A critical view of the quest for brain structural markers of Albert Einstein's special talents (a pot of gold under the rainbow).

Assertions regarding attempts to link glial and macrostructural brain events with cognitive performance regarding Albert Einstein, are critically reviewed. One basic problem arises from attempting to draw causal relationships regarding complex, delicately interactive functional processes involving finely tuned molecular and connectivity phenomena expressed in cognitive performance, based on highly variable brain structural events of a single, aged, formalin fixed brain. Data weaknesses and logical flaws are considered. In other instances, similar neuroanatomical observations received different interpretations and conclusions, as those drawn, e.g., from schizophrenic brains. Observations on white matter events also raise methodological queries. Additionally, neurocognitive considerations on other intellectual aptitudes of A. Einstein were simply ignored.

Cellular complexity in subcortical white matter: a distributed control circuit?

The subcortical white matter (SWM) has been traditionally considered as a site for passive-neutral-information transfer through cerebral cortex association and projection fibers. Yet, the presence of subcortical neuronal and glial "interstitial" cells expressing immunolabelled neurotransmitters/neuromodulators and synaptic vesicular proteins, and recent immunohistochemical and electrophysiological observations on the rat visual cortex as well as interactive regulation of myelinating processes support the possibility that SWM nests subcortical, regionally variable, distributed neuronal-glial circuits, that could influence information transfer. Their hypothetical involvement in regulating the timing and signal transfer probability at the SWM axonal components ought to be considered and experimentally analysed. Thus, the "interstitial" neuronal cells-associated with local glial cells-traditionally considered to be vestigial and functionally inert under normal conditions, they may well turn to be critical in regulating information transfer at the SWM.

The interlaminar glia: from serendipity to hypothesis.

An account of work performed at the UNA laboratories since 1992 on the detection and description of interlaminar glial processes, is presented. The incidental observation (serendipity) of longer than expected glial processes in the superficial layers of the cerebral cortex in hemiparkinsonian Cebus apella monkeys, was expanded afterwards to cover the largest possible sampling of representatives of mammalian orders and species, as well as in experimental and pathological conditions, in human and non-human primates. The term interlaminar was coined to differentiate these processes from the classical astroglial stellate, intralaminar ones. Such account grew to the point of inspiring, on speculative grounds, possible roles in the organization of the cerebral cortex. Interlaminar glial processes represent an essentially primate characteristic, affected by neuropathological conditions such as DS and AD and experimental procedures affecting normal sensory input, suggesting thalamic involvement in their normal expression. Their ontogenetic development, phylogenetic evolution and aging changes are described.

Predictors of cognitive enhancement after training in preschoolers from diverse socioeconomic backgrounds.

The association between socioeconomic status and child cognitive development, and the positive impact of interventions aimed at optimizing cognitive performance, are well-documented. However, few studies have examined how specific socio-environmental factors may moderate the impact of cognitive interventions among poor children. In the present study, we examined how such factors predicted cognitive trajectories during the preschool years, in two samples of children from Argentina, who participated in two cognitive training programs (CTPs) between the years 2002 and 2005: the School Intervention Program (SIP; N = 745) and the Cognitive Training Program (CTP; N = 333). In both programs children were trained weekly for 16 weeks and tested before and after the intervention using a battery of tasks assessing several cognitive control processes (attention, inhibitory control, working memory, flexibility and planning). After applying mixed model analyses, we identified sets of socio-environmental predictors that were associated with higher levels of pre-intervention cognitive control performance and with increased improvement in cognitive control from pre- to post-intervention. Child age, housing conditions, social resources, parental occupation and family composition were associated with performance in specific cognitive domains at baseline. Housing conditions, social resources, parental occupation, family composition, maternal physical health, age, group (intervention/control) and the number of training sessions were related to improvements in specific cognitive skills from pre- to post-training.

Linking childhood poverty and cognition: environmental mediators of non-verbal executive control in an Argentine sample.

Tests of attentional control, working memory, and planning were administered to compare the non-verbal executive control performance of healthy children from different socioeconomic backgrounds. In addition, mediations of several sociodemographic variables, identified in the literature as part of the experience of child poverty, between socioeconomic status and cognitive performance were assessed. Results show: (1) significant differences in performance between groups in most dependent variables analyzed - however, not in all variables associated with attentional control domains; (2) significant indirect effects of literacy activities on working memory and fluid processing domains, as well as computer resources effects on fluid processing; and (3) marginal indirect effects of computer resources on attentional control and working memory domains. These findings extend analysis of the impact of poverty on the development of executive control, through information based on the assessment of combined neurocognitive paradigms and the identification of specific environmental mediators.

Local and remote cellular responses following a surgical lesion in the Cebus apella cerebral cortex.

Distribution of bromodeoxyuridine immunoreactive (BrdU-IR) cell nuclei was analyzed at proximal and remote cortical sites in adult Cebus apella monkeys after a programmed surgical lesion placed either in the prefrontal or in the striate cerebral cortex. Increased GFAP-IR and vimentin-IR astrocytes, as well as IsolectinB4 labeled microglial cells, were observed both at lesional and perilesional areas. After injury at either location, the BrdU nuclear incorporation spread to supragranular layers in remote cortical areas functionally related to the injured cortex, probably due to involvement of degenerated cortico-cortical association fibers. Double labeling with Ki-67 suggested that remote BrdU-IR nuclei belong to proliferating cells, but the cell type remains to be determined, since these nuclei did not correspond to NeuN, MAP2, GFAP, Vimentin and isolectinB4 labeled cells. This remote effect should be incorporated to current clinical and experimental appraisal of cortical lesions.

Exposure to environmental enrichment prior to a cerebral cortex stab wound attenuates the postlesional astroglia response in rats.

Modulation of astroglial components involved in reactive postlesional responses in the rat cerebral cortex was analyzed following exposure to environmental enrichment (EE) condition prior to injury. For this purpose, changes in % immunoreactive (IR) area of GFAP, vimentin, EAAT1 and ezrin were evaluated in the perilesional zone after placing a cortical stab wound in the visual cerebral cortex of adult rats. GFAP-IR postlesional reactive astrocytosis in the perilesional cortex was significantly lower in the animal group exposed to EE during postnatal development. This GFAP-IR reaction seems to be associated with existing astroglia, because neither BrdU- nor endogenous Ki-67-labeled nuclei were found in the perilesional cortex analyzed. Increased ezrin-IR area in the visual cortex of rats exposed to EE condition suggests the formation of new synapses or the enhancement of astroglial involvement in the existing ones. No effects of EE were found on either EAAT1- or vimentin-IR area. Results suggest that exposure to EE conditions prior to injury attenuates the postlesional astroglia GFAP-response in the perilesional cortex of rats. Whether this attenuated postlesional astroglia GFAP-response promotes or not protective effects on the cortical neuropil remains to be explored in futures studies.

Neurociencia y educación: hacia la construcción de puentes interactivos / Neuroscience and education: towards the construction of interactive bridges

Introducción. El debate sobre las relaciones potenciales entre neurociencia y educación comenzó hace aproximadamente unas tres décadas. La articulación de conocimientos neurocientíficos y educativos implica contemplar que la emergencia de procesos cognitivos y emocionales durante el desarrollo, así como la posibilidad de influenciarlos a través de intervenciones específicas, podrían integrarse a los procesos de aprendizaje y enseñanza. Objetivo. Examinar las implicaciones emergentes de los vínculos entre neurociencia, psicología cognitiva y educación, y los requisitos para la construcción de puentes interactivos entre diferentes campos de conocimiento. Desarrollo. Dicha construcción implica la reducción de brechas epistemológicas, metodológicas, tecnológicas y prácticas. La consideración del desarrollo humano y los procesos de aprendizaje en términos de multiplicidad de niveles de análisis podría contribuir al enriquecimiento de un diálogo crítico y a producciones conjuntas genuinas. Se plantean consideraciones epistemológicas y metodológicas, y se presentan diversas propuestas acerca de cómo establecer los puentes entre las disciplinas. Conclusiones. Dado el estado incipiente de los esfuerzos interdisciplinarios, sería conveniente abordar la construcción de puentes desde diversos ángulos, en lugar de establecer un puente único. Se proponen elementos constitutivos básicos para la generación de puentes dinámicos orientados a integrar las relaciones complejas involucradas en los procesos de enseñanza y aprendizaje (AU)

Introduction. The debates on the potential interdisciplinary association between neuroscience and education began approximately three decades ago. In order for the integration of neuroscientific and educational knowledge to impact on learning and teaching it would imply the consideration of the emergence of several cognitive and emotional processes during development, and the possibility to influence them through specific interventions. Aim. To examine epistemological and methodological implications and bridging requirements in the interaction between neuroscience, cognitive psychology and education. Development. A dynamic interdisciplinary bridging consists in the identification and reduction of different epistemological, methodological, technological and practical gaps between those disciplines. Furthermore, the consideration of complex phenomena, such as human development and learning processes in terms of multiple levels of analysis, may contribute to the enrichment of a critical dialogue, but also to generate genuine integrated interventions. Historical and current conceptual perspectives attempting to bridge neuroscience and education are described. Conclusions. At present, interdisciplinary efforts between neuroscience and education are at a preliminary stage. In this context, bridging requires conceptual and methodological approaches that consider the complexity of developmental and learning phenomena and the participation of actors from different fields, instead of unique bridges. This paper intends to consider several basic principles aimed at developing a dynamic integration that assesses the complexity of development, learning and teaching processes (AU)

Cell contact-inhibition signaling as part of wound-healing processes in brain.

Cell contact-dependent signaling is a major regulatory mechanism in the organization of developing tissues and in the reorganization (post-injury responses) of specialized tissues in multicellular organisms. In this review we contribute to the further understanding of post-injury recovery processes in adult nervous tissue. We emphasize evidence that supports the involvement of cell contact-inhibition signaling in the cell proliferation, growth and differentiation that occurs during healing and neural reorganization after brain damage.

Astroglial dye-coupling: an in vitro analysis of regional and interspecies differences in rodents and primates.

A regional and interspecies comparative analysis of astroglial coupling was performed using astroglia-enriched subcultures, following Lucifer Yellow dye intracellular injections. Rat cerebral cortex subcultures showed a greater coupling level than striatal subcultures. Interspecies analysis demonstrated a significant difference in the level of astroglial coupling in human cerebral cortex, compared with that of rat or monkey. Results provide an ex vivo insight into brain regional and interspecies differences of astroglial coupling, which may be associated with in situ modular or conditional cellular assemblies of the brain neuropil.

Astroglial injury in an ex vivo model: contributions to its analysis in enriched cell cultures.

In vitro cell culture models have been proposed to analyze some of the complex structural and functional characteristics involved in astroglial changes after neural injury in vivo. This report contributes to analyze the proposed hypothesis that an experimentally induced discontinuity of a confluent cellular culture could represent a useful model for the analysis of the processes involved in a neural lesion. For this purpose, it was decided to characterize astroglial proliferation and dye coupling state after a "scratch wound" applied to confluent, astrocyte-enriched cell cultures, obtained from several rat brain regions. Proliferation was assessed in terms of bromodeoxyuridine nuclear incorporation as a function of lesion width, serum deprivation, time after confluence, brain region origin, postlesional culture medium changes and agitation, and after application of a gap-junction uncoupling agent. The proliferative reaction after injury was neither cell type-specific nor brain region specific, nor was significantly affected by neither of the above-mentioned variables. Furthermore, injury failed to significantly affect the astroglial dye coupling state. Results suggest that the proliferative response observed under present conditions would depend on the disruption of contact inhibition rather than on astroglial mitogenic signals released from the wound and operating by either extracellular or cell coupling mechanisms. Present results question the validity of astrocyte-enriched cell cultures as an experimental model of neural tissue injury in vivo, as they do not appear to reproduce fundamental characteristics expressed in situ.

Premorbid exercising in specific cognitive tasks prevents impairment of performance in parkinsonian monkeys.

Adult Cebus apella monkeys were exposed to either one, two or four series of cognitive tasks that place a demand on working memory and inhibitory control (Spatial Delayed Response and Object Retrieval Detour), before administration of the neurotoxin 1-methyl-1-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Following MPTP treatment, monkeys receiving more than one series successfully reached criteria at delays similar to those attained during the pre-MPTP stage for the Spatial Delayed Response task and avoided increased perseveration in the Object Retrieval Detour task. Results provide evidence that protection towards a neurotoxin in specific cognitive performances can be increased by repeated exposure to task-specific cognitive demands and that motor and cognitive impairment following MPTP treatment can be effectively dissociated in primates.

Immunohistochemical analysis of subcortical white matter astroglia of infant and adult primate brains, with a note on resident neurons.

An immunohistochemical analysis of brain subcortical white matter astroglia from human (infant, adult) and adult monkey (Cebus apella, Macaca nemestrina) cases without any known neurological disease, is described. Expression of synaptic vesicle-associated proteins, excitatory amino acid transporters (EAAT1 and EAAT2) and GABAA Ralpha2 receptor produced coarse punctate labeling in human adult white matter astrocytes. A finer, generalized, punctate labeling was observed in human infants and adult C. apella monkeys. Labeling of neuronal somata and processes with microtubule-associated proteins (MAP2a-c) and neuron nuclear (NeuN) antibodies, was also observed in subcortical white matter of humans and monkeys. Results suggest competence of subcortical white matter astroglia of the primate brain to participate in various transmitter regulatory pathways. It is also proposed that, collectively with resident neurons, they may exert some role in affecting the transfer of information that takes place through the various associational and projecting fiber systems coursing through this brain compartment.

Cerebral cortex astroglia and the brain of a genius: a propos of A. Einstein's.

The glial fibrillary acidic protein immunoreactive astroglial layout of the cerebral cortex from Albert Einstein and other four age-matched human cases lacking any known neurological disease was analyzed using quantification of geometrical features mathematically defined. Several parameters (parallelism, relative depth, tortuosity) describing the primate-specific interlaminar glial processes did not show individually distinctive characteristics in any of the samples analyzed. However, A. Einstein's astrocytic processes showed larger sizes and higher numbers of interlaminar terminal masses, reaching sizes of 15 microm in diameter. These bulbous endings are of unknown significance and they have been described occurring in Alzheimer's disease. These observations are placed in the context of the general discussion regarding the proposal--by other authors--that structural, postmortem characteristics of the aged brain of Albert Einstein may serve as markers of his cognitive performance, a proposal to which the authors of this paper do not subscribe, and argue against.

Development of interlaminar astroglial processes in the cerebral cortex of control and Down's syndrome human cases.

Glial cytoarchitecture in human cerebral cortex is constituted by two overlapping layouts: the (general mammalian) "glial syncytium" and the (primate-specific) "interlaminar glial palisade" (IGP) composed by astroglial cells, with long, radial processes that traverse several supragranular layers. In this study, the emergence and early organization of the IGP was analyzed using immunocytochemical procedures in postmortem infantile human control and age matched, Down's syndrome (DS) cases. In control cases, first signs of a radial array of unbranched astroglial processes were apparent at the end of the period of "physiological astrocytosis" (20-40 days of postnatal life), and its general profile (except perhaps the density of cell processes) reached the adult-like configuration by the second month of life. The initial organization of the IGP was similar in control and DS cases, although a breakdown in DS became manifest by the first year of age, or earlier, albeit with individual variations. These changes tended to evolve in a "mosaic" fashion and included partial disruption of the palisade, or persistence of the "physiological astrocytosis". These observations were compared against samples from elder DS cases with an Alzheimer's type of dementia (AtD). Collectively, results suggest that DS also involves astroglial alterations during early stages of brain development, and that those changes progress with age, until an AtD ensues during adult life.

Glutamate uptake by rat brain astroglia incubated in human cerebrospinal fluid.

BACKGROUND: The glial compartment is critical for the regulation of glutamate concentration within the extracellular space. Reportedly, several factors influence glutamate uptake and metabolism in rat astroglia, which also appears to be affected by regional variables. In vitro, glutamate uptake by astroglia grown and tested in artificial media is affected by extracellular potassium. This report analyzes glutamate uptake by astroglia tested in a physiological extracelullar medium, cerebrospinal fluid (CSF), instead of artificial media. MATERIAL/METHODS: Astroglial enriched subcultures of fronto-parietal cerebral cortex and striatum from 5-day-old rat pups were used to study glutamate uptake, using human CSF as the extracellular medium. RESULT: Cultured astrocytes display significant glutamate uptake. This uptake is increased if the potassium concentration is elevated from 3.45 to 12.0 mM in culture medium, but not in the presence of CSE Differential effects of the glial inhibitor L-alpha-aminoadipic acid (L-alpha-AA) were observed at high concentrations in the presence of CSF, compared with standard incubation conditions. This was not observed when D-aspartate was used as a specific uptake competitor, suggesting that changes mediated by the presence of CSF components may not be directly linked to the primary transport mechanism, but could interfere at a more non-specific level. CONCLUSIONS: These results confirm data from previous work on regional astroglial differences in glutamatergic management. Yet increased glutamate uptake following changes in extracellular potassium concentration depended on the nature of the culture medium used, since replacement of artificial culture medium by CSF resulted in no such increase.

Interlaminar astroglial processes in the cerebral cortex of great apes.

The present study was designed to document the architecture of neocortical astroglia in great apes, following glial fibrillary acidic protein immunohistochemistry. These anthropoid species were missing from previous phylogenetic descriptions of astroglia with interlaminar processes, a characteristic event of the cerebral cortex within the Primate Order. Pongo pygmaeus (orangutan), Gorilla gorilla (gorilla) and Pan troglodytes (chimpanzee) brain samples showed the typical "palisade" of interlaminar processes. Yet, those from Pan troglodytes were less uniform, showing extended cortical segments with astrocytic ("syncytial-type") appearance, intermingled with segments expressing the interlaminar "palisade". Present observations contribute to fill in missing data on the phylogenetic emergence of the cerebral cortex astroglial interlaminar processes. Considering the extreme consistency of the expression of astroglial interlaminar "palisades" among anthropoid species, this apparent variability among Pan individuals could be due to various possibilities, which are considered in this report.

Glial changes in primate cerebral cortex following long-term sensory deprivation.

Significant morphological modifications in the layout of primate-specific (interlaminar) astroglia were found in somatosensory areas 3a, 3b, 1 and 2 eleven to thirteen months after transection of the posterior spinal cord in adult Macaca monkeys. These observations plus lack of evidence of a persistent reactive astrocytosis suggest that changes in the spatial arrangement of interlaminar glia may be an integral part of the long-term process of structural reorganization of the cerebral cortex following cortical deafferentation.

Interlaminar astroglia of the cerebral cortex: a marker of the primate brain.

Evidence for "cable-like" processes stemming from astroglial cells in the supragranular cerebral cortex has been recently presented. In addition to what could be called the "general mammalian-like" astroglial architecture (the so-called "panglial syncytium") of the cerebral cortex, composed of typical stellate astrocytes (intralaminar astrocytes), the anthropoid species, mostly catarrhines, show a manifest vertical, radial distribution of long (interlaminar) astroglial processes. It can be tentatively proposed that evolutionary pressures resulted in the progressive appearance, in primates, of a new type of glial cell. Its soma has a superficial location and unusually long cellular processes that invade, in a predominant radial fashion, the supragranular region of the cerebral cortex. Their existence has been ignored for more than a century. On the neuronal side, modular (columnar) organization of the cerebral cortex may represent an evolutionary acquisition that could optimize communication and information processing, with the least volume compromise in terms of wiring. Yet, for such columns to be functionally operative, adequate isolation from neighboring units would be required. A "mass" operation of the astroglial architecture would tend to compromise spatial definition and the degrees of freedom of such columnar modules. It is proposed that the presence of a "palisade" of interlaminar glial processes represents a relatively recent evolutionary event, instrumental for the optimization of the modular (columnar) organization of the cerebral cortex. It is interesting that the supragranular cortical region has undergone the largest growth among mammalian species during brain evolution, and has been associated with a crucial role in cortico-cortical interactions.

Pobreza y desempeño ejecutivo en alumnos preescolares de la ciudad de Buenos Aires (Republica Argentina) / Poverty and executive performance in preschool pupils from Buenos Aires city (República Argentina)

El estudio de los efectos de la pobreza sobre el desempeño cognitivo durante las primeras fases del desarrollo, ha sido efectuado predominantemente en base a la definición de pobreza según el ingreso y el uso de paradigmas de inteligencia basados en la hipótesis de un factor general de funcionamiento cognitivo. En el presente trabajo se utilizó el concepto de Necesidades Básicas Insatisfechas (NBI) como criterio de pobreza y se aplicó un paradigma cognitivo de funcionamiento ejecutivo proveniente de la Neurociencia. El mismo plantea el análisis de componentes de comportamientos inteligentes orientados hacia objetivos y asociados a la activación de circuitos cerebrales que involucran centralmente a la región prefrontal. Se comparó el desempeño ejecutivo de 247 niños escolarizados de 3 a 5 años de edad, provenientes de hogares pobres (NBI) y no pobres o con Necesidades Básicas Satisfechas (NBS), y de jardines de infantes del Distrito Escolar 4 de la Ciudad de Buenos Aires (Boca-Barracas) y de distritos escolares de Vicente López y San Isidro del Gran Buenos Aires (Argentina). Se administró una batería de pruebas que evalúan componentes de flexibilidad cognitiva, logro de objetivos y control atencional. Los resultados obtenidos muestran perfiles de desempeño diferentes entre ambos grupos. El perfil de desempeño menos eficiente en términos de las variables estudiadas se observó en el grupo de niños proveniente de hogares pobres. Estos resultados constituyen un aporte significativo de un paradigma neurocientífico para la implementación de estrategias de intervención orientadas a estimular el funcionamiento cognitivo de tipo ejecutivo de niños de edad preescolar