Linear Ballistic Accumulator Modeling of Attentional Bias Modification Revealed Disturbed Evidence Accumulation of Negative Information by Explicit Instruction

In recent years, several attentional bias modification (ABM) studies have been conducted. Previous studies have suggested that explicit instruction (i.e., informing participants of the contingency of stimuli) enhances the effect of ABM. However, the specific working mechanism has not been identified. This is partly because reaction time (RT) data are typically reduced to an attention bias score, which is a mere difference of RT between experimental and control conditions. This data reduction causes a loss of information, as RT reflects various cognitive processes at play while making a response or decision. To overcome this issue, the present study applied linear ballistic accumulator (LBA) modeling to the outcomes (RT measures) of explicitly guided (compared to standard) ABM. This computational modeling approach allowed us to dissociate RTs into distinct components that can be relevant for attentional bias, such as efficiency of information processing or prior knowledge of the task;this provides an understanding of the mechanism of action underlying explicitly guided ABM. The analyzed data were RT-observed in the dot-probe task, which was administered before and after 3-days of ABM training. Our main focus was on the changes in LBA components that would be induced by the training. Additionally, we analyzed in-session performances over the 3 days of training. The LBA analysis revealed a significant reduction in processing efficiency (i.e., drift rate) in the congruent condition, where the target probe is presented in the same location as a negative stimulus. This explains the reduction in the overall attentional bias score, suggesting that explicit ABM suppresses processing of negative stimuli. Moreover, the results suggest that explicitly guided ABM may influence prior knowledge of the target location in the training task and make participants prepared to respond to the task. These findings highlight the usefulness of LBA-based analysis to explore the underlying cognitive mechanisms in ABM, and indeed our analyses revealed the differences between the explicit and the standard ABM that could not be identified by traditional RT analysis or attentional bias scores

Comprehensive behavioral phenotyping of calpastatin-knockout mice

<p>Abstract</p> <p>Background</p> <p>Calpastatin is an endogenous inhibitor of calpain, intracellular calcium-activated protease. It has been suggested to be involved in molecular mechanisms of long-term plasticity and excitotoxic pathways. However, functions of calpastatin in vivo are still largely unknown. To examine the physiological roles of calpastatin, we subjected calpastatin-knockout mice to a comprehensive behavioral test battery.</p> <p>Results</p> <p>Calpastatin-knockout mice showed decreased locomotor activity under stressful environments, and decreased acoustic startle response, but we observed no significant change in hippocampus-dependent memory function.</p> <p>Conclusion</p> <p>These results suggest that calpastatin is likely to be more closely associated with affective rather than cognitive aspects of brain function.</p

Percutaneous Transcatheter Ballon Valvuloplasty of a Stenosed Bioprosthetic Tricuspid Valve

Article信州医学雑誌 67(5): 289-292(2019)journal articl

Involvement of calpains in adult neurogenesis: implications for stroke

Calpains are ubiquitous proteases involved in cell proliferation, adhesion and motility. In the brain, calpains have been associated with neuronal damage in both acute and neurodegenerative disorders, but their physiological function in the nervous system remains elusive. During brain ischemia, there is a large increase in the levels of intracellular calcium, leading to the activation of calpains. Inhibition of these proteases has been shown to reduce neuronal death in a variety of stroke models. On the other hand, after stroke, neural stem cells (NSC) increase their proliferation and newly formed neuroblasts migrate towards the site of injury. However, the process of forming new neurons after injury is not efficient and finding ways to improve it may help with recovery after lesion. Understanding the role of calpains in the process of neurogenesis may therefore open a new window for the treatment of stroke. We investigated the involvement of calpains in NSC proliferation and neuroblast migration in two highly neurogenic regions in the mouse brain, the dentate gyrus (DG) and the subventricular zone (SVZ). We used mice that lack calpastatin, the endogenous calpain inhibitor, and calpains were also modulated directly, using calpeptin, a pharmacological calpain inhibitor. Calpastatin deletion impaired both NSC proliferation and neuroblast migration. Calpain inhibition increased NSC proliferation, migration speed and migration distance in cells from the SVZ. Overall, our work suggests that calpains are important for neurogenesis and encourages further research on their neurogenic role. Prospective therapies targeting calpain activity may improve the formation of new neurons following stroke, in addition to affording neuroprotection.Foundation for Science and Technology, (FCT, Portugal); COMPETE; FEDER [PTDC/SAU-NMC/112183/2009, PEst-C/SAU/LA0001/2013-2014, PEst-OE/EQB/LA0023/2013-2014]; NIH [GM 23244]; FCT [SFRH/BPD/78901/2011, SFRH/BD/38127/2007, SFRH/BD/78050/2011]info:eu-repo/semantics/publishedVersio

Potent amyloidogenicity and pathogenicity of Aβ43.

The amyloid-β peptide Aβ42 is known to be a primary amyloidogenic and pathogenic agent in Alzheimer\u27s disease. However, the role of Aβ43, which is found just as frequently in the brains of affected individuals, remains unresolved. We generated knock-in mice containing a pathogenic presenilin-1 R278I mutation that causes overproduction of Aβ43. Homozygosity was embryonic lethal, indicating that the mutation involves a loss of function. Crossing amyloid precursor protein transgenic mice with heterozygous mutant mice resulted in elevated Aβ43, impairment of short-term memory and acceleration of amyloid-β pathology, which accompanied pronounced accumulation of Aβ43 in plaque cores similar in biochemical composition to those observed in the brains of affected individuals. Consistently, Aβ43 showed a higher propensity to aggregate and was more neurotoxic than Aβ42. Other pathogenic presenilin mutations also caused overproduction of Aβ43 in a manner correlating with Aβ42 and with the age of disease onset. These findings indicate that Aβ43, an overlooked species, is potently amyloidogenic, neurotoxic and abundant in vivo

Topological Effect in Ring Polymers Studied by Monte Carlo Simulation(Knots and soft-matter physics: Topology of polymers and related topics in physics, mathematics and biology)

この論文は国立情報学研究所の電子図書館事業により電子化されました。バルクにおけるリングポリマーの拡がりをモンテカルロシミュレーション法を用いて検討した。フローリの指数νとセグメントの分布を、Bond Fluctuation Model(BFM)を使って広い範囲のセグメント数(10&le;N&le;1000)で求めた。シミュレーションの結果、νはNの増加とともに減少しN=1000でν=0.365まで低下するすることがわかり、これらは理論予測であるν=2/5よりも小さい。リングポリマーのバルクにおける拡がりは、末端がないトポロジーによる自分自身による拘束と隣接するリングポリマーとの相互作用の二つによって非摂動鎖よりも小さく、かつ、分子量依存性を示すことがわかった。セグメントの分布について求めたところ、リングポリマーのセグメント数が無限大の条件では、ν→1/3を持つことが考えられることから、1/3&le;ν≪0.365が得られ、実験結果をよく説明することが分かった。理論予測は、リングポリマーのトポロジーによるエントロピー低下を充分に考慮していなかったため、本研究の結果と理論予測の結果に差が生じていると結論できる。We studied equilibrium conformations of ring polymers in the melt over the wide range of segment number, N, up to 1000 by the Monte-Carlo simulation method and the bond fluctuation model (BFM), and obtained Flory's scaling exponent ν and the radial distribution function of segments. It is clear that ν for ring polymers is decreased with N, and ν goes down to 0.365 when N reaches 1000, whose value is smaller than the theoretically-predicted one, i.e., 2/5. Ring polymer chains in the melt are squeezed both by their own topological effect and the compression effect by the neighboring ring polymer coils, and they are perturbation chains in the melt. The difference in our study and the theory is that the estimation of topological entropy loss in ring polymers was ignored in the theoretical prediction, while it has been taken into consideration in this study. If polymer coils repel each other in the melt at N→∞, they have the limiting ν value of 1/3, and we conclude that ν is in the range 1/3&le;ν≪0.365 when the molecular weight of a ring polymer is high enough

Linear Ballistic Accumulator Modeling of Attentional Bias Modification Revealed Disturbed Evidence Accumulation of Negative Information by Explicit Instruction. / R and Stan codes

R and Stan code used for the LBA modeling in the present study, with a sample data

Predicting Online Item-Choice Behavior: A Shape-Restricted Regression Approach

This paper examines the relationship between user pageview (PV) histories and their itemchoice behavior on an e-commerce website. We focus on PV sequences, which represent time series of the number of PVs for each user–item pair. We propose a shape-restricted optimization model that accurately estimates item-choice probabilities for all possible PV sequences. This model imposes monotonicity constraints on item-choice probabilities by exploiting partial orders for PV sequences, according to the recency and frequency of a user’s previous PVs. To improve the computational efficiency of our optimization model, we devise efficient algorithms for eliminating all redundant constraints according to the transitivity of the partial orders. Experimental results using real-world clickstream data demonstrate that our method achieves higher prediction performance than that of a state-of-the-art optimization model and common machine learning methods