Selective Attention and Audiovisual Integration: Is Attending to Both Modalities a Prerequisite for Early Integration?

Interactions between multisensory integration and attention were studied using a combined audiovisual streaming design and a rapid serial visual presentation paradigm. Event-related potentials (ERPs) following audiovisual objects (AV) were compared with the sum of the ERPs following auditory (A) and visual objects (V). Integration processes were expressed as the difference between these AV and (A + V) responses and were studied while attention was directed to one or both modalities or directed elsewhere. Results show that multisensory integration effects depend on the multisensory objects being fully attended—that is, when both the visual and auditory senses were attended. In this condition, a superadditive audiovisual integration effect was observed on the P50 component. When unattended, this effect was reversed; the P50 components of multisensory ERPs were smaller than the unisensory sum. Additionally, we found an enhanced late frontal negativity when subjects attended the visual component of a multisensory object. This effect, bearing a strong resemblance to the auditory processing negativity, appeared to reflect late attention-related processing that had spread to encompass the auditory component of the multisensory object. In conclusion, our results shed new light on how the brain processes multisensory auditory and visual information, including how attention modulates multisensory integration processes

A retinotopic attentional trace after saccadic eye movements: evidence from event-related potentials

Saccadic eye movements are a major source of disruption to visual stability, yet we experience little of this disruption. We can keep track of the same object across multiple saccades. It is generally assumed that visual stability is due to the process of remapping, in which retinotopically organized maps are updated to compensate for the retinal shifts caused by eye movements. Recent behavioral and ERP evidence suggests that visual attention is also remapped, but that it may still leave a residual retinotopic trace immediately after a saccade. The current study was designed to further examine electrophysiological evidence for such a retinotopic trace by recording ERPs elicited by stimuli that were presented immediately after a saccade (80 msec SOA). Participants were required to maintain attention at a specific location (and to memorize this location) while making a saccadic eye movement. Immediately after the saccade, a visual stimulus was briefly presented at either the attended location (the same spatiotopic location), a location that matched the attended location retinotopically (the same retinotopic location), or one of two control locations. ERP data revealed an enhanced P1 amplitude for the stimulus presented at the retinotopically matched location, but a significant attenuation for probes presented at the original attended location. These results are consistent with the hypothesis that visuospatial attention lingers in retinotopic coordinates immediately following gaze shifts

Discrete cosmological models in the Brans-Dicke theory of gravity

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Exact, Inhomogeneous Solutions to Gravitational Theories in Cosmology

PhDSolving the backreaction and averaging problems is important as we enter the era of precision cosmology. Fundamentally, the idea that small-scale inhomogeneities can a ect the large-scale dynamics of the Universe lies in the non-linearity and non-commutativity properties of the Einstein eld equations. It is not necessarily the case that the dynamics of a perfectly homogeneous Friedmann universe are the same as an inhomogeneous one. However, di culties arise in nding suitable inhomogeneous solutions to the Einstein eld equations. Progress can be made by treating it as an initial data problem and solving the constraint equations. This gives rise to a family of solutions, the black hole lattices, which consist of linearly superposed Schwarzschild masses representing a universe with a discretised matter content. In this thesis, we present extensions and generalisations of these existing models. Firstly, we devised a novel way to include structure formation and its e ects. We did this in a quasi-static approach that involved splitting the black holes up into more masses and moving them along parameterised trajectories. For small values of this parameter, we could induce clustering as the black holes were su ciently close together. We found an extra apparent horizon encompassed the cluster and that in order to reduce backreaction, interaction energies within clustered masses needed to be included. Our next two extensions involved adding in extra elds, either electric charge or the cosmological constant. Finally we considered the lattices in an alternative scalar-tensor gravitational theory, Brans-Dicke. We found our lattices reduced to their relativistic versions in the appropriate limit, but for some values very far from general relativity, we could reduce backreaction to zero by altering the amount of background scalar eld. For all of our analyses we found that increasing the number of masses reduces the discrepancy between our lattice cosmologies and continuous counterparts

Changes in serine metabolism by a serum factor present in a group of episodic psychotic patients

__Abstract__ Addition of serum, obtained from patients suffering from an acute psychosis characterized by dysperceptions, to the culture media of fibroblasts altered the amino acid metabolism in these cells. After subculturing of fibroblasts in the presence of serum obtained from these patients, the concentrations of both serine and methionine were decreased in the medium as well as in the fibroblasts. Moreover, the concentration of taurine in the fibroblasts was increased. The specific activities of serine hydroxymethyltransferase and cystathionine β-synthase were also measured in the fibroblasts. It was found that both enzyme activities were significantly higher after subculturing with patients' serum as compared with serum obtained from healthy controls. It is concluded that a factor, present in the serum of these acute psychotic patients, is responsible for the observed changes in serine, taurine, and methionine concentrations in the fibroblasts as well as for the increased enzyme activities mentioned

Pathway Design for Acute Stroke Care in the Era of Endovascular Thrombectomy:A Critical Overview of Optimization Efforts

The efficacy of intravenous thrombolysis and endovascular thrombectomy (EVT) for acute ischemic stroke is highly time dependent. Optimal organization of acute stroke care is therefore important to reduce treatment delays but has become more complex after the introduction of EVT as regular treatment for large vessel occlusions. There is no singular optimal organizational model that can be generalized to different geographic regions worldwide. Current dominant organizational models for EVT include the drip-and-ship- and mothership model. Guidelines recommend routing of suspected patients with stroke to the nearest intravenous thrombolysis capable facility; however, the choice of routing to a certain model should depend on regional stroke service organization and individual patient characteristics. In general, design approaches for organizing stroke care are required, in which 2 key strategies could be considered. The first entails the identification of interventions within existing organizational models for optimizing timely delivery of intravenous thrombolysis and/or EVT. This includes adaptive patient routing toward a comprehensive stroke center, which focuses particularly on prehospital triage tools; bringing intravenous thrombolysis or EVT to the location of the patient; and expediting services and processes along the stroke pathway. The second strategy is to develop analytical or simulation model-based approaches enabling the design and evaluation of organizational models before their implementation. Organizational models for acute stroke care need to take regional and patient characteristics into account and can most efficiently be assessed and optimized through the application of model-based approaches

Synthesis and evaluation of dopamine D-3 receptor antagonist C-11-GR218231 as PET tracer for P-glycoprotein

While searching for a PET method to determine the density and occupancy of the dopamine D-3 receptor, we found evidence that suggested that the dopamine D-3 antagonist GR218231 could be a substrate of the P-glycoprotein efflux pump. P-glycoprotein protects the brain against toxic substances and xenobiotics, but it also hampers the delivery of various drugs into the brain. In this study, we aimed to explore whether radiolabeled GR218231 could be applied as a PET tracer for monitoring P-glycoprotein activity in the blood-brain barrier. Such an imaging technique could be useful for the development of new drugs and novel strategies to deliver drugs to the brain and for identification of undesirable drug-drug interactions. Methods: As a potential PET tracer, GR218231 was labeled with C-11 by reaction of the newly synthesized desmethyl precursor with C-11-methyl triflate. The biodistribution of C-11-GR218231 was determined in rats. To assess specific binding to the dopamine D3 receptor, blocking experiments with unlabeled GR218231 (0.2 and 2.5 mg/kg) were performed. To demonstrate the influence of P-glycoprotein on cerebral uptake of C-11-GR218231, the efflux pump was modulated with 50 mg/kg cyclosporine A. The sensitivity of C-11-GR218231 for P-glycoprotein modulation was assessed in dose-response studies, using escalating cyclosporine A dosages. Results: C-11-GR218231 was prepared in 53% +/- 8% decay-corrected radiochemical yield and had a specific activity of 15 +/- 10 GBq/mu mol (mean +/- SD). Biodistribution studies in rats revealed a low and homogeneous uptake in the brain. Pretreatment of the animals with unlabeled GR218231 did not demonstrate any specific binding. Modulation of P-glycoprotein with cyclosporine A caused a 12-fold higher C-11-GR218231 uptake in the brain, indicating that the low cerebral tracer uptake was caused by the P-glycoprotein efflux pump in the blood-brain barrier. Cyclosporine A close-escalation studies showed a dose-dependent sigmoidal increase in C-11-GR218231 uptake in brain and spleen (median effective dose [ED50], 23.3 +/- 0.6 and 38.4 +/- 2.4 mg/kg, respectively), whereas a dose-dependent decrease was observed in the pancreas (ED50, 36.0 +/- 4.4 mg/kg). Conclusion: Although C-11-GR218231 is unsuited for dopamine D3 receptor imaging with PET, it appears to be an attractive PET tracer for visualization and quantification of P-glycoprotein activity in the blood-brain barrier

Role of the police in linking individuals experiencing mental health crises with mental health services

BACKGROUND: The police are considered frontline professionals in managing individuals experiencing mental health crises. This study examines the extent to which these individuals are disconnected from mental health services, and whether the police response has an influence on re-establishing contact. METHODS: Police records were searched for calls regarding individuals with acute mental health needs and police handling of these calls. Mental healthcare contact data were retrieved from a Psychiatric Case Register. RESULTS: The police were called upon for mental health crisis situations 492 times within the study year, involving 336 individuals (i.e. 1.7 per 1000 inhabitants per year). Half of these individuals (N=162) were disengaged from mental health services, lacking regular care contact in the year prior to the crisis (apart from contact for crisis intervention). In the month following the crisis, 21% of those who were previously disengaged from services had regular care contact, and this was more frequent (49%) if the police had contacted the mental health services during the crisis. The influence of police referral to the services was still present the following year. However, for the majority (58%) of disengaged individuals police did not contact the mental health services at the time of crisis. CONCLUSIONS: The police deal with a substantial number of individuals experiencing a mental health crisis, half of whom are out of contact with mental health services, and police play an important role in linking these individuals to services. Training police officers to recognise and handle mental health crises, and implementing practical models of cooperation between the police and mental health services in dealing with such crises may further improve police referral of individuals disengaged from mental health services