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PubMed2006

Testing effective connectivity changes with structural equation modeling: what does a bad model tell us?

Structural equation modeling (SEM) is a statistical method that can assess changes in effective connectivity across tasks or between groups. In its initial application to neuroimaging data, anatomical connectivity provided the constraints to decompose interregional covariances to estimate effective connections. There have been concerns expressed, however, with the validity of interpreting effective connections for a model that does not adequately fit the data. We sought to address this concern by creating two population networks with different patterns of effective connectivity, extracting three samples sizes (N = 100, 60, 20), and then assessing whether the ability to detect effective connectivity differences depended on absolute model fit. Four scenarios were assessed: (1) elimination of a region showing no task differences; (2) elimination of connections with no task differences; (3) elimination of connections that carried task differences, but could be expressed through alternative indirect routes; (4) elimination of connections that carried task differences, and could not be expressed through indirect routes. We were able to detect task differences in all four cases, despite poor absolute model fit. In scenario 3, total effects captured the overall task differences even though the direct effect was no longer present. In scenario 4, task differences that were included in the model remained, but the missing effect was not expressed. In conclusion, it seems that when independent information (e.g., anatomical connectivity) is used to define the causal structure in SEM, inferences about task- or group-dependent changes are valid regardless of absolute model fit.

Algorithms↗
PubMed2007

Comparison of different cortical connectivity estimators for high-resolution EEG recordings.

The aim of this work is to characterize quantitatively the performance of a body of techniques in the frequency domain for the estimation of cortical connectivity from high-resolution EEG recordings in different operative conditions commonly encountered in practice. Connectivity pattern estimators investigated are the Directed Transfer Function (DTF), its modification known as direct DTF (dDTF) and the Partial Directed Coherence (PDC). Predefined patterns of cortical connectivity were simulated and then retrieved by the application of the DTF, dDTF, and PDC methods. Signal-to-noise ratio (SNR) and length (LENGTH) of EEG epochs were studied as factors affecting the reconstruction of the imposed connectivity patterns. Reconstruction quality and error rate in estimated connectivity patterns were evaluated by means of some indexes of quality for the reconstructed connectivity pattern. The error functions were statistically analyzed with analysis of variance (ANOVA). The whole methodology was then applied to high-resolution EEG data recorded during the well-known Stroop paradigm. Simulations indicated that all three methods correctly estimated the simulated connectivity patterns under reasonable conditions. However, performance of the methods differed somewhat as a function of SNR and LENGTH factors. The methods were generally equivalent when applied to the Stroop data. In general, the amount of available EEG affected the accuracy of connectivity pattern estimations. Analysis of 27 s of nonconsecutive recordings with an SNR of 3 or more ensured that the connectivity pattern could be accurately recovered with an error below 7% for the PDC and 5% for the DTF. In conclusion, functional connectivity patterns of cortical activity can be effectively estimated under general conditions met in most EEG recordings by combining high-resolution EEG techniques, linear inverse estimation of the cortical activity, and frequency domain multivariate methods such as PDC, DTF, and dDTF.

Analysis of Variance↗
PubMed2007

Impaired functional connectivity at EEG alpha and theta frequency bands in major depression.

Recent reports on functional brain imaging in major depression have lead to an assumption that observed psychopathology might be related to an altered brain functional connectivity. Our hypothesis was that an increase in brain functional connectivity occurs in major depression. As a measure of functional connectivity, the electroencephalogram (EEG) structural synchrony approach was used in 12 medication-free depressive outpatients and 10 control subjects. Differences in the number and strength of structurally synchronized EEG patterns were compared between groups. In depressive patients the number and strength of short cortex functional connections were significantly larger for the left than for the right hemisphere, while the number and strength of long functional connections were significantly larger for the right than for the left hemisphere. Some of the functional connections were positively correlated with the severity of depression, thus being predictive. These were short-range anterior, posterior, and left hemisphere functional connections for the alpha frequency band and short-range anterior functional connections for the theta frequency band. The topology of the most representative functional connections among all patients with major depression indicated that the right anterior and left posterior brain parts may discriminate depressive patients from healthy controls. The obtained data support our hypothesis that there is an increase in brain functional connectivity in major depression. This finding was interpreted within the semantic framework, where different specialization of left (monosemantic context) and right (polysemantic context) hemispheres is functionally insufficient in patients with depression.

Adult↗
PubMed1999

Forebrain connections of medial agranular cortex in the prairie vole, Microtus ochrogaster.

Fluorescent axonal tracers were used to investigate the connections of medial agranular cortex (frontal area 2, Fr2) in male prairie voles. The rostral and caudal portions of Fr2 (rFr2 and cFr2) have distinct but partially overlapping patterns of connections. Thalamic labeling after cFr2 injections was present in anteromedial nucleus (AM), ventrolateral nucleus (VL), lateral segment, mediodorsal nucleus (MDl), centrolateral nucleus (CL), ventromedial nucleus (VM), posterior nucleus (Po) and lateral posterior nucleus (LP). A band of labeled cells involving CL, central medial nucleus (CM) and rhomboid nucleus (Rh) formed a halo around the periphery of submedial (gelatinosus) nucleus (Sm). Within cFr2 there is a rostrocaudal gradient whereby projections from VL and MDl become progressively sparser caudally, whereas those from LP and Po become denser. Rostral Fr2 receives afferents from a similar group of thalamic nuclei, but has denser innervation from VL and MDl, lacks afferents from LP, and receives less input from nuclei around the periphery of Sm. Caudal Fr2 has extensive cortical connections including orbital cortex, rostral Fr2, Fr1, caudal parietal area 1 (Par1), parietal area 2 (Par2), and posterior parietal, retrosplenial and visual areas. Rostral Fr2 has similar connections with areas Fr1, Par1 and Par2; orbital connections focused in ventrolateral orbital cortex (VLO); connections with caudal Fr2; greatly reduced connections with posterior parietal cortex and the visual areas; and no connections with retrosplenial cortex. The axons linking rFr2 and cFr2 with each other and with other cortical areas travel predominately in the deep gray matter of layers VI and VII rather than in the white matter. Projections to the dorsal striatum from rFr2 are widespread in the head of the caudate, become progressively restricted to a dorsocentral focus more caudally, and disappear by the level of the anterior commissure. The projections from cFr2 are largely restricted to a focal dorsocentral region of the striatum and to the dorsolateral margin of the caudatoputamen. In comparison to area Fr2, the laterally adjacent area Fr1 has thalamic and cortical connections which are markedly restricted. Area Fr1 receives thalamic input from nuclei VL, anteroventral nucleus (AV), CL and Po, but none from mediodorsal nucleus (MD) or LP, and its input from VM is reduced. Cortical afferents to Fr1 originate from areas Fr2, caudal Par1 and Par2. Medial agranular cortex of prairie voles has a pattern of connections largely similar to that seen in rats, suggesting that area Fr2 in prairie voles is part of a cortical network that may mediate complex behaviors involving spatial orientation.

Animals↗
PubMed2006

Use of a neural mass model for the analysis of effective connectivity among cortical regions based on high resolution EEG recordings.

Assessment of brain connectivity among different brain areas during cognitive or motor tasks is a crucial problem in neuroscience today. Aim of this work is to use a neural mass model to assess the effect of various connectivity patterns in cortical electroencephalogram (EEG) power spectral density, and investigate the possibility to derive connectivity circuits from EEG data. To this end, a model of an individual region of interest (ROI) has been built as the parallel arrangement of three populations, each described as in Wendling et al. (Eur J Neurosci 15:1499-1508, 2002). Connectivity among ROIs includes three parameters, which specify the strength of connection in the different frequency bands. The following main steps have been followed: (1) we analyzed how the power spectral density (PSD) is significantly modified by the kind of coupling hypothesized among the ROIs; (2) with the model, and using an automatic fitting procedure, we looked for a simple connectivity circuit able to reproduce PSD of cortical EEG in three ROIs during a finger-movement task. The estimated parameters represent the strength of connections among the ROIs in the different frequency bands. Cortical EEGs were computed with an inverse propagation algorithm, starting from measurement performed with 96 electrodes on the scalp. The present study suggests that the model can be used as a simulation tool, able to mimic the effect of connectivity on EEG. Moreover, it can be used to look for simple connectivity circuits, able to explain the main features of observed cortical PSD. These results may open new prospectives in the use of neurophysiological models, instead of empirical models, to assess effective connectivity from neuroimaging information.

Brain Mapping↗
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↗
PubMedDate not supplied

Quantification of connectivity in cancellous bone, with special emphasis on 3-D reconstructions.

The connectivity of cancellous bone attracts increasing attention, as it has been hypothesized that a primary reason for decreasing strength and stiffness in osteoporosis is caused by a loss of trabecular elements and consequently a loss in connectivity. The Euler characteristic has in a few previous articles been used to express cancellous bone connectivity, but there are severe problems in using the Euler characteristic uncritically. The Euler characteristic of a three-dimensional structure is a topological invariant, which reports the number of particles of a structure plus the number of enclosed cavities minus the connectivity. As such, one must know the number of components and the number of enclosed cavities in order to use the Euler characteristic as an expression of connectivity. Another difficulty of using the Euler characteristic is that due to edge effects the Euler characteristic of an excised specimen provides a biased estimate of the Euler characteristic of the region from which the specimen was taken. In this article the intuitive concept of connectivity is given a precise mathematical definition, and a basic topological method for quantifying the connectivity of cancellous bone is presented. The method uses the Euler characteristic, but the above-mentioned problems are controlled. The development of the method and the practical implementation is based on a set of topological notes. It must be stressed that the method is free from assumptions concerning trabecular architecture, and that the method is unbiased. This is in contrast to previously presented methods. The unbiased and model-free method is used on a series of 3-D reconstructions of cancellous bone specimens, and it is demonstrated that the connectivity of cancellous bone is not simply related to volume fraction (density), and that biased and model-based 2-D methods aimed at determining connectivity do not have any general relationship to connectivity in cancellous bone.

Bone Density↗
PubMed2005

Principled and statistical connections in common sense conception.

Nominal concepts represent things as tokens of types. We report six experiments that investigate the nature of the relations we represent between the type of thing something is (e.g. DOG) and its other properties. The experiments provide evidence that we represent principled connections between the type of thing something is (e.g. DOG) and some of its properties (k-properties; e.g. having four legs for dogs), but not other properties (t-properties; e.g. being brown for dogs). Principled connections are different from logical, statistical, and causal connections. Principled connections, (i) license the expectation that tokens of the type will generally possess the k-property, (ii) license explanation of the presence of k-properties in tokens of a type by reference to the type of thing it is, and (iii) license normative expectations concerning the presence of the k-property in tokens of the type. The experiments provide evidence for all three of these aspects of principled connections. The experiments also demonstrate that principled connections must be distinguished from merely strong statistical connections. We suggest that principled connections are one of the fundamental types of relations (in addition to logical, statistical, and causal relations) in terms of which our conceptual knowledge is structured. We argue that principled connections reveal a formal mode of understanding and explanation. This mode of understanding complements other modes of understanding that have been studied within the theory-based approach to conceptual representation. Finally, we suggest that kind representations are distinguished from representations of mere types by the representation of principled connections to k-properties.

Analysis of Variance↗
PubMed2004

Estimation of the effective and functional human cortical connectivity with structural equation modeling and directed transfer function applied to high-resolution EEG.

Different brain imaging devices are presently available to provide images of the human functional cortical activity, based on hemodynamic, metabolic or electromagnetic measurements. However, static images of brain regions activated during particular tasks do not convey the information of how these regions are interconnected. The concept of brain connectivity plays a central role in the neuroscience, and different definitions of connectivity, functional and effective, have been adopted in literature. While the functional connectivity is defined as the temporal coherence among the activities of different brain areas, the effective connectivity is defined as the simplest brain circuit that would produce the same temporal relationship as observed experimentally among cortical sites. The structural equation modeling (SEM) is the most used method to estimate effective connectivity in neuroscience, and its typical application is on data related to brain hemodynamic behavior tested by functional magnetic resonance imaging (fMRI), whereas the directed transfer function (DTF) method is a frequency-domain approach based on both a multivariate autoregressive (MVAR) modeling of time series and on the concept of Granger causality. This study presents advanced methods for the estimation of cortical connectivity by applying SEM and DTF on the cortical signals estimated from high-resolution electroencephalography (EEG) recordings, since these signals exhibit a higher spatial resolution than conventional cerebral electromagnetic measures. To estimate correctly the cortical signals, we used a subject's multicompartment head model (scalp, skull, dura mater, cortex) constructed from individual MRI, a distributed source model and a regularized linear inverse source estimates of cortical current density. Before the application of SEM and DTF methodology to the cortical waveforms estimated from high-resolution EEG data, we performed a simulation study, in which different main factors (signal-to-noise ratio, SNR, and simulated cortical activity duration, LENGTH) were systematically manipulated in the generation of test signals, and the errors in the estimated connectivity were evaluated by the analysis of variance (ANOVA). The statistical analysis returned that during simulations, both SEM and DTF estimators were able to correctly estimate the imposed connectivity patterns under reasonable operative conditions, that is, when data exhibit an SNR of at least 3 and a LENGTH of at least 75 s of nonconsecutive EEG recordings at 64 Hz of sampling rate. Hence, effective and functional connectivity patterns of cortical activity can be effectively estimated under general conditions met in any practical EEG recordings, by combining high-resolution EEG techniques and linear inverse estimation with SEM or DTF methods. We conclude that the estimation of cortical connectivity can be performed not only with hemodynamic measurements, but also with EEG signals treated with advanced computational techniques.

Adult↗
PubMed1984

The univentricular atrioventricular connection: getting to the root of a thorny problem.

Most hearts described as "single ventricle" or "univentricular heart" possess 2 ventricular chambers, even though 1 is usually described as an "outlet chamber." This stems from the wide acceptance that the criterion of a single ventricle is the presence of a double-inlet atrioventricular (AV) connection. In recent years, using this criterion, an attempt was made to show how hearts with double-inlet right ventricle or "classic tricuspid atresia" were (in terms of ventricular morphology) just as univentricular as "single ventricle with outlet chamber." This attempt brought still further confusion to an already contentious topic. The root of the problem clearly is the injudicious use of the adjective "single" or "univentricular." Conventionally it is used to describe the ventricular mass. In most hearts with double-inlet connection it is not the ventricles that are univentricular; it is the AV connection. The concept of a univentricular AV connection, then, appropriately groups hearts with double-inlet along with those having absence of 1 AV connection. It distinguishes this entire group from those other hearts with biventricular AV connections (each atrium connected to its own ventricle). The term "univentricular AV connection" is thus a collective one for all those hearts in which the atria connect to only 1 ventricle. Confusion will be completely removed if individual hearts are described for what they are in terms of AV connection and ventricular morphology (for example, double-inlet left ventricle with rudimentary right ventricle rather than single ventricle with outlet chamber).

Heart Atria↗
PubMed1993

Relationship between intrinsic connections and functional architecture revealed by optical imaging and in vivo targeted biocytin injections in primate striate cortex.

In primate primary visual cortex, neurons sharing similar response properties are clustered together forming functional domains that appear as a mosaic of patches or bands, often traversing the entire cortical depth from the pia to the white matter. Similarly, each cortical site connects laterally through an extensive network of intrinsic projections that are organized in multiple clusters (patches) and reach distances of up to a few millimeters. The relationship between the functional domains and these laterally connected patches has remained a controversial issue despite intensive research efforts. To investigate this relationship, we obtained high-resolution functional maps of the cortical architecture by in vivo optical imaging. Subsequently, extracellular injections of the sensitive anterograde tracer biocytin were targeted into selected functional domains. Within the ocular dominance system, we found that long-range intrinsic connections tended to link the monocular regions of same-eye ocular dominance columns. Furthermore, we discovered that binocular domains formed a separate set of connections in area V1; binocular regions were selectively connected among themselves but were not connected to strictly monocular regions, suggesting that they constitute a distinct columnar system. In the other subsystem subserving orientation preference, patches of intrinsic connections tended to link domains sharing similar orientation preferences. Analyses of the precision of these connections indicated that in both functional subsystems, < 15% of the connections were between domains having orthogonal response properties. However, their selectivity was limited; approximately 30% +/- 10% of the interconnected patches contained neurons exhibiting orientation tuning that differed from those found at the injection sites by at least 45 degrees. At short range (up to 400 microns from the injection site), this casual trend seemed markedly accentuated; the local, synaptic-rich axonal and dendritic arbors crossed freely through columns of diverse functional properties. These complex sets of connections can endow cortical neurons with a rich diversity of response properties and broad tuning.

Animals↗
PubMed2000

The anatomical connections of the macaque monkey orbitofrontal cortex. A review.

The orbitofrontal cortex (OfC) is a heterogeneous prefrontal sector selectively connected with a wide constellation of other prefrontal, limbic, sensory and premotor areas. Among the limbic cortical connections, the ones with the hippocampus and parahippocampal cortex are particularly salient. Sensory cortices connected with the OfC include areas involved in olfactory, gustatory, somatosensory, auditory and visual processing. Subcortical structures with prominent OfC connections include the amygdala, numerous thalamic nuclei, the striatum, hypothalamus, periaqueductal gray matter, and biochemically specific cell groups in the basal forebrain and brainstem. Architectonic and connectional evidence supports parcellation of the OfC. The rostrally placed isocortical sector is mainly connected with isocortical areas, including sensory areas of the auditory, somatic and visual modalities, whereas the caudal non-isocortical sector is principally connected with non-isocortical areas, and, in the sensory domain, with olfactory and gustatory areas. The connections of the isocortical and non-isocortical orbital sectors with the amygdala, thalamus, striatum, hypothalamus and periaqueductal gray matter are also specific. The medial sector of the OfC is selectively connected with the hippocampus, posterior parahippocampal cortex, posterior cingulate and retrosplenial areas, and area prostriata, while the lateral orbitofrontal sector is the most heavily connected with sensory areas of the gustatory, somatic and visual modalities, with premotor regions, and with the amygdala.

Animals↗
PubMedDate not supplied

Connections of inferior temporal areas TEO and TE with parietal and frontal cortex in macaque monkeys.

Inferior temporal cortex is perhaps the highest visual processing area and much anatomical work has focused on its connections with other visual areas in temporal and occipital cortex. Here we report connections of inferior temporal cortex with regions in the frontal and parietal lobes. Inferior temporal areas TEO and TE were injected with WGA-HRP and 3H-AA, respectively, or vice versa, in 1-week-old infant and 3-4-year-old adult monkeys (Macaca mulatta). The results indicated that whereas TEO has more extensive connections with parietal areas, TE has more extensive connections with prefrontal areas. Thus, in the intraparietal sulcus, area TEO is connected with areas LIPd, LIPv, and V3A, and with the as yet undefined region between LIPv and V3A, whereas the connections of TE are predominantly with LIPd, and to a lesser extent with LIPv. In the prefrontal cortex, area TE is connected with areas 8 and 45 in the inferior limb of the anterior bank of the arcuate sulcus, with area 12 on the inferior prefrontal convexity, and with areas 11 and 13 on the orbital surface. By contrast, the connections of area TEO are limited to areas 8, 45, and 12. Furthermore, within prefrontal cortex, the projections from areas TEO and TE terminate in different layers in areas 8 and 45, such that those from TEO terminate in all layers, whereas those from TEO terminate in layers I and V/VI only. In contrast to the connections of areas TEO and TE with various medial temporal-lobe and subcortical structures, which are immature in infant monkeys (Webster et al., 1991, 1993b), the connections with parietal and prefrontal areas appear adult-like as early as 1 week of age.

Aging↗
PubMedDate not supplied

The connectional organization of the cortico-thalamic system of the cat.

Data on connections between the areas of the cerebral cortex and nuclei of the thalamus are too complicated to analyse with naked intuition. Indeed, the complexity of connection data is one of the major challenges facing neuroanatomy. Recently, systematic methods have been developed and applied to the analysis of the connectivity in the cerebral cortex. These approaches have shed light on the gross organization of the cortical network, have made it possible to test systematically theories of cortical organization, and have guided new electrophysiological studies. This paper extends the approach to investigate the organization of the entire cortico-thalamic network. An extensive collation of connection tracing studies revealed approximately 1500 extrinsic connections between the cortical areas and thalamic nuclei of the cat cerebral hemisphere. Around 850 connections linked 53 cortical areas with each other, and around 650 connections linked the cortical areas with 42 thalamic nuclei. Non-metric multidimensional scaling, optimal set analysis and non-parametric cluster analysis were used to study global connectivity and the 'place' of individual structures within the overall scheme. Thalamic nuclei and cortical areas were in intimate connectional association. Connectivity defined four major thalamo-cortical systems. These included three broadly hierarchical sensory or sensory/motor systems (visual and auditory systems and a single system containing both somatosensory and motor structures). The highest stations of these sensory/motor systems were associated with a fourth processing system composed of prefrontal, cingulate, insular and parahippocampal cortex and associated thalamic nuclei (the 'fronto-limbic system'). The association between fronto-limbic and somato-motor systems was particularly close.

Animals↗
PubMed2005

Connection patterns distinguish 3 regions of human parietal cortex.

Three regions of the macaque inferior parietal lobule and adjacent lateral intraparietal sulcus (IPS) are distinguished by the relative strengths of their connections with the superior colliculus, parahippocampal gyrus, and ventral premotor cortex. It was hypothesized that connectivity information could therefore be used to identify similar areas in the human parietal cortex using diffusion-weighted imaging and probabilistic tractography. Unusually, the subcortical routes of the 3 projections have been reported in the macaque, so it was possible to compare not only the terminations of connections but also their course. The medial IPS had the highest probability of connection with the superior colliculus. The projection pathway resembled that connecting parietal cortex and superior colliculus in the macaque. The posterior angular gyrus and the adjacent superior occipital gyrus had a high probability of connection with the parahippocampal gyrus. The projection pathway resembled the macaque inferior longitudinal fascicle, which connects these areas. The ventral premotor cortex had a high probability of connection with the supramarginal gyrus and anterior IPS. The connection was mediated by the third branch of the superior longitudinal fascicle, which interconnects similar regions in the macaque. Human parietal areas have anatomical connections resembling those of functionally related macaque parietal areas.

Adult↗
PubMed1993

Delayed effects of radiofrequency energy on accessory atrioventricular connections.

The purpose of this study was to determine the incidence and characteristics of delayed effects on conduction through accessory atrioventricular (AV) connections after apparently successful attempts at radiofrequency catheter ablation. Among 450 patients who had 471 accessory AV connections, the ablation procedure was unsuccessful in 26 patients (6%), as defined by persistent conduction through the accessory AV connection 60 minutes after the final application of radiofrequency energy. In 6/26 unsuccessfully treated patient (24%), conduction through the accessory AV connection disappeared on a delayed basis. At least once during the ablation procedure, conduction through each of these 6 accessory AV connections was transiently eliminated for 10 seconds to 60 minutes. Five of these accessory AV connections were left-sided and one was posteroseptal; one was concealed and five were manifest. Conduction through the accessory AV connection disappeared on a delayed basis 6-18 hours after the ablation procedure in 4 patients, and at some time between 1-5 days or 1-60 days in the other 2 patients. In 2 patients, the delayed effect was only transient, while in 4 patients, conduction through the accessory AV connections did not return during 5-23 months of follow-up. In conclusion, up to 15% of patients who undergo an apparently unsuccessful attempt at radiofrequency ablation of an accessory AV connection may later manifest a permanent loss of conduction through the accessory AV connection.

Adult↗
PubMed1997

Physiology and anatomy of synaptic connections between thick tufted pyramidal neurones in the developing rat neocortex.

1. Dual voltage recordings were made from pairs of adjacent, synaptically connected thick tufted layer 5 pyramidal neurones in brain slices of young rat (14-16 days) somatosensory cortex to examine the physiological properties of unitary EPSPs. Pre- and postsynaptic neurones were filled with biocytin and examined in the light and electron microscope to quantify the morphology of axonal and dendritic arbors and the number and location of synaptic contacts on the target neurone. 2. In 138 synaptic connections between pairs of pyramidal neurones 96 (70%) were unidirectional and 42 (30%) were bidirectional. The probability of finding a synaptic connection in dual recordings was 0.1. Unitary EPSPs evoked by a single presynaptic action potential (AP) had a mean peak amplitude ranging from 0.15 to 5.5 mV in different connections with a mean of 1.3 +/- 1.1 mV, a latency of 1.7 +/- 0.9 ms, a 20-80% rise time of 2.9 +/- 2.3 ms and a decay time constant of 40 +/- 18 ms at 32-24 degrees C and -60 +/- 2 mV membrane potential. 3. Peak amplitudes of unitary EPSPs fluctuated randomly from trial to trial. The coefficient of variation (c.v.) of the unitary EPSP amplitudes ranged from 0.13 to 2.8 in different synaptic connections (mean, 0.52; median, 0.41). The percentage of failures of single APs to evoke a unitary EPSP ranged from 0 to 73% (mean, 14%; median, 7%). Both c.v. and percentage of failures decreased with increasing mean EPSP amplitude. 4. Postsynaptic glutamate receptors which mediate unitary EPSPs at -60 mV were predominantly of the L-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor type. Receptors of the N-methyl-D-aspartate (NMDA) type contributed only a small fraction (< 20%) to the voltage-time integral of the unitary EPSP at -60 mV, but their contribution increased at more positive membrane potentials. 5. Branching patterns of dendrites and axon collaterals of forty-five synaptically connected neurones, when examined in the light microscope, indicated that the axonal and dendritic anatomy of both projecting and target neurones and of uni- and bidirectionally connected neurones was uniform. 6. The number of potential synaptic contacts formed by a presynaptic neurone on a target neurone varied between four and eight (mean, 5.5 +/- 1.1 contacts; n = 19 connections). Synaptic contacts were preferentially located on basal dendrites (63%, 82 +/- 35 microns from the soma, n = 67) and apical oblique dendrites (27%, 145 +/- 59 microns, n = 29), and 35% of all contacts were located on tertiary basal dendritic branches. The mean geometric distances (from the soma) of the contacts of a connection varied between 80 and 585 microns (mean, 147 microns; median, 105 microns). The correlation between EPSP amplitude and the number of morphologically determined synaptic contacts or the mean geometric distances from the soma was only weak (correlation coefficients were 0.2 and 0.26, respectively). 7. Compartmental models constructed from camera lucida drawings of eight target neurones showed that synaptic contacts were located at mean electrotonic distances between 0.07 and 0.33 from the soma (mean, 0.13). Simulations of unitary EPSPs, assuming quantal conductance changes with fast rise time and short duration, indicated that amplitudes of quantal EPSPs at the soma were attenuated, on average, to < 10% of dendritic EPSPs and varied in amplitude up to 10-fold depending on the dendritic location of synaptic contacts. The inferred quantal peak conductance increase varied between 1.5 and 5.5 nS (mean, 3 nS). 8. The combined physiological and morphological measurements in conjunction with EPSP simulations indicated that the 20-fold range in efficacy of the synaptic connections between thick tufted pyramidal neurones, which have their synaptic contacts preferentially located on basal and apical oblique dendrites, was due to differences in transmitter release probability of the projecting neurones and, to a lesser extent, to differenc

Action Potentials↗
PubMed1985

Cross sectional echocardiographic diagnosis of total anomalous pulmonary venous connection.

Total anomalous pulmonary venous connection can be diagnosed by cross sectional echocardiography. Information is, however, lacking concerning the diagnostic accuracy of this imaging method and any factors which may influence it. To predict the pulmonary venous connection 463 patients with congenital heart disease who had angiographic confirmation were prospectively examined. Total anomalous pulmonary venous connection was present in 34 (7%) patients and correctly detected in 33 (97% sensitivity). There were two false positive results (99% specificity). All 23 patients with atrial situs solitus with or without associated congenital heart defects were correctly detected. One false negative result occurred in a patient with right atrial isomerism and complex congenital heart disease with decreased pulmonary blood flow. Diagnosis of the type of total anomalous pulmonary venous connection, including the site and other anatomical details, was analysed and was correct in 24 of 34 (71%) patients. Errors included incorrect prediction of the site of total anomalous pulmonary venous connection in five patients with right atrial isomerism, atrioventricular canal defect, and pulmonary atresia, details of confluence interconnection in three of four patients with the mixed type of connection, undiagnosed pulmonary venous obstruction in three of the patients with right atrial isomerism, and failure to predict common pulmonary vein atresia in one patient. Factors which were related to incorrect echocardiographic diagnosis were abnormal atrial situs, mixed total anomalous pulmonary venous connection, and associated congenital cardiac defects, whereas age, weight, sex, clinical condition, and time during the study were not related. It is concluded that cross sectional echocardiography can be used to diagnose accurately total anomalous pulmonary venous connection. This method can be the definitive imaging and diagnostic method in symptomatic infants with total anomalous pulmonary venous connection who have atrial situs solitus, unifocal pulmonary venous connection, and no evidence of other major congenital cardiac defect.

Adolescent↗