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Undifferentiated, overlapping, and mixed connective tissue diseases.

Undifferentiated connective tissue disease (UCTD) is a term used by many rheumatologists to define a group of diffuse connective tissue disorders that lack definitive characteristics of any particular well-defined disorder. Overlapping connective tissue disease is often used interchangeably with UCTD but they both refer to diseases that are in evolution before all the characteristic clinical and laboratory symptoms are manifested. However, the clinical features of some of the overlapping connective tissue diseases appear to be better defined. The classical one is mixed connective tissue disease, where features of systemic lupus erythematosus, progressive systemic sclerosis, and polymyositis may exist together with a positive anti-extractable nuclear antibody and high titers of anti-ribonuclear protein antibody. This review attempts to clarify the confusion between these terms. The problems in the clinical and laboratory diagnosis of common connective tissue diseases that coexist are addressed and treatment options discussed. The long-term implications of making a diagnosis of a definitive connective tissue disease before all the required criteria are met should be kept in mind because the patient may never develop the disease and yet be subjected to psychological, social, and economic hardships.

Humans↗

Connective tissue in female urinary incontinence.

An effective closure of the female urethra in stress situations is dependent on an integrated action of various anatomical structures connected to the organ. The most important of these structures - from a functional aspect - are the suburethral vaginal wall, the pubourethral ligaments, the pubococcygeus muscles and the paraurethral connective tissues. In all these structures connective tissue is an essential ingredient. Hence, defects in the actual connective tissue - in particular the paraurethral connective tissue that connects the aforementioned structures to each other and to the urethra - will bring about an ineffective urethral closure. Female urinary incontinence may then be caused by defective connective tissue per se and/or by a disconnection of the aforementioned structures, whereby the urethra cannot be 'kinked' - that is, closed off in stress situations.

Collagen↗

Connective tissue diseases and the liver.

Connective tissue diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis, Sjögren's syndrome, and scleroderma are systemic disorders that may have an autoimmune basis. The system manifestations vary, and there is frequent overlap among the syndromes. Liver involvement in patients with connective tissue diseases has been well documented but is generally considered rare. Although advanced liver disease with cirrhosis and liver failure is rare in patients with connective tissue diseases, clinical and biochemical evidence of associated liver abnormalities is common. Previous treatment with potentially hepatotoxic drugs or coincident viral hepatitis has usually been implicated as the main causes of liver disease in patients with connective tissue diseases. However, even after careful exclusion of these etiologies, the question remains whether to classify the patient as having a primary liver disease with associated autoimmune, clinical, and laboratory features or as having liver disease as a manifestation of generalized connective tissue disease. The main example of this pathogenetic dilemma is autoimmune hepatitis and SLE-associated hepatitis, which have been regarded as two different entities, although they have features in common of autoimmune syndromes. Several clinical and histopathologic features have been used to discriminate autoimmune hepatitis from SLE, a relevant diagnostic exercise because complications and therapy are quite different. Although hepatic steatosis and abnormal results on biochemical liver function tests are the most common hepatic abnormalities associated with connective tissue diseases, other less frequent abnormalities have been noted, such as nodular regenerative hyperplasia, portal vein obliteration and portal hypertension, features of primary biliary cirrhosis, and rarely portal fibrosis with abnormal lobular architecture. Vascular disorders of the liver also have been described, such as Budd-Chiari syndrome. Histologic assessment may reveal a variety of subclinical liver diseases. The aim of this contribution is to review the current published data regarding liver involvement in connective tissue diseases.

Connective Tissue Diseases↗

Human extrahepatic biliary atresia: portal connective tissue activation related to ductular proliferation.

Surgical bile flow restoration in extrahepatic biliary atresia (EHBA) does not prevent the development of ongoing hepatic fibrosis and cirrhosis. Portal connective matrix was studied on liver biopsies obtained from seven children submitted to portoenterostomy. Electron microscopy and immunohistochemical techniques (using specific antibodies directed against collagen isotypes and associated glycoproteins) were performed. The study of extracellular and cellular components of connective matrix demonstrated the existence of two distinct areas according to their situation with regard to ductular proliferation: loose connective matrix--mainly composed of fibronectin, type III collagen, type IV collagen and laminin--associated with microvessels and myofibroblasts proliferation characterized periportal zones adjacent to bile ductules; in areas distant from ductular proliferation, connective matrix appeared dense, composed of type I and type III collagen associated with fibroblasts. The connective matrix pattern observed in periductular areas can be compared to that described in cicatricial and hypertrophic processes where the myofibroblastic cell population is known to play an important role in fibrosis development. Although the connective matrix activation process remains unclear in EHBA, it may be suggested that activation of a connective tissue cellular clone might be responsible for this portal fibromatosis.

Bile Ducts↗

Functional anatomy of the levator palpebrae superioris muscle and its connective tissue system.

AIMS/BACKGROUND: The connective tissue system of the levator palpebrae superioris muscle (LPS) consists of the septa surrounding its muscle sheath, the superior transverse ligament (STL) commonly referred to as 'Whitnall's ligament' and the common sheath which is the fascia between the LPS and the superior rectus muscle (SRM). The anterior band-like component of the common sheath is called transverse superior fascial expansion (TSFE) of the SRM and LPS. It mainly extends from the connective tissue of the trochlea to the fascia of the lacrimal gland. A detailed description of the relation between the LPS and its connective tissue is presented. Furthermore, the course of the LPS in the orbit is described. The study was conducted to provide a morphological basis for biomechanical and clinical considerations regarding ptosis surgery. METHODS: Postmortem dissections were performed in 16 orbits from eight cadavers. The microscopical anatomy was demonstrated in six formalin preserved orbits from six cadavers which had been sectioned in the frontal and sagittal plane and stained with haematoxylin and azophloxin. Surface coil magnetic resonance imaging in the sagittal and coronal plane was performed in five orbits from five normal volunteers using a T1 weighted spin echo sequence. RESULTS: The STL and the TSFE surround the LPS to form a fascial sleeve around the muscle which has attachments to the medial and lateral orbital wall. The TSFE, which is thicker than the STL, blends with Tenon's capsule. The STL and the fascial sheath of the LPS muscle are suspended from the orbital roof by a framework of radial connective tissue septa. MR images show that the TSFE is located between the anterior third of the superior rectus muscle and the segment of the LPS muscle where it changes its course from upwards to downwards. In this area, the LPS reaches its highest point in the orbit (culmination point). The culmination point is located a few millimetres posterior to the equator and superior to the globe. CONCLUSION: Whitnall's ligament can be considered to consist of two distinct parts--the TSFE inferior to the LPS and the STL superior to the LPS. Since the medial and lateral main attachments of Whitnall's ligament are situated inferior to the level of the culmination point of the LPS, the ligament itself is unlikely to suspend the levator muscle. However, a suspension of the LPS may be achieved by the radial connective tissue septa of the superior orbit. The TSFE in connection with the globe may have an additional supporting function. The elasticity of Whitnall's ligament and its connections with highly elastic structures including Tenon's capsule, may provide the morphological substrate for the previously proposed passive (that is, without orbicularis action) lowering of the lid during downward saccades.

Adult↗

Role of connective tissue proteases in the pathogenesis of chronic inflammatory lung disease.

The normal structure and function of the human lung is dependent on the maintenance of the connective tissue matrix. These structural macromolecules provide the template for normal parenchymal cell architecture on which efficient gas exchange depends. In addition, the organization and amount of this extracellular matrix accounts for much of the mechanical behavior of the lung parenchyma during the respiratory cycle. The preservation of this intricate connective tissue scaffold depends on the lung's capacity to prevent enzymatic disruption of the component matrix proteins. Specifically, the integrity of the normal connective tissue skeleton of the lung is determined by the maintenance of a balance between proteases capable of cleaving these structural elements and the specific protease inhibitors. The normal extracellular matrix is preserved when the local concentrations of protease inhibitors prohibits expression of active connective tissue proteases within the lung parenchyma. Conversely, the disruption of lung structure during the course of acute and chronic inflammatory diseases of the lung is often associated with an imbalance of protease-antiprotease activity. The consequence is the expression of unimpeded proteolytic attack on the connective tissue matrix of the lung. In this context, the nature of the pulmonary lesion and its physiologic consequences, reflect the specificity of the expressed proteases for the individual connective tissue components. Experimental evidence suggests that the differential expression of collagenase and elastase, prototypes of connective tissue proteases, may determine whether the pathologic outcome is fibrosis (e.g., idiopathic pulmonary fibrosis) or destruction (e.g., emphysema) of the alveolar structures.

Animals↗

Evaluation of human recession defects treated with coronally advanced flaps and either enamel matrix derivative or connective tissue. Part 1: Comparison of clinical parameters.

BACKGROUND: Recession defects around teeth have been treated with a variety of surgical techniques. Most of the literature suggests that the subepithelial connective tissue graft has the highest percentage of mean root coverage with the least variability. Previous studies have demonstrated that enamel matrix derivative (EMD) has the ability to improve clinical parameters. The purpose of this study was to compare the clinical efficacy of enamel matrix derivative placed under a coronally advanced flap to subepithelial connective tissue placed under a coronally advanced flap in patients with recession type defects. METHODS: Twenty patients with incisors or premolars presenting with a facial recession of > or = 4 mm in contralateral quadrants of the same jaw were treated; 17 patients completed the study. One tooth in each patient was randomized to receive either a coronally advanced flap with a subepithelial connective tissue graft (control) or a coronally advanced flap with EMD (test). Clinical parameters measured at baseline and at 6, 9, and 12 months included amount of recession; width at the coronal extent of the gingival defect; width of keratinized tissue; probing depth; clinical attachment level; inflammation score; plaque score; plaque index; alveolar bone level; tissue texture and color; and patient perception of pain, bleeding, swelling, and sensitivity. RESULTS: Results for both the test and control groups were similar for all measured clinical parameters with the exception of early healing, self-reported discomfort, and the amount of keratinized tissue obtained. The coronally advanced flap with EMD was superior to the subepithelial connective tissue graft with regard to early healing and patient-reported discomfort, whereas the subepithelial connective tissue graft demonstrated greater amount of keratinized tissue during the 12-month evaluation period. However, both the test and control showed a significant increase in the amount of keratinized tissue at 9 and 12 months compared to baseline. No significant difference in the amount of root coverage was found between the test and control groups (n = 19; P = 0.82). On average, a gain of 4.5 mm (range 4 to 8 mm) tissue covering the previously exposed root surfaces was achieved with both treatment groups. The average percentages of root coverage for control and test groups were 93.8% and 95.1%, respectively. One hundred percent root coverage was obtained 89.5% of the time with the coronally advanced flap with EMD and 79% of the time with the subepithelial connective tissue graft. CONCLUSION: Based on the results of this investigation, the addition of EMD to the coronally advanced flap resulted in root coverage similar to the subepithelial connective tissue graft but without the morbidity and potential clinical difficulties associated with the donor site surgery.

Adult↗

Connective tissue mast cells in contact with fibroblasts express IL-3 mRNA. Analysis of single cells by polymerase chain reaction.

Mast cell-fibroblast interactions have been extensively investigated in the last few years. Fibroblasts support the in vitro survival but not proliferation of mouse connective-tissue type mast cells. However, the factor(s) that allow their survival on fibroblast monolayers has not been identified. We have investigated the presence of mRNA for IL-3 and granulocyte-macrophage-CSF in single mouse mast cells, before and after co-culture with 3T3 fibroblasts, using the polymerase chain reaction technique. The system was calibrated first by using in vitro generated population of mouse bone-marrow derived mast cells (BMMC). Significant differences in the amplification of IL-3 cDNA were observed in each of the BMMC cells examined, whereas the amplification of cDNA for the alpha-subunit of the Fc epsilon RI were similar. Inasmuch as murine cultured IL-3-dependent mast cells differentiate into connective tissue-like mast cells when co-cultured with 3T3 fibroblasts without any exogenous supply of growth factors, it was of interest to determine whether these connective tissue-like mast cells produce IL-3 message. Separation of the differentiated BMMC from the fibroblast monolayer, by either trypsinization or by single cell manipulation revealed the synthesis of a detectable amount of IL-3 mRNA in these mast cells. Whether this IL-3 mRNA was induced by fibroblasts was further investigated using connective tissue mast cells freshly purified from the mouse peritoneal cavity. Only about 20% of these connective tissue mast cells produced detectable amount of granulocyte-macrophage-CSF mRNA whereas in less than 10% of the cells IL-3 mRNA was detected. However, when these connective tissue mast cells were co-cultured with 3T3 fibroblasts for 18 hours and then separated, IL-3 mRNA were detected in most of the cells whereas no such mRNA was detected in tissue mast cells incubated for 18 h with medium derived from 3T3 fibroblasts. Therefore we conclude that fibroblasts induce the accumulation of IL-3 mRNA in connective tissue mast cells. The production of IL-3 may play a role in the survival of this type of mast cells on the fibroblast monolayer.

Animals↗

[Gastroenterologic aspects of connective tissue diseases].

The connective tissue disorders are a protean group of acquired diseases which have in common widespread immunologic and inflammatory alterations of connective tissue. The acquired connective tissue diseases generally include the following clinical entities: rheumatoid arthritis, systemic lupus erythematosus, polymyositis, polyarteritis nodosa, scleroderma, mixed connective tissue disease, Sjögren's and Behcet's sindromes. These entities have certain features in common which include sinovitis, pleuritis, myocarditis, endocarditis, pericarditis, peritonitis, vasculitis, myositis, changes in skin, alteration of connective tissue and nephritis. Gastrointestinal and hepatic involvement in connective tissue disorders are not the most important features, nevertheless appear almost regularly. Anorexia, nausea, vomiting, abdominal pain, malabsorption may affect patients suffering by rheumatoid arthritis, systemic lupus erythematosus and other collagenophaties. In some cases mesenteric vasculitis may cause intestinal ischemia which may result in bowel infarction, mucosal ulceration, hemorrhage, perforation. After an extensive review of the existing literature the Authors make an accurate evaluation of gastrointestinal and hepatic alterations in connective tissue diseases.

Arthritis, Rheumatoid↗

Connective tissue changes in immobilised muscle.

The reduction in fibre length of muscles immobilised in a shortened position is accompanied by reduced compliance of the muscle. Since the intramuscular connective tissue framework distributes the forces passively imposed on a muscle by stretching, it was decided to investigate the amount and distribution of connective tissue in immobilised muscles. Biochemical analysis of the hydroxyproline content of muscles immobilised in the shortened position for different periods of time showed an increase in the ratio of collagen to muscle fibre tissue. This occurred during the first few days of immobilisation, before there was any significant loss of sarcomeres. Thus the increase in connective tissue appeared to result directly from immobilisation rather than from redistribution of connective tissue, following shortening of the fibres. A detailed histological analysis of muscle sections stained for connective tissue with Sirius Red showed that the early increase in connective tissue in immobilised muscles occurred in the perimysium rather than the endomysium, although after a longer period of immobilisation there was also a thickening of the endomysium. Ultrastructural analysis of the perimysium in normal muscle showed that the angle the collagen fibres made with the muscle fibres changed with the state of stretch of the muscle; when the muscle was shortened, the angle was larger than when the muscle was lengthened. In immobilised muscle, collagen fibres were found to be arranged at a more acute angle to the axis of the muscle fibres than was found in normal muscle; this would be expected to affect the compliance of the muscle. The experiments described indicate that the increased stiffness of immobilised muscles could result from both quantitative and qualitative changes in the connective tissue.

Animals↗

Histological aspects of connective tissue septa in the adult female pelvic region.

From very thick 7-8 cm thick sections of adult female specimine parts of the connective tissue septa system were isolated and their relationships to muscles, viscera and vessels were studied histologically. Following the identification of an integrated system of pelvic connective tissue septa as described in previous articles biomechanical views were formulated. The consideration of these views led to new questions concerning the correlation of the structure of the connective tissue septa at different places in the entire pelvic region. The septa appeared to continue uninterrupted into the fascia and the perimysium of the muscles. The interrelationships of the connective tissue fibres, the adipose tissue and the vessels is described. The adventitia of the pelvic veins are firmly attached to the connective tissue septa. The groundsubstance of the adipose tissue appeared to contain hydrophilic acid mucopolysaccharides. The arteries were found close to the septa but not attached to them freely embedded in the adipose tissue. The connective tissue septa appeared to be built as multi-layered, "puff-pastry"-like arranged structures. The possible functional aspects of the interrelationships of the connective tissue septa system with the vascular system are discussed.

Aged↗

[Orbital veins and arteries in relation to the connective tissue system of the orbit].

Our study revealed that the relationships between the vessels and the connective tissue, which forms a constant and bilateral symmetrical system of connective tissue septa bordering adipose tissue compartments, are characteristics and constant but essentially different for veins and arteries. The arteries run within the adipose tissue compartments only contacting the connective tissue septa where they perforate them. As to the veins, their relationship with the connective tissue apparatus is completely different. These vessels run within the septa firmly connected with their connective tissue fibres, forming a continuity between the adventitia of the veins and the walls of the adipose tissue compartments. This difference between arteries and veins results in a different spatial structure for the two vascular systems. The arterial system is a radiating system, whereas the venous system is an anastomosing complex of venous rings which are arranged circularly inside as well as outside the muscle cone. It seems likely that the relationships of the vessels, particularly of the veins, with the connective tissue apparatus play an important role in the well-functioning of the orbital blood-circulation.

Adipose Tissue↗

The connective tissue of the adult female pelvic region. A microscopical analysis.

Using special histological criteria, structures found during blunt dissection of the adult female pelvic region could be recognized in 0.7-0.8 cm thick transparent histologically stained serial sections of this region, as connective tissue ribbons. The connective tissue in the adult female pelvic region reveals an orderly constructed system of coherent connective tissue ribbons. These ribbons form a skeleton which borders several separate functional areas. Areas for the locomotive system of the leg areas containing the pelvic vessels and viscera are separated by an area of adipose tissue. This area is again bordered by a connective tissue ribbon. In the fossa ischiorectalis also connective tissue ribbons are found, bordering areas filled with adipose tissue. These connective tissue ribbons interconnect the musculus levator ani, the epidermis, the musculus obturatorius internus, and the musculus gluteus maximus. The architecture found in the sections has a bilateral symmetry and possesses interindividual uniformity. The three-dimensional architecture of this system of connective tissue ribbons will be described in a next article.

Adipose Tissue↗

Cortical connections of areas V3 and VP of macaque monkey extrastriate visual cortex.

The cortical connections of visual area 3 (V3) and the ventral posterior area (VP) in the macaque monkey were studied by using combinations of retrograde and anterograde tracers. Tracer injections were made into V3 or VP following electrophysiological recording in and near the target area. The pattern of ipsilateral cortical connections was analyzed in relation to the pattern of interhemispheric connections identified after transection of the corpus callosum. Both V3 and VP have major connections with areas V2, V3A, posterior intraparietal area (PIP), V4, middle temporal area (MT), medial superior temporal area (dorsal) (MSTd), and ventral intraparietal area (VIP). Their connections differ in several respects. Specifically, V3 has connections with areas V1 and V4 transitional area (V4t) that are absent for VP; VP has connections with areas ventral occipitotemporal area (VOT), dorsal prelunate area (DP), and visually responsive portion of temporal visual area F (VTF) that are absent or occur only rarely for V3. The laminar pattern of labelled terminals and retrogradely labeled cell bodies allowed assessment of the hierarchical relationships between areas V3 and VP and their various targets. Areas V1 and V2 are at a lower level than V3 and VP; all of the remaining areas are at a higher level. V3 receives major inputs from layer 4B of V1, suggesting an association with the magnocellular-dominated processing stream and a role in routing magnocellular-dominated information along pathways leading to both parietal and temporal lobes. The convergence and divergence of pathways involving V3 and VP underscores the distributed nature of hierarchical processing in the visual system.

Animals↗

Prospective angiographic study of the abnormalities of systemic venous connections in congenital and acquired heart disease.

UNLABELLED: Angiographic definition of systemic venous connections was obtained prospectively in 780 consecutive patients with congenital heart disease and 102 patients with acquired valvular heart disease undergoing cardiac catheterization. Attempts were made to enter the innominate vein and perform a balloon occlusion angiogram in each patient. In patients with congenital heart disease, bilateral superior vena cava were present in 32/771 patients (approximately 4%) with levocardia and 3/9 patients with dextrocardia. Among patients with bilateral superior vena cava (n = 35), an innominate vein of variable size that could be entered was present in six patients. Small tributaries connecting the right and left superior vena cava were found and entered in six patients. The superior vena cava was entered via its connection to morphologic left atrium in five patients and via the coronary sinus in 17 patients. Abnormalities of the inferior vena cava were seen in 7/780 patients. The following abnormalities of the inferior vena cava were noted: azygous continuation of rightsided inferior vena cava in levocardia -- 3 patients, hemiazygos continuation of the leftsided inferior vena cava in levocardia -- 1 patient, azygos continuation of the leftsided inferior vena cava in dextrocardia -- 1 patient, interruption of inferior vena cava below the liver with a plexus of veins joining the azygos vein -- 1 patient, and an inferior vena cava draining into the leftward aspect of the common atrium -- 1 patient. Abnormalities of the systemic venous connections were seen in 2/102 patients with acquired heart disease: bilateral superior vena cava in 1 patient and bilateral inferior vena cava in 1 patient. CONCLUSIONS: Abnormalities of systemic venous connections were seen in approximately 5% patients with congenital heart disease and approximately 2% patients with acquired heart disease. Small tributaries or an innominate vein of variable size often connect left and right superior vena. Contrast material can be injected into these connections to document the presence of bilateral superior vena cava.

Adolescent↗

Connections between the medial temporal cortex and the CA1 subfield of the hippocampal formation in the Japanese monkey (Macaca fuscata).

The connections between the medial temporal cortical areas and CA1 of the hippocampus were examined in the Japanese monkey (Macaca fuscata) by means of retrograde and anterograde tract-tracing methods with wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP) and fluorescent dyes (Fast Blue and Diamidino Yellow). The posterior parahippocampal (areas TF1, TF2, and TH), perirhinal (areas 35 and 36), and ventral inferotemporal areas (areas TEav and TEpv) were reciprocally connected with CA1. Projection fibers from CA1 to the medial temporal cortical areas originated in the pyramidal cell layer, whereas those from the medial temporal cortical areas to CA1 terminated in the molecular layer. Each of these cortical areas was reciprocally connected with the entire rostrocaudal extent of CA1. However, the intensity of the connections varied along the rostrocaudal axis of CA1: areas TH and TF2 were connected most markedly with the anterior and middle parts of CA1, respectively. Areas TF, 35, 36, TEav, and TEpv were connected predominantly with the posterior part of CA1. In the coronal plane of CA1, labeled cells were located in proximal CA1 (i. e., near the prosubiculum), but not in distal CA1 (i.e., near CA2). The medial temporal cortical areas in direct reciprocal connection with CA1 were presumed to be involved in the memory system, especially in the system for declarative memory.

Animals↗

Paucity of horizontal connections for binocular vision in V1 of naturally strabismic macaques: Cytochrome oxidase compartment specificity.

To describe the structural basis for lack of binocular fusion in strabismic primates, we investigated intrinsic horizontal connections within striate cortex (area V1) of normal and strabismic, adult macaque monkeys. The strabismic animals had early-onset natural esotropia (the visual axes deviated nasally), normal visual acuity in each eye, and the constellation of ocular motor deficits that typify human infantile strabismus. Horizontal patchy connections and synaptic boutons were labeled by injections of the neuronal tracer biotinylated dextran amine. Ocular dominance columns (ODCs), and blob vs. interblob compartments, were revealed by using cytochrome oxidase (CO). In layers 2/3 and 4B of the strabismic monkeys, patchy projections and boutons terminated much more frequently in same-eye (73%) as opposed to opposite-eye (27%) ODCs (normal monkeys 58% and 42%, respectively). The deficiency of binocular connections in the strabismic cortex was evident qualitatively as a "skip" pattern, in which every other row of ODCs had labeled patches. Analysis of V1 in normal monkeys revealed that the deficits in strabismic V1 were due mainly to a loss of binocular connections between neurons in CO-interblob compartments. In both normal and strabismic monkeys: (1) CO-blob compartment neurons showed a more pronounced bias for monocular connectivity, and (2) commitment of connections to the same CO-compartment as the injection site (blob-to-blob, or interblob-to-interblob) was moderately strong (64%) but far from absolute. These findings help elucidate the relative roles of visual experience vs. innate mechanisms in the development of axonal connections between ocular dominance domains and compartments within macaque V1. They also provide the first detailed description of the V1 maldevelopments associated with unrepaired natural, infantile-onset strabismus in primates.

Animals↗

Ipsilateral connections of the ventral premotor cortex in a new world primate.

The present study describes the pattern of connections of the ventral premotor cortex (PMv) with various cortical regions of the ipsilateral hemisphere in adult squirrel monkeys. Particularly, we 1) quantified the proportion of inputs and outputs that the PMv distal forelimb representation shares with other areas in the ipsilateral cortex and 2) defined the pattern of PMv connections with respect to the location of the distal forelimb representation in primary motor cortex (M1), primary somatosensory cortex (S1), and supplementary motor area (SMA). Intracortical microstimulation techniques (ICMS) were used in four experimentally naïve monkeys to identify M1, PMv, and SMA forelimb movement representations. Multiunit recording techniques and myelin staining were used to identify the S1 hand representation. Then, biotinylated dextran amine (BDA; 10,000 MW) was injected in the center of the PMv distal forelimb representation. After tangential sectioning, the distribution of BDA-labeled cell bodies and terminal boutons was documented. In M1, labeling followed a rostrolateral pattern, largely leaving the caudomedial M1 unlabeled. Quantification of somata and terminals showed that two areas share major connections with PMv: M1 and frontal areas immediately rostral to PMv, designated as frontal rostral area (FR). Connections with this latter region have not been described previously. Moderate connections were found with PMd, SMA, anterior operculum, and posterior operculum/inferior parietal area. Minor connections were found with diverse areas of the precentral and parietal cortex, including S1. No statistical difference between the proportions of inputs and outputs for any location was observed, supporting the reciprocity of PMv intracortical connections.

Animals↗