Behavior can be decoded across the cortex when individual differences are considered.

Group-level analyses have typically associated behavioral signatures with a constrained set of brain areas. Here we show that two behavioral metrics - reaction time (RT) and confidence - can be decoded across the cortex when each individual is considered separately. Subjects (N=50) completed a perceptual decision-making task with confidence. We built models decoding trial-level RT and confidence separately for each subject using the activation patterns in one brain area at a time after splitting the entire cortex into 200 regions of interest (ROIs). At the group level, we replicated previous results by showing that both RT and confidence could be decoded from a small number of ROIs (12.0% and 3.5%, respectively). Critically, at the level of the individual, both RT and confidence could be decoded from most brain regions even after Bonferroni correction (90.0% and 72.5%, respectively). Surprisingly, we observed that many brain regions exhibited opposite brain-behavior relationships across individuals, such that, for example, higher activations predicted fast RTs in some subjects but slow RTs in others. These results were further replicated in a second dataset. Lastly, we developed a simple test to determine the robustness of decoding performance, which showed that several hundred trials per subject are required for robust decoding. These results show that behavioral signatures can be decoded from a much broader range of cortical areas than previously recognized and suggest the need to study the brain-behavior relationship at both the group and the individual level.

Task learning is subserved by a domain-general brain network.

One of the most important human faculties is the ability to acquire not just new memories but the capacity to perform entirely new tasks. However, little is known about the brain mechanisms underlying the learning of novel tasks. Specifically, it is unclear to what extent learning of different tasks depends on domain-general and/or domain-specific brain mechanisms. Here human subjects (n = 45) learned to perform 6 new tasks while undergoing functional MRI. The different tasks required the engagement of perceptual, motor, and various cognitive processes related to attention, expectation, speed-accuracy tradeoff, and metacognition. We found that a bilateral frontoparietal network was more active during the initial compared with the later stages of task learning, and that this effect was stronger for task variants requiring more new learning. Critically, the same frontoparietal network was engaged by all 6 tasks, demonstrating its domain generality. Finally, although task learning decreased the overall activity in the frontoparietal network, it increased the connectivity strength between the different nodes of that network. These results demonstrate the existence of a domain-general brain network whose activity and connectivity reflect learning for a variety of new tasks, and thus may underlie the human capacity for acquiring new abilities.

Multiple brain activation patterns for the same task.

Meaningful variation in internal states that impacts cognition and behavior remains challenging to discover and characterize. Here we leveraged trial-to-trial fluctuations in the brain-wide signal recorded using functional MRI to test if distinct sets of brain regions are activated on different trials when accomplishing the same task. Across three different perceptual decision-making experiments, we estimated the brain activations for each trial. We then clustered the trials based on their similarity using modularity-maximization, a data-driven classification method. In each experiment, we found multiple distinct but stable subtypes of trials, suggesting that the same task can be accomplished in the presence of widely varying brain activation patterns. Surprisingly, in all experiments, one of the subtypes exhibited strong activation in the default mode network, which is typically thought to decrease in activity during tasks that require externally focused attention. The remaining subtypes were characterized by activations in different task-positive areas. The default mode network subtype was characterized by behavioral signatures that were similar to the other subtypes exhibiting activation with task-positive regions. Finally, in a fourth experiment, we tested whether multiple activation patterns would also appear for a qualitatively different, working memory task. We again found multiple subtypes of trials with differential activation in frontoparietal control, dorsal attention, and ventral attention networks. Overall, these findings demonstrate that the same cognitive tasks are accomplished through multiple brain activation patterns.

Important Features for Protein Foldings in Two Acyl Carrier Proteins from Enterococcus faecalis.

The emergence of multi-drug resistant Enterococcus faecalis raises a serious threat to global public health. E. faecalis is a gram-positive intestinal commensal bacterium found in humans. E. faecalis can endure extreme environments such as high temperature, pressure, and high salt, which facilitates them to cause infection in hospitals. E. faecalis has two acyl carrier proteins, AcpA (EfAcpA) in de novo fatty acid synthesis (FAS) and AcpB (EfAcpB) which utilizes exogenous fatty acids. Previously, we determined the tertiary structures of these two ACPs and investigated their structure-function relationships. Solution structures revealed that overall folding of these two ACPs is similar to those of other bacterial ACPs. However, circular dichroism (CD) experiments showed that the melting temperature of EfAcpA is 76.3°C and that of EfAcpB is 79.2°C, which are much higher than those of other bacterial ACPs. In this study, to understand the origin of their structural stabilities, we verified the important residues for stable folding of these two ACPs by monitoring thermal and chemical denaturation. Hydrogen/deuterium exchange and chemical denaturation experiments on wild-type and mutant proteins revealed that Ile10 of EfAcpA and Ile14 of EfAcpB mediate compact intramolecular packing and promote high thermostability and stable folding. E. faecalis may maximize efficiency of FAS and increase adaptability to the environmental stress by having two thermostable ACPs. This study may provide insight into bacterial adaptability and development of antibiotics against multi-drug-resistant E. faecalis.

Quantifying the contribution of subject and group factors in brain activation.

Research in neuroscience often assumes universal neural mechanisms, but increasing evidence points toward sizeable individual differences in brain activations. What remains unclear is the extent of the idiosyncrasy and whether different types of analyses are associated with different levels of idiosyncrasy. Here we develop a new method for addressing these questions. The method consists of computing the within-subject reliability and subject-to-group similarity of brain activations and submitting these values to a computational model that quantifies the relative strength of group- and subject-level factors. We apply this method to a perceptual decision-making task (n = 50) and find that activations related to task, reaction time, and confidence are influenced equally strongly by group- and subject-level factors. Both group- and subject-level factors are dwarfed by a noise factor, though higher levels of smoothing increases their contributions relative to noise. Overall, our method allows for the quantification of group- and subject-level factors of brain activations and thus provides a more detailed understanding of the idiosyncrasy levels in brain activations.

Structural study of acyl carrier protein of Enterococcus faecalis and its interaction with enzymes in de novo fatty acid synthesis.

Enterococcus faecalis has recently shown signs of high antibiotic resistance. These bacteria can endure extremes of temperature and this may be due to the high thermostability of its proteins. E. faecalis has two acyl carrier proteins (ACPs), AcpA (EfAcpA), which is essential for de novo fatty acid synthesis (FAS), and EfAcpB, which plays an auxiliary role in the incorporation of exogenous fatty acids. Structural studies on EfAcpA and its interaction with FAS enzymes have not yet been reported. Here, we investigated the structures of EfAcpA using NMR spectroscopy, showing that EfAcpA consists of three α-helices with a long α2α3 loop, while the other ACPs have four α-helices. CD experiments showed that the melting temperature of EfAcpA is 76.3 °C and the Ala mutation for Ile10 reduced it dramatically by 29.5 °C. Highly conserved Ile10 of EfAcpA mediates compact intramolecular packing and promotes high thermostability. A docking simulation of EfAcpA and ß-ketoacyl-ACP synthase III (EfKAS III) showed that the α2α3 loop of EfAcpA contributes to specific protein-protein interactions (PPI) with EfKAS III. Unconserved charged residues, Lys52 and Glu54, in the α2α3 loop of EfAcpA formed specific electrostatic interactions with Asp 226 and Arg217 of EfKAS III, respectively. Binding interactions between EfAcpA and EfKASIII may provide insights for designing PPI inhibitors targeting FAS in E. faecalis to overcome its antibacterial resistance.

Molecular mechanism underlying the TLR4 antagonistic and antiseptic activities of papiliocin, an insect innate immune response molecule.

SignificanceSimilar to mammalian TLR4/MD-2, the Toll9/MD-2-like protein complex in the silkworm, Bombyx mori, acts as an innate pattern-recognition receptor that recognizes lipopolysaccharide (LPS) and induces LPS-stimulated expression of antimicrobial peptides such as cecropins. Here, we report that papiliocin, a cecropin-like insect antimicrobial peptide from the swallowtail butterfly, competitively inhibits the LPS-TLR4/MD-2 interaction by directly binding to human TLR4/MD-2. Structural elements in papiliocin, which are important in inhibiting TLR4 signaling via direct binding, are highly conserved among insect cecropins, indicating that its TLR4-antagonistic activity may be related to insect Toll9-mediated immune response against microbial infection. This study highlights the potential of papiliocin as a potent TLR4 antagonist and safe peptide antibiotic for treating gram-negative sepsis.

Neural correlates of tactile hardness intensity perception during active grasping.

While tactile sensation plays an essential role in interactions with the surroundings, relatively little is known about the neural processes involved in the perception of tactile information. In particular, it remains unclear how different intensities of tactile hardness are represented in the human brain during object manipulation. This study aims to investigate neural responses to various levels of tactile hardness using functional magnetic resonance imaging while people grasp objects to perceive hardness intensity. We used four items with different hardness levels but otherwise identical in shape and texture. A total of Twenty-five healthy volunteers participated in this study. Before scanning, participants performed a behavioral task in which they received a pair of stimuli and they were to report the perceived difference of hardness between them. During scanning, without any visual information, they were randomly given one of the four objects and asked to grasp it. We found significant blood oxygen-level-dependent (BOLD) responses in the posterior insula in the right hemisphere (rpIns) and the right posterior lobe of the cerebellum (rpCerebellum), which parametrically tracked hardness intensity. These responses were supported by BOLD signal changes in the rpCerebellum and rpIns correlating with tactile hardness intensity. Multidimensional scaling analysis showed similar representations of hardness intensity among physical, perceptual, and neural information. Our findings demonstrate the engagement of the rpCerebellum and rpIns in perceiving tactile hardness intensity during active object manipulation.

Structural basis of the complementary activity of two ketosynthases in aryl polyene biosynthesis.

Aryl polyenes (APE) are one of the most widespread secondary metabolites among gram-negative bacteria. In Acinetobacter baumannii, strains belonging to the virulent global clone 2 (GC2) mostly contain APE biosynthesis genes; its relevance in elevated pathogenicity is of great interest. APE biosynthesis gene clusters harbor two ketosynthases (KSs): the heterodimeric KS-chain length factor complex, ApeO-ApeC, and the homodimeric ketoacyl-acyl carrier protein synthase I (FabB)-like KS, ApeR. The role of the two KSs in APE biosynthesis is unclear. We determined the crystal structures of the two KSs from a pathogenic A. baumannii strain. ApeO-ApeC and ApeR have similar cavity volumes; however, ApeR has a narrow cavity near the entrance. In vitro assay based on the absorption characteristics of polyene species indicated the generation of fully elongated polyene with only ApeO-ApeC, probably because of the funnel shaped active site cavity. However, adding ApeR to the reaction increases the throughput of APE biosynthesis. Mutagenesis at Tyr135 in the active site cavity of ApeR reduces the activity significantly, which suggests that the stacking of the aryl group between Tyr135 and Phe202 is important for substrate recognition. Therefore, the two KSs function complementarily in the generation of APE to enhance its production.

Enhancing Light Absorption and Prolonging Charge Separation in Carbon Quantum Dots via Cl-Doping for Visible-Light-Driven Photocharge-Transfer Reactions.

Limited light absorption beyond the UV region and rapid photocarrier recombination are critical impediments for the improved photocatalytic performance of carbon quantum dots (CQDs) under visible-light irradiation. Herein, we demonstrate single-step microwave-assisted syntheses of O-CQDs (typical CQDs terminated by carboxylic and hydroxyl functional groups) from a sucrose precursor and Cl-doped CQDs (Cl-CQDs) from a sucralose precursor in short reaction times and without using obligatory strong acids for Cl doping. The doping of Cl into the CQDs is observed to widen the absorption range and facilitate an enhanced separation of photoexcited charge carriers, which is confirmed by the results of optical absorption, photothermal response, and pump-probe ultrafast transient absorption spectroscopy measurements of the O-CQDs and Cl-CQDs. The photoexcited charge carriers with their longer lifetimes in Cl-CQDs enabled the quick degradation of methylene blue dye, rapid conversion of Ag+ ions to metallic Ag nanoparticles on the CQD surfaces, and reduction of GO to a well-dispersed rGO through the photoelectron transfer reactions under visible-light irradiation. The facile Cl doping strategy, hybridization of Ag nanoparticles or rGO to CQDs, and the elevated charge separation mechanism would open up new avenues in designing CQD-based materials for futuristic applications.

Deciphering the Binding Interactions between Acinetobacter baumannii ACP and ß-ketoacyl ACP Synthase III to Improve Antibiotic Targeting Using NMR Spectroscopy.

Fatty acid synthesis is essential for bacterial viability. Thus, fatty acid synthases (FASs) represent effective targets for antibiotics. Nevertheless, multidrug-resistant bacteria, including the human opportunistic bacteria, Acinetobacter baumannii, are emerging threats. Meanwhile, the FAS pathway of A. baumannii is relatively unexplored. Considering that acyl carrier protein (ACP) has an important role in the delivery of fatty acyl intermediates to other FAS enzymes, we elucidated the solution structure of A. baumannii ACP (AbACP) and, using NMR spectroscopy, investigated its interactions with ß-ketoacyl ACP synthase III (AbKAS III), which initiates fatty acid elongation. The results show that AbACP comprises four helices, while Ca2+ reduces the electrostatic repulsion between acid residues, and the unconserved F47 plays a key role in thermal stability. Moreover, AbACP exhibits flexibility near the hydrophobic cavity entrance from D59 to T65, as well as in the α1α2 loop region. Further, F29 and A69 participate in slow exchanges, which may be related to shuttling of the growing acyl chain. Additionally, electrostatic interactions occur between the α2 and α3-helix of ACP and AbKAS III, while the hydrophobic interactions through the ACP α2-helix are seemingly important. Our study provides insights for development of potent antibiotics capable of inhibiting A. baumannii FAS protein-protein interactions.

Overlapping and unique neural circuits are activated during perceptual decision making and confidence.

The period of making a perceptual decision is often followed by a period of rating confidence where one evaluates the likely accuracy of the initial decision. However, it remains unclear whether the same or different neural circuits are engaged during periods of perceptual decision making and confidence report. To address this question, we conducted two functional MRI experiments in which we dissociated the periods related to perceptual decision making and confidence report by either separating their respective regressors or asking for confidence ratings only in the second half of the experiment. We found that perceptual decision making and confidence reports gave rise to activations in large and mostly overlapping brain circuits including frontal, parietal, posterior, and cingulate regions with the results being remarkably consistent across the two experiments. Further, the confidence report period activated a number of unique regions, whereas only early sensory areas were activated for the decision period across the two experiments. We discuss the possible reasons for this overlap and explore their implications about theories of perceptual decision making and visual metacognition.

The suboptimality of perceptual decision making with multiple alternatives.

It is becoming widely appreciated that human perceptual decision making is suboptimal but the nature and origins of this suboptimality remain poorly understood. Most past research has employed tasks with two stimulus categories, but such designs cannot fully capture the limitations inherent in naturalistic perceptual decisions where choices are rarely between only two alternatives. We conduct four experiments with tasks involving multiple alternatives and use computational modeling to determine the decision-level representation on which the perceptual decisions are based. The results from all four experiments point to the existence of robust suboptimality such that most of the information in the sensory representation is lost during the transformation to a decision-level representation. These results reveal severe limits in the quality of decision-level representations for multiple alternatives and have strong implications about perceptual decision making in naturalistic settings.

Neural Activity Patterns in the Human Brain Reflect Tactile Stickiness Perception.

Our previous human fMRI study found brain activations correlated with tactile stickiness perception using the uni-variate general linear model (GLM) (Yeon et al., 2017). Here, we conducted an in-depth investigation on neural correlates of sticky sensations by employing a multivoxel pattern analysis (MVPA) on the same dataset. In particular, we statistically compared multi-variate neural activities in response to the three groups of sticky stimuli: A supra-threshold group including a set of sticky stimuli that evoked vivid sticky perception; an infra-threshold group including another set of sticky stimuli that barely evoked sticky perception; and a sham group including acrylic stimuli with no physically sticky property. Searchlight MVPAs were performed to search for local activity patterns carrying neural information of stickiness perception. Similar to the uni-variate GLM results, significant multi-variate neural activity patterns were identified in postcentral gyrus, subcortical (basal ganglia and thalamus), and insula areas (insula and adjacent areas). Moreover, MVPAs revealed that activity patterns in posterior parietal cortex discriminated the perceptual intensities of stickiness, which was not present in the uni-variate analysis. Next, we applied a principal component analysis (PCA) to the voxel response patterns within identified clusters so as to find low-dimensional neural representations of stickiness intensities. Follow-up clustering analyses clearly showed separate neural grouping configurations between the Supra- and Infra-threshold groups. Interestingly, this neural categorization was in line with the perceptual grouping pattern obtained from the psychophysical data. Our findings thus suggest that different stickiness intensities would elicit distinct neural activity patterns in the human brain and may provide a neural basis for the perception and categorization of tactile stickiness.

Human Brain Activity Related to the Tactile Perception of Stickiness.

While the perception of stickiness serves as one of the fundamental dimensions for tactile sensation, little has been elucidated about the stickiness sensation and its neural correlates. The present study investigated how the human brain responds to perceived tactile sticky stimuli using functional magnetic resonance imaging (fMRI). To evoke tactile perception of stickiness with multiple intensities, we generated silicone stimuli with varying catalyst ratios. Also, an acrylic sham stimulus was prepared to present a condition with no sticky sensation. From the two psychophysics experiments-the methods of constant stimuli and the magnitude estimation-we could classify the silicone stimuli into two groups according to whether a sticky perception was evoked: the Supra-threshold group that evoked sticky perception and the Infra-threshold group that did not. In the Supra-threshold vs. Sham contrast analysis of the fMRI data using the general linear model (GLM), the contralateral primary somatosensory area (S1) and ipsilateral dorsolateral prefrontal cortex (DLPFC) showed significant activations in subjects, whereas no significant result was found in the Infra-threshold vs. Sham contrast. This result indicates that the perception of stickiness not only activates the somatosensory cortex, but also possibly induces higher cognitive processes. Also, the Supra- vs. Infra-threshold contrast analysis revealed significant activations in several subcortical regions, including the pallidum, putamen, caudate and thalamus, as well as in another region spanning the insula and temporal cortices. These brain regions, previously known to be related to tactile discrimination, may subserve the discrimination of different intensities of tactile stickiness. The present study unveils the human neural correlates of the tactile perception of stickiness and may contribute to broadening the understanding of neural mechanisms associated with tactile perception.