Dolor y acortamiento aquíleo en pacientes con marcha de puntillas idiopática / Pain and Achilles tendon shortening in patients with idiopathic toe walking

Introducción: La marcha de puntillas idiopática (MPI) es una entidad heterogénea que asocia acortamientos musculares en las extremidades inferiores, dolor y trastornos del neurodesarrollo. Pretendemos estudiar la frecuencia de ciertas características clínicas en pacientes diagnosticados de MPI. Pacientes y métodos: De un total de 100 pacientes evaluados por marcha de puntillas en una consulta de rehabilitación infantil, se diagnosticó a 77 pacientes (24,7% mujeres) como con MPI con ayuda del cuestionario Toe Walking Tool. Mediante la maniobra de Silfverskiöld pudo determinarse el acortamiento aquíleo y mediante test adaptados también el dolor y la asociación con el trastorno por déficit de atención/hiperactividad (TDAH). En el grupo con dolor (n = 30), estudiamos su evolución mediante encuesta telefónica evaluando la intensidad, la localización, el absentismo escolar asociado y el tratamiento utilizado. Resultados: De los 77 pacientes, el 44,2% presentó antecedentes familiares de marcha de puntillas, el 37,7% tuvo acortamiento aquíleo y el 9,1%, de los flexores de la rodilla. El 9,1% de ellos tuvo TDAH confirmado y el 20,8%, sólo sospecha. A mayor edad, encontramos mayor frecuencia de dolor y menor ángulo de dorsiflexión pasiva del tobillo. El dolor fue de moderada-alta intensidad, produjo un 42,3% de absentismo escolar y se localizó predominantemente en la pantorrilla, el tobillo y el pie, y se prescribió fisioterapia, analgesia oral, ortesis y/o toxina botulínica principalmente. Conclusiones: El dolor en la MPI es frecuente, de intensidad moderada-alta, interfiere en la vida diaria y es más referido en niños más mayores que asocian menor dorsiflexión del tobillo. Encontramos asociación de la MPI y el TDAH con frecuencia, lo que anima a profundizar más su estudio como signo de alerta.(AU)

Introduction: Idiopathic toe walking (ITW) is a heterogeneous disorder, which is associated with muscle shortening in lower limbs, pain and neurodevelopmental disorders. We try to study the frequency of clinical features in patients with ITW. Patients and methods: Out of 100 patients evaluated with toe walking in a pediatric rehabilitation clinic, 77 (24,7% women) patients were diagnosed with ITW by means of TWT questionnaire. Achilles’ tendon shortening with Silfverskiöld manoeuvre, pain and attention deficit hyperactivity disorder (ADHD) were studied. In the group of patients with pain (n = 30), we studied pain evolution by means of a telephonic interview which assessed intensity, location, school absenteeism and used therapies. Results: Out of 77 patients, 44.2% had family history of toe walking. 37.7% and 9.1% showed Achilles’ tendon shortening and Knee flexor shortening, respectively. Confirmed diagnosed of ADHD was present in 9.1% and was suspected in 20.8%. The older the patient was, the higher frequency of pain and the lower passive ankle dorsiflexion. Pain has a moderate-severe intensity, was related with school absenteeism in 42.3% of the patients with pain. Pain was located mainly on the calf, the ankle and the foot. It was treated with physiotherapy, oral pain relievers, orthosis and botulinum toxin type A (BTxA). Conclusions: Pain in ITW is frequent, have a moderate-severe intensity, interferes in normal life and is referred in older children with lower ankle dorsiflexion. We found a common association between ITW and ADHD which points out ITW as alarm sign of learning problems.(AU)

[Pain and Achilles tendon shortening in patients with idiopathic toe walking]. / Dolor y acortamiento aquíleo en pacientes con marcha de puntillas idiopática.

INTRODUCTION: Idiopathic toe walking (ITW) is a heterogeneous disorder, which is associated with muscle shortening in lower limbs, pain and neurodevelopmental disorders. We try to study the frequency of clinical features in patients with ITW. PATIENTS AND METHODS: Out of 100 patients evaluated with toe walking in a pediatric rehabilitation clinic, 77 (24,7% women) patients were diagnosed with ITW by means of TWT questionnaire. Achilles' tendon shortening with Silfverskiold manoeuvre, pain and attention deficit hyperactivity disorder (ADHD) were studied. In the group of patients with pain (n = 30), we studied pain evolution by means of a telephonic interview which assessed intensity, location, school absenteeism and used therapies. RESULTS: Out of 77 patients, 44.2% had family history of toe walking. 37.7% and 9.1% showed Achilles' tendon shortening and Knee flexor shortening, respectively. Confirmed diagnosed of ADHD was present in 9.1% and was suspected in 20.8%. The older the patient was, the higher frequency of pain and the lower passive ankle dorsiflexion. Pain has a moderate-severe intensity, was related with school absenteeism in 42.3% of the patients with pain. Pain was located mainly on the calf, the ankle and the foot. It was treated with physiotherapy, oral pain relievers, orthosis and botulinum toxin type A (BTxA). CONCLUSIONS: Pain in ITW is frequent, have a moderate-severe intensity, interferes in normal life and is referred in older children with lower ankle dorsiflexion. We found a common association between ITW and ADHD which points out ITW as alarm sign of learning problems.

TITLE: Dolor y acortamiento aquíleo en pacientes con marcha de puntillas idiopática.Introducción. La marcha de puntillas idiopática (MPI) es una entidad heterogénea que asocia acortamientos musculares en las extremidades inferiores, dolor y trastornos del neurodesarrollo. Pretendemos estudiar la frecuencia de ciertas características clínicas en pacientes diagnosticados de MPI. Pacientes y métodos. De un total de 100 pacientes evaluados por marcha de puntillas en una consulta de rehabilitación infantil, se diagnosticó a 77 pacientes (24,7% mujeres) como con MPI con ayuda del cuestionario Toe Walking Tool. Mediante la maniobra de Silfverskiöld pudo determinarse el acortamiento aquíleo y mediante test adaptados también el dolor y la asociación con el trastorno por déficit de atención/hiperactividad (TDAH). En el grupo con dolor (n = 30), estudiamos su evolución mediante encuesta telefónica evaluando la intensidad, la localización, el absentismo escolar asociado y el tratamiento utilizado. Resultados. De los 77 pacientes, el 44,2% presentó antecedentes familiares de marcha de puntillas, el 37,7% tuvo acortamiento aquíleo y el 9,1%, de los flexores de la rodilla. El 9,1% de ellos tuvo TDAH confirmado y el 20,8%, sólo sospecha. A mayor edad, encontramos mayor frecuencia de dolor y menor ángulo de dorsiflexión pasiva del tobillo. El dolor fue de moderada-alta intensidad, produjo un 42,3% de absentismo escolar y se localizó predominantemente en la pantorrilla, el tobillo y el pie, y se prescribió fisioterapia, analgesia oral, ortesis y/o toxina botulínica principalmente. Conclusiones. El dolor en la MPI es frecuente, de intensidad moderada-alta, interfiere en la vida diaria y es más referido en niños más mayores que asocian menor dorsiflexión del tobillo. Encontramos asociación de la MPI y el TDAH con frecuencia, lo que anima a profundizar más su estudio como signo de alerta.

Parámetros de marcha en una muestra de referencia de escolares sanos españoles: descripción multivariante y asimetrías entre ciclos izquierdos y derechos / Gait parameters in a reference sample of healthy Spanish schoolchildren: multivariate descriptive statistics and asymmetries observed in left and right cycles

Introducción: El análisis instrumental de marcha (AIM) es una tecnología de uso creciente en la evaluación de trastornos motores infantiles. La evaluación de pacientes requiere una base de referencia de normalidad, pero existen pocas referencias infantiles españolas. Objetivo: Descripción de 16 variables de marcha de relevancia clínica en una muestra de referencia de escolares sanos. Estudio de sus relaciones lineales y asimetrías izquierda-derecha. Sujetos y métodos: Se midieron con AIM 16 variables de marcha en escolares sanos (n = 27, 5-13 años). Se estudiaron las asimetrías en cada variable (t de Student, muestras dependientes) y sus intervalos de confianza (95% de la media de diferencia estandarizada derecha menos izquierda, dz). Se representaron los valores y las asociaciones entre variables mediante «heatmap». Resultados: Se aportan tablas de normalidad para 16 variables del ciclo de marcha. Son significativamente asimétricos los valores medios de flexión mínima de cadera (dz: 0,25 IC del 95%, 0,11-0,39) y de máxima abducción de cadera en el balanceo (dz: -1,05 IC del 95%, —1,71; —0,27). Existen asociaciones funcionales entre las variables de marcha. Conclusiones: Presentamos una muestra de normalidad de escolares españoles donde se observan asimetrías entre los lados izquierdo y derecho y organización funcional entre sus variables (AU)

Introduction: Instrumental gait analysis is an emerging technology used increasingly to evaluate motor disorders in children. Normal reference data is necessary in order to evaluate patients, but there are few reference resources for the Spanish paediatric population. Objective: We aim to describe the values of 16 clinically relevant gait variables in healthy Spanish schoolchildren, and identify any linear associations or left-right asymmetries. Subjects and methods: The values of 16 gait variables were determined in schoolchildren (n = 27, aged 5-13 years) using instrumental gait analysis. We analysed asymmetries for each variable (Student’s t-test for dependent samples) and calculated their confidence intervals (95% of the standardised difference in right and left means [SMD]). Values and associations between variables were represented using a heat map. Results: Our project presents normal values tables for 16 variables in the gait cycle. Significant asymmetries were detected in the mean values for minimum hip flexion (SMD: 0.25 95% CI, 0.11-0.39) and peak hip abduction in swing (SMD: −1.05 95% CI: −1.71- − 0.27). Functional associations among gait variables are present. Conclusions: We present a reference dataset for Spanish school-aged children in which leftright asymmetries and functional associations may be observed for different variables (AU)

Gait parameters in a reference sample of healthy Spanish schoolchildren: multivariate descriptive statistics and asymmetries observed in left and right cycles.

INTRODUCTION: Instrumental gait analysis is an emerging technology used increasingly to evaluate motor disorders in children. Normal reference data is necessary in order to evaluate patients, but there are few reference resources for the Spanish paediatric population. OBJECTIVE: We aim to describe the values of 16 clinically relevant gait variables in healthy Spanish schoolchildren, and identify any linear associations or left-right asymmetries. SUBJECTS AND METHODS: The values of 16 gait variables were determined in schoolchildren (n=27, aged 5-13 years) using instrumental gait analysis. We analysed asymmetries for each variable (Student's t-test for dependent samples) and calculated their confidence intervals (95% of the standardised difference in right and left means [SMD]). Values and associations between variables were represented using a heat map. RESULTS: Our project presents normal values tables for 16 variables in the gait cycle. Significant asymmetries were detected in the mean values for minimum hip flexion (SMD: 0.25 95% CI, 0.11-0.39) and peak hip abduction in swing (SMD: -1.05 95% CI: -1.71--0.27). Functional associations among gait variables are present. CONCLUSIONS: We present a reference dataset for Spanish school-aged children in which left-right asymmetries and functional associations may be observed for different variables.

Expression of type 2 iodothyronine deiodinase in hypothyroid rat brain indicates an important role of thyroid hormone in the development of specific primary sensory systems.

Thyroid hormone is an important epigenetic factor in brain development, acting by modulating rates of gene expression. The active form of thyroid hormone, 3,5,3'-triiodothyronine (T3) is produced in part by the thyroid gland but also after 5'-deiodination of thyroxine (T4) in target tissues. In brain, approximately 80% of T3 is formed locally from T4 through the activity of the 5'-deiodinase type 2 (D2), an enzyme that is expressed mostly by glial cells, tanycytes in the third ventricle, and astrocytes throughout the brain. D2 activity is an important point of control of thyroid hormone action because it increases in situations of low T4, thus preserving brain T3 concentrations. In this work, we have studied the expression of D2 by quantitative in situ hybridization in hypothyroid animals during postnatal development. Our hypothesis was that those regions that are most dependent on thyroid hormone should present selective increases of D2 as a protection against hypothyroidism. D2 mRNA concentration was increased severalfold over normal levels in relay nuclei and cortical targets of the primary somatosensory and auditory pathways. The results suggest that these pathways are specifically protected against thyroid failure and that T3 has a role in the development of these structures. At the cellular level, expression was observed mainly in glial cells, although some interneurons of the cerebral cortex were also labeled. Therefore, the T3 target cells, mostly neurons, are dependent on local astrocytes for T3 supply.

Extensive divergence and convergence in the thalamocortical projection to monkey somatosensory cortex.

This study examined the extent of thalamocortical divergence as a potential determinant of activity-dependent representational plasticity in area 3b of adult monkey somatosensory cortex. Single or paired injections of anterogradely transported tracers, of varying anteroposterior extent, were made horizontally from behind in defined parts of the body representation in the ventral posterior lateral (VPL) and/or ventral posterior medial (VPM) thalamic nuclei, and the distribution and density of labeled thalamocortical terminations were mapped in cortex. Injections of increasing size in any dimension of VPL or VPM resulted in increasing accumulation of labeled terminals within the region of projection, implying extensive convergence of individual axons. Anteroposteriorly elongated injections labeled mediolaterally extended but anteroposteriorly restricted zones in cortex. Dorsoventral placement of an injection in VPL or VPM determined anteroposterior location of labeling in cortex. Dual injections separated mediolaterally or dorsoventrally by approximately 1 mm, and in different parts of the thalamic body or head-face representation gave rise to labeled thalamocortical terminations that overlapped extensively. For injection sites at different anteroposterior levels in VPL or VPM, the area of cortical convergence was related to their extent of anteroposterior coincidence. Labeled terminations arising from injections in immediately adjacent parts of VPL and VPM did not overlap in cortex. The extent of thalamocortical divergence and convergence revealed by these experiments is greater than that predictable from labeling of single axons and is sufficiently great to account for representational plasticity that exceeds the 1.5 mm cortical "distance limit."

Hypothyroidism alters the expression of prostaglandin D2 synthase/beta trace in specific areas of the developing rat brain.

Lipocalin-type prostaglandin D2 synthase is the enzyme responsible for the synthesis of prostaglandin D2, a major prostaglandin in the central nervous system. We analysed the effects of thyroid hormone deprivation on prostaglandin D2 synthase gene expression in the developing rat brain. By in situ hybridization, the strongest prostaglandin D2 synthase mRNA signal was detected in the leptomeninges and choroid plexus. The signal was greatly reduced in the cerebellar interlaminar meninges of hypothyroid rats aged 15 and 25 days. Immunohistochemical studies defined changes in the location of the prostaglandin D2 synthase protein. In control but not in hypothyroid animals, Cajal-Retzius neurons of cortical layer I, and pyramidal cortical plate neurons were intensely stained on postnatal day 5. Conversely, prostaglandin D2 synthase protein levels were higher in neurons of the CA1 and CA3 regions and the dentate gyrus of the hippocampus of hypothyroid animals on postnatal days 5, 15 and 25, and also in subplate neurons on postnatal days 15 and 25. In agreement with the in situ hybridization and northern blotting data, the major difference was found in the cerebellar interlaminar meninges of hypothyroid animals, where the protein was clearly down-regulated on postnatal days 15 and 25. These results show that hypothyroidism causes both age- and region-specific alterations in the expression and location of the prostaglandin D2 synthase during postnatal brain development, probably reflecting a cell-specific regulatory effect of thyroid hormone on the prostaglandin D2 synthase.

Subdivisions of macaque monkey auditory cortex revealed by calcium-binding protein immunoreactivity.

The aim of this investigation was to characterize auditory areas of the primate cerebral cortex on the basis of chemoarchitecture. Cortical areas of the supratemporal plane were delineated in Macaca fuscata (M. fuscata) by immunocytochemical staining for parvalbumin, staining for cytochrome oxidase, examination of cyto- and myeloarchitecture, and retrograde tracing of corticocortical connections. Comparative observations were made on Macaca fascicularis (M. fascicularis). Differential staining of fiber plexuses, probably of thalamic origin, identifies a central core zone of dense immunostaining and a surrounding zone of moderate-to-dense immunostaining composed of anteromedial, lateral, and posteromedial fields. Outside the second zone, there is a third anterolateral zone of weaker immunoreactivity, and, outside that zone, there is a fourth zone in which immunoreactivity is virtually absent. Differences in parvalbumin immunostaining in the auditory fields may reflect differences in relative contributions of thalamic inputs from parvalbumin-immunoreactive cells in the medial geniculate complex. The central core zone and the surrounding three fields can be correlated with major auditory fields previously defined by multiunit mapping and thalamocortical connectivity. The core zone contains a large principal field and an anterior extension. The pattern of corticocortical connections between these and adjoining fields suggests that the anteromedial, lateral, and posteromedial fields represent first steps in three streams of connections passing outward from auditory into association cortex. M. fuscata has an unusually large auditory cortex that is more deeply placed in the lateral sulcus in comparison to that of M. fascicularis. A small annectant gyrus provides a guide to the position of the primary auditory area.

Auditory thalamocortical pathways defined in monkeys by calcium-binding protein immunoreactivity.

This study investigated differentiation of Macaca fuscata auditory thalamus into chemically defined nuclei forming relays to auditory cortical areas. The thalamus was stained immunocytochemically for parvalbumin and 28 kDa calbindin in normals and in brains in which retrogradely transported tracers were injected into middle layers of auditory cortical areas or applied to the cortical surface. Parvalbumin- and calbindin-immunoreactive cells show a complementary distribution in ventral, anterodorsal, posterodorsal, and magnocellular medial geniculate nuclei. The ventral nucleus has a high density of parvalbumin cells and few calbindin cells, and the anterodorsal nucleus has a high density of parvalbumin cells and moderate numbers of calbindin cells. Both nuclei have a dense parvalbumin-immunoreactive neuropil formed by terminations of fibers ascending in the brachium of the inferior colliculus. The posterodorsal nucleus has approximately equal proportions of parvalbumin and calbindin cells; neuropil staining is weak but contains terminations of calbindin-immunoreactive fibers ascending in the midbrain tegmentum. The magnocellular nucleus contains domains of parvalbumin and calbindin cells. Parvalbumin cells in the ventral nucleus project to a central core of auditory cortex with densest parvalbumin immunoreactivity. Those in anterodorsal and posterodorsal nuclei project to surrounding auditory fields with less dense parvalbumin immunoreactivity; those in the magnocellular nucleus project widely to auditory and other fields. Injections of middle cortical layers label a large majority of parvalbumin cells in the ventral, anterodorsal, or posterodorsal nuclei and in the magnocellular nucleus. Superficial deposits label calbindin cells only, usually in more than one nucleus, implying a widespread projection system.

Patchy and laminar terminations of medial geniculate axons in monkey auditory cortex.

The object of this study was to identify the terminal distributions of thalamocortical axons arising in chemically characterized subdivisions of the medial geniculate complex. Large injections of wheat germ agglutinin-conjugated horseradish peroxidase or small injections of Phaseolus vulgaris leucoagglutinin were made in the medial geniculate complex of Macaca fuscata. The terminal distributions of labeled axons in the cortex were correlated with auditory cortical fields demonstrable by different intensities of immunoreactivity for parvalbumin. Fibers from the ventral nucleus terminated mainly in layer IV and deep portion of layer III (IIIB), with additional terminations in layers I-IIIA and in layer VI. In layers IIIB-IV, a major terminal plexus was formed by a small number of dense patches, 300-500 microns in diameter, surrounded by smaller satellite patches. The patches conformed to a similarly lobulated pattern of parvalbumin fiber immunoreactivity. Terminations of some individually labeled thalamocortical fibers were restricted to a single patch, whereas others innervated more than one patch by collateral branches. Fibers from the dorsal nuclei ending in areas of less dense parvalbumin immunoreactivity surrounding the primary auditory cortex formed much larger terminal patches centered largely in layer IIIB. Fibers from the magnocellular nucleus had relatively few terminal branches but innervated extremely wide areas by collaterals of single axons. Two types of axons arose from the magnocellular nucleus, one terminating preferentially in middle cortical layers and the other exclusively in layer I. These may arise respectively from parvalbumin- and calbindin-immunoreactive cell populations in the magnocellular nucleus.

Extent of intracortical arborization of thalamocortical axons as a determinant of representational plasticity in monkey somatic sensory cortex.

The extent of intracortical arborization of individual thalamocortical axons in area 3b of the somatic sensory cortex and the degree of overlap in the cortical projections of relay cells in the ventral posterior nucleus of the thalamus were examined in macaque monkeys. Paired intracortical deposits of Fast blue (FB) and Diamidino yellow (DY) separated by 100-1500 microns were made by inserting crystals of dye into the tracks of tungsten microelectrodes used to record receptive field data on area 3b cells. Each injection gave retrograde labeling of one or more clusters of cells extending in elongated anteroposterior arrays through the ventral posterior medial (VPM) or ventral posterior lateral (VPL) nucleus. Double-labeled cells were only found when the distance between the centers of the dye deposits was less than 600 microns. With interdeposit distances greater than 600 microns, most clusters of retrogradely labeled cells had a majority of cells labeled by FB or DY. However, even with interdeposit distances of 1-1.5 mm the labeled clusters also contained significant numbers of cells labeled with the other dye. These results and an accompanying regression analysis indicate that the extent of intracortical arborization of single thalamocortical axons in area 3b is no greater than 600 microns. However, adjoining cells in the same part of the thalamic body representation can project to cortical targets as discrepant as 1.5 mm. It is proposed that the fine grain of the cortical representation depends upon inputs from the majority population of each thalamic cell cluster.(ABSTRACT TRUNCATED AT 250 WORDS)

Calbindin and parvalbumin cells in monkey VPL thalamic nucleus: distribution, laminar cortical projections, and relations to spinothalamic terminations.

The ventral posterior lateral nucleus (VPL) of the monkey thalamus was investigated by histochemical staining for cytochrome oxidase (CO) activity and by immunocytochemical staining for the calcium-binding proteins parvalbumin and 28 kDa calbindin. Anterograde and retrograde tracing experiments were used to correlate patterns of differential distribution of CO activity and of parvalbumin and calbindin cells with the terminations of spinothalamic tract fibers and with the types of cells projecting differentially to superficial and deeper layers of primary somatosensory cortex (SI). VPL is composed of CO-rich and CO-weak compartments. Cells are generally smaller in the CO-weak compartment. Parvalbumin-immunoreactive cells and parvalbumin-immunoreactive medial lemniscal fiber terminations are confined to the CO-rich compartment. Calbindin-immunoreactive cells are found in both the CO-rich and CO-weak compartments. The CO-weak compartment, containing only calbindin cells, forms isolated zones throughout VPL and expands as a cap covering the posterior surface of the ventral posterior medial nucleus (VPM). Spinothalamic tract terminations tend to be concentrated in the CO-weak compartment, especially in the posterior cap. Other CO-weak, parvalbumin-negative, calbindin-positive nuclei, including the posterior, ventral posterior inferior, and anterior pulvinar and the small-celled matrix of VPM are also associated with concentrations of spinothalamic and caudal trigeminothalamic terminations. Parvalbumin cells are consistently larger than calbindin cells and are retrogradely labeled only after injections of tracers in middle and deep layers of SI. The smaller calbindin cells are the only cells retrogradely labeled after placement of retrograde tracers that primarily involve layer I of SI. The compartmental organization of VPL is similar to but less rigid than that previously reported in VPM. VPL and VPM relay cells projecting to different layers of SI cortex can be distinguished by differential immunoreactivity for the two calcium-binding proteins. The small-celled, CO-weak, calbindin-positive zones of VPL and VPM appear to form part of a wider system of smaller thalamic neurons unconstrained by traditional nuclear boundaries that are preferentially the targets of spinothalamic and caudal trigeminal inputs, and that may have preferential access to layer I of SI.

Area 3a in the cat. II. Projections to the motor cortex and their relations to other corticocortical connections.

It is well known that area 3a in the cat may monosynaptically influence the activity of neurons in the motor cortex. Much less information is available, however, on the anatomy of these connections. By using single or combined injections of different retrograde axonal tracers, we investigated the topography (horizontal and laminar) of area 3a neurons projecting to the motor cortex, and the anatomical relationships between these neurons and those projecting to other areas (2, 5, and SII) which, in turn, project to the motor cortex. Area 3a projects to all parts of area 4 gamma, to area 4 delta, and to the agranular area 6 in the lateral bank of the presylvian sulcus (area 6 alpha gamma), but not to other parts of areas 4 and 6. This projection exhibits a loose topographic organization along the mediolateral dimension of area 3a, and, in many cases, arises predominantly from the rostral half of this area. Although single small injections in the motor cortex produced two or more separate patches of retrograde labeling in 3a, after simultaneous injections of fluorochromes in two separate loci there often appeared in area 3a overlapping populations of neurons which were labeled retrogradely by each of the dyes, but with very few double-labeled neurons. In horseradish peroxidase (HRP) cases, 72% of area 3a neurons projecting to area 4 gamma were distributed in supragranular layers (mainly layer III), although the proportion of labeling in infragranular layers was larger when using fluorescent dyes. Double-labeled cells predominated in infragranular layers. These results have a bearing upon the functional roles that have been attributed to area 3a, as a cortical locus involved in muscle sensation, and a cortical relay to the motor cortex of rapid feedback information from muscle activity during movement.

Chronic deafferentation in monkeys differentially affects nociceptive and nonnociceptive pathways distinguished by specific calcium-binding proteins and down-regulates gamma-aminobutyric acid type A receptors at thalamic levels.

Chronic deafferentation of skin and peripheral tissues is associated with plasticity of representational maps in cerebral cortex and with perturbations of sensory experience that include severe "central" pain. This study shows that in normal monkeys the nonnociceptive, lemniscal component of the somatosensory pathways at spinal, brainstem, and thalamic levels is distinguished by cells and fibers immunoreactive for the calcium-binding protein parvalbumin, whereas cells of the nociceptive component at these levels are distinguished by immunoreactivity for 28-kDa calbindin. Long-term dorsal rhizotomies in monkeys lead to transneuronal degeneration of parvalbumin cells at brainstem and thalamic sites accompanied in the thalamus by a down-regulation of gamma-aminobutyric acid type A receptors and an apparent increase in activity of calbindin cells preferentially innervated by central pain pathways. Release from inhibition and imbalance in patterns of somatosensory inputs from thalamus to cerebral cortex may constitute subcortical mechanisms for inducing changes in representational maps and perturbations of sensory perception, including central pain.

Parvalbumin- and calbindin-containing neurons in the monkey medial geniculate complex: differential distribution and cortical layer specific projections.

Neuronal immunoreactivity for the calcium binding proteins, parvalbumin and calbindin, has been examined immunohistochemically in the monkey medial geniculate complex. Neurons containing one or other of these proteins were present in most (but not all) regions of the complex and were differentially distributed; parvalbumin immunoreactive neurons tended to form densely packed clusters in the ventral nucleus and rather loose arrangements in the anterodorsal and posterodorsal nuclei, whereas most calbindin neurons were scattered, with concentrations in the caudal end of the posterodorsal and in the magnocellular nuclei. In fluorescent tracer experiments combined with immunohistochemistry, it was found that parvalbumin and calbindin neurons project to layer IV and to layer I, respectively, of the primary auditory cortex. These results suggest the presence of parallel and chemically differentiated geniculocortical pathways which make different contributions to the neuronal circuitry of the auditory cortex.

Histochemical and immunocytochemical compartments of the thalamic VPM nucleus in monkeys and their relationship to the representational map.

The ventral posteromedial nucleus (VPM) of the monkey thalamus was investigated with correlative anatomical and physiological techniques. On the basis of staining for cytochrome oxidase (CO), VPM is divided into a lightly stained, background matrix domain and an intensely stained rod domain. The latter consists of elongated rods of large, medium, and small cells, 500 microns wide on average and extending anteroposteriorly, many of them through the full extent of the nucleus. The matrix, consisting of small cells, penetrates between the rods and expands at the dorsomedial, ventrolateral, and posterior aspects of VPM. Multiunit mapping reveals that VPM contains a dorsally situated representation of the contralateral side of the head, face, eye, and interior of the mouth and a medially situated representation of the ipsilateral side of the lips and interior of the mouth, and that the same small region is represented in the same relative position through the full anteroposterior extent of the nucleus. Earlier work had shown that single CO rods contain the representation of the same portion of the periphery throughout their length. The present study suggests that rods in equivalent positions may represent the same portion of the periphery from animal to animal. The cells of the rod and matrix domains show different patterns of immunoreactivity. Virtually all of the large- and medium-sized rod cells are immunoreactive for the calcium-binding protein parvalbumin, and many are stained by the monoclonal antibody CAT 301. Small GABA-immunoreactive cells and terminal-like puncta are highly concentrated in the rods but are dispersed in the matrix. In the matrix, all non-GABA cells are small, immunoreactive for 28-kDa calbindin, and not stained by CAT 301. They appear to form part of a wider system of calbindin-positive cells that extends into adjacent nuclei. The CO rods are indicative of the modularity of the lemniscal component of the trigeminal part of the somatic sensory system at thalamic levels. Thalamocortical relay neurons in this compartment of VPM express a calcium-binding protein and a surface proteoglycan that distinguishes them from relay neurons in the matrix compartment of the nucleus. In the following paper (Rausell and Jones, 1991), the rod and matrix compartments are shown also to have different patterns of input and output connections.

Chemically distinct compartments of the thalamic VPM nucleus in monkeys relay principal and spinal trigeminal pathways to different layers of the somatosensory cortex.

The ventral posteromedial nucleus (VPM) of the monkey thalamus was investigated with combined immunocytochemical, histochemical, and connection-tracing techniques. Injections of anterogradely transported tracers were placed selectively in the caudal nucleus of the spinal trigeminal nuclear complex, and retrogradely transported horseradish peroxidase (HRP) or fluorescent dyes were placed on the surface or into the depths of defined parts of the trigeminal representation in the first somatic sensory area (SI) of the cerebral cortex. The results are correlated with those of the preceding paper (Rausell and Jones, 1991), which demonstrated the presence of 2 domains in the nucleus on the basis of different patterns of cytochrome oxidase (CO) staining and calcium-binding protein immunoreactivity. The cells of the CO-defined rod and matrix domains receive inputs from different components of the trigeminal afferent system and project to different layers of SI. The large- and medium-sized relay cells of the CO-rich rods, which are immunoreactive for parvalbumin, all project to middle layers of SI. The small relay cells of the weakly-stained CO-matrix, surrounding and intervening between the rods, are immunoreactive for 28-kDa calbindin and project to superficial layers (I and II) of SI. Anterograde tracing studies reveal that the rod domain in VPM is innervated by fibers arising in the contra- and ipsilateral principal trigeminal nucleus, while the matrix domain (and calbindin-positive domains in adjacent nuclei) are innervated by fibers arising in the caudal nucleus of the spinal trigeminal complex. These results demonstrate the modularity and parallel streaming of the functional components of the trigeminal part of the somatic sensory system and suggest that lemniscal and nonlemniscal elements of the system gain access by separate routes to different layers of the SI cortex.

Segregation and heterogeneity of thalamic cell populations projecting to superficial layers of posterior parietal cortex: a retrograde tracer study in cat and monkey.

The thalamic neurons projecting to the superficial layers of areas 5 and 7 in the cat, and area 5 in the monkey, were investigated by using superficial deposits of either horseradish peroxidase or Fast Blue in one hemisphere. In the contralateral hemisphere injections of the same tracer involving the full cortical depth were made in homotopical locations, and the distribution and soma size of retrogradely labeled thalamocortical neurons in each side of the thalamus were compared. It was found that, in the cat, labeled neurons in the lateral posterior pulvinar complex, and in paralaminar regions of the ventrolateral complex, were fewer in number and smaller in size in cases of superficial deposits than in cases of deep injection. In more lateral portions of the ventrolateral complex, however, there were no size differences. In the monkey, similar differences in number and size appeared in the caudal division of the ventrolateral complex and in the lateral posterior and pulvinar nuclei, whereas no such differences were found for neurons labeled in the oral and medial divisions of the ventrolateral complex, and in the ventral posteroinferior nucleus. In all cases the intralaminar and midline nuclei exhibited retrogradely labeled neurons only when deep layers were injected. These and previous findings point to the existence of a widely distributed layer I-projecting system of neurons which, in most nuclei, are interspersed among neurons projecting mainly to middle or deep layers. In some nuclei, however, as is the case with the ventromedial nucleus proper, layer I-projecting system neurons would make up the whole nucleus. The cell groups located in a paralaminar position, which would be but a part of this system, could provide through their projections to layer I in the posterior parietal and frontal cortical regions a final path for recruiting responses and spontaneous spindling activities.

Organization of the association cortical afferent connections of area 5: a retrograde tracer study in the cat.

The association (intrahemispheric) cortico-cortical afferent connections of area 5 were studied in the cat by means of retrograde tracing techniques involving horseradish peroxidase (HRP) free or wheat germ agglutinin-conjugated (WGA-HRP) or fluorochrome injections. Single or multiple injections were placed in different parts of areas 5a and 5b, the medial division of area 5 (5m), or in the anterior suprasylvian area (SsA). Labeled cells were plotted on projection drawings of the coronal sections and on two-dimensional "maps" of the cerebral cortex, which were produced according to an accurate and consistent procedure. The major findings of this study are: 1. All divisions of the anterior parietal cortex (areas 3a, 3b, 1, and 2) project to area 5 and to SsA. These projections, however, show marked differences in amount and topographical distribution, depending on the mediolateral and rostrocaudal location of the injections. 2. The motor cortex (areas 4 and 6) also projects heavily to area 5 and to SsA in a well-organized topographic fashion: Area 4 projects mainly upon areas 5a, 5m, SsA, and the medial part of 5b; area 6 projects mainly upon the lateral part of 5b and SsA. Moreover, the upper bank of the cruciate sulcus (areas 4 tau and 4 delta) projects to medial parts of area 5, and the lower bank (areas 4 tau, 6a alpha, and 6a beta) projects to lateral parts of area 5. 3. The somatosensory areas in the anterior ectosylvian gyrus and surrounding cortices (SIIm, SII, and SIV) are connected primarily with medial parts of area 5 (particularly 5a), and SsA. 4. Areas 7 and 7m and a number of visual areas (19, SVA, AmLS, PmLS, 21, 20, 18, ALS, and PLS) project in varying degrees to lateral parts of area 5b. Some of these areas also send weak to moderate projections to the medial part of 5b and the lateral part of 5a. 5. Sparse projections arising from the dorsolateral prefrontal, cingular, retrosplenial, granular insular, and suprasylvian fringe cortices were found to distribute in area 5 and SsA, particularly in lateral portions of 5b. 6. Quite abundant intrinsic connections also found, which were loosely organized according to a complex topographic pattern. On the basis of these and previous results (Avendaño et al., 1985), the identity of area 5 in the cat is discussed, and comparisons are made between this area and sectors of adjoining cortex of cat and primates.

Thalamocortical neurons projecting to superficial and to deep layers in parietal, frontal and prefrontal regions in the cat.

Superficial HRP applications and deep injections were performed on symmetric foci of the same cortical region in primary somatosensory, motor and prefrontal areas. Retrogradely labeled neurons were analyzed for body size distribution and intensity of labeling. Neurons in the ventral posterior and ventralis lateralis nuclei projecting to layer I of the somatic sensory and motor cortices are smaller in size and less intensely labeled than neurons projecting to deeper layers. Neurons projecting to the prefrontal cortex from the ventromedialis and mediodorsalis nuclei had the same soma size and topography irrespective of the cortical layer affected by the HRP, although they varied in number and in intensity of labeling.