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In vivo mapping of functional domains and axonal connectivity in cat visual cortex using magnetic resonance imaging.

Noninvasive cognitive neuroimaging studies based on functional magnetic resonance imaging (fMRI) are of ever-increasing importance for basic and clinical neurosciences. The explanatory power of fMRI could be greatly expanded, however, if the pattern of the neuronal circuitry underlying functional activation could be made visible in an equally noninvasive manner. In this study, blood oxygenation level-dependent (BOLD)-based fMRI and diffusion tensor imaging (DTI) were performed in the same cat visual cortex, and the foci of fMRI activation utilized as seeding points for 3D DTI fiber reconstruction algorithms, thus providing the map of the axonal circuitry underlying visual information processing. The methods developed in this study will lay the foundation for in vivo neuroanatomy and the ability for noninvasive longitudinal studies of brain development.

Algorithms↗

Molecular determinants of the face map development in the trigeminal brainstem.

The perception of external sensory information by the brain requires highly ordered synaptic connectivity between peripheral sensory neurons and their targets in the central nervous system. Since the discovery of the whisker-related barrel patterns in the mouse cortex, the trigeminal system has become a favorite model for study of how its connectivity and somatotopic maps are established during development. The trigeminal brainstem nuclei are the first CNS regions where whisker-specific neural patterns are set up by the trigeminal afferents that innervate the whiskers. In particular, barrelette patterns in the principal sensory nucleus of the trigeminal nerve provide the template for similar patterns in the face representation areas of the thalamus and subsequently in the primary somatosensory cortex. Here, we describe and review studies of neurotrophins, multiple axon guidance molecules, transcription factors, and glutamate receptors during early development of trigeminal connections between the whiskers and the brainstem that lead to emergence of patterned face maps. Studies from our laboratories and others' showed that developing trigeminal ganglion cells and their axons depend on a variety of molecular signals that cooperatively direct them to proper peripheral and central targets and sculpt their synaptic terminal fields into patterns that replicate the organization of the whiskers on the muzzle. Similar mechanisms may also be used by trigeminothalamic and thalamocortical projections in establishing patterned neural modules upstream from the trigeminal brainstem.

Animals↗

Spontaneous structure formation in a network of chaotic units with variable connection strengths.

As a model of temporally evolving networks, we consider a globally coupled logistic map with variable connection weights. The model exhibits self-organization of network structure, reflected by the collective behavior of units. Structural order emerges even without any interunit synchronization of dynamics. Within this structure, units spontaneously separate into two groups whose distinguishing feature is that the first group possesses many outwardly directed connections to the second group, while the second group possesses only a few outwardly directed connections to the first. The relevance of the results to structure formation in neural networks is briefly discussed.

Journal Article↗

DT-MRI denoising and neuronal fiber tracking.

Diffusion tensor imaging can provide the fundamental information required for viewing structural connectivity. However, robust and accurate acquisition and processing algorithms are needed to accurately map the nerve connectivity. In this paper, we present a novel algorithm for extracting and visualizing the fiber tracts in the CNS, specifically in the brain. The automatic fiber tract mapping problem will be solved in two phases, namely a data smoothing phase and a fiber tract mapping phase. In the former, smoothing of the diffusion-weighted data (prior to tensor calculation) is achieved via a weighted TV-norm minimization, which strives to smooth while retaining all relevant detail. For the fiber tract mapping, a smooth 3D vector field indicating the dominant anisotropic direction at each spatial location is computed from the smoothed data. Neuronal fibers are then traced by calculating the integral curves of this vector field. Results are expressed using three modes of visualization: (1) Line integral convolution produces an oriented texture which shows fiber pathways in a planar slice of the data. (2) A streamtube map is generated to present a 3D view of fiber tracts. Additional information, such as degree of anisotropy, can be encoded in the tube radius, or by using color. (3) A particle system form of visualization is also presented. This mode of display allows for interactive exploration of fiber connectivity with no additional preprocessing.

Algorithms↗

Two new templates for epidemiology applications: linked micromap plots and conditioned choropleth maps.

This paper describes two interactive templates for representing spatially indexed estimates. Both templates use a matrix layout of small panels. The first template, called linked micromap plots, can represent multivariate estimates associated with each spatially indexed study unit. The second template, called conditioned choropleth maps, shows the connection between a dependent variable, as represented in a classed choropleth map, and two explanatory variables. The paper describes the cognitive considerations that motivate the layouts and representation details. The discussion also addresses topics of data quality and access, hypothesis generation, and interactive features such as pan and zoom and dynamic conditioning via sliders. The examples show epidemiological (mortality rates) and environmental (toxic concentrations) applications.

Benzene↗

Successful release of entrapped circumferential mapping catheters in patients undergoing pulmonary vein isolation for atrial fibrillation.

OBJECTIVES: The purpose of this study was to demonstrate a method for successful and safe release of an entrapped circular catheter. BACKGROUND: Segmental pulmonary vein (PV) isolation is widely practiced for patients with symptomatic drug-refractory atrial fibrillation. A circular mapping catheter is sometimes used with this technique to map the electrical connection between the left atrium (LA) and the PVs. This catheter reportedly can become entrapped in the mitral valve apparatus. Attempts to free the entrapped catheter can result in serious complications, including damage to the mitral valve chordae tendineae or fracture of the catheter itself. METHODS: Three patients were referred for PV isolation for atrial fibrillation. A circular mapping catheter was used to map the sites of LA-PV electrical connections. RESULTS: During the procedure, the circular mapping catheter became entrapped in the mitral valve apparatus in two patients and in the PV in one patient. A series of maneuvers, which included use of another catheter and guiding sheaths as well as pushing forward rather than pulling back on the entrapped catheter, allowed safe and successful release of the entrapped catheter in all patients. CONCLUSIONS: Entrapment of the circular mapping in the mitral valve apparatus or the PVs during PV isolation is a rare complication associated with use this catheter. We describe a series of maneuvers that may allow safe and successful release of the entrapped catheter.

Adult↗

Effects of monocular deprivation and reverse suture on orientation maps can be explained by activity-instructed development of geniculocortical connections.

Mature visual cortex shows a single, binocularly matched orientation map. This matching develops without visual experience. It persists despite early monocular deprivation that largely eliminates one eye's map, followed by reverse suture (deprivation of the previously open eye and opening of the previously deprived eye), even though the two eyes lack common visual experience in this case. These results have been interpreted to suggest that the structure of orientation maps either is innately predetermined or, if it arises through self-organization, is determined by external cues such as boundary conditions or a "scaffolding" of horizontal connections. We show, to the contrary, that these results are the expected outcomes if orientation maps develop through activity-instructed, correlation-based development of the geniculocortical connections without additional cues. A weak, binocularly correlated orientation map is known to exist before deprivation onset; we previously showed how this can arise through activity-instructed development. Now we show that this initial correlation between the two eyes' maps can persist or increase despite deprivation sufficient to cause massive loss of the deprived eye's geniculocortical synaptic strength, followed by reverse suture. Given sufficient early correlated map development, each map's fate is "dynamically committed": the two eyes' maps will converge upon a common outcome, even if developing independently. This dynamic fate commitment is retained even after severe deprivation.

Animals↗

Shot-gun sequencing strategy for long-range genome mapping: a pilot study.

We have recently proposed a strategy for construction of long-range physical maps based on random sequencing of NotI linking and jumping clones. Here, we present results of sequence comparison between 168 NotI linking (100 of them were sequenced from both sides) and 81 chromosome 3-specific jumping clones. We were able to identify 14 NotI jumping clones (17%), each joined with two NotI linking clones. The average size of chromosomal jumps was about 650 kb. The assembled 42 NotI genomic fragments correspond to 12-15% of chromosome 3. These results demonstrate the value of random sequencing of NotI linking and jumping clones for genome mapping. This mapping proposal can be used for connecting physical and genetic maps of the human genome and will be a valuable supplement to YAC and cosmid library based mapping projects.

Animals↗

Detection of the drainage site in anomalous pulmonary venous connection by two-dimensional Doppler color flow-mapping echocardiography.

Ten patients with total and one with partial anomalous pulmonary venous connection were studied by two-dimensional Doppler color flow-mapping echocardiography. In cases of anomalous pulmonary venous drainage into the innominate vein through the vertical vein, flow away from the transducer was detected in the echo space behind the atria in the subxiphoid four-chamber approach. In the suprasternal approach, flow toward the transducer was detected at the junction of the vertical and innominate veins. In the case of an anomalous pulmonary vein connecting directly into the superior vena cava, an area of flow toward the transducer, which was triangular in shape, was detected in the dilated superior vena cava. In the two cases in which the pulmonary vein drained into the coronary sinus, the flow toward the transducer was observed at the ostium of the coronary sinus in the subxiphoid four-chamber view, and it appeared as if the blood flow was emerging from this point. In a case of the paracardiac type of total anomalous pulmonary venous connection with drainage into the posterior wall of the right atrium, the flow toward the transducer occurred higher in the right atrium than in the cases with drainage into the coronary sinus. In a case with the infradiaphragmatic type of total anomalous pulmonary venous connection, continuous flow toward the transducer, which passed through the diaphragm in an anomalous vessel, was detected from the subxiphoid area. The downward flow in the anomalous vessel changed to an upward flow at the site of drainage into the hepatic vein.(ABSTRACT TRUNCATED AT 250 WORDS)

Brachiocephalic Veins↗

Visual projection map specified by topographic expression of transcription factors in the retina.

Topographical maps of neuronal connectivity occur in various brain regions. In the visual system of birds, retinal ganglion-cell axons from the anterior retina connect to a posterior part of the optic tectum, and posterior retinal axons connect to the anterior part, thereby establishing a point-to-point projection map. The chemoaffinity theory predicts that the orderly retinotectal projection is generated by a topographical arrangement of molecules. We report here that we have found several genes topographically expressed along the nasotemporal (anterior-posterior) axis in the embryonic chicken retina. Among these, two transcriptional regulators, belonging to the winged-helix family are expressed in a mutually exclusive manner in either the nasal or temporal part of the retina. Misexpression of each factor causes misprojection on the tectum along the rostrocaudal axis, showing that topographical expression of these transcription factors controls formation of the retinotectal map.

Alkaline Phosphatase↗

Molecular maps of red cell deformation: hidden elasticity and in situ connectivity.

Fluorescence-imaged micropipette aspiration was used to map redistribution of the proteins and lipids in highly extended human red blood cell membranes. Whereas the fluid bilayer distributed uniformly (+/- 10 percent), the underlying, solidlike cytoskeleton of spectrin, actin, and protein 4.1 exhibited a steep gradient in density along the aspirated projection, which was reversible on release from deformation. Quantitation of the cytoskeletal protein density gradients showed that skeletal elasticity is well represented by a grafted polymer network with a ratio of surface dilation modulus to shear modulus of approximately 2:1. Fractionally mobile integral proteins, such as band 3, and highly mobile receptors, such as CD59 as well as glycophorin C in protein 4.1-deficient cells, appeared to be squeezed out of areas dense in the underlying network and enriched in areas of network dilation. This complementary segregation demonstrates patterning of cell surface components by cytoskeletal dilation.

Actins↗

Molecular gradients and development of retinotopic maps.

Gradients of axon guidance molecules have long been postulated to control the development of the organization of neural connections into topographic maps. We review progress in identifying molecules required for mapping and the mechanisms by which they act, focusing on the visual system, the predominant model for map development. The Eph family of receptor tyrosine kinases and their ligands, the ephrins, remain the only molecules that meet all criteria for graded topographic guidance molecules, although others fulfill some criteria. Recent reports further define their modes of action and new roles for them, including EphB/ephrin-B control of dorsal-ventral mapping, bidirectional signaling of EphAs/ephrin-As, bifunctional action of ephrins as attractants or repellents in a context-dependent manner, and complex interactions between multiple guidance molecules. In addition, spontaneous patterned neural activity has recently been shown to be required for map refinement during a brief critical period. We speculate on additional activities required for map development and suggest a synthesis of molecular and cellular mechanisms within the context of the complexities of map development.

Animals↗

The organization and connections of somatosensory cortex in marmosets.

Microelectrode mapping methods were used to define and describe 3 representations of the body surface in somatosensory cortex of marmosets: S-I proper or area 3b of anterior parietal cortex, S-II, and the parietal ventral area (PV) of the upper bank of the lateral sulcus. In the same animals, injections of anatomical tracers were placed into electrophysiologically determined sites in area 3b or S-II. Mapping results and patterns of connections were later related to architectonic fields that were delimited in sections cut parallel to the surface of manually flattened cortex and stained for myelin. There were several major results. (1) Recordings from area 3b revealed a characteristic somatotopic organization of foot to face in a mediolateral sequence as previously reported in other members of the marmoset family (Carlson et al., 1986). (2) Multiple injections of WGA-HRP in area 3b demonstrated dense, patchy interconnections with ipsilateral S-II, PV, area 3a, and area 1, less dense interconnections with primary motor cortex (M-I), the supplementary motor area (SMA), limbic cortex of the medial wall (L), and rostrolateral parietal cortex of the lateral sulcus (PR), and callosal connections with areas 3b, S-II, and PV. Injections of 3 different tracers into the representation of 3 body regions in area 3b indicated that the connections with areas 3a, 3b, 1, S-II, and PV are topographically organized. (3) Recordings from cortex on the upper bank of the lateral sulcus demonstrated a somatotopic representation of the body surface that matches that of S-II of other mammals. S-II immediately adjoined areas 3b along the dorsal lip of the lateral sulcus. The face representation in S-II was adjacent to the face representation in 3b while the trunk, hindlimb, and forelimb were represented in a caudorostral sequence deeper in the sulcus. (4) Injections in S-II revealed ipsilateral connections with areas 3a, 3b, 1, a presumptive area 2, PV, PR, M-I, SMA, limbic cortex, the frontal eye fields, and the frontal ventral visual area. Dense callosal connections were with S-II and PV. (5) The recordings also revealed a systematic representation just rostral to S-II that has not been previously described in primates.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

EEG mapping: current status and future prospects.

EEG mapping is the topographical display of parameters evaluated from multichannel EEG recordings. Different problems connected with EEG mapping are: number of electrodes, interpolation between electrodes, types of reference and statistical treatment of maps. These problems are discussed briefly and examples are given. To complete this report, a short historical background along with some comments about the clinical settings have been provided and attention given to future prospects.

Brain Mapping↗

[The brain is shaped by stimulation and challenge].

The healthy adult brain retains a certain capacity for plasticity and functional reorganization throughout the life span. Morphologic, neuropsychological and neuroimaging studies have demonstrated that neuronal connections and cortical maps can be remodeled by our experience and activities. Activity-induced increase in neuronal connections may to some extent compensate for neuronal loss during aging. Increased knowledge of the potential capability of the adult brain to compensate for brain lesions is likely to improve rehabilitation strategies.

Adult↗

Mean phase error and the map-correlation coefficient.

In judging the effectiveness of methods of solving crystal structures, or in phase refinement and development, two criteria are commonly used. The first is the mean phase error, which may be weighted in some way, and the second is the map correlation coefficient which describes the similarity of a map with estimated phases to that with true phases. It is shown that these two measures are directly related and that given the individual phase errors the map correlation coefficient may be found without the need to calculate a map. Various aspects of this connection are examined, including the map correlation coefficient when weights are used for calculating maps and the conditions under which phase extension leads to maps with a higher map correlation coefficient - which involves a balance between the advantage of employing more data and the disadvantage that the extra data may have a higher average phase error.

Journal Article↗

Retinotopic axis specificity and selective clustering of feedback projections from V2 to V1 in the owl monkey.

Cortical maps and feedback connections are ubiquitous features of the visual cerebral cortex. The role of the feedback connections, however, is unclear. This study was aimed at revealing possible organizational relationships between the feedback projections from area V2 and the functional maps of orientation and retinotopy in area V1. Optical imaging of intrinsic signals was combined with cytochrome oxidase histochemistry and connectional anatomy in owl monkeys. Tracer injections were administered at orientation-selective domains in regions of pale and thick cytochrome oxidase stripes adjacent to the border between these stripes. The feedback projections from V2 were found to be more diffuse than the intrinsic horizontal connections within V1, but they nevertheless demonstrated clustering. The clusters of feedback axons projected preferentially to interblob cytochrome oxidase regions. The distribution of preferred orientations of the recipient domains in V1 was broad but appeared biased toward values similar to the preferred orientation of the projecting cells in V2. The global spatial distribution of the feedback projections in V1 was anisotropic. The major axis of anisotropy was systematically parallel to a retinotopic axis in V1 corresponding to the preferred orientation of the cells of origin in V2. We conclude that the feedback connections from V2 to V1 might play a role in enhancing the response in V1 to collinear contour elements.

Animals↗

Topographic guidance labels in a sensory projection to the forebrain.

Visual connections to the mammalian forebrain are known to be patterned by neural activity, but it remains unknown whether the map topography of such higher sensory projections depends on axon guidance labels. Here, we show complementary expression and binding for the receptor EphA5 in mouse retina and its ligands ephrin-A2 and ephrin-A5 in multiple retinal targets, including the major forebrain target, the dorsal lateral geniculate nucleus (dLGN). These ligands can act in vitro as topographically specific repellents for mammalian retinal axons and are necessary for normal dLGN mapping in vivo. The results suggest a general and economic modular mechanism for brain mapping whereby a projecting field is mapped onto multiple targets by repeated use of the same labels. They also indicate the nature of a coordinate system for the mapping of sensory connections to the forebrain.

Aging↗