Serial versus parallel search: A model comparison approach based on reaction time distributions

For 50 years or so, visual search experiments have been used to examine how humans find behaviourally relevant objects in complex visual scenes. For the same length of time, there has been a dispute over whether this search is performed in a serial or parallel fashion. In this paper, we approach this dispute by numerically fitting a serial search model and a parallel search model to reaction time (RT) distributions from three visual search experiments (feature search, conjunction search, spatial configuration search). In order to do so, we used a free-likelihood method based on a novel kernel density estimator (KDE). The serial search model was the Competitive Guided Search (CGS) model by Moran et al. [(2013). Competitive guided search: Meeting the challenge of benchmark RT distributions. Journal of Vision, 13(8), 24–24.]. We were able to replicate the ability of CGS to model RT distributions from visual search experiments, and demonstrated that CGS generalizes well to new data. The parallel model was based on the biased-competition theory and utilized a very simple biologicallyplausible winner-take-all (WTA) mechanism from Heinke and Humphreys’s [(2003). Attention, spatial representation and visual neglect: Simulating emergent attention and spatial memory in the Selective Attention for Identification Model (SAIM). Psychological Review, 110(1), 29–87.]. With this mechanism, SAIM has been able to explain a broad range of attentional phenomena but it was not specifically designed to model RT distributions in visual search. Nevertheless, the WTA was able to reproduce these distributions. However, a direct comparison of the two models suggested that the serial CGS is slightly better equipped to explain the RT distributions than the WTA mechanism. The CGS’s success was mainly down the usage of the Wald distribution which was specifically designed to model visual search. Future WTA versions will have to find a biologically plausible mechanism to reproduce such a RT distribution. Finally, both models suffered from a failure to generalize across all display sizes. From these comparisons, we developed suggestions for improving the models and motivated empirical studies to devise a stronger test for the two types of searches

Early brainstem [18F]THK5351 uptake is linked to cortical hyper-excitability in healthy aging

BACKGROUND: Neuronal hyper-excitability characterizes the early stages of Alzheimer's disease (AD). In animals, early misfolded tau and amyloid-beta (Aβ) protein accumulation, both central to AD neuropathology, promote cortical excitability and neuronal network dysfunction. In healthy humans, misfolded tau and Aβ aggregates are first detected, respectively, in the brainstem and frontomedial and temporobasal cortices, decades prior to the onset of AD cognitive symptoms. Whether cortical excitability is related to early brainstem tau, and its associated neuroinflammation, and cortical Aβ aggregations remains unknown. METHODS: We probed frontal cortex excitability, using transcranial magnetic stimulation combined with electroencephalography, in a sample of 64 healthy late middle-aged individuals (50-69 y; 45 women). We assessed whole-brain [18F]THK5351 positron emission tomography (PET) uptake as a proxy measure of tau/neuroinflammation, and whole-brain Aβ burden with [18F]Flutemetamol or [18F]Florbetapir radiotracers. RESULTS: We find that higher [18F]THK5351 uptake in a brainstem monoaminergic compartment is associated with increased cortical excitability (r = .29, p = .02). By contrast, [18F]THK5351 PET signal in the hippocampal formation, although strongly correlated with brainstem signal in whole-brain voxel-based quantification analyses (pFWE-corrected < .001), was not significantly associated with cortical excitability (r = .14, p = .25). Importantly, no significant association was found between early Aβ cortical deposits and cortical excitability (r = -.20, p = .11). CONCLUSION: These findings reveal potential brain substrates for increased cortical excitability in preclinical AD and may constitute functional in vivo correlates of early brainstem tau accumulation and neuroinflammation in humans. TRIAL REGISTRATION: EudraCT 2016-001436-35. FUNDING: F.R.S.-FNRS Belgium, Wallonie-Bruxelles International, ULiège, Fondation Simone et Pierre Clerdent, European Regional Development Fund

ENIGMA-Sleep:Challenges, opportunities, and the road map

Neuroimaging and genetics studies have advanced our understanding of the neurobiology of sleep and its disorders. However, individual studies usually have limitations to identifying consistent and reproducible effects, including modest sample sizes, heterogeneous clinical characteristics and varied methodologies. These issues call for a large-scale multi-centre effort in sleep research, in order to increase the number of samples, and harmonize the methods of data collection, preprocessing and analysis using pre-registered well-established protocols. The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) consortium provides a powerful collaborative framework for combining datasets across individual sites. Recently, we have launched the ENIGMA-Sleep working group with the collaboration of several institutes from 15 countries to perform large-scale worldwide neuroimaging and genetics studies for better understanding the neurobiology of impaired sleep quality in population-based healthy individuals, the neural consequences of sleep deprivation, pathophysiology of sleep disorders, as well as neural correlates of sleep disturbances across various neuropsychiatric disorders. In this introductory review, we describe the details of our currently available datasets and our ongoing projects in the ENIGMA-Sleep group, and discuss both the potential challenges and opportunities of a collaborative initiative in sleep medicine

シェリング哲学の研究 (その1) : 自然哲学から同一哲学への展開

textabstractWhile they account for one-fifth of new cancer cases, rare cancers are difficult to study. A higher than average degree of uncertainty should be accommodated for clinical as well as for population-based decision making. Rules of rational decision making in conditions of uncertainty should be rigorously followed and would need widely informative clinical trials. In principle, any piece of new evidence would need to be exploited in rare cancers. Methodologies to explicitly weigh and combine all the available evidence should be refined, and the Bayesian logic can be instrumental to this end. Likewise, Bayesian-design trials may help optimize the low number of patients liable to be enrolled in clinical studies on rare cancers, as well as adaptive trials in general, with their inherent potential of flexibility when properly applied. While clinical studies are the mainstay to test hypotheses, the potential of electronic patient records should be exploited to generate new hypotheses, to create external controls for future studies (when internal controls are unpractical), to study effectiveness of new treatments in real conditions. Framework study protocols in specific rare cancers to stepwisely test sets of new agents, as from the early post-phase I development stage, should be encouraged. Also the compassionate and the off-label settings should be exploited to generate new evidence, and flexible regulatory innovations such as adaptive licensing could convey new agents early to rare cancer patients, while generating evidence. Though validation of surrogate end points is problematic in rare cancers, the use of an updated notion of tumor response may be of great value in the single patient to optimize the use of therapies, all the more the new ones. Disease-based communities, involving clinicians and patients, should be regularly consulted by regulatory bodies when setting their policies on drug approval and reimbursement in specific rare cancers

Arenaran sesquiterpenes from the nudibranch Chromodoris strigata and its dietary sponge Acanthodendrilla sp. 2510: spectroscopic and computational studies

Oxygenated sesquiterpenes were isolated from the sponge Acanthodendrilla sp. 2510 and identified as caparrapi oxide (1) and the bioactive oxocene sesquiterpene, arenaran A (2). An extract of the nudibranch Chromodoris strigata, found feeding on the sponge, also contained 2. Also characterized from the sponge extract were three compounds 3–5 derived from the oxocene skeleton of arenaran A that possessed hydroperoxy functionality. The structure and stereochemistry of each compound was identified using 1D and 2D NMR spectroscopic and mass spectrometry techniques, in combination with X-ray crystallography and molecular modelling/computational studies. Isolation of the hydroperoxy products provided insight into the reactivity of the oxocene skeleton

Risk factors of Alzheimer’s disease in case of super-aging: A cross-sectional and exploratory study.

peer reviewe

Catalyst-Controlled Stereoselective Synthesis Secures the Structure of the Antimalarial Isocyanoterpene Pustulosaisonitrile-1

Three new isocyanoditerpenes (5-7) have been characterized from Australian specimens of the nudibranch Phyllidiella pustulosa. The planar structure and (3R,6S,7R) absolute configuration of pustulosaisonitrile-1 were deduced by spectroscopic analyses at 900 MHz informed by molecular modeling, DFT calculations, and computational NMR chemical shift predictions and by comparison of experimental electronic circular dichroism (ECD) data with TDDFT-ECD calculations for the truncated model compound 8. A catalyst-controlled enantio- and diastereoselective total synthesis of the two most likely diastereomeric candidates for the structure of 5 solidified its (3R,6S,7R,10S,11R,14R) absolute configuration. Three individual enantioselective methods provided stereochemical control at key positions, permitting an unambiguous final structural assignment. Isocyanide 5 and synthetic diastereomers 5a and 5c showed activity against Plasmodium falciparum malaria parasites (IC ∼1 μM)

Correction to Catalyst-Controlled Stereoselective Synthesis Secures the Structure of the Antimalarial Isocyanoterpene Pustulosaisonitrile‑1

Correction to Catalyst-Controlled Stereoselective Synthesis Secures the Structure of the Antimalarial Isocyanoterpene Pustulosaisonitrile‑