Random positions of dendritic spines in human cerebral cortex

Dendritic spines establish most excitatory synapses in the brain and are located in Purkinje cell’s dendrites along helical paths, perhaps maximizing the probability to contact different axons. To test whether spine helixes also occur in neocortex, we reconstructed >500 dendritic segments from adult human cortex obtained from autopsies. With Fourier analysis and spatial statistics, we analyzed spine position along apical and basal dendrites of layer 3 pyramidal neurons from frontal, temporal, and cingulate cortex. Although we occasionally detected helical positioning, for the great majority of dendrites we could not reject the null hypothesis of spatial randomness in spine locations, either in apical or basal dendrites, in neurons of different cortical areas or among spines of different volumes and lengths. We conclude that in adult human neocortex spine positions are mostly random. We discuss the relevance of these results for spine formation and plasticity and their functional impact for cortical circuits.

Random positioning of dendritic spines in the human cerebral cortex

Dendritic spines establish most excitatory synapses in the brain and are located in Purkinje cell?s dendrites along helical paths, perhaps maximizing the probability to contact different axons. To test whether spine helixes also occur in neocortex, we reconstructed ?500 dendritic segments from adult human cortex obtained from autopsies. With Fourier analysis and spatial statistics, we analyzed spine position along apical and basal dendrites of layer 3 pyramidal neurons from frontal, temporal, and cingulate cortex. Although we occasionally detected helical positioning, for the great majority of dendrites we could not reject the null hypothesis of spatial randomness in spine locations, either in apical or basal dendrites, in neurons of different cortical areas or among spines of different volumes and lengths. We conclude that in adult human neocortex spine positions are mostly random. We discuss the relevance of these results for spine formation and plasticity and their functional impact for cortical circuits.

Remote Effects of Hippocampal Sclerosis on Effective Connectivity during Working Memory Encoding: A Case of Connectional Diaschisis?

Accumulating evidence suggests a role for the medial temporal lobe (MTL) in working memory (WM). However, little is known concerning its functional interactions with other cortical regions in the distributed neural network subserving WM. To reveal these, we availed of subjects with MTL damage and characterized changes in effective connectivity while subjects engaged in WM task. Specifically, we compared dynamic causal models, extracted from magnetoencephalographic recordings during verbal WM encoding, in temporal lobe epilepsy patients (with left hippocampal sclerosis) and controls. Bayesian model comparison indicated that the best model (across subjects) evidenced bilateral, forward, and backward connections, coupling inferior temporal cortex (ITC), inferior frontal cortex (IFC), and MTL. MTL damage weakened backward connections from left MTL to left ITC, a decrease accompanied by strengthening of (bidirectional) connections between IFC and MTL in the contralesional hemisphere. These findings provide novel evidence concerning functional interactions between nodes of this fundamental cognitive network and sheds light on how these interactions are modified as a result of focal damage to MTL. The findings highlight that a reduced (top-down) influence of the MTL on ipsilateral language regions is accompanied by enhanced reciprocal coupling in the undamaged hemisphere providing a first demonstration of “connectional diaschisis.”

TMS- EEG Signatures of GABAergic Neurotransmission in the Human Cortex

Combining transcranial magnetic stimulation (TMS) and electroencephalography (EEG) constitutes a powerful tool to directly assess human cortical excitability and connectivity. TMS of the primary motor cortex elicits a sequence of TMS-evoked EEG potentials (TEPs). It is thought that inhibitory neurotransmission through GABA-A receptors (GABAAR) modulates early TEPs (<50 ms after TMS), whereas GABA-B receptors (GABABR) play a role for later TEPs (at ∼100 ms after TMS). However, the physiological underpinnings of TEPs have not been clearly elucidated yet. Here, we studied the role of GABAA/B-ergic neurotransmission for TEPs in healthy subjects using a pharmaco-TMS-EEG approach. In Experiment 1, we tested the effects of a single oral dose of alprazolam (a classical benzodiazepine acting as allosteric-positive modulator at α1, α2, α3, and α5 subunit-containing GABAARs) and zolpidem (a positive modulator mainly at the α1 GABAAR) in a double-blind, placebo-controlled, crossover study. In Experiment 2, we tested the influence of baclofen (a GABABR agonist) and diazepam (a classical benzodiazepine) versus placebo on TEPs. Alprazolam and diazepam increased the amplitude of the negative potential at 45 ms after stimulation (N45) and decreased the negative component at 100 ms (N100), whereas zolpidem increased the N45 only. In contrast, baclofen specifically increased the N100 amplitude. These results provide strong evidence that the N45 represents activity of α1-subunit-containing GABAARs, whereas the N100 represents activity of GABABRs. Findings open a novel window of opportunity to study alteration of GABAA-/GABAB-related inhibition in disorders, such as epilepsy or schizophrenia.

Safety study of transcranial static magnetic field stimulation (tSMS) of the human cortex

Transcranial static magnetic field stimulation (tSMS) in humans reduces cortical excitability. Objective: The objective of this study was to determine if prolonged tSMS (2 h) could be delivered safely in humans. Safety limits for this technique have not been described. Methods: tSMS was applied for 2 h with a cylindric magnet on the occiput of 17 healthy subjects. We assessed tSMS-related safety aspects at tissue level by measuring levels of neuron-specific enolase (NSE,a marker of neuronal damage) and S100 (a marker of glial reactivity and damage). We also included an evaluation of cognitive side effects by using a battery of visuomotor and cognitive tests. Results: tSMS did not induce any significant increase in NSE or S100. No cognitive alteration was detected. Conclusions: Our data indicate that the application of tSMS is safe in healthy human subjects, at least within these parameters

On nonlinearity in neural encoding models applied to the primary visual cortex

Within the regression framework, we show how different levels of nonlinearity influence the instantaneous firing rate prediction of single neurons. Nonlinearity can be achieved in several ways. In particular, we can enrich the predictor set with basis expansions of the input variables (enlarging the number of inputs) or train a simple but different model for each area of the data domain. Spline-based models are popular within the first category. Kernel smoothing methods fall into the second category. Whereas the first choice is useful for globally characterizing complex functions, the second is very handy for temporal data and is able to include inner-state subject variations. Also, interactions among stimuli are considered. We compare state-of-the-art firing rate prediction methods with some more sophisticated spline-based nonlinear methods: multivariate adaptive regression splines and sparse additive models. We also study the impact of kernel smoothing. Finally, we explore the combination of various local models in an incremental learning procedure. Our goal is to demonstrate that appropriate nonlinearity treatment can greatly improve the results. We test our hypothesis on both synthetic data and real neuronal recordings in cat primary visual cortex, giving a plausible explanation of the results from a biological perspective.

A stereological study of synapse number in the epileptic human hippocampus

Hippocampal sclerosis is the most frequent pathology encountered in resected mesial temporal structures from patients with intractable temporal lobe epilepsy (TLE). Here, we have used stereological methods to compare the overall density of synapses and neurons between non-sclerotic and sclerotic hippocampal tissue obtained by surgical resection from patients with TLE. Specifically, we examined the possible changes in the subiculum and CA1, regions that seem to be critical for the development and/or maintenance of seizures in these patients. We found a remarkable decrease in synaptic and neuronal density in the sclerotic CA1, and while the subiculum from the sclerotic hippocampus did not display changes in synaptic density, the neuronal density was higher. Since the subiculum from the sclerotic hippocampus displays a significant increase in neuronal density, as well as a various other neurochemical changes, we propose that the apparently normal subiculum from the sclerotic hippocampus suffers profound alterations in neuronal circuits at both the molecular and synaptic level that are likely to be critical for the development or maintenance of seizure activity

Pyramidal cells in prefrontal cortex: comparative observations reveal unparalleled specializations in neuronal structure among primate species

The most ubiquitous neuron in the cerebral cortex, the pyramidal cell, is characterized by markedly different dendritic structure among different cortical areas. The complex pyramidal cell phenotype in granular prefrontal cortex (gPFC) of higher primates endows specific biophysical properties and patterns of connectivity, which differ from those in other cortical regions. However, within the gPFC, data have been sampled from only a select few cortical areas. The gPFC of species such as human and macaque monkey includes more than 10 cortical areas. It remains unknown as to what degree pyramidal cell structure may vary among these cortical areas. Here we undertook a survey of pyramidal cells in the dorsolateral, medial, and orbital gPFC of cercopithecid primates. We found marked heterogeneity in pyramidal cell structure within and between these regions. Moreover, trends for gradients in neuronal complexity varied among species. As the structure of neurons determines their computational abilities, memory storage capacity and connectivity, we propose that these specializations in the pyramidal cell phenotype are an important determinant of species-specific executive cortical functions in primates.

Empowering and assisting natural human mobility: The simbiosis walker

This paper presents the complete development of the Simbiosis Smart Walker. The device is equipped with a set of sensor subsystems to acquire user-machine interaction forces and the temporal evolution of user's feet during gait. The authors present an adaptive filtering technique used for the identification and separation of different components found on the human-machine interaction forces. This technique allowed isolating the components related with the navigational commands and developing a Fuzzy logic controller to guide the device. The Smart Walker was clinically validated at the Spinal Cord Injury Hospital of Toledo - Spain, presenting great acceptability by spinal chord injury patients and clinical staff

Impacto y protección radiológica asociados al transporte de residuos de alta actividad (RAA) al almacén temporal centralizado (ATC) en España

Las cuestiones relacionadas con el transporte de residuos radiactivos de alta actividad (RAA) al previsto almacén temporal centralizado (ATC) en Villar de Cañas (Cuenca) están de actualidad, debido a la movilidad que se espera en un futuro próximo, el compromiso con el medio ambiente, la protección de las personas, así, como la normativa legal reguladora. En esta tesis se ha evaluado el impacto radiológico asociado a este tipo de transportes mediante una nueva herramienta de procesamiento de datos, que puede ser de utilidad y servir como documentación complementaria a la recogida en el marco legal del transporte. Además puede facilitar el análisis desde una perspectiva más científica, para investigadores, responsables públicos y técnicos en general, que pueden utilizar dicha herramienta para simular distintos escenarios de transportes radiactivos basados únicamente en datos de los materiales de entrada y las rutas elegidas. Así, conociendo el nivel de radiación a un metro del transporte y eligiendo una ruta, obtendremos los impactos asociados, tales como las poblaciones afectadas, la dosis recibida por la persona más expuesta, el impacto radiológico global, las dosis a la población en el trayecto y el posible detrimento de su salud. En España se prevé una larga “ruta radiactiva” de más de 2.000 kilómetros, por la que el combustible nuclear gastado se transportará presumiblemente por carretera desde las centrales nucleares hasta el ATC, así como los residuos vitrificados procedentes del reprocesado del combustible de la central nuclear Vandellos I, que en la actualidad están en Francia. Como conclusión más importante, se observa que la emisión de radiaciones ionizantes procedentes del transporte de residuos radiactivos de alta actividad en España, en operación normal, no es significativa a la hora de generar efectos adversos en la salud humana y su impacto radiológico puede considerarse despreciable. En caso de accidente, aunque la posibilidad del suceso es remota, las emisiones, no serán determinantes a la hora de generar efectos adversos en la salud humana. Issues related to the transport of high level radioactive wastes (HLW) to the new centralised temporary storage facility to be built in Villar de Cañas (Cuenca) are attracting renewed attention due to the mobility expected in the near future for these materials, the commitment to the environment, the protection of persons and the legal regulatory standards. This study assesses the radiological impacts associated with this type of transport by means of a new dataprocessing tool, which may be of use and serve as documentation complementary to that included in the legal framework covering transport. Furthermore, it may facilitate analysis from a more scientific perspective for researchers, public servants and technicians in general, who may use the tool to simulate different radioactive transport scenarios based only on input materials data and the routes selected. Thus, by knowing the radiation level at a distance of one metre from the transport and selecting a route, it is possible to obtain the associated impacts, such as the affected populations, the dose received by the most exposed individual, the overall radiological impact and the doses to the public en route and the possible detriment to their health. In Spain a long “radioactive route” of more than 2,000 kilometres is expected, along which spent nuclear fuels will be transported – foreseeably by road – from the nuclear power plants to the CTS facility. The route will also be used for the vitrified wastes from fuel reprocessing of the fuel from Vandellós I nuclear power plant, which are currently in France. In conclusion, it may be observed that the emission of ionising radiations from transport of high level radioactive wastes in Spain is insignificant, in normal operations, as regards the generation of adverse effects for human health, and that the radiological impact may be considered negligible. In the event of an accident, the possibility of which is remote, the emissions will not be also a very determining factor as regards adverse effects for human health.

Lateral orbitofrontal cortex involvement in initial negative aesthetic impression formation

It is well established that aesthetic appreciation is related with activity in several different brain regions. The identification of the neural correlates of beauty or liking ratings has been the focus of most prior studies. Not much attention has been directed towards the fact that humans are surrounded by objects that lead them to experience aesthetic indifference or leave them with a negative aesthetic impression. Here we explore the neural substrate of such experiences. Given the neuroimaging techniques that have been used, little is known about the temporal features of such brain activity. By means of magnetoencephalography we registered the moment at which brain activity differed while participants viewed images they considered to be beautiful or not. Results show that the first differential activity appears between 300 and 400 ms after stimulus onset. During this period activity in right lateral orbitofrontal cortex (lOFC) was greater while participants rated visual stimuli as not beautiful than when they rated them as beautiful. We argue that this activity is associated with an initial negative aesthetic impression formation, driven by the relative hedonic value of stimuli regarded as not beautiful. Additionally, our results contribute to the understanding of the nature of the functional roles of the lOFC.

Human midbrain precursors activate the expected developmental genetic program and differentiate long-term to functional A9 dopamine neurons in vitro. Enhancement by Bcl-XL

Understanding the molecular programs of the generation of human dopaminergic neurons (DAn) from their ventral mesencephalic (VM) precursors is of key importance for basic studies, progress in cell therapy, drug screening and pharmacology in the context of Parkinson's disease. The nature of human DAn precursors in vitro is poorly understood, their properties unstable, and their availability highly limited. Here we present positive evidence that human VM precursors retaining their genuine properties and long-term capacity to generate A9 type Substantia nigra human DAn (hVM1 model cell line) can be propagated in culture. During a one month differentiation, these cells activate all key genes needed to progress from pro-neural and prodopaminergic precursors to mature and functional DAn. For the first time, we demonstrate that gene cascades are correctly activated during differentiation, resulting in the generation of mature DAn. These DAn have morphological and functional properties undistinguishable from those generated by VM primary neuronal cultures. In addition, we have found that the forced expression of Bcl-XL induces an increase in the expression of key developmental genes (MSX1, NGN2), maintenance of PITX3 expression temporal profile, and also enhances genes involved in DAn long-term function, maintenance and survival (EN1, LMX1B, NURR1 and PITX3). As a result, Bcl-XL anticipates and enhances DAn generation.

Spatio-temporal filtering with morphological operators for robust cell migration estimation in "in-vivo" images

The understanding of the embryogenesis in living systems requires reliable quantitative analysis of the cell migration throughout all the stages of development. This is a major challenge of the "in-toto" reconstruction based on different modalities of "in-vivo" imaging techniques -spatio-temporal resolution and image artifacts and noise. Several methods for cell tracking are available, but expensive manual interaction -time and human resources- is always required to enforce coherence. Because of this limitation it is necessary to restrict the experiments or assume an uncontrolled error rate. Is it possible to obtain automated reliable measurements of migration? can we provide a seed for biologists to complete cell lineages efficiently? We propose a filtering technique that considers trajectories as spatio-temporal connected structures that prunes out those that might introduce noise and false positives by using multi-dimensional morphological operators.

An approach to a model of the visual cortex: disorders of vision

One of the most challenging problems that must be solved by any theoretical model purporting to explain the competence of the human brain for relational tasks is the one related with the analysis and representation of the internal structure in an extended spatial layout of múltiple objects. In this way, some of the problems are related with specific aims as how can we extract and represent spatial relationships among objects, how can we represent the movement of a selected object and so on. The main objective of this paper is the study of some plausible brain structures that can provide answers in these problems. Moreover, in order to achieve a more concrete knowledge, our study will be focused on the response of the retinal layers for optical information processing and how this information can be processed in the first cortex layers. The model to be reported is just a first trial and some major additions are needed to complete the whole vision process.

New generation of human machine interfaces for controlling UAV through depth based gesture recognition

New forms of natural interactions between human operators and UAVs (Unmanned Aerial Vehicle) are demanded by the military industry to achieve a better balance of the UAV control and the burden of the human operator. In this work, a human machine interface (HMI) based on a novel gesture recognition system using depth imagery is proposed for the control of UAVs. Hand gesture recognition based on depth imagery is a promising approach for HMIs because it is more intuitive, natural, and non-intrusive than other alternatives using complex controllers. The proposed system is based on a Support Vector Machine (SVM) classifier that uses spatio-temporal depth descriptors as input features. The designed descriptor is based on a variation of the Local Binary Pattern (LBP) technique to efficiently work with depth video sequences. Other major consideration is the especial hand sign language used for the UAV control. A tradeoff between the use of natural hand signs and the minimization of the inter-sign interference has been established. Promising results have been achieved in a depth based database of hand gestures especially developed for the validation of the proposed system.