Functional MRI of facial emotion recognition deficits in schizophrenia and their electrophysiological correlates

Empirical evidence suggests impaired facial emotion recognition in schizophrenia. However, the nature of this deficit is the subject of ongoing research. The current study tested the hypothesis that a generalized deficit at an early stage of face-specific processing (i.e. putatively subserved by the fusiform gyrus) accounts for impaired facial emotion recognition in schizophrenia as opposed to the Negative Emotion-specific Deficit Model, which suggests impaired facial information processing at subsequent stages. Event-related potentials (ERPs) were recorded from 11 schizophrenia patients and 15 matched controls while performing a gender discrimination and a facial emotion recognition task. Significant reduction of the face-specific vertex positive potential (VPP) at a peak latency of 165 ms was confirmed in schizophrenia subjects whereas their early visual processing, as indexed by P1, was found to be intact. Attenuated VPP was found to correlate with subsequent P3 amplitude reduction and to predict accuracy when performing a facial emotion discrimination task. A subset of ten schizophrenia patients and ten matched healthy control subjects also performed similar tasks in the magnetic resonance imaging scanner. Patients showed reduced blood oxygenation level-dependent (BOLD) activation in the fusiform, inferior frontal, middle temporal and middle occipital gyrus as well as in the amygdala. Correlation analyses revealed that VPP and the subsequent P3a ERP components predict fusiform gyrus BOLD activation. These results suggest that problems in facial affect recognition in schizophrenia may represent flow-on effects of a generalized deficit in early visual processing.

Functional MRI BOLD response to Tower of London performance of first-episode schizophrenia patients using cortical pattern matching

Due to its three-dimensional folding pattern, the human neocortex; poses a challenge for accurate co-registration of grouped functional; brain imaging data. The present study addressed this problem by; employing three-dimensional continuum-mechanical image-warping; techniques to derive average anatomical representations for coregistration; of functional magnetic resonance brain imaging data; obtained from 10 male first-episode schizophrenia patients and 10 age-matched; male healthy volunteers while they performed a version of the; Tower of London task. This novel technique produced an equivalent; representation of blood oxygenation level dependent (BOLD) response; across hemispheres, cortical regions, and groups, respectively, when; compared to intensity average co-registration, using a deformable; Brodmann area atlas as anatomical reference. Somewhat closer; association of Brodmann area boundaries with primary visual and; auditory areas was evident using the gyral pattern average model.; Statistically-thresholded BOLD cluster data confirmed predominantly; bilateral prefrontal and parietal, right frontal and dorsolateral; prefrontal, and left occipital activation in healthy subjects, while; patients’ hemispheric dominance pattern was diminished or reversed,; particularly decreasing cortical BOLD response with increasing task; difficulty in the right superior temporal gyrus. Reduced regional gray; matter thickness correlated with reduced left-hemispheric prefrontal/; frontal and bilateral parietal BOLD activation in patients. This is the; first study demonstrating that reduction of regional gray matter in; first-episode schizophrenia patients is associated with impaired brain; function when performing the Tower of London task, and supports; previous findings of impaired executive attention and working memory; in schizophrenia.

Functional neuroanatomy of auditory mismatch processing : an event-related fMRI study of duration-deviant oddballs

This study was designed to identify the neural networks underlying automatic auditory deviance detection in 10 healthy subjects using functional magnetic resonance imaging. We measured blood oxygenation level-dependent contrasts derived from the comparison of blocks of stimuli presented as a series of standard tones (50 ms duration) alone versus blocks that contained rare duration-deviant tones (100 ms) that were interspersed among a series of frequent standard tones while subjects were watching a silent movie. Possible effects of scanner noise were assessed by a “no tone” condition. In line with previous positron emission tomography and EEG source modeling studies, we found temporal lobe and prefrontal cortical activation that was associated with auditory duration mismatch processing. Data were also analyzed employing an event-related hemodynamic response model, which confirmed activation in response to duration-deviant tones bilaterally in the superior temporal gyrus and prefrontally in the right inferior and middle frontal gyri. In line with previous electrophysiological reports, mismatch activation of these brain regions was significantly correlated with age. These findings suggest a close relationship of the event-related hemodynamic response pattern with the corresponding electrophysiological activity underlying the event-related “mismatch negativity” potential, a putative measure of auditory sensory memory.

Functional brain maps of Tower of London performance : a positron emission tomography and functional magnetic resonance imaging study

Regional cerebral blood flow (rCBF) and blood oxygenation level-dependent (BOLD) contrasts represent different physiological measures of brain activation. The present study aimed to compare two functional brain imaging techniques (functional magnetic resonance imaging versus [15O] positron emission tomography) when using Tower of London (TOL) problems as the activation task. A categorical analysis (task versus baseline) revealed a significant BOLD increase bilaterally for the dorsolateral prefrontal and inferior parietal cortex and for the cerebellum. A parametric haemodynamic response model (or regression analysis) confirmed a task-difficulty-dependent increase of BOLD and rCBF for the cerebellum and the left dorsolateral prefrontal cortex. In line with previous studies, a task-difficulty-dependent increase of left-hemispheric rCBF was also detected for the premotor cortex, cingulate, precuneus, and globus pallidus. These results imply consistency across the two neuroimaging modalities, particularly for the assessment of prefrontal brain function when using a parametric TOL adaptation.

Disrupted sensory gating in pathological gambling

Background Some neurochemical evidence as well as recent studies on molecular genetics suggest that pathologic gambling may be related to dysregulated dopamine neurotransmission. Methods The current study examined sensory (motor) gating in pathologic gamblers as a putative measure of endogenous brain dopamine activity with prepulse inhibition of the acoustic startle eye-blink response and the auditory P300 event-related potential. Seventeen pathologic gamblers and 21 age- and gender-matched healthy control subjects were assessed. Both prepulse inhibition measures were recorded under passive listening and two-tone prepulse discrimination conditions. Results Compared to the control group, pathologic gamblers exhibited disrupted sensory (motor) gating on all measures of prepulse inhibition. Sensory motor gating deficits of eye-blink responses were most profound at 120-millisecond prepulse lead intervals in the passive listening task and at 240-millisecond prepulse lead intervals in the two-tone prepulse discrimination task. Sensory gating of P300 was also impaired in pathologic gamblers, particularly at 500-millisecond lead intervals, when performing the discrimination task on the prepulse. Conclusions In the context of preclinical studies on the disruptive effects of dopamine agonists on prepulse inhibition, our findings suggest increased endogenous brain dopamine activity in pathologic gambling in line with previous neurobiological findings.

Differential susceptibility to performance degradation across categories of facial emotion - a model confirmation

Patients with a number of psychiatric and neuropathological conditions demonstrate problems in recognising facial expressions of emotion. Research indicating that patients with schizophrenia perform more poorly in the recognition of negative valence facial stimuli than positive valence stimuli has been interpreted as evidence of a negative emotion specific deficit. An alternate explanation rests in the psychometric properties of the stimulus materials. This model suggests that the pattern of impairment observed in schizophrenia may reflect initial discrepancies in task difficulty between stimulus categories, which are not apparent in healthy subjects because of ceiling effects. This hypothesis is tested, by examining the performance of healthy subjects in a facial emotion categorisation task with three levels of stimulus resolution. Results confirm the predictions of the model, showing that performance degrades differentially across emotion categories, with the greatest deterioration to negative valence stimuli. In the light of these results, a possible methodology for detecting emotion specific deficits in clinical samples is discussed.

Optimal eradication: When to stop looking for an invasive plant

The notion of being sure that you have completely eradicated an invasive species is fanciful because of imperfect detection and persistent seed banks. Eradication is commonly declared either on an ad hoc basis, on notions of seed bank longevity, or on setting arbitrary thresholds of 1% or 5% confidence that the species is not present. Rather than declaring eradication at some arbitrary level of confidence, we take an economic approach in which we stop looking when the expected costs outweigh the expected benefits. We develop theory that determines the number of years of absent surveys required to minimize the net expected cost. Given detection of a species is imperfect, the optimal stopping time is a trade-off between the cost of continued surveying and the cost of escape and damage if eradication is declared too soon. A simple rule of thumb compares well to the exact optimal solution using stochastic dynamic programming. Application of the approach to the eradication programme of Helenium amarum reveals that the actual stopping time was a precautionary one given the ranges for each parameter. © 2006 Blackwell Publishing Ltd/CNRS.

Mimicking the tumour microenvironment (TME): Angiogenesis in tumour progression

Two-dimensional (2D) substrates cannot accurately mimic the complex matrix of native TME, whereas 3D models can recapitulate the natural tumour progression in vitro. As part of the tumour stroma, fibroblasts and endothelial cells (ECs) are well-known to not only support tumour growth but also to reduce the efficacy of anti-cancer drugs. Particularly, ECs are involved in the process of tumour vascularisation which represents a crucial step in the progression of cancer. Most of the previous studies are carried out in animal models or 2D cultures; hence, a detailed evaluation of experimental data is poor. To address this issue, we aim to develop a novel 3D in vitro approach, to mimic native tumour angiogenesis in 3D and to quantify the developed vascular network.

Evaluation of Interconnect Fabrics for an Embedded MPSoC in 28 nm FD-SOI

Embedded many-core architectures contain dozens to hundreds of CPU cores that are connected via a highly scalable NoC interconnect. Our Multiprocessor-System-on-Chip CoreVAMPSoC combines the advantages of tightly coupled bus-based communication with the scalability of NoC approaches by adding a CPU cluster as an additional level of hierarchy. In this work, we analyze different cluster interconnect implementations with 8 to 32 CPUs and compare them in terms of resource requirements and performance to hierarchical NoCs approaches. Using 28nm FD-SOI technology the area requirement for 32 CPUs and AXI crossbar is 5.59mm2 including 23.61% for the interconnect at a clock frequency of 830 MHz. In comparison, a hierarchical MPSoC with 4 CPU cluster and 8 CPUs in each cluster requires only 4.83mm2 including 11.61% for the interconnect. To evaluate the performance, we use a compiler for streaming applications to map programs to the different MPSoC configurations. We use this approach for a design-space exploration to find the most efficient architecture and partitioning for an application.

Collaborative data exploration interfaces - From participatory sensing to participatory sensemaking

As technological capabilities for capturing, aggregating, and processing large quantities of data continue to improve, the question becomes how to effectively utilise these resources. Whenever automatic methods fail, it is necessary to rely on human background knowledge, intuition, and deliberation. This creates demand for data exploration interfaces that support the analytical process, allowing users to absorb and derive knowledge from data. Such interfaces have historically been designed for experts. However, existing research has shown promise in involving a broader range of users that act as citizen scientists, placing high demands in terms of usability. Visualisation is one of the most effective analytical tools for humans to process abstract information. Our research focuses on the development of interfaces to support collaborative, community-led inquiry into data, which we refer to as Participatory Data Analytics. The development of data exploration interfaces to support independent investigations by local communities around topics of their interest presents a unique set of challenges, which we discuss in this paper. We present our preliminary work towards suitable high-level abstractions and interaction concepts to allow users to construct and tailor visualisations to their own needs.

In vitro pre-vascularisation of tissue-engineered constructs: A co-culture perspective

In vitro pre-vascularization is one of the main vascularization strategies in the tissue engineering field. Culturing cells within a tissue-engineered construct (TEC) prior to implantation provides researchers with a greater degree of control over the fate of the cells. However, balancing the diverse range of different cell culture parameters in vitro is seldom easy and in most cases, especially in highly vascularized tissues, more than one cell type will reside within the cell culture system. Culturing multiple cell types in the same construct presents its own unique challenges and pitfalls. The following review examines endothelial-driven vascularization and evaluates the direct and indirect role other cell types have in vessel and capillary formation. The article then analyses the different parameters researchers can modulate in a co-culture system in order to design optimal tissue-engineered constructs to match desired clinical applications.

Global, regional, and national disability-adjusted life years (DALYs) for 306 diseases and injuries and healthy life expectancy (HALE) for 188 countries, 1990–2013: Quantifying the epidemiological transition

Background The Global Burden of Disease Study 2013 (GBD 2013) aims to bring together all available epidemiological data using a coherent measurement framework, standardised estimation methods, and transparent data sources to enable comparisons of health loss over time and across causes, age–sex groups, and countries. The GBD can be used to generate summary measures such as disability-adjusted life-years (DALYs) and healthy life expectancy (HALE) that make possible comparative assessments of broad epidemiological patterns across countries and time. These summary measures can also be used to quantify the component of variation in epidemiology that is related to sociodemographic development. Methods We used the published GBD 2013 data for age-specific mortality, years of life lost due to premature mortality (YLLs), and years lived with disability (YLDs) to calculate DALYs and HALE for 1990, 1995, 2000, 2005, 2010, and 2013 for 188 countries. We calculated HALE using the Sullivan method; 95% uncertainty intervals (UIs) represent uncertainty in age-specific death rates and YLDs per person for each country, age, sex, and year. We estimated DALYs for 306 causes for each country as the sum of YLLs and YLDs; 95% UIs represent uncertainty in YLL and YLD rates. We quantified patterns of the epidemiological transition with a composite indicator of sociodemographic status, which we constructed from income per person, average years of schooling after age 15 years, and the total fertility rate and mean age of the population. We applied hierarchical regression to DALY rates by cause across countries to decompose variance related to the sociodemographic status variable, country, and time. Findings Worldwide, from 1990 to 2013, life expectancy at birth rose by 6·2 years (95% UI 5·6–6·6), from 65·3 years (65·0–65·6) in 1990 to 71·5 years (71·0–71·9) in 2013, HALE at birth rose by 5·4 years (4·9–5·8), from 56·9 years (54·5–59·1) to 62·3 years (59·7–64·8), total DALYs fell by 3·6% (0·3–7·4), and age-standardised DALY rates per 100 000 people fell by 26·7% (24·6–29·1). For communicable, maternal, neonatal, and nutritional disorders, global DALY numbers, crude rates, and age-standardised rates have all declined between 1990 and 2013, whereas for non–communicable diseases, global DALYs have been increasing, DALY rates have remained nearly constant, and age-standardised DALY rates declined during the same period. From 2005 to 2013, the number of DALYs increased for most specific non-communicable diseases, including cardiovascular diseases and neoplasms, in addition to dengue, food-borne trematodes, and leishmaniasis; DALYs decreased for nearly all other causes. By 2013, the five leading causes of DALYs were ischaemic heart disease, lower respiratory infections, cerebrovascular disease, low back and neck pain, and road injuries. Sociodemographic status explained more than 50% of the variance between countries and over time for diarrhoea, lower respiratory infections, and other common infectious diseases; maternal disorders; neonatal disorders; nutritional deficiencies; other communicable, maternal, neonatal, and nutritional diseases; musculoskeletal disorders; and other non-communicable diseases. However, sociodemographic status explained less than 10% of the variance in DALY rates for cardiovascular diseases; chronic respiratory diseases; cirrhosis; diabetes, urogenital, blood, and endocrine diseases; unintentional injuries; and self-harm and interpersonal violence. Predictably, increased sociodemographic status was associated with a shift in burden from YLLs to YLDs, driven by declines in YLLs and increases in YLDs from musculoskeletal disorders, neurological disorders, and mental and substance use disorders. In most country-specific estimates, the increase in life expectancy was greater than that in HALE. Leading causes of DALYs are highly variable across countries. Interpretation Global health is improving. Population growth and ageing have driven up numbers of DALYs, but crude rates have remained relatively constant, showing that progress in health does not mean fewer demands on health systems. The notion of an epidemiological transition—in which increasing sociodemographic status brings structured change in disease burden—is useful, but there is tremendous variation in burden of disease that is not associated with sociodemographic status. This further underscores the need for country-specific assessments of DALYs and HALE to appropriately inform health policy decisions and attendant actions.