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PubMed2000

Local linear independent component analysis based on clustering.

In standard Independent Component Analysis (ICA), a linear data model is used for a global description of the data. Even though linear ICA yields meaningful results in many cases, it can provide a crude approximation only for general nonlinear data distributions. In this paper a new structure is proposed, where local ICA models are used in connection with a suitable grouping algorithm clustering the data. The clustering part is responsible for an overall coarse nonlinear representation of the data, while linear ICA models of each cluster are used for describing local features of the data. The goal is to represent the data better than in linear ICA while avoiding computational difficulties related with nonlinear ICA. Several data grouping methods are considered, including standard K-means clustering, self-organizing maps, and neural gas. Connections to existing methods are discussed, and experimental results are given for artificial data and natural images. Furthermore, a general theoretical framework encompassing a large number of methods for representing data is introduced. These range from global, dense representation methods to local, very sparse coding methods. The proposed local ICA methods lie between these two extremes.

Algorithms↗
PubMed2000

Topographic mapping from the retina to the midbrain is controlled by relative but not absolute levels of EphA receptor signaling.

Topographic maps are a fundamental feature of sensory representations in nervous systems. The formation of one such map, defined by the connection of ganglion cells in the retina to their targets in the superior colliculus of the midbrain, is thought to depend upon an interaction between complementary gradients of retinal EphA receptors and collicular ephrin-A ligands. We have tested this hypothesis by using gene targeting to elevate EphA receptor expression in a subset of mouse ganglion cells, thereby producing two intermingled ganglion cell populations that express distinct EphA receptor gradients. We find that these two populations form separate maps in the colliculus, which can be predicted as a function of the net EphA receptor level that a given ganglion cell expresses relative to its neighbors.

Animals↗
PubMed1998

The development of topography in the hamster geniculo-cortical projection.

Precise point-to-point connectivity is the basis of ordered maps of the visual field. The immaturity of the newborn hamster's visual system has allowed us to examine emerging topography in the geniculo-cortical projection well before thalamic axons have reached their cortical target, layer IV. Using anterograde transneuronal labeling with wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP), we visualized the ingrowth of the whole population of geniculate fibers in the neonatal hamster. Two days after birth (P2), the bulk of the fibers is in the deep cortical layers and the subplate. At the same age, injections of paired retrograde tracers (red and green fluorescent latex microspheres) into area 17 reveal an unordered projection from the dorsal lateral geniculate nucleus (dLGN) to cortex. Individual labeled cells are found throughout the dLGN, and quantitative analysis reveals no segregation of the red and the green populations. At P6, when the pattern of geniculate back label appears ordered and essentially adult-like, geniculate fibers have reached layer IV. The role of selective cell death in this process was investigated by making a tracer injection at P2 and allowing the animals to survive to P6 or P12, when the map is mature. The results show early labeled neurons that made inappropriate connections when the projection was scattered surviving through the period of geniculate cell death. We conclude that the geniculo-cortical map develops from an initially unordered projection to the subplate and the lower cortical layers. Selective cell death appears not to contribute significantly to this process.

Animals↗
PubMedDate not supplied

The functional organization of local circuits in visual cortex: insights from the study of tree shrew striate cortex.

We have used a combination of anatomical and physiological techniques to explore the functional organization of vertical and horizontal connections in tree shrew striate cortex. Our studies of vertical connections reveal a remarkable specificity in the laminar arrangement of the projections from layer IV to layer III that establishes three parallel intracortical pathways. The pathways that emerge from layer IV are not simple continuations of parallel thalamocortical pathways. Layer IV and its connections with layer II/III restructure the inputs from the LGN, combining the activity from ON and OFF channels and from the left and right eye and transmit the products of this synthesis to separate strata within the overlying layers. In addition, studies of two other prominent vertical connection pathways, the projections from layer VI to layer IV and from layer II/III to layer V suggest that the parallel nature of these systems is perpetuated throughout the cortical depth. Our studies of horizontal connections have revealed a systematic relationship between a neuron's orientation preference and the distribution of its axon arbor across the cortical map of visual space. Horizontal connections in layer II/III extend for greater distances and give rise to a greater number of terminals along an axis of the visual field map that corresponds to the neuron's preferred orientation. These findings suggest that the contribution of horizontal inputs to the response properties of layer II/III neurons is likely to be greater in regions of visual space that lie along the axis of preferred orientation (endzones) than along the orthogonal axis (side zones). Topographically aligned horizontal connections may contribute to the orientation preference of layer II/III neurons and could account for the axial specificity of some receptive field surround effects. Together, these results emphasize that specificity in the spatial arrangement of local circuit axon arbors plays an important role in shaping the response properties of neurons in visual cortex.

Animals↗
PubMed2004

Measuring interregional functional connectivity using coherence and partial coherence analyses of fMRI data.

Understanding functional connectivity within the brain is crucial to understanding neural function; even the simplest cognitive operations are supported by highly distributed neural circuits. We developed a novel method to measure task-related functional interactions between neural regions by applying coherence and partial coherence analyses to functional magnetic resonance imaging (fMRI) data. Coherence and partial coherence are spectral measures that estimate the linear time-invariant (LTI) relationship between time series. They can be used to generate maps of task-specific connectivity associated with seed regions of interest (ROIs). These maps may then be compared across tasks, revealing nodes with task-related changes of connectivity to the seed ROI. To validate the method, we applied it to an event-related fMRI data set acquired while subjects performed two sequence tapping tasks, one of which required more bimanual coordination. Areas showing increased functional connectivity with both tasks were the same as those showing increased activity. Furthermore, though there were no significant differences in mean activity between the two tasks, significant increases in interhemispheric coherence were found between the primary motor (M1) and premotor (PM) regions for the task requiring more bimanual coordination. This increase in interhemispheric connectivity is supported by other brain imaging techniques as well as patient studies.

Adolescent↗
PubMed2001

Diffusion tensor imaging and axonal tracking in the human brainstem.

Diffusion tensor MRI was used to demonstrate in vivo anatomical mapping of brainstem axonal connections. It was possible to identify the corticospinal tract (CST), medial lemniscus, and the superior, medial, and inferior cerebellar peduncles. In addition, the cerebral peduncle could be subparcellated into component tracts, namely, the frontopontine tract, the CST, and the temporo-/parieto-/occipitopontine tract. Anatomical landmarks and tracking thresholds were established for each fiber and, using these standards, reproducibility of automated tracking as assessed by intra- and interrater reliability was found to be high (kappa > 0.82). Reconstructed fibers corresponded well to existing anatomical knowledge, validating the tracking. Information on the location of individual tracts was coregistered with quantitative MRI maps to automatically measure MRI parameters on a tract-by-tract basis. The results reveal that each tract has a unique spatial signature in terms of water relaxation and diffusion anisotropy.

Adult↗
PubMed2000

Diversity and cell type specificity of local excitatory connections to neurons in layer 3B of monkey primary visual cortex.

In the primary visual cortex of macaque monkeys, laminar and columnar axonal specificity are correlated with functional differences between locations. We describe evidence that embedded within this anatomical framework is finer specificity of functional connections. Photostimulation-based mapping of functional input to 31 layer 3B neurons revealed that input sources to individual cells were highly diverse. Although some input differences were correlated with neuronal anatomy, no 2 neurons received excitatory input from the same cortical layers. Thus, input diversity reveals far more cell types than does anatomical diversity. This implies relatively little functional redundancy; despite trends related to laminar or columnar position, pools of neurons contributing uniquely to visual processing are likely relatively small. These results also imply that similarities in the anatomy of circuits in different cortical areas or species may not indicate similar functional connectivity.

Animals↗
PubMed2004

The motor cortex and facial expression: new insights from neuroscience.

BACKGROUND: For more than a century, unusual and complex deficits in facial expression have been known to occur following localized brain damage. Some brain injuries leave the face with pronounced alterations in affect whereas others result in movement disorders such as blepharospasm and Meige syndrome. There is also a historic trail of clinical observations that document deficits in either voluntary or emotional control of the facial muscles following central nervous system damage. REVIEW SUMMARY: Recent studies in the nonhuman primate cerebral cortex reveal the existence of multiple cortical facial representations in the frontal lobe and adjacent anterior cingulate cortex. These comprise the facial representation of the primary motor cortex (M1), ventral lateral premotor cortex (LPMCv), supplementary motor cortex (M2), rostral cingulate motor cortex (M3), and caudal cingulate motor cortex (M4). Homologous facial representations reside in the human brain based on observations following cortical stimulation, functional neuroimaging, and localized surgical resection. In the nonhuman primate, all these facial representations have been found to be directly interconnected through topographically organized corticocortical connections, and each facial area has also been found to send direct corticobulbar projections to the facial motor nucleus. The facial representations of M2 and M3 are both located on the medial wall of the hemisphere, in the vascular territory of the anterior cerebral artery. Both preferentially give rise to bilateral projections to parts of the facial nucleus that innervate the upper facial musculature as demonstrated in the monkey. The facial representation of M1, LPMCv, and M4 preferentially give rise to contralateral axonal projections ending in parts of the facial nucleus that innervate the lower facial musculature. The facial representation of M1 and LPMCv both reside in the vascular territory of the middle cerebral artery (MCA). The classic clinical presentation of paralysis in the contralateral lower facial musculature and intact bilateral upper facial musculature following typical MCA in infarction in the human parallels this mapping pattern of corticobulbar connections found in the nonhuman primate. CONCLUSIONS: Facial movements are undoubtedly under the powerful influence of the cerebral cortex and are essential for the appropriate execution of many important functions such as mastication, swallowing, and social interaction, including speech and nonverbal communication. This information provides a theoretic template for interpreting the clinical effects of neuropathologic disease and localized cortical trauma on facial movements.

Animals↗
PubMed1994

Successful and unsuccessful sites of radiofrequency catheter ablation of accessory atrioventricular connections.

Local electrograms from 47 consecutive patients who underwent successful radiofrequency catheter ablation of 49 accessory atrioventricular (AV) connections were analyzed. One hundred twenty-two local electrograms were recorded at 27 successful and 95 unsuccessful sites immediately before radiofrequency catheter ablation of 27 manifest accessory AV connections during preexcited sinus rhythm or atrial pacing. Continuous electric activity was found in 96% of successful sites versus 71% of unsuccessful sites (p < 0.01). Possible accessory pathway (AP) potentials were present only in 15% of successful and 2% of unsuccessful sites, respectively (p < 0.05). All measured time intervals were significantly shorter for successful sites as compared to unsuccessful sites of ablation of manifest accessory AV connections. Unipolar electrograms from the tip of the ablation catheter of each successful and unsuccessful ablation site were available for the last 16 patients with manifest accessory AV connections. A PQS pattern of the unipolar electrogram was associated with a higher success rate, whereas a PrS pattern never resulted in successful ablation of an accessory AV connection. Multivariate logistic regression analysis of the local electrogram characteristics of rapidly conducting, concealed accessory AV connections revealed the interval between the onset of the local ventricular and atrial electrogram (VoAo interval) as the only independent variable associated with successful sites for radiofrequency catheter ablation. The only study patient with a slowly conducting, concealed accessory AV connection underwent successful ablation with the first lesion of radiofrequency energy at the site with the shortest VoAo interval. We conclude that (1) the shortest local AV intervals and local ventricular electrograms preceding the earliest onset of the delta wave in any surface lead are predictive of successful ablation of manifest accessory AV connections; (2) the shortest local VA intervals during orthodromic AV reentry tachycardia or right ventricular pacing are predictive of successful ablation of concealed accessory AV connections; and (3) unipolar recordings from the tip of the ablation catheter should be recorded routinely during mapping of manifest accessory AV connections to identify appropriate target sites for radiofrequency energy applications.

Action Potentials↗
PubMed1998

A distributed environment for physical map construction.

MOTIVATION: With the main focus of the Human Genome Project shifting to sequencing, bioinformatics support for constructing large-scale genomic maps of other organisms is still required. We attempt to provide for this with our work, aimed at the delivery of robust and user-friendly contig-building software on the WWW. RESULTS: We present a prototype distributed analytical environment for molecular biologists working in the area of genomic mapping. It consists of the WWW server for constructing contigs from users' data with a hypertext output connected to Java-based map visualization software. AVAILABILITY: Freely available on http://www.mpimg-berlin-dahlem.mpg. de/ approximately andy/server/ CONTACT: andy@rag3.rz-berlin.mpg.de

Algorithms↗
PubMed1992

NASPE Young Investigator Awardee 1992. Three-dimensional electrogram mapping improves ablation of left-sided accessory pathways.

Conventional electrogram mapping techniques for localization of accessory pathways during radiofrequency ablation procedures are time consuming and often inaccurate. We hypothesized that a computer generated, three-dimensional electrogram of retrograde atrial activation created from signal-averaged sequential endocardial bipolar electrograms (collected from the atrial aspect of the mitral annulus using a single transseptal catheter and then time aligned to a known myocardial activation reference) would improve left-sided accessory pathway atrial insertion site identification and increase ablation efficiency. Ablation efficiency was defined by procedure time, fluoroscopy time, duration of radiofrequency energy required to achieve initial accessory pathway block, cumulative ablation energy per procedure, and number of radiofrequency energy applications. Patients with single left-sided accessory atrioventricular connections were studied. Standard mapping results in 31 patients (group A) were compared to a three-dimensional electrogram approach used in 26 patients (group B). Three-dimensional electrogram mapping reduced procedure time (group A 3.8 +/- 1.6 vs group B 2.8 +/- 0.9 hours, P < 0.004), fluoroscopy time (group A 45.3 +/- 35.0 vs group B 25.1 +/- 10.5 min, P < 0.02), time to accessory pathway block (group A 2.6 +/- 1.5 vs group B 1.2 +/- 0.5 sec, P < 0.002), cumulative radiofrequency energy (group A 2126 +/- 2207 vs group B 636 +/- 586 joules, P < 0.0008), and radiofrequency energy applications (group A 5.0 +/- 4.4 vs group B 1.7 +/- 1.2, P < 0.0002). We conclude that three-dimensional electrogram mapping improves left-sided accessory pathway atrial insertion localization, reduces ablation procedure time and radiation exposure, and improves ablation efficiency.

Adult↗
PubMed2004

Detection and masking of spoiled food smells by odor maps in the olfactory bulb.

Two major causes of spoiled food smells such as fatty, fishy off-flavors are alkylamines liberated by bacterial actions and aliphatic acids-aldehydes generated by lipid oxidation. Using the method of intrinsic signal imaging, we mapped alkylamine-responsive glomeruli to a subregion of the aliphatic acid-responsive and aldehyde-responsive cluster in the odor maps of rat olfactory bulb. Extracellular single-unit recordings from mitral-tufted cells in the subregion showed that individual cells responded to the alkylamines in addition to acids and aldehydes. Responses of mitral-tufted cells tended to last for a long period (5-88 sec) even after the cessation of the alkylamine stimulation. These results suggest that the subregion is part of the representation of the fatty, fishy odor quality. Fennel and clove, spices known to add flavor and mask the fatty, fishy odor, activated glomeruli in the surrounding clusters and suppressed the alkylamine-induced and acid-aldehyde-induced responses of mitral cells, suggesting that the odor masking is mediated, in part, by lateral inhibitory connections in the odor maps of the olfactory bulb.

Amines↗
PubMed2001

Intracortical origin of visual maps.

Previous experiments indicate that the shape of maps of preferred orientation in the primary visual cortex does not depend on visual experience. We propose a network model that demonstrates that the orientation and direction selectivity of individual units and the structure of the corresponding angle maps could emerge from local recurrent connections. Our model reproduces the structure of preferred orientation and direction maps, and explains the origin of their interrelationship. The model also provides an explanation for the correlation between position shifts of receptive fields and changes of preferred orientations of single neurons across the surface of the cortex.

Action Potentials↗
PubMed1974

Identification and mapping of the replication genes of an R factor, R100-1, integrated into the chromosome of Escherichia coli K-12.

A stable Hfr strain of Escherichia coli K-12 was obtained by integrative suppression by an R factor, R100-1. The R factor was integrated into the right of 81 min, and chromosome transfer occurred counterclockwise. Mating experiments revealed two linkage groups of genes on the R factor. Drug-resistant transductants of a dnaA-ts recipient from an R-factor Hfr and from an R(+) strain differ in their drug resistance patterns, temperature sensitivity, and transferability of drug resistance as well as chromosome markers. Transductants that transferred chromosome markers were further classified as to the origin and direction of chromosome transfer. For temperature-sensitive transductants, the reversion frequency to temperature resistance was determined, and these revertants were scored for transfer of drug resistance as well as chromosome markers. Two genes responsible for integrative suppression (designated as repA) and the other for autonomous replication (designated as repB) were identified and mapped. The arrangement of genes on the R factor is... (sul, str, cml)... repA... tra... (tet, repB).... The map of the autonomously replicating R factor is probably a circle connecting both sides of this linear map. Thus, a method has been established to map a plasmid that could not finely be analyzed under autonomous state by transduction. It also permits genetic analysis of genes responsible for replication of the plasmid without making use of a conditional mutant of itself but with that of the host, dnaA.

Anti-Bacterial Agents↗
PubMed2003

Permanent or transitory effects on neurocognitive components of the CNV complex induced by brain dysfunctions, lesions and ablations in humans.

Since the mid-1960s, essentially using electrophysiological methods, our research group has examined the effects of different brain diseases in humans, both on first- and second-order conditioned responses and on some types of neurocognitive potentials of the CNV complex. This didactic lecture will focus on our various attempts to identify and understand the neuroanatomical and neurophysiological substrates involved in cognitive information processing followed by the conception and execution of sensory-motor and behavioural responses evoked by significant acoustic stimuli, in both pathological situations and normal control subjects. Great interest was, e.g. aroused in the early 1970s by the rare, fortunately unrepeatable, opportunity of examining the CNV patterns in various psychiatric patients treated with psychosurgical Freeman-Watts bilateral prefrontal 'radical' lobotomy, also with repeated recordings (The Responsive Brain (1976) 158; Multidisciplinary Perspectives in Event-Related Brain-Potentials Research (1978) 376) or bimedial bifrontal cingulotomy (Multidisciplinary Perspectives in Event-Related Brain Potential Research (1978) 383). In the same period, investigations into CNV activity recorded in patients submitted to complete callosotomy ('split brain': Attention and Performance, vol. IV (1972) 221; Electroenceph. Clin. Neurophysiol. Suppl. 33 (1973) 161) were also begun and were continued into the 1980s, also with regard to other types of ERP (Brain 111 (1988) 553; J. Cog. Neurosci. 2 (1990) 258). All these data furnished unique information about the sub-second dynamics of unilateral or bihemispheric cortico-cortical and cortico-subcortical interconnections in humans. In recent years, with a classic method of analysis based on sequential scalp-topographic bidimensional neuroelectric mapping and 21/19 electrodes connected to three different references, and binaural/monaural clicks as warning signals (S1), we have repeatedly examined the CNV activity of 11 selected patients submitted to complete ablation of the damaged cortical areas, with uni- or bilateral lesions restricted to the prefrontal or associative parieto-temporal areas. We have always used the standard CNV paradigm (S1-S2 motor-response) which evokes a complex of neurocognitive potentials, including the P300 from S1, which are well-known, since they are certainly among the most studied ERPs in the various ages and races of normal subjects, psychiatric patients and subjects with different brain diseases. The most important results have been, (1) In normal subjects the MRI and the latency differences of CNV component measurements along the bidirectional pathways functionally interconnecting ipsilateral distant associative cortical areas (e.g. the arcuate-superior longitudinal complex bundle) were accounted for by the transcortical conduction time, which varies in our scalp recordings from 1 cm/0.74 to 1.28 ms ( approximately 9.8 m/s). (2) Constantly, no true auditory S1-elicited N1a, b, c, P2, N2, P300 components or CNV slow waves (O- and E-wave) were recordable over the whole of the ablated cortical areas, but only clearly identifiable volume-conducted EP/ERPs generated in other hemispheric structures. (3) The post-S1 ERP/CNV complexes on the intact hemisphere were found to be within the normal limits. (4) Effects of severe disruption on the S1 ERP/CNV complexes evocable on the site and on remote ipsilateral apparently normal anatomo-functionally interconnected brain regions were observed in 5 patients, 4 of whom had extensive frontocortical ablations. In two of the latter the distant disruptive action on the CNV components over the neuroradiologically normal ipsilateral two-way connected post-rolandic sensory and association areas was seen to be partially reversible, showing aspects of a probable slowly evolving diaschisis-like effect. Similar deactivation of some ERP components was observed in reverse on the ipsilateral dorsolateral frontocortical region in the fifth patient with a large parieto-temporal cortex ablation. These data require confirmahese data require confirmation, and when this phenomenon is observable, it must be appropriately monitored with different methods of functional neuroimaging. This will serve not only for medical and neuropsychophysiological diagnosis purposes, but also particularly for a correct and really useful planning of neuro-rehabilitation activities in selected cases.

Brain Diseases↗
PubMed1997

Male-predominant carboxylesterase expression in the reproductive system of molluscs and insects: immunochemical and biochemical similarity between Mytilus male associated polypeptide (MAP) and Drosophila sex-specific esterase S.

We suggested that sexual differentiation of the reproductive system in gonochoric species of invertebrates can be characterized by common molecular mechanisms in spite of high morphological divergences of reproductive tract organs in different animal groups. The present study focused on this problem and report our observations on biochemical characteristics of male-associated polypeptide (MAP) identified in the gonad tissue of bivalve molluscs, Mytilus galloprovincialis, in comparison to those of male-specific carboxylesterase (esterase S) of Drosophila virilis ejaculatory bulbs. We provide evidences for the immunochemical similarity of Mytilus MAP and Drosophila esterase S. We also show that MAP is characterized by esterase activity toward both, alpha- and beta-naphthyl acetates. Using immunofluorescence, we found MAP in the gonad (mantle) connective tissue, membranes of follicles and around gonad ducts but not in sperm cells. Nevertheless, the levels of MAP expression depend on presence or absence of ripe spermatozoa in the gonad follicles. In mature gonads before spawning, MAP is expressed at high level, while in the spent gonads only traces of this polypeptide could be detected. Using Western immunoblot, MAP was not observed in spermatozoa obtained by biopsy of gonad follicles. In contrast, we found this protein in spawned sperm cells. Thus, we suggest that spawning may be required to establish the trafficking mechanisms that control whether MAP is retained or excreted by the gonad. Taken together, the results indicate that MAP of M. galloprovincialis is structurally and functionally related to esterase S of D. virilis ejaculatory bulbs.

Amino Acids↗
PubMed2003

Novel map descriptors for characterization of toxic effects in proteomics maps.

We consider a novel numerical characterization of proteomics maps based on the construction of a graph obtained by connecting all protein spots in a proteomics map that are at distance equal to, or smaller than, a critical distance D(c). We refer to the so constructed graph as a cluster graph and we calculate four associated characteristic matrices, previously considered in the literature: (1) the Euclidean-distance matrix ED; (2) the neighborhood-distance matrix ND; (3) the path-distance matrix based on the shortest paths between connected spots PD; and (4) the quotient matrix Q, the elements of which are given as the quotient of the corresponding elements of ED and ND matrices. Numerical descriptors for proteomics maps include in particular the leading eigenvalue of the Q matrix and the family of associated "higher order" matrices defined as powers of Q. These map descriptors show considerable sensitivity to perturbations of proteomics maps by toxicants.

Animals↗
PubMed2004

Graphical modeling of the joint distribution of alleles at associated loci.

Pairwise linkage disequilibrium, haplotype blocks, and recombination hotspots provide only a partial description of the patterns of dependences and independences between the allelic states at proximal loci. On the gross scale, where recombination and spatial relationships dominate, the associations can be reasonably described in these terms. However, on the fine scale of current high-density maps, the mutation process is also important and creates associations between loci that are independent of the physical ordering and that can not be summarized with pairwise measures of association. Graphical modeling provides a standard statistical framework for characterizing precisely these sorts of complex stochastic data. Although graphical models are often used in situations in which assumptions lead naturally to specific models, it is less well known that estimation of graphical models is also a developed field. We show how decomposable graphical models can be fitted to dense genetic data. The objective function is the maximized log likelihood for the model penalized by a multiple of the model's degrees of freedom. We also describe how this can be modified to incorporate prior information of locus position. Simulated annealing is used to find good solutions. Part of the appeal of this approach is that categorical phenotypes can be included in the same analysis and association with polymorphisms can be assessed jointly with the interlocus associations. We illustrate our method with genotypic data from 25 loci in the ELAC2 gene. The results contain third- and fourth-order locus interactions and show that, at this density of markers, linkage disequilibrium is not a simple function of physical distance. Graphical models provide more flexibility to express these features of the joint distribution of alleles than do monotonic functions connecting physical and genetic maps.

Alleles↗