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Silicone breast implants and connective tissue disease: an updated review of the epidemiologic evidence.

Numerous meta-analyses, weight-of-the-evidence, and critical reviews have summarized data from case-control and cohort studies, published through 1999, which have been conducted to evaluate the potential association between cosmetic silicone breast implants and the occurrence of well-defined connective tissue diseases, as well as a hypothesized new atypical disease, which does not fulfill established diagnostic criteria for any known connective tissue disease. These reviews have unanimously concluded that there is no evidence of an association between breast implants and any of the traditional connective tissue diseases evaluated individually or combined or atypical connective tissue disease. We have performed an updated review of the results of epidemiologic studies published since 1999. Two long-term follow-up studies of women with breast implants in Denmark and a retrospective cohort study in Australia found no excess of definite connective tissue disease, including rheumatoid arthritis, systemic sclerosis, systemic lupus erythematosus and Sjogren's syndrome, among women with cosmetic breast implants compared with breast reduction or other plastic surgery controls or women in the general population. No consistent evidence was observed of increased risk of definite connective tissue disease in women with extracapsular ruptures in 2 studies which evaluated risk by rupture status among women with cosmetic breast implants. The results of several studies provide no evidence of a higher frequency of undefined connective tissue disease among women with cosmetic breast implants or of a rheumatic symptom profile unique to these women and/or indicative of a specific atypical connective tissue disease. In conclusion, the most recent epidemiologic investigations have been remarkably consistent with earlier epidemiologic studies in finding no evidence of an excess of any individual connective tissue disease or all connective tissue diseases combined, including both established and atypical or undefined connective tissue disease, among women with cosmetic silicone breast implants. Thus, the conclusions reached in earlier independent reviews have not changed based on data published during the subsequent years.

Australia↗

Connectional networks within the orbital and medial prefrontal cortex of macaque monkeys.

The intrinsic cortico-cortical connections within the orbital and medial prefrontal cortex (OMPFC) were demonstrated with retrograde and anterograde tracers injected into each of the architectonic areas that constitute this region. Although many of the connections linked neighboring areas, others selectively connected relatively distant areas. Most, but not all, of the connections were reciprocal. Altogether, the connections formed at least two distinct networks within the OMPFC. The "orbital" prefrontal network linked most of the areas within the orbital cortex, with very few connections to medial prefrontal areas. Areas Iam, Iapm, Ial, 12l, 12m, and 12r in the caudal and lateral parts of the orbital cortex (which received inputs from several sensory modalities) had convergent connections with areas 13l, 13m, and 13b in the central orbital cortex, with further connections to the rostral orbital area 11l. For the connections between areas Iapm, Iam, Ial, 13m, 13l, and 11l, rostrally directed fibers arose mainly in layer V, whereas caudally directed fibers originated mainly in layer III. The "medial" prefrontal network selectively involved medial areas 14r, 14c, 24, 25, 32, and 10m, rostral orbital areas 10o and 11m, and agranular insular area Iai in the posterior orbital cortex. Two orbital areas, 13a and 12o, had substantial connections to both networks and may serve as points of interaction between them; otherwise there were relatively few interconnections. The two networks also had distinct connections with other cortical regions, with limbic structures, and with the mediodorsal thalamic nucleus. Their role in guidance of affective behaviour is discussed.

Animals↗

Cortical connections of striate and extrastriate visual areas in tree shrews.

The ipsilateral and contralateral cortical connections of visual cortex of tree shrews (Tupaia belangeri) were investigated by placing restricted injections of fluorochrome tracers, wheat germ agglutinin-horseradish peroxidase, or biotinylated dextran amine into area 17 (V1), area 18 (V2), or the adjoining temporal dorsal area (TD). As previously reported, V1 was characterized by a widespread, patchy pattern of intrinsic connections; ipsilateral connections with V2, TD, and to a lesser extent, other areas of the temporal cortex; and contralateral connections with V1, V2, and TD. A surface-view of the myelin pattern in V1 revealed a patchwork of light and dark module-like regions. The ipsilateral connections with V2 and TD were roughly topographic, whereas heterotopic locations in V1 were callosally connected. Injections in V2 labeled as much as one third of V2 in a patchy pattern, and portions of ipsilateral V1 and TD in roughly topographic patterns. In addition, connections with several other visual areas in the temporal lobe were revealed. Contralaterally, most of the label was in V2, with some in V1 and TD. Injections in TD demonstrated connections within the region, and with adjoining portions of the temporal cortex, V2, and V1. There were sparse connections with an oval of densely myelinated cortex, which we have termed the temporal inferior area (TI). Callosal connections were concentrated in TD, but also included V2. The results provide further evidence for modular organizations within V1 and V2, and reveal for the first time the complete patterns of cortical connections of V2 and TD. The results are consistent with the proposal that at least three visual areas, the temporal anterior area, TA, the temporal dorsal area, TD, and the temporal posterior area, TP, exist along the rostrolateral border of V2 in tree shrews; suggest visual involvement of at least three other areas, the temporal inferior area, TI, the temporal anterior lateral area, and the temporal posterior inferior area located more ventrally in the temporal cortex; and fortify the conclusion that TD is the likely homologue of the middle temporal visual area of primates. Because tree shrews are considered close relatives of primates, the evidence for several visual areas along the border of V2 is more compatible with theories that propose a series of visual areas along V2 in primates, rather than a single visual area, V3.

Animals↗

Metal nuclearity modulated four-, six-, and eight-connected entangled frameworks based on mono-, bi-, and trimetallic cores as nodes.

To investigate the relationship between network connectivity and metal nuclearity, we designed and synthesized a series of three-dimensional (3D) entangled coordination frameworks based on different metal cores, namely [Zn(2)(bdc)(2)(L)(2)]2H(2)O (1), [Zn(bdc)(L)(0.5)] (2), [Zn(oba)(L)(0.5)] (3) and [Cd(3)(bdc)(3)(L)(2)(H(2)O)(2)] (4) by self-assembly of d(10) metal salts with the flexible long-chain ligand 1,4-bis(1,2,4-triazol-1-yl)butane (L), and with the rigid and nonrigid aromatic dicarboxylate ligands 1,4-benzenedicarboxylate (bdc) and 4,4'-oxybis(benzoate) (oba). Compound 1 exhibits a threefold interpenetrated diamondoid array typically based on a tetrahedral second building unit (SBU) at a single Zn center. Compound 2 adopts a threefold interpenetrated alpha-polonium-type network that is built from bimetallic cores as six-connected vertices. The structure of 3 also consists of dinuclear units; it comprises a novel (3,4)-connected threefold interpenetrated net with complex (4610)(46(2)10(3)) topology when single zinc centers act as four-connected nodes (or the alpha-Po topology if dinuclear units are considered as six-connected nodes). Compound 4, derived from a crosslinked fivefold interpenetrated diamond-like substructure, is an unusual example of a self-penetrating coordination framework displaying an unprecedented eight-connected 4(20)6(8) topology with trinuclear cadmium clusters as eight-connected nodes which, to our knowledge, not only defines a new topology for eight-connected coordination networks, but also represents the highest connected topology presently known for self-penetrating systems. Detailed structural comparison of these complexes indicates that the increase in metal nuclearity induces the progressive increase in the connectivities of the ultimate nets: that is, the metal nuclearity plays a significant role in tuning the connectivity of a specific network. The thermal and luminescent properties of these compounds are discussed.

Journal Article↗

Differential connections of the temporal pole with the orbital and medial prefrontal networks in macaque monkeys.

Previous studies indicate that the orbital and medial prefrontal cortex (OMPFC) is organized into "orbital" and "medial" networks, which have distinct connections with cortical, limbic, and subcortical structures. In this study, retrograde and anterograde tracer experiments in monkeys demonstrated differential connections between the medial and orbital networks and the dorsal and ventral parts of the temporal pole. The dorsal part, including dysgranular and granular areas (TGdd and TGdg), is reciprocally connected with the medial network areas on the medial wall and gyrus rectus (areas 10m, 10o, 11m, 13a, 14c, 14r, 25, and 32) and on the lateral orbital surface (areas Iai and 12o). The strongest connections are with areas 10m (caudal part), 14c, 14r, 25, 32, and Iai. The agranular temporal pole (TGa) is connected with several areas, but most strongly with medial network area 25. The granular area around the superior temporal sulcus (TGsts) and the ventral dysgranular and granular areas (TGvd and TGvg) are reciprocally connected with the orbital network (especially areas 11l, 13b, 13l, 13m, Ial, Iam, and Iapm). TGsts is strongly connected with the entire orbital network, whereas areas TGvd and TGvg have lighter and more limited connections. Intrinsic connections within the temporal pole are also restricted to dorsal or ventral parts. Together with evidence that the dorsal and ventral temporal pole are differentially connected to auditory and visual areas of the superior and inferior temporal cortex, the results indicate separate connections between these systems and the medial and orbital prefrontal networks.

Animals↗

Afferent and efferent connections of the striate and extrastriate visual cortex of the normal and reeler mouse.

In order to analyze the role of lamination in establishing the precisely ordered connectional pattern of the neocortex, we compared the afferent and efferent connections of the visual cortical areas in normal mice with those of the mutant mouse reeler (rl). The reeler mutation causes disruption of the laminar organization of the neocortex; all classes of neurons are present but are abnormally located. The corticocortical and thalamocortical connection os visual cortical areas 17, 18a, and 18b were determined in normal and reeler mice with injections of horseradish peroxidase (HRP) or HRP conjugated with wheat germ agglutinin (HRP-WGA). The diffusion of HRP-WGA is highly restricted due to the surface binding properties of the lectin; it was particularly effective in demonstrating retinotopically ordered connections. We found that the patterns of connections made the reeler mutant are indistinguishable from normal. Cortical loci in area 17 are reciprocally connected to homotopic locations in areas 18a and 18b. Area 17 is also reciprocally connected with dorsal lateral geniculate nucleus of the thalamus and projects to the superior colliculus. Areas 18a and 18b are reciprocally connected with each other and with the lateral posterior and lateral nuclei of the thalamus, respectively. In addition, we found evidence of reciprocal connections between the lateral posterior nucleus and area 17, and between the lateral nucleus and areas 17 and 18a. The results indicate the neurons in visual cortical areas of the reeler mutant mouse are capable of forming retinotopically organized corticocortical and thalamocortical connections in a pattern similar to that found in normal animals. Thus the genetic anomaly producing incorrect neuronal positioning during development of the reeler cortex does not seriously impede the pathway and target recognition mechanisms responsible for formation of functionally appropriate cortical connections.

Animals↗

Cortical connections of area 17 in tree shrews.

In order to better understand the organization of extrastriate cortex in tree shrews, injections in area 17 of wheat germ agglutinin or tritiated proline were used to reveal an intrinsic pattern of connections, ipsilateral connections with area 18 and two other subdivisions of cortex, and callosal connections with areas 17 and 18 of the opposite cerebral hemisphere. Areal patterns of connections were best seen in sections cut parallel to the surface of flattened cortex. Within area 17, periodic foci of labeled terminations and cells extended from and surrounded injection sites as described by Rockland et al. ('82). Single injections produced multiple foci of labeled terminations and cells in area 18. The foci tended to fuse into short bands that sometimes crossed the width of area 18. Double injections produced more foci, and multiple injections tended to produce more continuous regions of label. An overall retinotopic pattern was evident with rostral area 17 connected to rostral area 18 and caudal area 17 connected to caudal area 18. Terminations extended through layers II-VI, with some increase in density in layer IV. Cells in area 18 projecting back to area 17 were in layers III and V. The injections also allowed identification of previously undefined subdivisions of visual cortex in temporal cortex immediately adjoining area 18. Dense reciprocal connections were observed in a 13 mm2 oval of cortex on the lateral border of the middle section of area 18 that we define as the temporal dorsal area, TD. Connections indicate a crude topographic organization with lower field represented rostrally and upper field caudally. Inputs were most dense in the middle cortical layers, and labeled cells were supragranular, and less frequently, infragranular. A 10-mm2 oval of cortex near the posterior edge of the hemisphere, the temporal posterior area (TP), contained labeled cells after area 17 injections, but terminal labeling was only obvious in the dorsal part. Single injections sometimes produced quite separate dorsal and ventral zones of label in TP, suggesting a small separate dorsal division. A crude retinotopic order appears to exist within ventral TP, with the lower field most ventral. Labeled cells were largely supragranular. A fourth zone of ipsilateral connections was in posterior limbic cortex bordering area 17 on the ventromedial surface of the cerebral hemisphere. The callosal connections were reciprocal and included regions 1 mm wide on either side of the area 17 and area 18 border. Callosal connections were rougly homotopic. Callosal terminations included superficial layers, and projecting cells were both supragranular and infragranular.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

A reticular pattern of intrinsic connections in primate area V2 (area 18).

A system of periodic intrinsic connections is demonstrated in area V2 (area 18) of squirrel and macaque monkeys by large injections of tritiated amino acids, horseradish peroxidase (HRP), and fluorescent latex beads. These connections originate from pyramidal neurons concentrated in layers 3 and 5. Terminations occur in all cortical layers, largely coextensive with labeled neurons but more restricted in layer 4. This multilaminar distribution contrasts with the mainly supragranular localization of periodic intrinsic connections in V1 (area 17), and may imply a close interaction, in V2, of periodic intrinsic connections with pulvinocortical, as well as with corticocortical terminations (concentrated, respectively, in layers 3 and 5, and in lower 3 and 4). As in V1, the tangential configuration of these connections in V2 is reticular or latticelike, and is detectable for 2.5-3.0 mm from an injection site of HRP, 3H amino acids, or latex beads. Cross-sectional widths of labeled regions vary from 250 to 800 micron in squirrel monkey and from 400 to 1,000 micron in macaque, depending on which portion of the lattice is measured. When periodic intrinsic connections are compared with stripes labeled histochemically by cytochrome oxidase (CO), no clear relationship is obvious between the two systems. This result contrasts with the orderly tangential alignment reported between CO-reactive zones in V2 and certain extrinsic connections; namely, pulvinocortical terminations (Livingstone and Hubel, '82) and clusters of neurons projecting to area V4 (DeYoe and Van Essen, '84). Other extrinsic connections, however, such as backgoing connections from V2 to V1, do not seem to have a periodic distribution. Thus, although some discontinuous cortical connections relate to each other in a precise mosaic fashion, intrinsic and some extrinsic connections may observe different modes of organization.

Animals↗

Interhemispheric connections of the somatosensory cortex in the rabbit.

Corpus callosal connections of somatosensory cortex were studied in rabbits by combining anatomical tracing and electrophysiological mapping in the same animals. The results show that callosal connections are unevenly distributed in SI and SII. In SI, the representations of all body surfaces caudal to the neck and midline structures of the head have dense callosal connections. Conversely, connections are sparse to absent within representations of laterally positioned surfaces of the head, such as the sinus hairs, vibrissae, and nonmidline portions of the lips. Almost all of SII has dense callosal connections; only the representations of the vibrissae and sinus hairs have moderate callosal connections. The laminar distribution of callosal connections in rabbit SI and SII is similar to that observed in other mammals. Callosal terminations extend from the inner portion of layer I to the outer portion of layer VI, are moderately denser in the supragranular layers, and are sparse in layer IV. Callosally projecting cells are found predominantly in layers II, III, and V and are sparse in layers IV and VI. These data further emphasize the direct correspondence between the pattern of callosal connections in SI and the functional importance of particular body surfaces. Hence, representations of body surfaces important in the exploration of the environment are relatively free of callosal connections, whereas representations of midline and more lateral surfaces, less significant in tactile exploration, receive dense callosal connections. Callosal connections in rabbits are distributed extensively throughout responsive koniocortical regions rather than being relegated to distinct, specialized regions of "unresponsive" dysgranular cortex as in rodents.

Animals↗

Cortical connections of areas 17 (V-I) and 18 (V-II) of squirrels.

Connections of visual cortex in squirrels were investigated by placing WGA-HRP injections, and in some cases fluorescent dyes, into area 17 (V-I) or area 18 (V-II). Results were related to architectonic fields determined in brain sections cut parallel to the surface of manually flattened cortex and to limited microelectrode mapping data. Injections in area 17 provided evidence for 1) a patchy pattern of horizontal intrinsic connections extending 1-2 mm from the injection site; 2) uneven, widely distributed connections with area 18 (V-II) and adjoining occipital-temporal (OT) cortex; and 3) callosal connections of large portions of area 17 with the 17/18 border zone. While restricted locations in area 17 had uneven interconnections over several mm of area 18, more rostral locations in area 17 related to more rostral locations in area 18, demonstrating a topographic tendency. Injections in area 18 revealed 1) zones of discontinuous connections with area 17 that followed a topographic pattern, 2) patches of intrinsic connections that spread over distances of up to 6-8 mm from the injection site; 3) two zones of uneven connections with OT cortex suggesting the locations of at least two visual areas, OTr and OTc; 4) connections with limbic cortex rostromedial to areas 17 and 18; 5) sparse connections with regions of temporal cortex lateral to OT; and 6) uneven callosal connections with area 18 and OT cortex. The widespread and unevenly distributed intrinsic callosal interconnection patterns of areas 17 and 18 contrast with the restricted excitatory receptive fields of neurons and the retinotopic patterns of representation in these fields. Although physiological evidence is presently lacking, the patchy connections suggest that areas 17 and 18 in squirrels are modularly organized.

Animals↗

Visual projections induced into the auditory pathway of ferrets: II. Corticocortical connections of primary auditory cortex.

Although the development of corticocortical projections has been well studied, less is known about the role of sensory inputs in the specification of these connections. As part of an ongoing series of studies in our laboratory, we have examined the role of thalamic input modality in the development of corticocortical connections. These studies involve making unilateral lesions and inducing retinal inputs into the auditory thalamus (MGN) during early development in ferrets, thereby conferring visual responsiveness on primary auditory cortex (AI). In this way we can examine the role of input identity in cortical specification in general, and connectivity patterns specifically. A previous paper (Pallas et al. [1990] J. Comp. Neurol. 298:50-68) described the pattern of thalamocortical and corticothalamic connections of auditory cortex in normal and lesioned animals. This study compares the pattern of auditory corticocortical connections in normal and lesioned animals. We injected neuroanatomical tracers into AI and mapped out the distribution of retrogradely labelled cells in the cortex. We report that the cortical inputs to ferret AI resembled those in cats, and that the pattern of ipsi- and contralateral corticocortical connections of ferret AI with visual input was similar to the normal pattern. Auditory cortex with visual input did not make ectopic connections with visual cortex, but maintained its connections with other auditory cortical areas. These results suggest that the overall corticocortical connections of an area are not influenced by the modality or activity pattern of its inputs. In particular, altering the input activity to a cortical area does not seem to promote the formation of entirely new connections, although small changes in the strength of existing connections are possible (Sur et al. [1990] Trends Neurosci. 13:227-233).

Animals↗

The differential regulation of formation of chemical and electrical connections in Helisoma.

Novel chemical and electrical connections form between neurons not normally connected in the buccal ganglia of the snail Helisoma. We examined the cellular and environmental conditions required for the formation of each type of connection. Previous work in situ showed that novel electrical connections could form in response to axotomy. We have now found that axotomy can evoke the formation of novel unidirectional chemical connections between neurons B5 and B4 in addition to a novel electrical connection. The novel chemical connections display all of the normal properties of chemical synapses in Helisoma ganglia. These connections, however, are transient in nature and break 4 days following axotomy. Previous work has shown that conjoint outgrowth is required for the formation of electrical connections. In cell culture we have investigated whether conjoint outgrowth is also required for chemical synaptogenesis. Using neurons B5 and B19 we have found that when neuron pairs make contact in cell culture, under conditions of synchronous neurite extension, both electrical and chemical synapses form. However, if one neuron has ceased extension prior to contact by a growing neuron, electrical synapses never form (Hadley et al., 1983, 1985) but chemical synapses do form. Furthermore, the addition of serotonin (10(-6) M) to culture medium to inhibit neurite extension of B19, but not that of B5, selectively prevents the formation of electrical connections while permitting the formation of chemical synapses. Thus, the timing of contact in relation to the state of neurite extension can specify the type of connection a given neuron can form.

Animals↗

Differential properties of GABAergic synaptic connections in rat hippocampal cell cultures.

Based on the effect of prolonged tetanic stimulation (30 Hz, 4 sec), we divided GABAergic synaptic connections in hippocampal cell cultures into two groups: connections facilitated ( approximately 45%) and connections depressed ( approximately 55%) by the tetanic stimulation. In order to reveal possible reasons for the differential effect of the tetanization, we compared several properties of the connections belonging to both groups. We found that, on average, evoked IPSCs in the connections facilitated by the tetanization have a smaller amplitude and larger coefficient of variation (CV) of IPSC amplitude compared to connections depressed by the tetanization. We also estimated quantal parameters for both groups of connections assuming that transmitter release is reasonably described by a binomial distribution. We found that a background release probability (P) is substantially lower in the connections facilitated by the tetanization (P approximately 0.5) than in the connections depressed by the tetanization (P approximately 0.9) and suggest that this difference may underlie the differential effect of the tetanization. We also found that the tetanization induces the opposite effect on connections made by distinct presynaptic neurons with the same postsynaptic cell (convergent connections) in a fraction of postsynaptic neurons studied (3 out of 9). These results support the idea that properties of the presynaptic neuron are of primary importance for the observed differential effect of the tetanization, but they do not exclude a role of the postsynaptic neuron in this effect.

Animals↗

An investigation of functional and anatomical connectivity using magnetic resonance imaging.

This article examines functional and anatomical connectivity in healthy human subjects measured with magnetic resonance imaging methods. Anatomical connectivity in white matter is obtained from measurements of the diffusion tensor. A Monte-Carlo simulation determines the probability that a particle diffuses between two points, with the probability of a jump in a particular direction from a given voxel being based on the local value of the diffusion tensor components. Functional connectivity between grey matter pixels is assessed without recourse to a specific activation paradigm, by calculating the correlation coefficient between random fluctuations in the blood oxygenation level-dependent signal time course in different pixels. The methods are used to examine the anatomical and functional connectivities between crowns of adjacent gyri. A high functional connectivity was found between grey matter pixels, with white matter displaying only very low correlation. A comparison of the measurements of anatomical and functional connectivity found that there is no simple correlation between these measures, except that low values of functional connectivity were not found together with high values of anatomical connectivity. Furthermore pairs of regions situated around the central sulcus indicated a dependence of the two connectivity measures on each other. These results are in accordance with an interpretation that regions which are clearly directly linked by white matter fiber tracts should show high functional connectivity, but that the inverse need not be true as functional connectivity may also be indirectly mediated via more distant grey matter regions.

Algorithms↗

Bilateral connections from ventral group inspiratory neurons to phrenic motoneurons in the rat determined by cross-correlation.

We examined the functional connections from inspiratory neurons in the ventrolateral medulla to phrenic motoneurons in 11 Sprague-Dawley rats with intact vagi anaesthetized with sodium pentobarbital and paralysed with pancuronium bromide. Cross-correlation histograms were computed between the extracellular activity of 70 of these neurons and the discharge of the phrenic nerves; 38 contralateral only, 10 ipsilateral only and 22 bilaterally. A total of 22 peaks were detected in the cross-correlation histograms. These were classified as indicating common activation or synaptic connection according to their latencies to onset, and those suggesting connections as monosynaptic or paucisynaptic according to their half-amplitude widths. Nine peaks suggesting monosynaptic excitation of phrenic motoneurons were detected for 7 ventral group inspiratory neurons; 4 with contralateral connections and not tested for ipsilateral connections, 2 with bilateral connections, and 1 with a monosynaptic contralateral connection and a paucisynaptic ipsilateral connection. Four peaks suggesting paucisynaptic excitation of phrenic motoneurons were detected for 3 ventral group inspiratory neurons; 1 with bilateral connections, 1 with a contralateral connection only, and 1 (previously mentioned) with a paucisynaptic ipsilateral connection and a monosynaptic contralateral excitation. The remaining 9 peaks were classified as due to a common activation of the phrenic motoneurons and the ventral group inspiratory neurons. Cross-correlation histograms were also computed between the left and right phrenic nerve discharges in 5 rats and all displayed central broad peaks indicative of common activation, possibly due to excitation from bilaterally projecting medullary inspiratory neurons. We concluded that there is a substantial bilateral excitation of phrenic motoneurons by inspiratory neurons in the ventral medullary group of the rat.

Animals↗

Functional connectivity in fMRI: A modeling approach for estimation and for relating to local circuits.

Although progress has been made in relating neuronal events to changes in brain metabolism and blood flow, the interpretation of functional neuroimaging data in terms of the underlying brain circuits is still poorly understood. Computational modeling of connection patterns both among and within regions can be helpful in this interpretation. We present a neural network model of the ventral visual pathway and its relevant functional connections. This includes a new learning method that adjusts the magnitude of interregional connections in order to match experimental results of an arbitrary functional magnetic resonance imaging (fMRI) data set. We demonstrate that this method finds the appropriate connection strengths when trained on a model system with known, randomly chosen connection weights. We then use the method for examining fMRI results from a one-back matching task in human subjects, both healthy and those with schizophrenia. The results discovered by the learning method support previous findings of a disconnection between left temporal and frontal cortices in the group with schizophrenia and a concomitant increase of right-sided temporo-frontal connection strengths. We then demonstrate that the disconnection may be explained by reduced local recurrent circuitry in frontal cortex. This method extends currently available methods for estimating functional connectivity from human imaging data by including both local circuits and features of interregional connections, such as topography and sparseness, in addition to total connection strengths. Furthermore, our results suggest how fronto-temporal functional disconnection in schizophrenia can result from reduced local synaptic connections within frontal cortex rather than compromised interregional connections.

Brain↗

Prefrontal connections of the parabelt auditory cortex in macaque monkeys.

In the present study, we determined connections of three newly defined regions of auditory cortex with regions of the frontal lobe, and how two of these regions in the frontal lobe interconnect and connect to other portions of frontal cortex and the temporal lobe in macaque monkeys. We conceptualize auditory cortex as including a core of primary areas, a surrounding belt of auditory areas, a lateral parabelt of two divisions, and adjoining regions of temporal cortex with parabelt connections. Injections of several different fluorescent tracers and wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) were placed in caudal (CPB) and rostral (RPB) divisions of the parabelt, and in cortex of the superior temporal gyrus rostral to the parabelt with parabelt connections (STGr). Injections were also placed in two regions of the frontal lobe that were labeled by a parabelt injection in the same case. The results lead to several major conclusions. First, CPB injections label many neurons in dorsal prearcuate cortex in the region of the frontal eye field and neurons in dorsal prefrontal cortex of the principal sulcus, but few or no neurons in orbitofrontal cortex. Fine-grain label in these same regions as a result of a WGA-HRP injection suggests that the connections are reciprocal. Second, RPB injections label overlapping prearcuate and principal sulcus locations, as well as more rostral cortex of the principal sulcus, and several locations in orbitofrontal cortex. Third, STGr injections label locations in orbitofrontal cortex, some of which overlap those of RPB injections, but not prearcuate or principal sulcus locations. Fourth, injections in prearcuate and principal sulcus locations labeled by a CPB injection labeled neurons in CPB and RPB, with little involvement of the auditory belt and no involvement of the core. In addition, the results indicated that the two frontal lobe regions are densely interconnected. They also connect with largely separate regions of the frontal pole and more medial premotor and dorsal prefrontal cortex, but not with the extensive orbitofrontal region which has RPB and STGr connections. The results suggest that both RPB and CPB provide the major auditory connections with the region related to directing eye movements towards stimuli of interest, and the dorsal prefrontal cortex for working memory. Other auditory connections to these regions of the frontal lobe appear to be minor. RPB has connections with orbitofrontal cortex, important in psychosocial and emotional functions, while STGr primarily connects with orbital and polar prefrontal cortex.

Animals↗

Cardiac connections: the segmental approach to radiologic diagnosis in congenital heart disease.

The segmental approach to the diagnosis and classification of congenital heart disease, which emphasizes the importance of the connections (proximal-to-distal relationships) of cardiac chambers and great vessels, is presented. The radiologic identification of great vessels and cardiac chambers and their connections is described, considering, in turn, three major segments: the atria together with the systemic and pulmonary veins, the ventricles with their atrioventricular valves and the great arteries with their outflow tracts. Cardiac and great vascular connections can be described with greatest clarity by using the atria as the starting point. The atrial situs is defined as solitus, inversus or ambiguus, the great veins connecting to the atria normally or anomalously. The ventricles may be connected to the atria in concordant or discordant fashion or a double inlet ventricle may be present. The ventriculo-arterial connections can be classified as normal, transposition, double outlet right ventricle or double outlet left ventricle. The angiocardiographic techniques and criteria that differentiate these connection disorders and identify the transitional cases between them are discussed and illustrated. A complete diagnosis must indicate not only the connections of the three major segments but also the malformations and abnormalities of spatial position that may be present. Certain associations are of value in predicting the positions and connections of the cardiac chambers and great vessels, making it possible to formulate helpful rules to aid the progress of a diagnostic study. The fallibility of such rules is discussed, emphasizing the need to define connection disorders in terms of the connections rather than in terms of malformations or of abnormalities in spatial position of the individual parts.

Angiocardiography↗