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PubMed2005

Evaluating frequency-wise directed connectivity of BOLD signals applying relative power contribution with the linear multivariate time-series models.

In this article, we propose a statistical method to evaluate directed interactions of functional magnetic-resonance imaging (fMRI) data. The multivariate autoregressive (MAR) model was combined with the relative power contribution (RPC) in this analysis. The MAR model was fitted to the data to specify the direction of connections, and the RPC quantifies the strength of connections. As the RPC is computed in the frequency domain, we can evaluate the connectivity for each frequency component. From this, we can establish whether the specified connections represent low- or high-frequency connectivity, which cannot be examined solely using the estimated MAR coefficients. We applied this analysis method to fMRI data obtained during visual motion tasks, confirming previous reports of bottom-up connectivity around the frequency corresponding to the block experimental design. Furthermore, we used the MAR model with exogenous variables (MARX) to extend our understanding of these data, and to show how the input to V1 transfers to higher cortical areas.

Cerebral Cortex↗
PubMed2005

Reduced functional connectivity between V1 and inferior frontal cortex associated with visuomotor performance in autism.

Some recent evidence has suggested abnormalities of the dorsal stream and possibly the mirror neuron system in autism, which may be responsible for impairments of joint attention, imitation, and secondarily for language delays. The current study investigates functional connectivity along the dorsal stream in autism, examining interregional blood oxygenation level dependent (BOLD) signal cross-correlation during visuomotor coordination. Eight high-functioning autistic men and eight handedness and age-matched controls were included. Visually prompted button presses were performed with the preferred hand. For each subject, functional connectivity was computed in terms of BOLD signal correlation with the mean time series in bilateral visual area 17. Our hypothesis of reduced dorsal stream connectivity in autism was only in part confirmed. Functional connectivity with superior parietal areas was not significantly reduced. However, the autism group showed significantly reduced connectivity with bilateral inferior frontal area 44, which is compatible with the hypothesis of mirror neuron defects in autism. More generally, our findings suggest that dorsal stream connectivity in autism may not be fully functional.

Adolescent↗
PubMed2005

A Bayesian approach to modeling dynamic effective connectivity with fMRI data.

A state-space modeling approach for examining dynamic relationship between multiple brain regions was proposed in Ho, Ombao and Shumway (Ho, M.R., Ombao, H., Shumway, R., 2005. A State-Space Approach to Modelling Brain Dynamics to Appear in Statistica Sinica). Their approach assumed that the quantity representing the influence of one neuronal system over another, or effective connectivity, is time-invariant. However, more and more empirical evidence suggests that the connectivity between brain areas may be dynamic which calls for temporal modeling of effective connectivity. A Bayesian approach is proposed to solve this problem in this paper. Our approach first decomposes the observed time series into measurement error and the BOLD (blood oxygenation level-dependent) signals. To capture the complexities of the dynamic processes in the brain, region-specific activations are subsequently modeled, as a linear function of the BOLD signals history at other brain regions. The coefficients in these linear functions represent effective connectivity between the regions under consideration. They are further assumed to follow a random walk process so to characterize the dynamic nature of brain connectivity. We also consider the temporal dependence that may be present in the measurement errors. ML-II method (Berger, J.O., 1985. Statistical Decision Theory and Bayesian Analysis (2nd ed.). Springer, New York) was employed to estimate the hyperparameters in the model and Bayes factor was used to compare among competing models. Statistical inference of the effective connectivity coefficients was based on their posterior distributions and the corresponding Bayesian credible regions (Carlin, B.P., Louis, T.A., 2000. Bayes and Empirical Bayes Methods for Data Analysis (2nd ed.). Chapman and Hall, Boca Raton). The proposed method was applied to a functional magnetic resonance imaging data set and results support the theory of attentional control network and demonstrate that this network is dynamic in nature.

Attention↗
PubMed2006

Thalamo-cortical connectivity in children born preterm mapped using probabilistic magnetic resonance tractography.

Our aim was to investigate the feasibility of studying white matter tracts and connections between the thalamus and the cortex in 2-year-old infants who were born preterm by probabilistic magnetic resonance (MR) tractography. Using this approach, we were able to visualize and quantify connectivity distributions in a number of white matter tracts, including the corticospinal tracts, optic radiations, fibers of the genu and splenium of the corpus callosum, superior longitudinal fasciculus and inferior fronto-occipital fasciculus, and to map the distribution within thalamus of fibers connecting to specific cortical regions. In eleven infants with no MR evidence of focal cerebral lesions and appropriate neurodevelopment as shown by general quotient (GQ) scores above 100, we mapped cortical connections to the thalamus that appeared similar to those reported in adults. However, in a proof-of-principle experiment, we examined one further child with marked white matter abnormalities and found that the volume and pattern of thalamo-cortical connections were severely disrupted. This technique promises to be a useful tool for assessing connectivity in the developing brain and in infants with lesions.

Cerebral Cortex↗
PubMed2006

Mechanisms of hemispheric specialization: insights from analyses of connectivity.

Traditionally, anatomical and physiological descriptions of hemispheric specialization have focused on hemispheric asymmetries of local brain structure or local functional properties, respectively. This article reviews the current state of an alternative approach that aims at unraveling the causes and functional principles of hemispheric specialization in terms of asymmetries in connectivity. Starting with an overview of the historical origins of the concept of lateralization, we briefly review recent evidence from anatomical and developmental studies that asymmetries in structural connectivity may be a critical factor shaping hemispheric specialization. These differences in anatomical connectivity, which are found both at the intra- and inter-regional level, are likely to form the structural substrate of different functional principles of information processing in the two hemispheres. The main goal of this article is to describe how these functional principles can be characterized using functional neuroimaging in combination with models of functional and effective connectivity. We discuss the methodology of established models of connectivity which are applicable to data from positron emission tomography and functional magnetic resonance imaging and review published studies that have applied these approaches to characterize asymmetries of connectivity during lateralized tasks. Adopting a model-based approach enables functional imaging to proceed from mere descriptions of asymmetric activation patterns to mechanistic accounts of how these asymmetries are caused.

Animals↗
PubMed2007

Connections of the caudal anterior cingulate cortex in rabbit: neural circuitry participating in the acquisition of trace eyeblink conditioning.

The caudal anterior cingulate cortex (cAC) is an essential component of the circuitry involved in acquisition of forebrain-dependent trace eyeblink conditioning. Lesions of the cAC prevent trace eyeblink conditioning [Weible AP, McEchron MD, Disterhoft JF (2000) Cortical involvement in acquisition and extinction of trace eyeblink conditioning. Behav Neurosci 114(6):1058-1067]. The patterns of activation of cAC neurons recorded in vivo suggest an attentional role for this structure early in training [Weible AP, Weiss C, Disterhoft JF (2003) Activity profiles of single neurons in caudal anterior cingulate cortex during trace eyeblink conditioning in the rabbit. J Neurophysiol 90(2):599-612]. The goal of the present study was to identify connections of the portion of the rabbit cAC previously demonstrated to be involved in trace eyeblink conditioning, using the neuronal tract tracer wheat germ agglutinin conjugated to horseradish peroxidase, to better understand how the cAC contributes to the process of associative learning. Reciprocal connections with the claustrum provide a route for the transfer of sensory information between the cAC and neocortical and allocortical regions also involved in learning. Connections with components of the basal forebrain cholinergic system are described, with relevance to the proposed attentional role of the cAC. Reciprocal and unidirectional connections were in evidence in multiple thalamic regions, including the medial dorsal nucleus, which have been implicated in a variety of conditioning paradigms. Anterograde connections with the caudate and lateral pontine nuclei provide access to forebrain motor and brainstem sensory circuitry, respectively. The relevance of these connections to acquisition of the trace conditioned reflex is discussed.

Animals↗
PubMed2002

Total cavopulmonary connection with an extracardiac conduit: experience with 100 patients.

BACKGROUND: In the Fontan procedures total cavopulmonary connection with an extracardiac conduit is a concern. The potential benefits of an extracardiac conduit may be the avoidance of postoperative supraventricular arrhythmias over the long-term, hemodynamic benefits due to laminar flow, possibility of completion without anoxic arrest, and applicability to anomalous systemic or pulmonary venous return, or both anomalous systemic and pulmonary venous return. We demonstrate early to midterm results of total cavopulmonary connection with an extracardiac conduit. METHODS: Between March 1994 and February 2000, a total of 100 patients underwent total cavopulmonary connection with an extracardiac conduit. In 27 patients, who underwent a single stage total cavopulmonary connection operation, 7 were done without palliation. Seventy-three patients had undergone a bidirectional Glenn shunt before completion of the total cavopulmonary connection. We used an expanded polytetrafluoroethylene tube graft as the extracardiac conduit. RESULTS: Cardiopulmonary bypass time was 133.2+/-55.2 minutes. Myocardial ischemic time was 38.5+/-23.2 minutes in 40 patients who needed cardioplegic cardiac arrest for intracardiac procedures. Intraoperative fenestration was done in only 1 patient. There were no operative deaths. During follow-up of 37.3 months, there were 5 late deaths. When compared with the patients treated by the lateral tunnel technique in our institute, there was no significant difference in actuarial survival rate, but the event free rate of the extracardiac conduit group was significantly superior to the lateral tunnel group. CONCLUSIONS: Total cavopulmonary connection with the extracardiac conduit produced good results in short to midterm follow-up.

Adolescent↗
PubMed1999

Damus-Kaye-Stansel connections in children with previously transected pulmonary arteries.

BACKGROUND: In patients with a univentricular arteriovenous connection, transection of the main pulmonary artery may be performed as part of a bidirectional cavopulmonary shunt or Fontan procedure. The proximal stump of the pulmonary artery may remain in the systemic circulation. In cases with a discordant ventriculoarterial connection, subsequent restriction of the bulboventricular foramen may lead to subaortic stenosis. The subaortic stenosis can be corrected in some patients by directing the systemic flow through a combined nonobstructed aortopulmonary outlet, as in the Damus-Kaye-Stansel connection. Previous closure of the pulmonary artery has been considered by some investigators to be a relative contraindication to the Damus-Kaye-Stansel procedure, unless an allograft root can be added to the circuit after excision of the closed pulmonary stump. METHODS: Three patients with previously transected pulmonary arteries underwent a modified Damus-Kaye-Stansel connection using the native pulmonary valve and the proximal pulmonary artery stump. RESULTS: The native pulmonary valves have functioned well despite thrombus formation in the proximal stump in 2 patients before Damus conversion. All 3 patients are alive and well after 108, 19, and 3 months, with competent nonobstructed ventriculoarterial connections. CONCLUSIONS: If transection and closure of the pulmonary artery as part of a previous palliation has spared the pulmonary valve, then the native pulmonary outlet might be used for a safe Damus-Kaye-Stansel connection.

Child↗
PubMed2003

Functional and effective frontotemporal connectivity and genetic risk for schizophrenia.

BACKGROUND: Functional neuroimaging and electrophysiologic studies have found disturbed frontotemporal interaction in schizophrenia. We sought to determine whether abnormalities of frontotemporal connectivity are trait markers of genetic risk for schizophrenia. METHODS: We investigated 64 schizophrenia patients, 79 of their clinically unaffected siblings, and 88 unrelated normal controls with an auditory oddball electroencephalogram (EEG) evoked potential paradigm. We measured: 1) frontotemporal event-related EEG-coherence (i.e. a measure of functional connectivity); and 2) we performed structural equation modeling of the effective connectivity between the frontal P300 and temporoparietal P300-amplitude. RESULTS: Schizophrenic patients and their siblings showed a reduction of frontotemporal coherence. At peak activation during the P300 time-window, a negative ("inhibitory") frontotemporal path coefficient was found in normal controls, whereas a positive coefficient was seen in schizophrenic patients with siblings being intermediate. Intra-class correlations between sib-pairs and relative risk estimates of the applied connectivity measures were non-significant. Topographic correlation matrix analyses suggested that the altered functional and effective frontotemporal connectivity indirectly reflect regional abnormalities of increased activation variance. CONCLUSIONS: Impaired interaction of the frontotemporal macro-circuit indirectly reflects genetically determined abnormalities of frontal and temporoparietal microcircuits. The reasons why frontotemporal connectivity appears to be a poor predictor of genetic risk for schizophrenia are discussed.

Adult↗
PubMed2000

Revision of previous Fontan connections to total extracardiac cavopulmonary anastomosis: A multicenter experience.

BACKGROUND: Conversion to total extracardiac cavopulmonary anastomosis is an option for managing patients with dysfunction of a prior Fontan connection. METHODS: Thirty-one patients (19.9 +/- 8.8 years) underwent revision of a previous Fontan connection to total extracardiac cavopulmonary anastomosis at four institutions. Complications of the previous Fontan connection included atrial tachyarrhythmias (n = 20), progressive heart failure (n = 17), Fontan pathway obstruction (n = 10), effusions (n = 10), pulmonary venous obstruction by an enlarged right atrium (n = 6), protein-losing enteropathy (n = 3), right atrial thrombus (n = 2), subaortic stenosis (n = 1), atrioventricular valve regurgitation (n = 3), and Fontan baffle leak (n = 5). Conversion to an extracardiac cavopulmonary connection was performed with a nonvalved conduit from the inferior vena cava to the right pulmonary artery, with additional procedures as necessary. RESULTS: There have been 3 deaths. Two patients died in the perioperative period of heart failure and massive effusions. The third patient died suddenly 8 months after the operation. All surviving patients were in New York Heart Association class I (n = 20) or II (n = 7), except for 1 patient who underwent heart transplantation. Early postoperative arrhythmias occurred in 10 patients: 4 required pacemakers, and medical therapy was sufficient in 6. In 15 patients, pre-revision arrhythmias were improved. Effusions resolved in all but 1 of the patients in whom they were present before revision. The condition of 2 patients with protein-losing enteropathy improved within 30 days. CONCLUSIONS: Conversion of a failing Fontan connection to extracardiac cavopulmonary connection can be achieved with low morbidity and mortality. Optimally, revision should be undertaken early in symptomatic patients before irreversible ventricular failure ensues.

Adolescent↗
PubMed2003

Hypoventilation improves oxygenation after bidirectional superior cavopulmonary connection.

OBJECTIVE: Bidirectional superior cavopulmonary connection may be complicated by systemic hypoxemia. Previous work has shown that hyperventilation worsens systemic oxygenation in patients after bidirectional superior cavopulmonary connection. The likely mechanism is that hyperventilation-induced hypocarbia decreases cerebral, superior vena caval, and pulmonary blood flow. The aim of the current study was to determine whether the converse approach, hypoventilation, improves oxygenation after bidirectional superior cavopulmonary connection. METHODS: This is a prospective, patient-controlled study of 15 patients (median age 8.0 months, range 4.7-15.5) who underwent bidirectional superior cavopulmonary connection. Patients were studied in the intensive care unit, within 8 hours of surgery, while sedated, paralyzed, and mechanically ventilated. To avoid acidosis during hypoventilation, sodium bicarbonate was administered before hypoventilation. Cerebral blood flow velocity was measured by transcranial Doppler sonography of the middle cerebral artery. RESULTS: Hypoventilation following administration of sodium bicarbonate (pH-buffered hypoventilation) produced hypercarbia (mean Pco(2) = 58 mm Hg versus 42 mm Hg at baseline). During hypoventilation, there were significant increases in both mean arterial Po(2) (from 50 mm Hg at baseline to 61 mm Hg; P <.05) and mean systemic oxygen saturation (from 86% at baseline to 90%; P <.05). These increases occurred despite accompanying, small increases in pulmonary artery pressure and transpulmonary gradient. Hypoventilation also produced an increase in mean cerebral blood flow velocity (from 37 cm/s at baseline to 55 cm/s; P <.05) and a decrease in the arteriovenous oxygen saturation difference across the upper body (from 33% at baseline to 23%; P <.05), consistent with increased cerebral blood flow. CONCLUSIONS: This study demonstrates that hypoventilation improves systemic oxygenation in patients after bidirectional superior cavopulmonary connection. The likely mechanism for this effect is that hypoventilation-induced hypercarbia decreases cerebral vascular resistance, thus increasing cerebral, superior vena caval, and pulmonary blood flow. Hypoventilation may be a useful clinical strategy in patients who are hypoxemic in the early postoperative period after bidirectional superior cavopulmonary connection.

Acid-Base Equilibrium↗
PubMed2003

Sodium nitroprusside infusion after bidirectional superior cavopulmonary connection: preserved cerebral blood flow velocity and systemic oxygenation.

OBJECTIVE: Systemic hypertension is common in patients after bidirectional superior cavopulmonary connection. It can be treated with a vasodilator, such as sodium nitroprusside. However, it is possible that systemic hypertension is necessary to maintain cerebral blood flow in the face of cerebral venous hypertension. Furthermore, bidirectional superior cavopulmonary connection places the cerebral and pulmonary vascular beds in series. Thus treatment of systemic hypertension by lowering blood pressure might decrease cerebral blood flow, pulmonary blood flow, and systemic oxygen levels. The aim of the current study was to determine the effects of sodium nitroprusside on cerebral blood flow velocity and systemic oxygenation in patients after bidirectional superior cavopulmonary connection. METHODS: This is a prospective patient-controlled study of 9 patients (median age, 7 months; age range, 4 to 12 months) undergoing bidirectional superior cavopulmonary connection. Patients were studied in the intensive care unit within 6 hours of surgical intervention while sedated, paralyzed, and mechanically ventilated. Sodium nitroprusside was infused to achieve a decrease in mean systemic blood pressure of approximately 20%. Cerebral blood flow velocity was measured by means of transcranial Doppler ultrasonography of the middle cerebral artery. RESULTS: During sodium nitroprusside infusion, mean systemic blood pressure decreased (from 69 +/- 6 mm Hg at baseline to 58 +/- 6 mm Hg, P <.05). However, there was no accompanying change in 2 indicators of cerebral blood flow: blood flow velocity in the middle cerebral artery and arteriovenous oxygen saturation difference across the upper body. Both arterial Po(2) and systemic oxygen saturation were also preserved during sodium nitroprusside infusion. CONCLUSIONS: Sodium nitroprusside decreases systemic blood pressure in patients after bidirectional superior cavopulmonary connection. This decrease occurs without accompanying changes in cerebral blood flow velocity or systemic oxygen levels. These findings suggest that cerebral and pulmonary blood flows are preserved during sodium nitroprusside infusion. Sodium nitroprusside appears to be an appropriate agent for the treatment of systemic hypertension after bidirectional superior cavopulmonary connection.

Antihypertensive Agents↗
PubMed2003

Computational fluid dynamics in the evaluation of hemodynamic performance of cavopulmonary connections after the Norwood procedure for hypoplastic left heart syndrome.

OBJECTIVE: Computational fluid dynamics have been used to study the hemodynamic performance of surgical operations, resulting in improved design. Efficient designs with minimal energy losses are especially important for cavopulmonary connections. The purpose of this study was to compare hydraulic performance between the hemi-Fontan and bidirectional Glenn procedures, as well as the various types of completion Fontan operations. METHODS: Three-dimensional models were constructed of typical hemi-Fontan and bidirectional Glenn operations according to anatomic data derived from magnetic resonance scans, angiocardiograms, and echocardiograms. Boundary conditions were imposed, and fluid dynamics were calculated from a mathematic code. Power losses, flow distribution to each lung, and pressures were measured at three predetermined levels of pulmonary arteriolar resistance. Models of the lateral tunnel, total cavopulmonary connection, and extracardiac conduit completion Fontan operations were constructed, and power losses, total flow distribution, vena caval and pulmonary arterial pressures, and flow distribution of inferior vena caval return were calculated. RESULTS: The hemi-Fontan and bidirectional Glenn procedures performed nearly identically, with similar power losses and nearly equal flow distributions to each lung at all levels of pulmonary arteriolar resistance. However, the lateral tunnel Fontan procedure as performed after the hemi-Fontan operation had lower power losses (6.9 mW, pulmonary arteriolar resistance 3 units) than the total cavopulmonary connection (40.5 mW) or the extracardiac conduit (42.9 mW), although the inclusion of an enlargement patch toward the right in the total cavopulmonary connection was effective in reducing the difference (10.0 mW). Inferior vena caval flow to the right lung was 52% for the lateral tunnel, compared with 19%, 30%, 19%, and 15% for the total cavopulmonary connection, total cavopulmonary connection with right-sided enlargement patch, extracardiac conduit, and extracardiac conduit with a bevel to the left lung, respectively. CONCLUSIONS: According to these methods, the hemi-Fontan and bidirectional Glenn procedures performed equally well, but important differences in energy losses and flow distribution were found after the completion Fontan procedures. The superior hydraulic performance of the lateral tunnel Fontan operation after the hemi-Fontan procedure relative to any other method may be due to closer to optimal caval offset achieved in the surgical reconstruction.

Cardiac Surgical Procedures↗
PubMed2003

Extracardiac total cavopulmonary connection using a tissue-engineered graft.

OBJECTIVE: Extracardiac and lateral tunnel total cavopulmonary connection are currently 2 major options for patients with a single ventricle physiology. However, each procedure has some disadvantages over the other. We developed a new technique of extracardiac total cavopulmonary connection using a tissue-engineered graft to overcome some of the disadvantages previously associated with both the extracardiac and lateral tunnel procedures. METHODS: Between February 2001 and October 2002, 8 patients underwent an extracardiac total cavopulmonary connection using a tissue-engineered graft in our institution. Collected bone marrow cells (1 x 10(8) mononucleocytes) from a patient (approximately 1-4 mL/kg body weight) were seeded onto a biodegradable scaffold composed of polycaprolactone-polylactic acid copolymer reinforced with woven polylactic acid. After a 2- to 4-hour cultivation, the seeded scaffold was implanted as an extracardiac conduit during the total cavopulmonary connection operation. RESULTS: There were no hospital or late deaths. At a mean follow-up of 13.4 months (range 4-25 months), all patients are alive and asymptomatic with no need for repeat surgery. A postoperative catheter examination or computed tomography showed all tissue-engineered grafts to be patent and revealed no stenosis, obstruction, or aneurysmal change in the 8 patients. CONCLUSION: We believe that extracardiac total cavopulmonary connection using a tissue-engineered graft has the potential to overcome some of the disadvantages previously associated with extracardiac or lateral tunnel total cavopulmonary connection. However, an extended follow-up period is required to clarify the long-term clinical outcome for the tissue-engineered graft.

Adolescent↗
PubMed2004

Hypoplasia of the small pulmonary arteries in total anomalous pulmonary venous connection with obstructed pulmonary venous drainage.

OBJECTIVE: Preoperative pulmonary venous obstruction has been reported to be a risk factor negatively impacting survival in total anomalous pulmonary venous connection. We examined lung tissue from total anomalous pulmonary venous connection patients with pulmonary venous obstruction and demonstrated hypoplasia of small pulmonary arteries to elucidate the mechanism underlying the poor outcome. METHODS: Ten total anomalous pulmonary venous connection patients with preoperative pulmonary venous obstruction between the ages of 2 days and 10 months were studied. As histological parameters, we assessed the size of small pulmonary arteries in relation to the size of accompanying bronchioles to identify small pulmonary artery underdevelopment. Other parameters, such as the radial alveolar count, which reflects alveolar maturity, intimal lesions, lymphangiectasia, and the medial thickness of small pulmonary arteries and small pulmonary veins, were also examined. As a control group, we examined 24 autopsy cases with no congenital heart or pulmonary disease. RESULTS: When the radius of the accompanying bronchiole was 100 microm, the radius of small pulmonary artery in the control group was found to enlarge for the first 2 months and then remain stable at approximately 80 microm from 2 to 10 months. In total anomalous pulmonary venous connection with preoperative pulmonary venous obstruction, the radius was significantly lower than in the control (47.0 +/- 21.8 microm versus 75.9 +/- 9.8 microm, P <.001), and the difference between dead and surviving patients was significant at P <.001 (33.0 +/- 14.6 microm versus 68.2 +/- 9.2 microm). Examination of the alveoli yielded an radial alveolar count of 4.6 +/- 1.5 in the control group and 4.4 +/- 0.8 in the total anomalous pulmonary venous connection patients, and the difference was not significant (P =.71). CONCLUSIONS: The small pulmonary arteries of total anomalous pulmonary venous connection patients with preoperative pulmonary venous obstruction were underdeveloped compared with controls but their alveolae were not hypoplastic. These results suggested that the small pulmonary artery hypoplasia may be responsible for the poor outcome of these patients.

Age Factors↗
PubMed1997

The connections of the primate subthalamic nucleus: indirect pathways and the open-interconnected scheme of basal ganglia-thalamocortical circuitry.

The current view of basal ganglia organization holds that functionally corresponding subregions of the frontal cortex, basal ganglia and thalamus form several parallel segregated basal ganglia-thalamocortical circuits. In addition, this view states that striatal output reaches the basal ganglia output nuclei (the substantia nigra pars reticulata (SNR) and the internal segment of the globus pallidus (GPi)) via a 'direct' pathway, and via an 'indirect pathway' which traverses the external segment of the globus pallidus (GPe) and the subthalamic nucleus (STN). However, the topographical relationships of GPe and STN, and their topographical relationships with the basal ganglia-thalamocortical circuits are still unclear. The present work reviewed primate data on the topographical organization of STN afferents from GPe, and STN efferents to the pallidum, striatum and SNR, and examined these data with respect to a tripartite (motor, associative and limbic) functional subdivision of the striatum and pallidum. This examination indicated the following. (1) On the basis of its efferent connections, the STN may be divided into a motor and an associative territories, as well as a smaller limbic territory, each projecting to corresponding areas in the pallidum and striatum. (2) Efferents from GPe are in a position to contact subthalamic cells projecting to GPi/SNR, thus providing anatomical support for the existence of indirect pathways. (3) Moreover, given the tripartite division of the striatum, pallidum, and STN, the available data indicate the existence of indirect pathways connecting functionally corresponding subregions of the striatum, pallidum, and STN, as well as indirect pathways connecting functionally non-corresponding subregions. On the basis of the above we suggested that there may be two types of indirect pathways, one which terminates in the same subregion in GPi/SNR as the direct pathway arising from the same striatal subregion, and another which terminates in a different GPi/SNR subregion than the direct pathway arising from the same striatal subregion. We termed the former a 'closed indirect pathway' and the latter an 'open indirect pathway'. The application of these concepts to the surveyed data suggested the existence of three closed indirect pathways, each connecting the corresponding functional (motor, associative, and limbic) regions of the striatum, pallidum, STN, and SNR, as well as of two open indirect pathways, one connecting the associative striatum to the motor subregions of the basal ganglia, and the other connecting the associative striatum to the limbic subregions of the basal ganglia. While the organization of the closed indirect pathways fits the closed segregated arrangement of basal ganglia-thalamocortical circuitry, the organization of the open indirect pathways fits the recently suggested open interconnected scheme of basal ganglia thalamocortical circuitry. The clinical implications of this scheme for Huntington's disease are discussed.

Animals↗
PubMed2000

Synaptic connectivity in hippocampal neuronal networks cultured on micropatterned surfaces.

Embryonic rat hippocampal neurons were grown on patterned silane surface in order to organize synapse formations in a controlled manner. The surface patterns were composed of trimethoxysilylpropyl-diethylenetriamine (DETA) lines separated by tridecafluoro-1,1,2,2-tetrahydrooctyl-1-dimethylchlorosilane (13F) spaces. Pre- and post-synaptic specializations were identified by immunostaining for synapsin I and microtubule-associated protein-2 (MAP-2). Functional synaptic connections were examined by recording simultaneously from pairs of neurons using the whole-cell configuration of the patch-clamp technique. Spontaneous and evoked synaptic currents were recorded in neurons cultured for 2-14 days. The formation of functional connections was accompanied by the appearance of spontaneous synaptic currents (SSCs), which could be detected after approximately 3 days in culture in the absence of evoked synaptic currents (ESCs). ESCs were detected only after approximately 7 days in culture, mostly in the form of unidirectional synaptic connections. Other forms of synaptic connectivity, such as bidirectional and autaptic connections, were also identified. Both transient GABAergic and glutamatergic signals mediated the transmissions between communicating cells. These results demonstrate the combination of various types of synaptic connections forming simple and complex networks in neurons cultured on line (DETA)-space (13F) patterns. Finally, precisely synchronized SSCs were recorded in neuron pairs cultured on pattern indicating the existence of a fast-acting feedback mechanism mediated by pre-synaptic GABA(A) receptors.

Alkanes↗
PubMed2002

Reduction of early thalamic input alters adult corticocortical connectivity.

The functional specificity of mammalian isocortex requires that precise connections be established between cortical areas and their targets. While recent studies of cortical development have focused on intrinsic specification, the role of extrinsic factors has received considerably less attention. In the present study, we examined how early removal of thalamic input affects the development of visual corticocortical connections. Hamster pups received ablations of visual thalamic nuclei on the day of birth. At 30 days of age, an injection of horseradish peroxidase (HRP) was placed into the area of cortex deafferented by the early thalamic ablation to retrogradely label adult corticocortical connections. Ablated animals displayed a significant increase in the number of corticocortical connections compared to control animals. The increased connectivity in ablated animals was primarily due to a significant increase in the number of corticocortical projections arising from non-visual areas. These results demonstrate that an intact thalamocortical projection is necessary for the development of normal cortical connectivity.

Animals↗