Visual attention deficits in schizophrenia can arise from inhibitory dysfunction in thalamus or cortex

Schizophrenia is associated with diverse cognitive deficits, including disorders of attention-related oculomotor behavior. At the structural level, schizophrenia is associated with abnormal inhibitory control in the circuit linking cortex and thalamus. We developed a spiking neural network model that demonstrates how dysfunctional inhibition can degrade attentive gaze control. Our model revealed that perturbations of two functionally distinct classes of cortical inhibitory neurons, or of the inhibitory thalamic reticular nucleus, disrupted processing vital for sustained attention to a stimulus, leading to distractibility. Because perturbation at each circuit node led to comparable but qualitatively distinct disruptions in attentive tracking or fixation, our findings support the search for new eye movement metrics that may index distinct underlying neural defects. Moreover, because the cortico-thalamic circuit is a common motif across sensory, association, and motor systems, the model and extensions can be broadly applied to study normal function and the neural bases of other cognitive deficits in schizophrenia.R01 MH057414 - NIMH NIH HHS; R01 MH101209 - NIMH NIH HHS; R01 NS024760 - NINDS NIH HHSPublished versio

The emotional gatekeeper: a computational model of attentional selection and suppression through the pathway from the amygdala to the inhibitory thalamic reticular nucleus

In a complex environment that contains both opportunities and threats, it is important for an organism to flexibly direct attention based on current events and prior plans. The amygdala, the hub of the brain's emotional system, is involved in forming and signaling affective associations between stimuli and their consequences. The inhibitory thalamic reticular nucleus (TRN) is a hub of the attentional system that gates thalamo-cortical signaling. In the primate brain, a recently discovered pathway from the amygdala sends robust projections to TRN. Here we used computational modeling to demonstrate how the amygdala-TRN pathway, embedded in a wider neural circuit, can mediate selective attention guided by emotions. Our Emotional Gatekeeper model demonstrates how this circuit enables focused top-down, and flexible bottom-up, allocation of attention. The model suggests that the amygdala-TRN projection can serve as a unique mechanism for emotion-guided selection of signals sent to cortex for further processing. This inhibitory selection mechanism can mediate a powerful affective 'framing' effect that may lead to biased decision-making in highly charged emotional situations. The model also supports the idea that the amygdala can serve as a relevance detection system. Further, the model demonstrates how abnormal top-down drive and dysregulated local inhibition in the amygdala and in the cortex can contribute to the attentional symptoms that accompany several neuropsychiatric disorders.R01MH057414 - NIMH NIH HHS; R01 MH057414 - NIMH NIH HHS; R01 MH101209 - NIMH NIH HHS; R01NS024760 - NINDS NIH HHS; R01MH101209 - NIMH NIH HHS; R01 NS024760 - NINDS NIH HH

Interaction patterns for smart spaces: a confident interaction design solution for pervasive sensitive IoT services

Smart spaces represent a powerful tool for deploying the new pervasive sensitive services based on Internet of Things products and developed in current Information Society close to users. Researchers have focused their efforts on new techniques to improve systems and products in this area but neglecting the human factors related to psychological aspects of the user and their psycho-social relationship with the deployment space where they live. This research proposes to take into account these cognitive features in early stages of the design of smart spaces by defining a set of interaction patterns. By using this set of interaction patterns it is possible to influence over the confidence that users can develop during the use of IoT products and services based on them. An evaluative verification has been carried out to assess how this design engineering approach provide a real impact on the generation of confidence in the users of this kind of technology

The use of on-line characterization technologies during the manufacture of nanostructured materials

Tese de doutoramento em Ciência e Engenharia de Polímeros e CompósitosSince their potential has become widely recognized, one of the major research lines on polymer-clay nanocomposites has focused on the preparation of well dispersed systems, which involves investigating their compounding (including their structural and morphological characterization) and the determination of their physical and mechanical performances. Currently, there is an understanding that a high degree of dispersion, particularly exfoliation, of the nanoclay is required to improve the overall performance. Although the influencing parameters are known – interfacial adhesion, chemical affinity and operating conditions – the effect of each on the onset and extent of the organoclay dispersion are still subject of debate. Twin screw extrusion allows for control of the main variables (shear, stress and time), but also, due to the typical modular construction, offers a high degree of freedom in creating the adequate screw design and enables knowledgeable alteration of the barrel. These features offer a solid basis for the development and implementation of apt on-line/in-line monitoring techniques, able to follow up the evolution of dispersion of polymer-clay nanocomposites during processing. This research included the validation, implementation and application of a methodology based on inline Near-Infrared (NIR) Spectroscopy for the characterization of the dispersion along the extruder axis. The results showed that the operating conditions have great impact on the dispersion level, but also that degradation may affect the interfacial chemistry of the system, altering the dispersion pathways. Overall the results obtained confirm that NIR is a valid tool for the on-line characterization of these materials, offering the possibility of assessing in real time the clay dispersion, enabling proper corrective and optimization actions over the material characteristics in a timely manne

Distinction of Neurons, Glia and Endothelial Cells in the Cerebral Cortex: An Algorithm Based on Cytological Features

The estimation of the number or density of neurons and types of glial cells and their relative proportions in different brain areas are at the core of rigorous quantitative neuroanatomical studies. Unfortunately, the lack of detailed, updated, systematic, and well-illustrated descriptions of the cytology of neurons and glial cell types, especially in the primate brain, makes such studies especially demanding, often limiting their scope and broad use. Here, following extensive analysis of histological materials and the review of current and classical literature, we compile a list of precise morphological criteria that can facilitate and standardize identification of cells in stained sections examined under the microscope. We describe systematically and in detail the cytological features of neurons and glial cell types in the cerebral cortex of the macaque monkey and the human using semithin and thick sections stained for Nissl. We used this classical staining technique because it labels all cells in the brain in distinct ways. In addition, we corroborate key distinguishing characteristics of different cell types in sections immunolabeled for specific markers counterstained for Nissl and in ultrathin sections processed for electron microscopy. Finally, we summarize the core features that distinguish each cell type in easy-to-use tables and sketches, and structure these key features in an algorithm that can be used to systematically distinguish cellular types in the cerebral cortex. Moreover, we report high inter-observer algorithm reliability, which is a crucial test for obtaining consistent and reproducible cell counts in unbiased stereological studies. This protocol establishes a consistent framework that can be used to reliably identify and quantify cells in the cerebral cortex of primates as well as other mammalian species in health and disease

Recent developments on on-line rheometry to monitor the extrusion process

On-line rheometers are generally inserted between extruder and die and generate data that is typically utilized for quality control purposes. However, on-line rheometers have also the potential to detect changes in structure, morphology, or composition of a given material system, thus assisting materials research and processing optimization, if they can be used along the axis of the extruder or compounder. The authors have previously developed on-line capillary and rotational/oscillatory rheometers that can be inserted and used at specific locations along the extruder. Since these devices are operated manually, their manipulation may be cumbersome and data may lack reliability. This work presents new versions of these rheometers, with improved functionalities and motorized operation. Details on the validation of one of them is also given.This study was carried out within the frame of the MULTIHYBRIDS IP 026685-2IP project, 6th Framework EC Program. The authors also gratefully acknowledge funding by FEDER via FCT, Fundação para a Ciência e Tecnologia, under the POCI 2010 and Plurianual programs

Retinal nerve fiber layer abnormalities in Alzheimer's disease

Retinal nerve fiber layer (RNFL) photographs from 26 patients with Alzheimer's disease and 23 normal, age-matched, control subjects were reviewed for quality and abnormalities by two observers. A higher proportion of Alzheimer's patients showed RNFL abnormalities when compared to control subjects. There was some disagreement between the two observers regarding quality and frequency of abnormalities, reflecting suboptimal quality of the photographs obtained in patients with advanced Alzheimer's disease. Although these findings add to the clinical and histopathological evidence that ganglion cell degeneration occurs in Alzheimer's disease, the difficulty in obtaining and evaluating retinal nerve fiber layer photographs, especially in advanced cases, may limit the clinical usefulness of retinal nerve fiber layer analysis in such patients.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73257/1/j.1600-0420.1996.tb00090.x.pd

Two New Polymorphic Cocrystals of Zafirlukast: Preparation, Crystal Structure, and Stability Relations

Two new cocrystals of zafirlukast with piperazine, existing in five different solid forms, have been discovered during a cocrystal screening. The crystal structure of one of these forms has been determined by single crystal X-ray diffraction, and the stability landscape of the crystalline forms of the new cocrystal has been studied. In the present article, we extend the knowledge about the solid state of this important pharmaceutical drug for the treatment of asthma by reporting the crystal structures of two new solvates (acetonitrile and butanol) and the elusive anhydrous Form X, which have been solved by single crystal X-ray diffraction