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Evidence for multiple generators in evoked responses using finite difference field mapping: auditory evoked fields.

Electric potential maps and magnetic field maps have been used to study brain electrical activity. During the temporal course of an evoked cortical response, the electrical activity of specific neuronal subpopulations change in a sequential manner giving rise to measurable electrical potentials and magnetic fields. For these potentials and fields, both the amplitude and rate of amplitude change have characteristic, time-dependent waveforms. Presently, amplitude waveforms from multiple locations are used to generate magnetic field and electric potential maps which have been found to be useful in understanding the activity of the neurons which give rise to these maps (Romani 1990). This paper introduces a data transformation technique which results in a derived map that we have termed a "finite difference field map" (FDFM). This mapping technique provides information associated with the rate at which the amplitude of the neuronal electric activity changes. In this paper, some advantage of FDFM analysis are illustrated by application of this technique to the study of the auditory evoked cortical field (AECF) N1m waveform. Using data obtained from normal subjects it will be demonstrated that application of the FDFM technique allows the localization of the primary N1m source at an earlier latency than is possible using the conventional waveform data. The source location determined at an early latency by FDFM analysis was identical to that obtained at later from the conventional field data. These data suggest that the primary N1m source is stationary. In addition, analysis of the time sequence of FDFM field maps contains evidence of a second spatially separate source which is co-active with primary N1m source.

Adult↗

Chlordiazepoxide and dizocilpine, but not morphine, selectively impair acquisition under a novel repeated-acquisition and performance task in rats.

RATIONALE: Some classes of drugs can selectively affect learning (i.e., acquisition of behavior) at doses that do not affect performance (i.e., previously learned behavior). Some drugs (e.g., benzodiazepines) show selective effects on acquisition across a wide variety of tasks. Other drugs [e.g., N-methyl-D-aspartate (NMDA) antagonists and opiate agonists], however, show selective effects under some tasks, but not others. OBJECTIVES: The purpose of this study was to examine the effects of the NMDA-antagonist dizocilpine (0.01-0.3 mg/kg), the opiate-agonist morphine (1.0-17.0 mg/kg), and the benzodiazepine chlordiazepoxide (3.0-30.0 mg/kg) in rats under a novel repeated-acquisition and performance task. METHODS: Nose pokes to a correct location within a 2x3 stimulus array on a computer touch screen were reinforced with food. In the acquisition component, the correct location changed across sessions but remained constant within sessions; in the performance component, the correct location was constant both across and within sessions. RESULTS: Both chlordiazepoxide and dizocilpine selectively impaired accuracy in the acquisition component at doses that did not affect accuracy in the performance component or overall response speed. Morphine, however, did not affect acquisition without affecting performance or response speed. CONCLUSIONS: These results with rats resembled those previously obtained for response-sequence learning in primates, rather than those previously reported for spatial learning in rats. Therefore, previous discrepancies in results for NMDA antagonists and opiate agonists across tasks probably were not a function of the species studied, but, rather, they more likely were a function of unique variables controlling acquisition within each task.

Animals↗

The development of catecholaminergic innervation in chick spinal cord.

This combined biochemical and histofluorescent study of the embryonic chick was designed to investigate the temporal and spatial development of noradrenergic pathways in the spinal cord. The sequence of catecholaminergic innervation was analyzed by measuring the specific uptake of [3H]norepinephrine, the levels of endogenous norepinephrine, and the distribution of catecholamine histofluorescence. Uptake studies showed early axons present in all levels of spinal cord by 10 days incubation with subsequent increases of uptake activity appearing in a rostrocaudal fashion. Endogenous norepinephrine values were low until day 14, at which time transmitter levels began to increase, approaching hatched values on incubation day 17. Morphologic studies demonstrated catecholaminergic terminals first in the intermediate gray matter and later concentrated in the ventral and dorsal horns. These observations were interpreted to indicate that: (1) noradrenergic axons are an early descending supraspinal pathway; (2) arborization of this system occurs in a rostral-caudal sequence; and (3) monoaminergic uptake mechanisms develop prior to and independent of neurotransmitter synthesis and storage. The development of this noradrenergic system parallels alteration in spinal cord physiology and refinements in the motility of the embryo.

Animals↗

Averaging of spectral power and phase via vector diagram best fits without reference electrode or reference channel.

A method is proposed to average results of Fourier analysis over epochs without assigning zero amplitude values to any electrode or zero phase values to any channel. The Fourier sine and cosine values of each electrode define its entry location into a vector diagram for the frequency component. The entry constellations thus formed are translated so that the mean of all entries (the virtual average reference which is the location of best fit) is at the centre of each constellation, and then they are rotated around the means into angles of best fit so that the sum of the squared distances between corresponding entries is minimal. The method leads to non-ambiguous mean results, with variance information for all recording points. Approaches for the assessment of the constellations, their transformation into field maps, and the problems with conventional phase measurements vs. real electrodes are discussed. The virtual average reference (spatial high pass filter) is proposed for assessing the time sequence (phase differences) between entry points, thus describing the internal structure of the constellations without bias and without reference to a zero phase point. Comparison of voltage and current density result constellations and consideration of reference-independent descriptors of the scalp field potential maps support the validity of the average reference for the approach.

Electroencephalography↗

Histamine release by neurotensin in the rat hindquarter: structure-activity studies.

Histamine releasing effects of neurotensin (NT) and several NT fragments and structural analogues were measured in the rat perfused hindquarter. The results show that the chemical groups responsible for histamine release are located in the C-terminal sequence Arg9-Pro10-Tyr11-Ile12-Leu13-OH. Both the spatial configuration and positive charge of Arg8 and Arg9 appear to contribute to the histamine releasing effect of NT. Optimization of the histamine releasing effect of NT requires both a free C-terminal carboxyl group and the presence in position 11 of NT of an aromatic residue, with the L-configuration, bearing an heteroatom capable of hydrogen bonding with the receptor. The results indicate that the structural requirements of NT to induce histamine release from the rat perfused hindquarter are similar to those involved in other peripheral biological actions of NT.

Animals↗

Supine MR mammography using VIBE with parallel acquisition technique for the planning of breast-conserving surgery: clinical feasibility.

Volumetric interpolated breath-hold examination (VIBE), which provides both high-spatial and high-temporal resolution images, is a useful sequence for determining the extent of breast cancer. The VIBE sequence in combination with the parallel acquisition technique allows for a single breath-hold evaluation of the breast. We evaluated the clinical feasibility of MR mammography in the supine oblique position (supine MRM) using this technique for planning breast conservation surgery. The accuracy of determination of the tumor extent with a deviation of less than 2 cm in length was 90% (36/40). Two cases showed a positive surgical margin (7.4%). Supine MRM is feasible for the planning of breast-conserving surgery.

Adult↗

Assessment of coronary artery bypass grafts patency with different magnetic resonance technologies.

OBJECTIVE: The aim of the study was to evaluate the diagnostic accuracy of different magnetic resonance (MR) sequences in the assessment of coronary artery bypass graft patency and the evaluation of distal anastomoses with a spin echo sequence (Haste). PATIENTS AND METHODS: Twenty-five patients were examined with all the three techniques and 185 patients with 481 distal anastomoses were examined with the Haste sequence at a 1.5 TMR scanner and coronary angiography. A two-dimensional T(2)-weigthed breath-hold half-Fourier acquisition single-shot turbo spin echo sequence (Haste), a Navigator sequence and a gadolinium-enhanced Fisp-3-D sequence were performed. All images were evaluated independently by a radiologist and cardiologist and compared to the conventional coronary angiography. The observers were blinded to the coronary angiography findings, but informed in regard to the surgical graft anastomosis. RESULTS: With the Haste sequence 80% of the distal anastomoses were recognized. The sensitivity and specificity for the evaluation of the distal anastomosis with the Haste sequence was 94% and 75%. The Navigator and the Fisp-3-D sequences showed a sensitivity of 74% and 94% and a specificity of 78% and 88%. CONCLUSION: The best results were achieved with the Haste sequence, a reliable assessment of graft patency of the distal anastomosis is possible. The best imaging of proximal IMA segments was possible with the Fisp-3-D sequence. Due to the low sensitivity and specificity, the use of the Navigator sequence was stopped in our center. Further improvements of the spatial resolution and the image quality are necessary to recommend this MR techniques for routine clinical use.

Aged↗

Depth-dependent microbial succession and interspecies hydrogen transfer drive pit mud maturation in Chinese strong-flavor baijiu fermentation.

Microbial communities in fermentation pit mud play a key role in determining the quality of Chinese strong-flavor baijiu (CSFB). However, the ecological processes underlying pit mud maturation across spatial and temporal scales remain unclear. In this study, amplicon sequencing and metagenomic analyses were employed to investigate the taxonomic succession, community assembly, and metabolic functions of bacterial and archaeal communities during the transition from fresh pit mud (FPM) to new pit mud (NPM) and old pit mud (OPM). A pronounced depth-dependent succession pattern was observed, with 4 cm representing a critical ecological boundary separating distinct community structures and maturation trajectories. During surface-layer maturation, community assembly shifted from stochastic to deterministic processes, accompanied by homogeneous selection and increasing network complexity. In contrast, stochastic processes remained dominant throughout deep-layer maturation. Metagenomic analyses revealed a functional transition from lactate and acetate production, primarily associated with Lactobacillus in FPM and NPM, to butyrate and caproate production associated with Clostridium and Caproiciproducens in OPM. This functional transition was accompanied by enhanced amino acid metabolism, which was associated with the enrichment of Proteiniphilum and Aminobacterium. Notably, methanogen-mediated interspecies hydrogen transfer (IHT) emerged as a key ecological feature during pit mud maturation. In OPM, IHT networks primarily involving Methanobacterium and Methanosarcina linked methanogenesis with reverse β-oxidation through diverse hydrogen-transfer pathways, reinforcing metabolic interactions underlying caproate production. These findings provide new insights into the ecological mechanisms underlying pit mud maturation and offer a theoretical basis for the directed cultivation of high-quality pit mud in CSFB production.

Hydrogen↗

Conditioning and cognition.

Animals' abilities to use internal representations of absent objects to guide adaptive behavior and acquire new information, and to represent multiple spatial, temporal, and object properties of complex events and event sequences, may underlie many aspects of human perception, memory, and symbolic thought. In this review, two classes of simple associative learning tasks that address these core cognitive capacities are discussed. The first set, including reinforcer revaluation and mediated learning procedures, address the power of Pavlovian conditioned stimuli to gain access, through learning, to representations of upcoming events. The second set of investigations concern the construction of complex stimulus representations, as illustrated in studies of contextual learning, the conjunction of explicit stimulus elements in configural learning procedures, and recent studies of episodic-like memory. The importance of identifying both cognitive process and brain system bases of performance in animal models is emphasized.

Animals↗

Orbital and ocular imaging using 3- and 1.5-T MR imaging systems.

The goal of this article is to familiarize general radiologists and clinicians (particularly ophthalmologists, neuro-ophthalmologists, neurologists, and neurosurgeons) with the recent introduction of clinical MR imaging scanners operating at a magnetic field strength of 3-T and to compare them with the more common standard scanners operating at 1.5-T. In this study, MR imaging at 3-T was found to offer superior depiction of orbital and intracranial anatomy and pathologic findings. Spin echo, high spatial resolution, T2-weighted, thin-section MR imaging sequences are especially useful and sensitive at 3-T for the evaluation of orbital, ocular, and intracranial anatomy and pathologic findings. The authors din that time-of-flight (TOF) MR angiography at 3-T surpasses the best MR angiography at 1.5-T and that two-dimensional TOF venography and three-dimensional contrast MR venography at 3-T offer superior visualization of intracranial and facial veins as compared with MR venography at 1.5-T. We believe that with further quality image production and efficient coil design, 3-T MR imaging should hold the promise of playing an important role in the diagnostic imaging evaluation of ocular, orbital, and optic pathway pathologic findings.

Artifacts↗

Spatio-temporal working memory and frontal lesions in man.

The delayed-response paradigm is thought to be a marker of the activity of the dorsolateral convexity of primates' prefrontal cortex, as this procedure requires the activation of working memory processes. Although the role of the dorsolateral prefrontal cortex (DLPC) in working memory seems to be well established, much remains to be understood about the processes this structure actually controls: encoding domain-specific information, its retention in short-term memory, its monitoring in working memory, or its selection and retrieval when a specific response program is required. To clarify the role of the DLPC in delayed-response tasks in humans, a set of sequencing paradigms was designed which incorporates the dissociation of (1) spatial and temporal parameters, (2) recall and recognition processes, and (3) the presence or absence of a delay. Performance of a group of patients with DLPC lesions (n = 8) was compared to that of age-matched normal subjects (n = 8). To verify the specificity of the results obtained for the DLPC lesioned patients, the performance of patients with a temporal lobotomy was also studied (n = 10). A significant effect of the delay was observed only in patients with DLPC lesions, affecting both their spatial and spatio-temporal recall, whereas their spatio-temporal recognition was normal. These findings suggest that the DLPC plays a role in the retrieval of visuospatial information for guiding a response program.

Brain Injuries↗

Functional relationship between forward and backward digit repetition and a non-verbal analogue.

It has been suggested that the forward digit span employs a verbal representation of sequences of digits, whereas the backward digit span employs a spatial representation. This was tested by comparing the two digit spans with a non-verbal analogue of the forward digit span. The latter did not explain any of the variation in the backward digit span when the forward digit span was stastically controlled. It is concluded that the two digit spans employ a common verbal representation.

Adult↗

Effects of tachycardia with normal and ectopic ventricular activation on S-T segment potential and patterns in the dog.

Tachycardia induced by atrial pacing in the dog increases the intensity of potentials recorded on the body surface during the ST-T interval. The effects of tachycardia caused by ectopic right or left ventricular stimulation on ventricular recovery potentials were studied in 30 dogs. Rate was increased in a stopwise manner from 90 to 250 beats per minute by atrial pacing (ten dogs), or by left atrial-right ventricular sequential pacing (ten dogs), or by left atrial-left ventricular sequential pacing (ten dogs). ECG effects were determined by construction of body surface isopotential maps from voltages registered from 84 torso electrodes using a P-R segment baseline. Ectopic stimulation intensified the repolarization maximum and shifted its location to correspond with sites of epicardial stimulation. These findings reflect a reduced cancellation of transventricular differences in recovery times, with earliest recovery occurring at earliest activated sites. Increasing rate with any one activation pattern linearly increased potential extrema magnitudes without further changes of spatial features. This singular response to tachycardia regardless of activation sequence is consistent with an increase in the apparent moment of a repolarization dipole without alteration of its orientation.

Animals↗

Opto-electronic sensing of body surface topology changes during radiotherapy for rectal cancer.

PURPOSE: The CT body surface underpins millimeter scale dose computation in radical radiotherapy. A lack of technology has prevented measurement of surface topology changes during irradiation. Consequently, body changes are incorporated into plans statistically. We describe the technology for dynamic measurement of continuous surface topology at submillimeter resolution and suggest appropriately modified planning. MATERIALS AND METHODS: An interferometer casts cosinusoidal fringes across the surface of a patient on a treatment couch. Motion-induced changes to the spatial phase of the fringes are used to generate dynamic sequences of body height maps. Volume-conserving CT warping, guided by height change, is used to illustrate potential planning perturbations. RESULTS: We present the results for a prone patient with rectal carcinoma. At most of the simultaneously measured 440 x 440 points in each of the 898 body height maps in a dynamic sequence, the standard deviations were <1-2 mm, with occasional points of 6 mm. Surface motion predominantly occurred along the small of the back. This motion was periodic and could take the spine and bladder across the 95% isodose contour. CONCLUSIONS: Surface changes are most likely to be within 3 mm during irradiation, despite the effects of breathing and the discomfort of lying prone. The dosimetric effects are acceptable.

Algorithms↗

Comparison of multi-echo spiral and echo planar imaging in functional MRI.

Multi-echo spiral and echo-planar (EPI) imaging sequences were compared in functional imaging experiments at 3 Tesla. Both sequence types allow calculation of the effective transversal relaxation time T(2)* and the initial signal intensity I(0). These parameters can be used in evaluation of the functional signal with respect to inflow effects and other vascular sources. Prior to functional magnetic resonance imaging (fMRI) experiments T(2)* measurements in the human brain were performed with single- and multi-echo FLASH (fast low angle shot) and compared with EPI und spiral imaging sequences. These experiments resulted in T(2)* values ranging from 42.9 to 53.8 ms in a ROI including white and gray matter and CSF in a prefrontal brain region, and allowed validation of the quantitative results of the fast single-shot techniques. In functional experiments with motor stimulation mean absolute T(2)* increases during stimulation of 1.1 +/- 0.6 ms and 1.4 +/- 0.9 ms were found with multi-echo EPI and spiral imaging, respectively, averaged over the activated pixels. In addition, absolute T(2)* values and the size of activated areas obtained with both sequences are comparable. In these investigations spiral imaging allowed higher spatial resolution due to more efficient use of available gradient performance.

Adult↗

NMR-microscopy with TrueFISP at 11.75T.

The purpose of this paper is to demonstrate that a fully balanced gradient echo technique (TrueFISP) can be used for microscopic experiments at high static magnetic field strengths. TrueFISP experiments were successfully performed on homogeneous and inhomogeneous objects at 11.75T. High-resolution TrueFISP images were obtained from phantoms, plants, formalin-fixed samples, and from an isolated beating rat heart with an in-plane resolution of 78 micro m and a slice thickness of 500 micro m. The signal-to-noise ratio (SNR) gain of TrueFISP compared to conventional gradient echo or spin echo sequences will allow faster acquisition times or an improvement in spatial resolution for microscopic experiments.

Animals↗

Structural unity among viral origin binding proteins: crystal structure of the nuclease domain of adeno-associated virus Rep.

Adeno-associated virus (AAV), unique among animal viruses in its ability to integrate into a specific chromosomal location, is a promising vector for human gene therapy. AAV Replication (Rep) protein is essential for viral replication and integration, and its amino terminal domain possesses site-specific DNA binding and endonuclease activities required for replication initiation and integration. This domain displays a novel endonuclease fold and demonstrates an unexpected structural relationship to other viral origin binding proteins such as the papillomavirus E1 protein and the SV40 T antigen. The active site, located at the bottom of a positively charged cleft, is formed by the spatial convergence of a divalent metal ion and two conserved sequence motifs that define the rolling circle replication superfamily.

Amino Acid Sequence↗

High-throughput sequence determination of cyclic peptide library members by partial Edman degradation/mass spectrometry.

Cyclic peptides provide attractive lead compounds for drug discovery and excellent molecular probes in biomedical research. Large combinatorial libraries of cyclic peptides can now be routinely synthesized by the split-and-pool method and screened against biological targets. However, post-screening sequence determination of hit peptides has been problematic. In this report, a high-throughput method for the sequence determination of cyclic peptide library members has been developed. TentaGel microbeads (90 mum) were spatially segregated into outer and inner layers; cyclic peptides were displayed on the bead surface, whereas the inner core of each bead contained the corresponding linear peptide as the encoding sequence. After screening of the cyclic peptide library against a macromolecular target, the identity of hit peptides was determined by sequencing the linear encoding peptides inside the bead using a partial Edman degradation/mass spectrometry method. On-bead screening of an octapeptide library (theoretical diversity of 160 000) identified cyclic peptides that bind to streptavidin. A 400-member library of tyrocidine A analogues was synthesized on TentaGel macrobeads and solution-phase screening of the library directly against bacterial cells identified a tyrocidine analogue of improved antibacterial activity. Our results demonstrate that the new method for cyclic peptide sequence determination is reliable, operationally simple, rapid, and inexpensive and should greatly expand the utility of cyclic peptides in biomedical research.

Anti-Infective Agents↗