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.

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.

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.

Photonic processing subsystem based on visual cortex architecture

Optical signal processing in any living being is more complex than the one obtained in artificial systems. Cortex architecture, although only partly known, gives some useful ideas to be employed in communications. To analyze some of these structures is the objective of this paper. One of the main possibilities reported is handling signals in a parallel way. As it is shown, according to the signal characteristics each signal impinging onto a single input may be routed to a different output. At the same time, identical signals, coming to different inputs, may be routed to the same output without internal conflicts. This is due to the change of some of their characteristics in the way out when going through the intermediate levels. The simulation of this architecture is based on simple logic cells. The basis for the proposed architecture is the five layers of the mammalian retina and the first levels of the visual cortex.

Determinación de los parámetros de diseño a aplicar al proyecto de grandes yates a motor, en base a nuevos requerimientos de eficiencia energética y protección del medioambiente marino

Durante los últimos años, la construcción de grandes yates ha evolucionado hacia conceptos y diseños más complejos dónde se ha priorizado en muchas ocasiones la estética arquitectónica y exigencias de confort de los armadores y operadores dejando en segundo plano aspectos clave de seguridad. Diferentes Organismos Internacionales y las Sociedades de Clasificación han venido adaptando sus requisitos a la problemática específica de este tipo de buques, tratando de compatibilizar tendencias de diseño con exigencias de resistencia, integridad estructural, estanqueidad y seguridad entre otras. En la actualidad, la construcción de grandes yates con esloras incluso por encima de los 100 metros, el aumento del número de pasajeros por encima del límite tradicional de 12, las nuevas tendencias de ahorro energético y protección medioambiental que se están implantando en la industria en general y marítima en particular, plantean una serie de desafíos tanto a los diseñadores como a las Sociedades de Clasificación que deben avanzar en sus reglamentaciones para cubrir estos y otros aspectos. Son precisamente estos aspectos medioambientales, tradicionalmente relegados en la industria de grandes yates los que están ocupando en la actualidad un primer plano en los desarrollos de normativa de diferentes Organismos Internacionales y Nacionales. El impacto que estas nuevas normativas van a tener sobre el diseño de grandes yates a motor centra el desarrollo de esta Tesis. Hasta donde ha podido conocer el doctorando, esta es la primera vez que en una Tesis Doctoral se abordan los principales mecanismos que regulan el diseño y la construcción de grandes yates a motor, se estudian y analizan las regulaciones internacionales en materia de protección medioambiental y de eficiencia energética aplicables a los yates, se seleccionan y describen un conjunto de tecnologías maduras de carácter medioambiental, susceptibles de ser empleadas en yates y se determina los parámetros y aspectos del diseño a aplicar al proyecto de grandes yates a motor como resultado de la aplicación de estas tecnologías, analizados bajo la perspectiva de la Sociedad de Clasificación y de los Organismos Internacionales. La Tesis comienza con un análisis de la industria de construcción de grandes yates, la flota existente de grandes yates, la cartera actual de pedidos y la evolución esperada del mercado. Aquí se pone de manifiesto que a pesar de la crisis económica global de los últimos años, este mercado goza relativamente de buena salud y las previsiones son favorables, particularmente para el sector en Europa. A continuación se aborda el estado del arte del diseño de yate grande, sus peculiaridades, particularmente estructurales y de armamento, que le diferencian de otros tipos de buques y las tendencias en su diseño. Se pone de manifiesto cómo el proyecto de estos yates ha evolucionado hacia yates de gran tamaño y complejidad técnica, debido a la demanda y necesidades actuales y cómo ha influido en aspectos como la disposición estructural. Seguidamente se describen los principales mecanismos que regulan el diseño y construcción de grandes yates, particularmente el Código de Grandes Yates Comerciales de la Maritime & Coastguard Agency del Reino Unido, y las Reglas y Reglamentos de la Sociedad de Clasificación Lloyd’s Register para la Clasificación de yates; por ser ambas organizaciones las que lideran el Registro y la Clasificación respectivamente de este tipo de buques, objeto del estudio. El doctorando ejerce su actividad profesional como inspector de Lloyd’s Register en una oficina técnica de apoyo y evaluación de diseño, siendo especialista en grandes yates, lo que ha permitido exponer de primera mano el punto de vista de la Sociedad de Clasificación. En el siguiente Capítulo se describen las principales reglamentaciones internacionales de carácter medioambiental que afectan al diseño, construcción y operación de los yates, algunas de las cuales, como es el caso del Convenio Internacional para el Control y la Gestión del Agua de Lastre y Sedimentos de los buques (BWM 2004) aún no ha entrado en vigor a la fecha de terminación de esta Tesis. Seguidamente se realiza una selección de tecnologías desde el punto de vista de protección medioambiental y ahorro energético y su aplicación al diseño y construcción de grandes yates. Algunas de estas tecnologías son maduras y ya habían sido utilizadas con éxito en otros tipos de buques, pero su aplicación a los yates entraña ciertos desafíos que se describen en este Capítulo. A continuación se determinan y analizan los principales parámetros de diseño de los yates grandes a motor como consecuencia de las tecnologías estudiadas y se indican una serie de aspectos de diseño bajo la perspectiva de la Sociedad de Clasificación y de los Organismos Marítimos Internacionales. Finalmente se llega a una serie de conclusiones y se identifican futuras líneas de investigación en relación a las tecnologías descritas en este trabajo. ABSTRACT In recent years, the building of large yachts has evolved into more complex concepts and designs where often prioritized architectural aesthetics and comfort requirements of owners and operators leaving in the background key security aspects. Several international organizations and classification societies have been adapting their requirements to the specific problems of this type of vessel, trying to reconcile demands design trends with resistance, structural integrity, watertightness and safety among others. At present, the building of large yachts with lengths even above 100 meters, the increase in passenger numbers over the traditional limit of 12, new trends of energy saving and environmental protection are being implemented in the marine industry in particular, they pose a number of challenges to both designers and classification societies that should update and improve their regulations to cover these and other aspects. It is precisely these environmental issues, traditionally relegated to the large yacht industry, which are currently occupying center stage in the development of rules of different international and national bodies. The impact that these new standards will have on the design of large motor yachts focuses the development of this thesis. As far as it is known, this is the first time in a doctoral thesis the main mechanisms regulating the design and construction of large motor yachts are addressed, the international regulations on environmental protection and energy efficiency requirements for yachts are studied and analyzed, a set of mature environmental technologies, capable of being applied to yachts are selected and described, the parameters and design aspects to be applied to large yacht projects as a result of the application of these technologies are determined and analyzed from the perspective of the Classification Society and international organizations. The thesis begins with an analysis of the shipbuilding industry of large yachts, the existing fleet of large yachts, the current backlog and the expected market developments. Here it becomes clear that despite the global economic crisis of recent years, this market enjoys relatively good health and prospects are favorable, particularly for the sector in Europe. Then the state of the art of large yacht design, its peculiarities, particularly structural and outfitting, that differentiate it from other types of ships and trends in design is discussed. It shows how the project of these yachts has evolved to large yachts and technical complexity, due to the demand and needs and how it has influenced the structural arrangement aspects. Then the main mechanisms regulating the design and construction of large yachts, particularly the Large Commercial Yacht Code developed by the Maritime & Coastguard Agency (UK) and the Lloyd’s Register Rules & Regulations for the Classification of Special Service Craft including yachts are described; the two organizations to be leading the registration and classification respectively of such vessels under study. The doctoral student practices his profession as a senior specialist to Lloyd’s Register in a technical support office, dealing with the design assessment of large yachts, which allowed exposing firsthand view of the Classification Society. In the next chapter describes the main international environmental regulations, affecting the design, construction and operation of yachts, some of which, such as the International Convention for the Control and Management of Ships' Ballast Water and Sediments (BWM 2004) has not yet entered into force at the date of completion of this thesis. Following is a selection of technologies from the point of view of environmental protection and energy saving and its application to design and construction of large yachts. Some of these technologies are mature and have already been used successfully in other ship types, but their application to yachts entails certain challenges that are described in this chapter. Then identifies and analyzes the main design parameters of large motor yachts as a result of the technologies studied and a number of design aspects are given from the perspective of Classification Society and international maritime organizations. Finally, a number of conclusions are exposed, and future research is identified in relation to the technologies described in this Thesis.