Brachmann-Cornelia de Lange syndrome with a papilloma of the choroid plexus: analyses of molecular genetic characteristics of the patient and the tumor. A single-case study.

PURPOSE: A 10-month-old girl with a Brachmann-Cornelia de Lange syndrome and a choroid plexus papilloma of the brain was studied at the Hospital Infantil de México Federico Gómez (HIMFG) in Mexico City. METHODS AND RESULTS: Presumptive papilloma of the third ventricle was evidenced on CT and MR images and removed. Pathological analysis confirmed its origin. A posterior radiosurgery was required due to a tumor relapse. Karyotypes (GTG bands) of the patient and her parents undertaken at HIMFG were normal. Array comparative genomic hybridization (array CGH) analyses of blood DNA of the patient and her parents carried out at BlueGnome's Laboratory in Cambridge, UK, set in evidence amplification of genes SPNS2, GGT6, SMTNL2, PELP1, MYBBP1A, and ALOX15 in chromosome 17p of the patient. Since MYBBP1A is a proto-oncogene and ALOX15 participates in the development of cancer and metastases of tumors, further fluorescent in situ hybridization (FISH) analyses of these two genes were implemented at HIMFG. Amplification of the two genes was found in the tumor of the case under study but not in an unrelated papilloma of the choroid plexus. DISCUSSION: Further analyses of the association of choroid plexus papillomas with disorders of psycho-neural development and its relationship to molecular genetic modifications at chromosome 17p are now under way at HIMFG.

Genetic structure of three Native Mexican communities based on mtDNA haplogroups, and ABO and Rh blood group systems.

OBJECTIVE: The goals of this population genetics study were to describe mtDNA haplogroups and ABO and Rh blood group systems of 3 Native Mexican populations, to determine their genetic variability, and to compare their haplogroups with those of 13 Native Mexican populations previously reported. MATERIAL AND METHODS: The three communities under analysis were a Tepehua-speaking community from Huehuetla (Hidalgo state), an Otomi-speaking community from San Antonio el Grande (Hidalgo state), and a Zapotec-speaking community from Juchitán (Oaxaca state). Every subject studied in each community had four grandparents who were born in the same community and spoke the same language. The four Amerindian mtDNA haplogroups (A, B, C and D) were studied by restriction analysis and gel electrophoresis. RESULTS: Regarding the blood groups, the O group was the most frequent in the three populations (97.2, 94.7, and 86.2%, respectively), as well as the Rh+ group (100, 100, 84%). The three populations analyzed were in Hardy-Weinberg equilibrium. In respect to the mtDNA haplogroups, A, B, C and D, their percentage was 33.3, 36.1, 13.9 and 5.6 % in Huehuetla; 39.5, 13.2, 39.5 and 2.6 % in San Antonio el Grande, and 55.3, 21.0, 7.9 and 5.2 % in Juchitán. Between 5 and 11% of the haplogroups were of non-Amerindian origin, probably due to admixture with Caucasian and African populations, as has been reported in the past. No statistically-significant differences were found among the three populations studied or between them and 13 previously reported Native Mexican populations.

Glioblastoma multiforme in children: experience at Hospital Infantil de Mexico Federico Gomez.

OBJECTIVE: To evaluate clinical evolution of pediatric patients diagnosed with glioblastoma multiforme (GBM) at Hospital Infantil de México Federico Gómez. METHODS: Cases of patients treated from January to May, 2007, were included in this study. Variables analyzed were: age, diagnosis, size of tumor, histopathological description, degree of resection, time of stay in hospital, complications and outcome using Pearson's chi-squared test and logistic regression. CONCLUSION: Sixteen patients were identified. Mean age of presentation was 8.8. An increased frequency of complications was observed in younger patients and longer survival rates in patients with greater resections; main mode of presentation was directly related to intracranial hypertension; size of tumor was not related to evolution or outcome. Modern histological classifications especially designed for children are deemed necessary to accurately diagnose GBM.

Different Food Odors Control Brain Connectivity in Impulsive Children.

BACKGROUND: Impulsivity is a complex multi-dimensional combination of behaviors which include: ineffective impulse control, premature decision-making and inability to delay gratification. OBJECTIVE: The aim of this work was to explore how food odor perception and its emotional value is affected in impulsive children. METHODS: Here we compared two cohorts of impulsive and control children with ages between 10 and 16 years. Both groups underwent a functional magnetic resonance imaging experiment, in which foodrelated odor-cues were presented to all of them. RESULTS: Differences in regions of blood oxygen level dependent activation, as well as connectivity, were calculated. Activations were significant for all odors in the impulsive group in the temporal lobe, cerebellum, supplementary motor area, frontal cortex, medial cingulate cortex, insula, precuneus, precentral, para-hippocampal and calcarine cortices. CONCLUSION: Connectivity results showed that the expected emotional reward, based on odor perceived and processed in temporal lobes, was the main cue driving responses of impulsive children. This was followed by self-consciousness, the sensation of interaction with the surroundings and feelings of comfort and happiness, modulated by the precuneus together with somatosensory cortex and cingulum. Furthermore, reduced connectivity to frontal areas as well as to other sensory integration areas (piriform cortex), combined to show different sensory processing strategies for olfactory emotional cues in impulsive children. Finally, we hypothesize that the cerebellum plays a pivotal role in modulating decision-making for impulsive children.

Lexical tonal discrimination in Zapotec children. A study of the theta rhythm.

BACKGROUND: Zapotec is a language used mainly in the state of Oaxaca in Mexico of tonal characteristic; homophone words with difference in fundamental frequency with different meanings. Our objective was to analyze changes in the electroencephalographic (EEG) theta rhythm during word discrimination of lexical tonal bi-syllabic homophone word samples of Zapotec. METHODS: We employed electroencephalography analysis during lexical tonal discrimination in 12 healthy subjects 9-16 years of age. RESULTS: We observed an increase in theta relative power between lexical discrimination and at rest eyes-open state in right temporal site. We also observed several significant intra- and inter-hemispheric correlations in several scalp sites, mainly in left fronto-temporal and right temporal areas when subjects were performing lexical discrimination. CONCLUSIONS: Our data suggest more engagement of neural networks of the right hemisphere are involved in Zapotec language discrimination.

Strategies for tonal and atonal musical interpretation in blind and normally sighted children: an fMRI study.

INTRODUCTION: Early childhood is known to be a period when cortical plasticity phenomena are at a maximum. Music is a stimulus known to modulate these mechanisms. On the other hand, neurological impairments like blindness are also known to affect cortical plasticity. Here, we address how tonal and atonal musical stimuli are processed in control and blind young children. We aimed to understand the differences between the two groups when processing this physiological information. RESULTS: Atonal stimuli produced larger activations in cerebellum, fusiform, and temporal lobe structures than tonal. In contrast, tonal stimuli induced larger frontal lobe representations than atonal. Control participants presented large activations in cerebellum, fusiform, and temporal lobe. A correlation/connectivity study showed that the blind group incorporated larger amounts of perceptual information (somatosensory and motor) into tonal processing through the function of the anterior prefrontal cortex (APC). They also used the visual cortex in conjunction with the Wernicke's area to process this information. In contrast, controls processed sound with perceptual stimuli from auditory cortex structures (including Wernicke's area). In this case, information was processed through the dorsal posterior cingulate cortex and not the APC. The orbitofrontal cortex also played a key role for atonal interpretation in this group. DISCUSSION: Wernicke's area, known to be involved in speech, was heavily involved for both groups and all stimuli. The two groups presented clear differences in strategies for music processing, with very different recruitment of brain regions.

Analysis of chromosome 17 miRNAs and their importance in medulloblastomas.

MicroRNAs (miRNAs) are small sequences of nucleotides that regulate posttranscriptionally gene expression. In recent years they have been recognized as very important general regulators of proliferation, differentiation, adhesion, cell death, and others. In some cases, the characteristic presence of miRNAs reflects some of the cellular pathways that may be altered. Particularly medulloblastomas (MB) represent entities that undergo almost characteristic alterations of chromosome 17: from loss of discrete fragments and isochromosomes formation to complete loss of one of them. An analysis of the major loci on this chromosome revealed that it contains at least 19 genes encoding miRNAs which may regulate the development and differentiation of the brain and cerebellum. miRNAs are regulators of real complex networks; they can regulate from 100 to over 300 messengers of various proteins. In this review some miRNAs are considered to be important in MB studies. Some of them are miRNA-5047, miRNA-1253, miRNA-2909, and miRNA-634. Everyone can significantly affect the development, growth, and cell invasion of MB, and they have not been explored in this tumor. In this review, we propose some miRNAs that can affect some genes in MB, and hence the importance of its study.

Error related negativity and multi-source interference task in children with attention deficit hyperactivity disorder-combined type.

OBJECTIVE: To compare performance of children with attention deficit hyperactivity disorders-combined (ADHD-C) type with control children in multi-source interference task (MSIT) evaluated by means of error related negativity (ERN). METHOD: We studied 12 children with ADHD-C type with a median age of 7 years, control children were age- and gender-matched. Children performed MSIT and simultaneous recording of ERN. RESULTS: We found no differences in MSIT parameters among groups. We found no differences in ERN variables between groups. We found a significant association of ERN amplitude with MSIT in children with ADHD-C type. Some correlation went in positive direction (frequency of hits and MSIT amplitude), and others in negative direction (frequency of errors and RT in MSIT). CONCLUSION: Children with ADHD-C type exhibited a significant association between ERN amplitude with MSIT. These results underline participation of a cingulo-fronto-parietal network and could help in the comprehension of pathophysiological mechanisms of ADHD.

Lexical tonal discrimination in Zapotec children. A study of the theta rhythm / Discriminación tonal léxica en niños zapotecas. Un estudio del ritmo theta

Abstract Background: Zapotec is a language used mainly in the state of Oaxaca in Mexico of tonal characteristic; homophone words with difference in fundamental frequency with different meanings. Our objective was to analyze changes in the electroencephalographic (EEG) theta rhythm during word discrimination of lexical tonal bi-syllabic homophone word samples of Zapotec. Methods: We employed electroencephalography analysis during lexical tonal discrimination in 12 healthy subjects 9-16 years of age. Results: We observed an increase in theta relative power between lexical discrimination and at rest eyes-open state in right temporal site. We also observed several significant intra- and inter-hemispheric correlations in several scalp sites, mainly in left fronto-temporal and right temporal areas when subjects were performing lexical discrimination. Conclusions: Our data suggest more engagement of neural networks of the right hemisphere are involved in Zapotec language discrimination.

Resumen Introducción: El zapoteco es un lenguaje hablado principalmente en el estado de Oaxaca, en México, que tiene la característica de ser tonal; es decir, las palabras homófonas que difieren en la altura del fundamental tienen diferente significado. El objetivo de este trabajo fue analizar los cambios del ritmo theta del electroencefalograma en el curso de la discriminación de palabras bisilábicas homófonas en zapoteco. Método: Se empleó el análisis espectral del electroencefalograma durante la discriminación tonal léxica del lenguaje zapoteco en 12 niños sanos de 9-16 años. Resultados: Se observó una mayor potencia relativa theta en la región temporal derecha durante la discriminación léxica en comparación con el registro de reposo-ojos abiertos. También se observaron varias correlaciones significativas intra e interhemisféricas con predominio entre la región frontotemporal izquierda y temporal derecha mientras se realizaba la discriminación tonal léxica. Conclusión: Estos resultados sugieren que hay un mayor compromiso de las redes neuronales en el hemisferio derecho que participan en la discriminación del lenguaje zapoteco.

Error related negativity and multi-source interference task in children with attention deficit hyperactivity disorder-combined type / La negatividad relacionada al error en una tarea de interferencia multifuente en niños con trastorno por déficit de atención-hiperactividad tipo combinado

Objective To compare performance of children with attention deficit hyperactivity disorders-combined (ADHD-C) type with control children in multi-source interference task (MSIT) evaluated by means of error related negativity (ERN). Method We studied 12 children with ADHD-C type with a median age of 7 years, control children were age- and gender-matched. Children performed MSIT and simultaneous recording of ERN. Results We found no differences in MSIT parameters among groups. We found no differences in ERN variables between groups. We found a significant association of ERN amplitude with MSIT in children with ADHD-C type. Some correlation went in positive direction (frequency of hits and MSIT amplitude), and others in negative direction (frequency of errors and RT in MSIT). Conclusion Children with ADHD-C type exhibited a significant association between ERN amplitude with MSIT. These results underline participation of a cingulo-fronto-parietal network and could help in the comprehension of pathophysiological mechanisms of ADHD. .

Objetivo Comparar el rendimiento de un grupo de niños con trastorno por déficit de atención-hiperactividad de tipo combinado (TDAH-C), con niños controles, en la tarea de interferencia multi-fuente (TIMF), evaluado por la negatividad relacionada al error (NRE). Método Estudiamos 12 niños con TDAH-C con una mediana de 7 años, los controles estuvieron pareados por edad y género. Los niños realizaron la TIMF con registros simultáneos de NRE. Resultados No encontramos diferencias en los parámetros de la TIMF entre grupos. No encontramos diferencias en las variables de la NRE entre grupos. Encontramos asociaciones significativas entre la amplitud de la NRE en niños con TDAH-C. Una correlación fue en dirección positiva: (frecuencia de aciertos y amplitud de TIMF), y otras fueron en dirección negativa (frecuencia de errores y el tiempo de respuesta en la TIMF). Conclusión Los niños con TDAH-C presentan una asociación significativa entre la amplitud de la NRE con la TIMF. Los resultados sugieren la participación de la red cíngulo-fronto-parietal y pueden ayudar en la comprensión de los mecanismos fisiopatológicos del TDAH-C. .

Holoprosencephaly in Mexico: first reported autopsy case by Dr. Agustín Arellano.

INTRODUCTION: Holoprosencephaly with cyclocephaly is an early disturbance of organogenesis and has been classified as a severe brain malformation starting in 1755 by Eller in Germany, then in 1822 by Etienne Geoffroy de Saint-Hilaire in France, and finally in 1828 by Tiedemann in Germany. In 1839, Dr. Arellano published in Mexico a necropsy case of holoprosencephaly. This was the fourth publication worldwide on this kind of pathological alteration. Furthermore, in reference to diaphragmatic herniation, Arellano's paper is the fourth world report, having appeared 9 years before Bochdalek's publication. We have not found any other report that appeared before 1839 in the Americas on this particular malformation, and we consider that Arellano's paper was the first of its kind on the American continent. CONCLUSION: As is well known, the publications of this Mexican medical researcher were, for his time, at the level of those of the most developed countries. It is also important to know that the medical journal where Arellano's work was published, the "Periódico de la Academia de Medicina de Mégico(sic)," founded and directed by Dr. Manuel Carpio in 1836, is the direct forerunner of the present Gaceta Médica de México, the oldest currently published journal in the Americas.

The first neuroanatomical text published on the American continent: Mexico City, 1579.

UNLABELLED: DETAILS OF PUBLICATION: The first neuroanatomy text published on the American continent was included in the Tractado de Anothomia y Chirugia by Fr. Agustín Farfán, O.S.A., who received his M.D. in 1569 from the Royal and Pontifical University of Mexico. It was printed in 1579 by Antonio Ricardo, a Piedmontese who had settled in Mexico City, capital of New Spain. CONTENT: . This text encompasses a very correct and complete neuroanatomy of an eminently Galenic type.

Surgery of tumors of the cerebellum and prefrontal cortex, and sensory memory and motor planning disturbances in children.

OBJECT: This study addressed the integration of sensory short-term memory (SSTM) and motor planning (MP) in the lateral cerebellar region, where the dentate nucleus is localized, and in the prefrontal cortex (PF). METHODS: Boucher and Lewis's test of SSTM and MP was administered pre- and postsurgically to 8 patients of either sex, between 5 and 19 years of age, with tumors of the cerebellum, PF (area 9 medial) or the parieto-occipital region, and on one occasion to 8 corresponding controls. RESULTS: Whereas lesions of the midline portions of the cerebellum and of the parietal-occipital region did not appear to cause any cognitive defects, patients with lesions affecting either the lateral cerebellar region or PF exhibited statistically significant deficits of SSTM and MP. CONCLUSIONS: The lateral cerebellum seems to act in concert with PF to integrate different cognitive activities related to holding objects in SSTM and planning motor strategies in reference to them.

Cerebral Anatomy of the Spider Monkey Ateles Geoffroyi Studied Using Magnetic Resonance Imaging. First Report: a Comparative Study with the Human Brain Homo Sapiens / Anatomía Cerebral del mono araña Ateles geoffroyi estudiada utilizando imágenes de resonancia magnética. Primer reporte: estudio comparativo con el cerebro humano Homo Sapiens

The objective of the present qualitative study was to analyze the morphological aspects of the inner cerebral anatomy of two species of primates, using magnetic resonance images (MRI): spider monkey (A. geoffroyi) and human (H. sapiens), on the basis of a comparative study of the cerebral structures of the two species, focusing upon the brain of the spider monkey and, primarily, its limbic system. In spite of being an endemic Western hemisphere species, a fact which is by its own right interesting for research due to this animal’s social organization and motor functions, the spider monkey (A. geoffroyi) has hardly been studied in regard to its neuroanatomy. MRI was carried out, in one spider monkey, employing a General Electric Signa 1.5 T scanner. This investigation was carried in accordance to international regulations for the protection of animals in captivity, taking into account all protective means utilized in experimental handling, and not leaving behind any residual effects, either physiological or behavioral. From a qualitative point of view, the brains of the spider monkey and the human were found to have similar structures. In reference to shape, the most similar structures were found in the limbic system; proportionally, however, cervi cal curvature, amygdala, hippocampus, anterior commissure and the colliculi, were larger in the spider monkey than in the human.

El objetivo del presente estudio cualitativo fue analizar los aspectos morfológicos de la anatomía cerebral interna utilizando imágenes de resonancia magnética (IRM) en dos especies de primates, El mono Araña (A. geoffroyi) y el humano (H. sapiens), tomando como base un estudio comparativo de las estructuras cerebrales de las dos especies, concentrándose primordialmente en el sistema límbico del cerebro del mono araña. Aunque es una especie común en el hemisferio occidental, es interesante para estudiar dada su organización social y funciones motoras, el mono araña (A. geoffroyi) ha sido poco estudiado en cuanto a su neuroanatomía. Las IRM fueron hechas a un mono araña utilizando un resonador General Electrics Signa 1.5 T. Esta investigación se llevo a cabo conforme a las leyes internacionales para la protección de animales en cautiverio y teniendo en cuenta todas las medidas de protección para el manejo experimental para evitar cualquier efecto residual de índole comportamental o fisiológico. Desde un punto de vista cualitativo, los cerebros del mono araña y el humano tenían estructuras similares. Con respecto a la forma, las estructuras más parecidas fueron encontradas en el sistema límbico, sin embargo la curvatura cervical, la amígdala, el hipocampo, la comisura anterior y el colículo fueron más grandes proporcionalmente en el mono araña que en el humano.

Neurotransmisores del sistema límbico. Hipocampo, GABA y memoria. Primera parte

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Summary: Introduction. The entire hippocampus is derived from the telencephalon. Embryologically, it is made up of the most archaic cortices. Through special phylogenetic and ontogenetic telencephalization processes, it will arrive at its particular mesial basal position. This structure has three components: a) Retrocommisural hippocampus, or hippocampus proper (RH). b) Supracommisural hippocampus (SH). c) Precommisural hippocampus (PH). The RH is situated in the most medial part of the 5th temporal gyrus (5 TG). The outer/upper face of the RH is to be found in the temporal recess of the lateral ventricle. It is called pes hippocampi or albeus. Inwards, it is limited by the choroid fissure, outwards and downwards by the parenchyma of the 5th TG, forwards, by the amygdala of the striatal body and, backwards, by the isthmus. The fornix is a continuation of efferent pathways from CA3, CA1 and the subiculum. By means of a circular course, it ascends over the thalamus and, descending in front of Monro's foramina and traversing the hypothalamus, reaches the mammillary bodies. It consists of fimbria, posterior pillars and a body and anterior pillars. The latter pass behind the anterior white commisure (AWC), and make up the anterior portion of Monro's foramina. The SH originates in the RH. At the level of the splenium of the corpus callosum (CC), the fornix produces two striae, medial and lateral, and the dentate gyrus turns from fasciola cineria into induceum griseum. These structures are to be found in both hemispheres and, traveling over the CC, will reach the preoptic and hypothalamic septal areas, as well as the PH. The PH is a small fiber contingent which stems from the fornix at the level and in front of the AWC. Memory. General aspects. There is general agreement that the main role of the hippocampus is that of creating new memories relative to experienced events (episodic or autobiographic memory). Some researchers, however, prefer to think of the hippocampus as part of a major medial temporal lobe memory system responsible for declarative memory. This memory would include, besides episodic memory, memory of events. Another very important hippocampal function would relate to storage of semantic (conceptual) memories. Engrams. Memory and synaptic plasticity. Engrams are hypothetical means whereby memory traces are stored as physical or chemical changes in the brain in response to external stimuli. The existence of engrams has been proposed by diverse scientific theories which try to explain the persistence of memory and how some memories are stored in the brain. The term engram was coined by Sermon and explored by Pavlov Lashley tried to locate the engram and failed in finding a sole biological locus for the same which made him think that memories were not localized in any particular part of the brain, but distributed throughout the cerebral cortex. Afterwards, in 1949, Hebb, a student of Lashley's, published his empiricist theories in The Organization of Behavior. Hebb referred to Lorente de Nó's reverberating circuits to propose a mechanism for maintaining activity in the cerebral cortex after the external stimulus had ceased: the so called central autonomous process. This led him to consider the cellular assembly, a complex reverberating circuit which could be assembled by experience. Changes in synaptic resistance with experience were eventually named Hebb's, or the Hebbian, synapse. Hebbian theory describes a basic mechanism for synaptic plasticity by means of which an increment in synaptic efficacy stems from repetitive and persistent stimulation of the post-synaptic cell. This theory receives the name of Hebb's rule. The fact that memory is persistent stresses the relevance of understanding those factors which maintain synaptic strength and prevent undesired synaptic changes. There is evidence that recurrent inhibitory connections in region CA1 of Ammon's horn of the hippocampus might contribute in this sense by modulating the ability to induce long-term potentiation (LTP) or long-term depression (LTD) of synaptic activity, given by a sequence of high-or low-frequency stimulations, respectively. The hippocampus seems to be able to select the most relevant from the least relevant aspects of a definite experience in order to transform them into long-term memory. According to the concept of Emotional Tagging, for example, through the activation of the amygdala by emotionally suggestive events, the experience will be tagged as important and synaptic plasticity promoted in other cerebral regions, such as the hippocampus. Recently, it has been shown that activation of the amygdala transforms transient plasticity into long-term plasticity. This finding directly relates to the afore mentioned hypothesis of emotional tagging, since activation of this organ could trigger neuromodulatory systems, further reduce the activation threshold of the synaptic marker and facilitate transformation of early into late memory at the level of the hippocampus via direct amygdalar action on the latter organ. γ-aminobutyric acid. γ-aminobutyric acid (GABA), together with its different receptor subunits, functions as an inhibitor neurotrans-mitter in hippocampus and memory activities. GABA and memory. LTP has been a widely studied mechanism of synaptic plasticity and, as we have mentioned, it is intimately related to diverse memory and learning processes in mammals. It has been observed in pyramidal cells of area CA1 of the hippocampus of young C57BL/6 mice that the pairing of pre-synaptic stimulation with just one post-synaptic action potential will be sufficient to induce LTP, whereas in the adult animal this stimulation must be paired with several post-synaptic action potentials to achieve such induction. This change might result from a modification during maturation of GABAergic inhibitory processes. A bath of muscimol, a GABAA agonist, given to sections of hippocampal area CA1 will increase the range of frequencies inducing LTD, while in the presence of picrotoxin, a GABAA antagonist, LTD will be induced only at very low stimulation frequencies. The resulting recurrent inhibition appears to stem from GABAergic input to pyramidal neurons of CA1. In this way, post-synaptic spike activity could increase GABAergic feedback inhibition, and thus favor LTD. However, in experiments in which the pairing of stimulating action potentials is set apart in time, LTD, LTP or no plasticity may be observed. An explanation for these results could be that, in the presence of picrotoxin, and therefore GABA inhibition, the first action potential may have a greater tendency to "back propagate", so that only one spike would be enough to cause LTP instead of LTD, and affect memory processes differently.

Neurotransmisores del sistema límbico. Hipocampo. GABA y memoria. Segunda parte

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Summary: Action of GABA agonists and antagonists on memory. The θ rhythm. Muscimol may directly alter memory. Recently, a modified matching to position (MTP) paradigm was employed aimed at influencing the type of associations a rat may use to solve the task. The main behavioral manipulation was the application of a differential outcomes procedure (DOP). DOP implies correlating each event to be remembered with a different reward condition. This procedure will result in the development of specific reward expectations which will in turn increase and guide choice behavior. Such different reward expectations will not be present when the reward assignation used is either common or random (non-differential outcomes procedure, NOP). Intraventricular infusion of muscimol or CSF in rats carrying out a delayed MTP using either a MOP or an NOP protocol will affect both groups of rats, but the nature of the deficit will differ depending on the reinforcement contingencies. Rats trained in DOP will show general non-mnemonic damage independent of delay, i.e., performance will be affected at all delay intervals employed. On the contrary, rats trained in NOP will show delay-dependent damage. This appears to demonstrate that muscimol may also have untoward memory effects, which further indicates that activation of GABA receptors will affect a set of memory associations and functions. Difficulties experienced in the past regarding LTP induction at the level of the CA3-CA1 synapse using time-based spike presentation protocols have been disconcerting given the preeminence of these synapses as a model system for the study of synaptic plasticity. Results previously discussed in experiments using picrotoxin as a GABA inhibitor have suggested that such difficulties arise from the requirement that, for LTP to be induced, CA1 dendrites must be persistently and totally activated. Doublets used in this case represent a minimal burst, or level of post-synaptic stimulation for LTP induction that subsumes greater depolarizations. In vitro, synaptically induced bursts would correspond to regenerative electrical events in apical dendrites of pyramidal neurons. The same requirements for dendritic activation would be satisfied in vivo during the θ rhythm, which is present during active exploration. Therefore, GABA might serve as an engram modulator through the activation of the hippocampal θ rhythm. Effect of μ-opioid receptors on hippocampal memory activity. Hippocampal μ-opioid receptors (MOR) have been involved in the formation of memory associated with the abuse of opioid drugs. When chronically activated, and during programmed drug abstinence, MORs acutely modulate hippocampal synaptic plasticity At the level of neuronal networks, MORs increase excitability of area CA1 by means of a disinhibition of pyramidal cells. The specific inhibitory interneuronal subtypes which become affected by activation of MORs are not known. Nevertheless, not all subtypes are inhibited and some subtypes preferentially express these receptors. In one study, the effect of activation of MORs on inhibitory patterns and propagation of excitatory activity in CA1 of rat hippocampus was investigated through cortical images created using voltage-sensitive dyes. MOR activation increased excitatory activity originated by the increased stimulating input to stratum oriens (i.e., Schäffer collateral and commissural [SCC] fibers, as well as the retrograde pathway), to stratum radiatum (i.e., SCC fibers) and to stratum lacunosum-moleculare (i.e., the perforant pathway and the thalamus). Increased excitatory activity was additionally facilitated by propagation through the neural network of area CA1. This was observed as a proportionally greater increment of amplitudes of excitatory activity in sites distant from the originally evoked activity. Such facilitation was noted in excitatory activity propagating from three sites of stimulation. The increment and facilitation were prevented with GABAA receptor antagonists (bicuculline, 30 μM), but not with GABAB receptor antagonists (CGP, 10 μM). Besides, MOR activation inhibited inhibitory post-synaptic potentials (IPSPs) in every layer of area CA1. These findings suggest that MOR-originated suppression of GABA release to GABAA receptors increases every type of input to pyramidal CA1 neurons and facilitates propagation of excitatory activity through the neural network of area CA1. Cannabis indica and memory. Cannabinoids (derived from Cannabis indica, or marihuana) disturb memory processes in mammalians. In spite of the fact that the neuronal cannabinoid CB1 receptor was identified several years ago, the neuronal network mechanisms mediating these effects are still controversial. Tritium-labeled GABA-releasing experiments have been used to test for the localization of this receptor at a cellular and subcellular level in the human hippocampus. CB1 expression detected with this technique is limited to hippocampal interneurons, most of which, it could be determined, are cholecystokinin-containing basket neurons. The CB1-positive neuronal somata show immune staining of their cytoplasm, but not of their somatodendritic plasma membrane. CB1-immunoreactive axonic terminals densely cover the entire hippocampus and form symmetrical synapses, characteristic of GABAergic neuronal boutons. It could thus be observed that WIN 55,212-2, a CB1-receptor agonist, considerably reduces the release of tritium-labeled GABA, and that this effect is preventable using the receptor antagonist, SR 141716A. This single pattern of expression and pre-synaptic modulation of GABA release suggests the existence of a preserved role of CB1 receptors in the control of inhibitory hippocampal networks responsible for the generation and maintenance of fast and slow oscillation patterns. Therefore, a probable mechanism whereby cannabinoids could affect associational processes in memory might be a disturbance of synchrony of rhythmical events in distinct neuronal populations. GABA effects against aging. Certain components which stimulate GABAergic neurotransmission might prevent the hippocampal and striatal degeneration which typically appears with old age and causes memory deterioration. On using a 4-vessel occlusion model in animals to study the effect of ischemia on expression of GABAA receptor subunits, which are vulnerable in region CA1 and resistant in region CA3 of Amnion's horn, an increment in expression of GABAA2, GABA B2, GABA G2 units and a decrement in expression of GABA A1 and GABA A3 subunits in region CA3 were obtained. On the contrary, there was no change in region CA1 or the dentate gyrus under the same conditions. These data speak in favor of the stimulation of type 2 receptor GABAergic subunits which might protect certain hippocampal areas against a harmful neurodegenerative effect, for example, of memory activities during old age.

Neurotransmisores del sistema límbico. Amígdala. Segunda parte

Resumen: Los neurotransmisores de la amígdala en el sistema límbico comprenden, entre otros, a las monoaminas (noradrenalina [NA]), la acetilcolina (ACh), los corticoides y la histamina. Ciertas drogas infundidas a la amígdala podrían modular la consolidación en la memoria de la inhibición del entrenamiento dirigido a evitar situaciones de estrés. La administración de anta gonistas de los receptores de la β NA en la amígdala afecta la retención en la memoria por un lapso de un día cuando se administra inmediatamente después del entrenamiento, pero no surte ningún efecto cuando se administra a las seis horas. Infusiones intraamigdalinas de NA acompañadas de antagonistas de aquellos receptores atenuarán el trastorno mnemónico. De manera importante, se ha podido determinar que la NA produce un incremento de la consolidación de la memoria, que depende tanto del tiempo como de la dosis de aplicación cuando el fármaco se infunde a la amígdala inmediatamente después de la inhibición de este tipo de entrenamiento. La amígdala, la neocorteza y el hipocampo son regiones meta del sistema cerebral frontal basal colinérgico, que se relaciona estrechamente con diversas funciones del aprendizaje y la memo ria. Cualquier neurotransmisor con actividad fosforiladora o desfosforiladora podrá regular el estado de sensibilidad a la ACh, así como las propiedades funcionales de las neuronas amigdalinas. Es posible, entonces, que exista una modulación entre los estados de aprendizaje y de recuerdo de lo aprendido en la amígdala, la neocorteza y el hipocampo que esté regida por receptores muscarínicos acetilcolinérgicos. Por medio de receptores presinápticos de la histamina 3 (H3) y un mecanismo por el momento aún desconocido, la histamina disminuye o aumenta la transmisión sináptica excitadora en el BLA. Tal modulación histaminérgica de la actividad neuronal cumple un papel importante en los procesos fisiológicos y patofisiológicos del miedo, el aprendizaje y la memoria de la emo ción y los trastornos afectivos.

Abstract: Neurotransmitters of the amygdala in the limbic system include monoamines (noradrenaline [NA]) acetylcholine (ACh), corticoids and histamine. Drugs infused into the amygdala may modulate consolidation in memory of inhibition of training directed to avoid stressful situations. Administration of antagonists of β NA receptors to the amygdala will affect retention in memory for a whole day when given immediately after training, but will have no effect when given six hours after training a test animal. Intra-amygdalar infusions of NA which may be accompanied by antagonists of those receptors will attenuate the memory disturbance. It is worth mentioning that later studies have been able to show that NA will produce an increment of memory consolidation, which will depend on the time as well as on the dose of application, when the drug is infused to the amygdala shortly after inhibition of training directed to avoid stressful situations. The amygdala, the neocortex and the hippocampus are target regions of the frontal basal cholinergic brain system, which has different effects on cognitive functions, such as memory and learning. Any neurotransmitter with phosphorylating or dephosphorylating activity may regulate the sensitive state of ACh, as well as the functional properties of amygdalar neurons. It is possible, then, that modulation mechanisms may exist between learning and recall states in the amygdala, the neocortex and the hippocampus, which could be controlled by muscarinic acetylcholinergic receptors. Through pre-synaptic receptors of histamine 3 (H3) and a currently unknown mechanism, histamine will decrease or increase excitatory synaptic transmission in BLA. Such histaminergic modulation of neuronal activity will play an important role in fear-related physiological and patho-physiological processes, learning and memory of emotion, and affective disturbances.

Tumores intracraneanos del niño / Pediatric intracranial tumors

Introducción. Los tumores intracraneanos (TIC) pediátricos son las neoplasias sólidas más frecuentes en niños. Se presenta la experiencia del Hospital Infantil de México Federico Gómez (HIMFG) de los últimos 36 años. Material y métodos. Se utilizaron los siguientes archivos del HIMFG: Clínico, de los Departamentos de Neurocirugía y de Patología. Los resultados se compararon con los datos del Hospital for Sick Children de Toronto y del Instituto Nacional de Pediatría de México, D. F. Resultados. En el HIMFG, 55% de los pacientes eran del sexo masculino. Predominaron desde lactantes mayores hasta escolares, con más de 50%. Los tumores fueron: 397 supratentoriales y 413 infratentoriales. Los más frecuentes fueron: astrocitomas (32%), meduloblastomas (19%), craneofaringiomas (11%) y ependimomas (10%); en el quinto lugar quedaron los germinomas (4%). Los gliomas mixtos, los meningiomas, los tumores neuroectodérmicos primitivos y los ependimoblastomas representaron de 1 a 3%. Conclusiones. En el HIMFG, los 4 tipos más frecuentes de tumor fueron: astrocitomas, meduloblastomas, craneofaringiomas y ependimomas. El trabajo de campo del HIMFG ha tenido un desarrollo exponencial desde la mitad de los años setenta. Actualmente, el volumen de pacientes manejado por el HIMFG es semejante a, o rebasa discretamente, al de otras instituciones.

Introduction. Pediatric intracranial tumors (PIC) make up the most frequent solid neoplastic pathology in children. We present an analysis of the experience of Hospital Infantil de Mexico Federico Gomez (HIMFG), in Mexico City, over the course of 36 years in this regard. Material and methods. Cases from the archives of the Department of Clinical Records, Department of Neurosurgery and Department of Pathology at HIMFG were used for this analysis. Results were compared to data published by the Hospital for Sick Children of Toronto (HSCT) and by Instituto Nacional de Pediatria (INP) in Mexico City. Results. Of 810 cases reviewed at HIMFG, 55% belonged to the male gender. By age, older-infant and grade-school-children cases predominated (> 50%). Of those, 397 cases were supratentorial and 413 infratentorial. Most frequent tumors were: astrocytomas (23%), medulloblastomas , craniopharyngiomas (11%) and ependymomas (10%). Fifth place was occupied by germinomas (4%). Mixed gliomas, meningiomas, primitive neuroectodermal tumors and ependymoblastomas were the last (1 to 3%). Conclusions. At HIMFG, the most frequent tumour types were: astrocytomas, medulloblastomas, craniopharyngiomas and ependymomas. Since the 70s, on the number of patients presenting with intracranial tumors at HIMFG has grown exponentially, and the amount carried out till now at this hospital parallels, or slightly exceeds, that carried out at similar institutions in Mexico and abroad.

Neurotransmisores del sistema límbico. I. Amígdala. Primera parte

Resumen Los neurotransmisores de la amígdala en el sistema límbico comprenden, entre otros, al ácido γ-aminobutírico (GABAA,B,G), el ácido glutámico (GLU) y el N-metil-D-aspartato (NMDA), así como a las monoaminas [dopamina (DA) e hidroxitriptamina (5-HT)]. El GABA es el principal neurotransmisor inhibidor. Su actividad inhibidora se bloquea, por ejemplo, por los efectos ansiolíticos de las benzodiacepinas, tanto en la amígdala como en otros centros del sistema límbico (tálamo, corteza prefrontal, hipocampo, etc.) conectados con esta estructura. Igualmente, la corteza prefrontal cerebral regula los procesos de memoria en los que esté involucrado un componente afectivo a través de conexiones inhibidoras GABAérgicas sobre el núcleo lateral (LA) de la amígdala. Al estimularse las vías córtico-amigdalinas y tálamo-amigdalinas, se produce una excitación seguida de una inhibición mediadas por receptores del GABA en el LA. Una reducción de la inhibición puede obtenerse ya sea al estimular conjuntamente ambas vías, o al estimular primero una y luego la otra vía. Ambos tipos de depresión se regulan por inhibidores presinápticos del GABAB en interneuronas del LA que conectan con el núcleo central (CE) de la amígdala, y que aparentemente llegan por una u otra vía. Este dato apoya la existencia de un ingreso monosináptico convergente de información al LA, ingreso que interviene en la respuesta a diferentes condiciones estresantes y que limita una actividad neuronal excesiva. El GLU es el principal neurotransmisor excitador. Al estimularse la amígdala durante la aversión condicionada contra ciertos sabores por este neurotransmisor, se produce una inhibición de la actividad hipotalámica procedente de vías GABAérgicas amigdalinas que van al hipotálamo. El LA es parte del circuito neural que subyace al condicionamiento pavloviano al miedo. En este circuito, el bloqueo de los receptores de NMDA glutámicos en el LA antes del entrenamiento altera el aprendizaje del condicionamiento al miedo, pero el bloqueo previo a la prueba también altera dicha expresión. Se ha visto que un bloqueo específico causa una disrupción del circuito que interviene en el aprendizaje de este condicionamiento, mas no de la consolidación en la memoria del proceso en un momento posterior al aprendizaje. La estimulación de los colículos inferiores (CI) causa un aumento significativo de los niveles de DA en la corteza prefrontal (PFC). Asimismo, el complejo basolateral de la amígdala (BLA) sirve como filtro de la información con carga negativa que promueve el escape y que asciende a estructuras más elevadas del tallo cerebral. Se ha observado que la desactivación del BLA interfiere con la activación de los egresos dopaminérgicos corticales producidos por una estimulación con carga negativa de los CI. Se ha podido demostrar que la información con carga negativa que asciende desde los CI cursa con una modulación opuesta dada por mecanismos de DA/5-HT que descienden desde la PFC. Estos procesos parecen regularse por filtros localizados en el BLA. Existe la posibilidad de que la DA proveniente del BLA module las respuestas de la DA del nucleus accumbens durante el estrés indirectamente por medio de conexiones de la primera con la corteza prefrontal medial, la cual inhibirá, por medio de la DA, la transmisión dopaminérgica de este núcleo.

Summary Neurotransmitters of the amygdala in the limbic system include, among others, γ-aminobutyric acid (GABAA,B.G), glutamic acid (GLU) and N-methyl-D-aspartate (NMDA), as well as the monoamines [dopamine (DA) and 5-hydroxytriptamine (5-HT)]. GABA is the main inhibitory neurotransmitter. Its inhibitory activity will be blocked, for example, by the anxiolytic effects of benzodiazepines both in the amygdala and in other nuclei of the limbic system (thalamus, prefrontal cortex, hippocampus, etc.) connected to this structure. Similarly, the cerebral prefrontal cortex will regulate memory and learning processes in which an affective component may be involved through GABAergic inhibitory connections reaching the lateral nucleus (LA) of the amygdala. On stimulating cortico- and thalamo-amygdalar pathways, an excitation will be produced followed by an inhibition, both of which are mediated by GABA receptors in LA. A reduction of the second inhibition may be obtained either by joint stimulation of both pathways or by stimulation of the first and then the other pathway. Both types of depression can be regulated by presynaptic inhibitors of GABAB in LA interneurons connecting with the central nucleus of the amygdala, and which apparently arrive via either the cortical or the thalamic pathway. These data support the existence of a convergent monosynaptic information input which will be active in response to different stressful conditions, and which will limit excessive neuronal activity. GLU is the main excitatory neurotransmitter. When the amygdala is excited in the course of aversive conditioning against certain flavors by this neurotransmitter, a further inhibition of hypothalamic activity will be produced arriving via GABAergic amygdalar pathways to the hypothalamus. LA is part of the neural circuit underlying pavlovian fear conditioning. In this circuit, blocking glutamate NMDA receptors in LA before training will alter acquisition of fear conditioning, but blocking this nucleus before testing will also alter such expression. Recent research has shown that blocking will cause specific disruption of the circuits participating in fear learning, and not of memory consolidation of this process some time after learning. Stimulation of the inferior colliculi (IC) will cause a significant increment of DA levels in prefrontal cortex (PFC). Likewise, the basolateral complex (BLA) of the amygdala will serve as a filter of aversive information ascending to upper structures of the brainstem. In this regard, it has been observed that deactivation of BLA will interfere with activation of cortical dopaminergic outputs produced by aversive stimulation arriving from the IC. Aversive information ascending from the IC has been shown to be modulated by DA/5-HT mechanisms descending from PFC. These processes appear to be regulated by filters located in BLA. In the same fashion, there is the possibility that DA from the basolateral amygdala may modulate responses of DA from the nucleus accumbens during stress indirectly via connections of the amygdala with the PFC, which will inhibit, again, via DA, dopaminergic transmission of the nucleus accumbens.

Aspectos neurológicos del desarrollo normal y patológico del lenguaje / Neurological aspects of normal and pathologic development of language

Información actualizada en torno a diversos temas neurológicos del desarrollo normal y alterado del lenguaje. De igual forma, se analizan los conocimientos obtenidos sobre los fundamentos neuropsicológicos y neurológicos del lenguaje, analizando también el desarrollo, maduración y patología de las vías y centros auditivos, visuales, motores, sensoriales, cognoscitivos y lingüísticos del sistema nervioso central. El libro se divide en: A. Conceptos anatómicos y fisiológicos B. Lenguaje normal C. Lenguaje anormal D. Afasia E. Dislexia y disgrafía F. Autismo