amplitudes for the muscle stimulation. It is concluded that non-nociceptive and nociceptive electrical stimuli applied to skin and muscle are processed in the common cerebral areas, but exhibit differential SEP effects.
Adult↗
Correct Hox gene expression established independently of position in Caenorhabditis elegans.
The Hox genes are expressed in a conserved sequence of spatial domains along the anteroposterior (A/P) body axes of many organisms. In Drosophila, position-specific signals located along the A/P axis establish the pattern of Hox gene expression. In the nematode Caenorhabditis elegans, it is not known how the pattern of Hox gene expression is established. C. elegans uses lineal control mechanisms and local cell interactions to specify early blastomere identities. However, many cells expressing the same Hox gene are unrelated by lineage, suggesting that, as in Drosophila, domains of Hox gene expression may be defined by cell-extrinsic A/P positional signals. To test this, we have investigated whether posterior mesodermal and ectodermal cells will express their normal posterior Hox gene when they are mispositioned in the anterior. Surprisingly, we find that correct Hox gene expression does not depend on cell position, but is highly correlated with cell lineage. Thus, although the most striking feature of Hox gene expression is its positional specificity, in C. elegans the pattern is achieved, at least in part, by a lineage-specific control system that operates without regard to A/P position.
Animals↗
Spatiotemporal single-cell profiling reveals T cell clonal dynamics and phenotypic plasticity in human graft-versus-host disease.
Allogeneic hematopoietic cell transplantation cures hematologic diseases but is limited by acute graft‑versus‑host disease. How human T cell clones drive epithelial injury remains poorly mapped. We studied 31 transplant recipients, integrating longitudinal T cell antigen receptor (TCR) profiling with single-cell RNA sequencing/TCR sequencing and spatial transcriptomics to track T cell clonal dynamics. We developed DecompTCR to resolve temporal dynamics and adapted computational tools to map clone phenotypes and niches in tissue. Our analyses revealed that cyclophosphamide selectively depletes alloreactive clones, although insufficient early expansion leads to incomplete depletion and severe disease. Severe graft‑versus‑host disease is marked by persistent expansion of alloreactive clones, rewiring of homeostatic cell types and diversification of donor-derived CD8+ clonotypes that acquire Hobit (ZNF683)+ tissue‑resident memory T (TRM) cell programs during migration to epithelium. Spatial deconvolution identified CD8+ effector/Hobit+ TRM hubs near intestinal stem‑cell-rich crypt bases and crypt‑loss regions. This clonotype‑resolved framework links tissue‑instructed TRM cell remodeling to localized epithelial injury, nominating early-repertoire dynamics and spatial hub burden as biomarkers.
Journal Article↗
Cholinesterase inhibitors ameliorate behavioral deficits induced by MK-801 in mice.
Enhancing cholinergic function has been suggested as a possible strategy for ameliorating the cognitive deficits of schizophrenia. The purpose of this study was to examine the effects of acetylcholinesterase (AChE) inhibitors in mice treated with the noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist, MK-801, which has been suggested as an animal model of the cognitive deficits of schizophrenia. Three separate experiments were conducted to test the effects of physostigmine, donepezil, or galantamine on deficits in learning and memory induced by MK-801. In each experiment, MK-801 (0.05 or 0.10 mg/kg) or saline was administered i.p. 20 min prior to behavioral testing over a total of 12 days. At 30 min prior to administration of MK-801 or saline, one of three doses of the AChE inhibitor (ie physostigmine-0.03, 0.10, or 0.30 mg/kg; donepezil-0.10, 0.30, or 1.00 mg/kg; or galantamine-0.25, 0.50, or 1.00 mg/kg) or saline was administered s.c. Behavioral testing was performed in all experimental animals using the following sequence: (1) spatial reversal learning, (2) locomotion, (3) fear conditioning, and (4) shock sensitivity. Both doses of MK-801 produced impairments in spatial reversal learning and in contextual and cued memory, as well as hyperlocomotion. Physostigmine and donepezil, but not galantamine, ameliorated MK-801-induced deficits in spatial reversal learning and in contextual and cued memory in a dose-dependent manner. Also, physostigmine, but not donepezil or galantamine, reversed MK-801-induced hyperlocomotion. Galantamine, but not physostigmine or donepezil, altered shock sensitivity. These results suggest that AChE inhibitors may differ in their capacity to ameliorate learning and memory deficits produced by MK-801 in mice, which may have relevance for the cognitive effects of cholinomimetic drugs in patients with schizophrenia.
Animals↗
Minimal features of paxillin that are required for the tyrosine phosphorylation of focal adhesion kinase.
Tyrosine phosphorylation of FAK (focal adhesion kinase) regulates signalling that results from the interaction of integrins with extracellular matrix and growth factor receptors. A critical step in this process is the phosphorylation of Tyr397 of FAK, which creates a binding site for Src family kinases, PI3K (phosphoinositide 3-kinase) and Shc (Src homology and collagen homology). An intact Tyr397 site is required for FAK-mediated regulation of cell migration, survival signals and full responsiveness to soluble growth factors. We showed previously that the adaptor protein paxillin is required for the overall tyrosine phosphorylation of FAK in embryonic stem cells [Wade, Bohl and Vande Pol (2002) Oncogene 21, 96-107]. In the present paper, we identify the minimal structural features of paxillin that are required to support overall FAK tyrosine phosphorylation and Tyr397 phosphorylation. Paxillin contains N-terminal leucine-rich LD motifs that bind directly to FAK and four LIM (Lin-11, Isl-1 and Mec-3) domains in the C-terminus. We show that paxillin LIM domains 1, 2 and 3 are each required for FAK tyrosine phosphorylation, while LIM4 is dispensable. In addition to paxillin LIM domains 1, 2 and 3, a single LD motif on paxillin is required to support FAK tyrosine phosphorylation in embryonic stem cells. Both sequence and spatial requirements exist for LD motifs to support FAK tyrosine phosphorylation. Interestingly, synthetic LD motifs that fail to bind FAK in vitro are able to fully support FAK tyrosine phosphorylation, indicating that minimal interactions of LD motifs with FAK suffice. Our results demonstrate at least four distinct structural domains of paxillin support at least three distinct functions that are each required for FAK tyrosine phosphorylation.
Amino Acid Motifs↗
Cellular sources of noncollagenous matrix proteins: role of fat-storing cells in fibrogenesis.
The main types of noncollagenous ECM proteins in liver are FN, laminin, PGs and elastin. Also present is a pure carbohydrate polymer, hyaluronic acid. Their concentrations increase during fibrogenesis in a specific sequence and spatial distribution. FN is among the first to appear. The accumulation of matrix proteins in the space of Disse (perisinusoidal fibrosis) is most important for some clinical consequences of fibrosis. Perisinusoidal FSC are the cell type responsible for exaggerated ECM formation at sites of tissue injury, since these cells synthesize at a high rate in vitro all the noncollagenous matrix components occurring in fibrotic liver matrix (FN, laminin, dermatan sulfate, chondroitin sulfate, hyaluronic acid) and since FSC proliferate and transform into myofibroblast-like cells with an enhanced matrix protein synthesis rate. Recent experimental data suggest strong cellular cooperation of these cells with activated liver macrophages or Kupffer cells, platelets, and regenerating hepatocytes, which leads via a paracrine mechanism involving TGF beta, TGF alpha/EGF, PDGF, and probably other cytokines to stimulated proteoglycan synthesis, proliferation, and transformation into myofibroblast-like cells. The latter cell type has the potential of auto-stimulation (by an autocrine process) involving secretion of TGF beta and TGF alpha/EGF. Based on these findings, a model of FSC activation is proposed (Fig. 10).
Animals↗
Memory performances in young, elderly, and very old healthy individuals versus patients with Alzheimer's disease: evidence for discontinuity between normal and pathological aging.
In this study we compared memory performances of 29 probable patients with AD (17 mildly and 12 moderately demented) with those of 39 healthy young subjects, 36 elderly subjects (matched with the AD group for age and years of schooling), and 19 healthy very old subjects. In most of the memory tasks used in the present study, a progressive decline in performance was observed passing from the Young to the Elderly to the Very Old to the AD group. However, patients with AD were selectively impaired in the backward reproduction of verbal and spatial span sequences and in the semantic encoding of verbal material. These data are consistent with the hypothesis of not only quantitative but also a qualitative discontinuity between the process of normal aging and the dementia syndrome.
Adult↗