In search of a human self-regulation system.

The capacity for self-regulation allows people to control their thoughts, behaviors, emotions, and desires. In spite of this impressive ability, failures of self-regulation are common and contribute to numerous societal problems, from obesity to drug addiction. Such failures frequently occur following exposure to highly tempting cues, during negative moods, or after self-regulatory resources have been depleted. Here we review the available neuroscientific evidence regarding self-regulation and its failures. At its core, self-regulation involves a critical balance between the strength of an impulse and an individual's ability to inhibit the desired behavior. Although neuroimaging and patient studies provide consistent evidence regarding the reward aspects of impulses and desires, the neural mechanisms that underlie the capacity for control have eluded consensus, with various executive control regions implicated in different studies. We outline the necessary properties for a self-regulation control system and suggest that the use of resting-state functional connectivity analyses may be useful for understanding how people regulate their behavior and why they sometimes fail in their attempts.

Evolving MRSA: High-level ß-lactam resistance in Staphylococcus aureus is associated with RNA Polymerase alterations and fine tuning of gene expression.

Most clinical MRSA (methicillin-resistant S. aureus) isolates exhibit low-level ß-lactam resistance (oxacillin MIC 2-4 µg/ml) due to the acquisition of a novel penicillin binding protein (PBP2A), encoded by mecA. However, strains can evolve high-level resistance (oxacillin MIC ≥256 µg/ml) by an unknown mechanism. Here we have developed a robust system to explore the basis of the evolution of high-level resistance by inserting mecA into the chromosome of the methicillin-sensitive S. aureus SH1000. Low-level mecA-dependent oxacillin resistance was associated with increased expression of anaerobic respiratory and fermentative genes. High-level resistant derivatives had acquired mutations in either rpoB (RNA polymerase subunit ß) or rpoC (RNA polymerase subunit ß') and these mutations were shown to be responsible for the observed resistance phenotype. Analysis of rpoB and rpoC mutants revealed decreased growth rates in the absence of antibiotic, and alterations to, transcription elongation. The rpoB and rpoC mutations resulted in decreased expression to parental levels, of anaerobic respiratory and fermentative genes and specific upregulation of 11 genes including mecA. There was however no direct correlation between resistance and the amount of PBP2A. A mutational analysis of the differentially expressed genes revealed that a member of the S. aureus Type VII secretion system is required for high level resistance. Interestingly, the genomes of two of the high level resistant evolved strains also contained missense mutations in this same locus. Finally, the set of genetically matched strains revealed that high level antibiotic resistance does not incur a significant fitness cost during pathogenesis. Our analysis demonstrates the complex interplay between antibiotic resistance mechanisms and core cell physiology, providing new insight into how such important resistance properties evolve.

Role of Aging and the Immune Response to Respiratory Viral Infections: Potential Implications for COVID-19.

Aging impairs immunity to promote diseases, especially respiratory viral infections. The current COVID-19 pandemic, resulting from SARS-CoV-2, induces acute pneumonia, a phenotype that is alarmingly increased with aging. In this article, we review findings of how aging alters immunity to respiratory viral infections to identify age-impacted pathways common to several viral pathogens, permitting us to speculate about potential mechanisms of age-enhanced mortality to COVID-19. Aging generally leads to exaggerated innate immunity, particularly in the form of elevated neutrophil accumulation across murine and large animal studies of influenza infection. COVID-19 patients who succumb exhibit a 2-fold increase in neutrophilia, suggesting that exaggerated innate immunity contributes to age-enhanced mortality to SARS-CoV-2 infection. Further investigation in relevant experimental models will elucidate the mechanisms by which aging impacts respiratory viral infections, including SARS-CoV-2. Such investigation could identify therapies to reduce the suffering of the population at large, but especially among older people, infected with respiratory viruses.

Insights into the global effect on Staphylococcus aureus growth arrest by induction of the endoribonuclease MazF toxin.

A crucial bacterial strategy to avoid killing by antibiotics is to enter a growth arrested state, yet the molecular mechanisms behind this process remain elusive. The conditional overexpression of mazF, the endoribonuclease toxin of the MazEF toxin-antitoxin system in Staphylococcus aureus, is one approach to induce bacterial growth arrest, but its targets remain largely unknown. We used overexpression of mazF and high-throughput sequence analysis following the exact mapping of non-phosphorylated transcriptome ends (nEMOTE) technique to reveal in vivo toxin cleavage sites on a global scale. We obtained a catalogue of MazF cleavage sites and unearthed an extended MazF cleavage specificity that goes beyond the previously reported one. We correlated transcript cleavage and abundance in a global transcriptomic profiling during mazF overexpression. We observed that MazF affects RNA molecules involved in ribosome biogenesis, cell wall synthesis, cell division and RNA turnover and thus deliver a plausible explanation for how mazF overexpression induces stasis. We hypothesize that autoregulation of MazF occurs by directly modulating the MazEF operon, such as the rsbUVW genes that regulate the sigma factor SigB, including an observed cleavage site on the MazF mRNA that would ultimately play a role in entry and exit from bacterial stasis.

Cellular senescence: friend or foe to respiratory viral infections?

Cellular senescence permanently arrests the replication of various cell types and contributes to age-associated diseases. In particular, cellular senescence may enhance chronic lung diseases including COPD and idiopathic pulmonary fibrosis. However, the role cellular senescence plays in the pathophysiology of acute inflammatory diseases, especially viral infections, is less well understood. There is evidence that cellular senescence prevents viral replication by increasing antiviral cytokines, but other evidence shows that senescence may enhance viral replication by downregulating antiviral signalling. Furthermore, cellular senescence leads to the secretion of inflammatory mediators, which may either promote host defence or exacerbate immune pathology during viral infections. In this Perspective article, we summarise how senescence contributes to physiology and disease, the role of senescence in chronic lung diseases, and how senescence impacts acute respiratory viral infections. Finally, we develop a potential framework for how senescence may contribute, both positively and negatively, to the pathophysiology of viral respiratory infections, including severe acute respiratory syndrome due to the coronavirus SARS-CoV-2.

Genetic risk for obesity predicts nucleus accumbens size and responsivity to real-world food cues.

Obesity is a major public health concern that involves an interaction between genetic susceptibility and exposure to environmental cues (e.g., food marketing); however, the mechanisms that link these factors and contribute to unhealthy eating are unclear. Using a well-known obesity risk polymorphism (FTO rs9939609) in a sample of 78 children (ages 9-12 y), we observed that children at risk for obesity exhibited stronger responses to food commercials in the nucleus accumbens (NAcc) than children not at risk. Similarly, children at a higher genetic risk for obesity demonstrated larger NAcc volumes. Although a recessive model of this polymorphism best predicted body mass and adiposity, a dominant model was most predictive of NAcc size and responsivity to food cues. These findings suggest that children genetically at risk for obesity are predisposed to represent reward signals more strongly, which, in turn, may contribute to unhealthy eating behaviors later in life.

Reward-related regions form a preferentially coupled system at rest.

Neuroimaging studies have implicated a set of striatal and orbitofrontal cortex (OFC) regions that are commonly activated during reward processing tasks. Resting-state functional connectivity (RSFC) studies have demonstrated that the human brain is organized into several functional systems that show strong temporal coherence in the absence of goal-directed tasks. Here we use seed-based and graph-theory RSFC approaches to characterize the systems-level organization of putative reward regions of at rest. Peaks of connectivity from seed-based RSFC patterns for the nucleus accumbens (NAcc) and orbitofrontal cortex (OFC) were used to identify candidate reward regions which were merged with a previously used set of regions (Power et al., 2011). Graph-theory was then used to determine system-level membership for all regions. Several regions previously implicated in reward-processing (NAcc, lateral and medial OFC, and ventromedial prefrontal cortex) comprised a distinct, preferentially coupled system. This RSFC system is stable across a range of connectivity thresholds and shares strong overlap with meta-analyses of task-based reward studies. This reward system shares between-system connectivity with systems implicated in cognitive control and self-regulation, including the fronto-parietal, cingulo-opercular, and default systems. Differences may exist in the pathways through which control systems interact with reward system components. Whereas NAcc is functionally connected to cingulo-opercular and default systems, OFC regions show stronger connectivity with the fronto-parietal system. We propose that future work may be able to interrogate group or individual differences in connectivity profiles using the regions delineated in this work to explore potential relationships to appetitive behaviors, self-regulation failure, and addiction.

Sub-Inhibitory Doses of Individual Constituents of Essential Oils Can Select for Staphylococcus aureus Resistant Mutants.

Increased bacterial resistance to food preservation technologies represents a risk for food safety and shelf-life. The use of natural antimicrobials, such as essential oils (EOs) and their individual constituents (ICs), has been proposed to avoid the generation of antimicrobial resistance. However, prolonged application of ICs might conceivably lead to the emergence of resistant strains. Hence, this study was aimed toward applying sub-inhibitory doses of the ICs carvacrol, citral, and (+)-limonene oxide to Staphylococcus aureus USA300, in order to evaluate the emergence of resistant strains and to identify the genetic modifications responsible for their increased resistance. Three stable-resistant strains, CAR (from cultures with carvacrol), CIT (from cultures with citral), and OXLIM (from cultures with (+)-limonene oxide) were isolated, showing an increased resistance against the ICs and a higher tolerance to lethal treatments by ICs or heat. Whole-genome sequencing revealed in CAR a large deletion in a region that contained genes encoding transcriptional regulators and metabolic enzymes. CIT showed a single missense mutation in aroC (N187K), which encodes for chorismate synthase; and in OXLIM a missense mutation was detected in rpoB (A862V), which encodes for RNA polymerase subunit beta. This study provides a first detailed insight into the mechanisms of action and S. aureus resistance arising from exposure to carvacrol, citral, and (+)-limonene oxide.

Whole-Genome Sequencing and Genetic Analysis Reveal Novel Stress Responses to Individual Constituents of Essential Oils in Escherichia coli.

Food preservation by the use of essential oils (EOs) is being extensively studied because of the antimicrobial properties of their individual constituents (ICs). Three resistant mutants (termed CAR, CIT, and LIM) of Escherichia coli MG1655 were selected by subculturing with the ICs carvacrol, citral, and (+)-limonene oxide, respectively. These derivative strains showed increased MIC values of ICs and concomitantly enhanced resistance to various antibiotics (ampicillin, trimethoprim, chloramphenicol, tetracycline, kanamycin, novobiocin, norfloxacin, cephalexin, and nalidixic acid) compared to those for the parental strain (wild type [WT]). Whole-genome sequencing (WGS) of these hyperresistant strains permitted the identification of single nucleotide polymorphisms (SNPs) and deletions in comparison to the WT. In order to analyze the contribution of these mutations to the increased antimicrobial resistance detected in hyperresistant strains, derivative strains were constructed by allelic reversion. A role of the SoxR D137Y missense mutation in CAR was confirmed by growth in the presence of some ICs and antibiotics and by its tolerance to ICs but not to lethal heat treatments. In CIT, increased resistance relied on contributions by several detected SNPs, resulting in a frameshift in MarR and an in-frame GyrB ΔG157 mutation. Finally, both the insertion resulting in an AcrR frameshift and large chromosomal deletions found in LIM were correlated with the hyperresistant phenotype of this strain. The nature of the obtained mutants suggests intriguing links to cellular defense mechanisms previously implicated in antibiotic resistance.IMPORTANCE The antimicrobial efficacy of ICs has been proven over the years, together with their potential to improve traditional heat treatments by reducing treatment intensity and, consequently, adverse effects on food quality. However, the mechanisms of bacterial inactivation by ICs are still not well understood, in contrast to antibiotics. We performed WGS of three E. coli strains that are hyperresistant to ICs. The information provided detailed insight into the mechanisms of bacterial resistance arising from exposure to carvacrol, citral, and (+)-limonene oxide. Future experiments will undoubtedly yield additional insights into genes and pathways contributing to the acquisition of endogenous resistance to ICs.

The Dorsal Medial Prefrontal Cortex Responds Preferentially to Social Interactions during Natural Viewing.

UNLABELLED: Humans display a strong tendency to make spontaneous inferences concerning the thoughts and intentions of others. Although this ability relies upon the concerted effort of multiple brain regions, the dorsal medial prefrontal cortex (DMPFC) is most closely associated with the ability to reason about other people's mental states and form impressions of their character. Here, we investigated this region's putative social category preference using fMRI as 34 participants engaged in uninstructed viewing of a complex naturalistic stimulus. Using a data-driven "reverse correlation" approach, we characterize the DMPFC's stimulus response profile from ongoing neural responses to a dynamic movie stimulus. Results of this analysis demonstrate that the DMPFC's response profile is dominated by the presence of scenes involving social interactions between characters. Subsequent content analysis of video clips created from this response profile confirmed this finding. In contrast, regions of the inferotemporal and parietal cortex were selectively tuned to faces and actions, both features that often covary with social interaction but may be difficult to disentangle using standard event-related approaches. Together, these findings suggest that the DMPFC is finely tuned for processing social interaction above other categories and that this preference is maintained during unrestricted viewing of complex natural stimuli such as movies. SIGNIFICANCE STATEMENT: Recently, studies have brought into question whether the dorsal medial prefrontal cortex (DMPFC), a region long associated with social cognition, is specialized for the processing of social information. We examine the response profile of this region during natural viewing of a reasonably naturalistic stimulus (i.e., a Hollywood movie) using a data-driven reverse correlation technique. Our findings demonstrate that, during natural viewing, the DMPFC is strongly tuned to the social features of the stimulus above other categories. Moreover, this response differs from other areas with previously well characterized response profiles such as the lateral and medial fusiform gyrus. These findings suggest that this region's dominant function in everyday situations is to support reasoning about the thoughts and intentions of conspecifics.

Molecular Bases Determining Daptomycin Resistance-Mediated Resensitization to ß-Lactams (Seesaw Effect) in Methicillin-Resistant Staphylococcus aureus.

Antimicrobial resistance is recognized as one of the principal threats to public health worldwide, yet the problem is increasing. Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) strains are among the most difficult to treat in clinical settings due to the resistance of MRSA to nearly all available antibiotics. The cyclic anionic lipopeptide antibiotic daptomycin (DAP) is the clinical mainstay of anti-MRSA therapy. The decreased susceptibility to DAP (DAP resistance [DAPr]) reported in MRSA is frequently accompanied by a paradoxical decrease in ß-lactam resistance, a process known as the "seesaw effect." Despite the observed discordance in resistance phenotypes, the combination of DAP and ß-lactams has been proven to be clinically effective for the prevention and treatment of infections due to DAPr MRSA strains. However, the mechanisms underlying the interactions between DAP and ß-lactams are largely unknown. In the study described here, we studied the role of mprF with DAP-induced mutations in ß-lactam sensitization and its involvement in the effective killing by the DAP-oxacillin (OXA) combination. DAP-OXA-mediated effects resulted in cell wall perturbations, including changes in peptidoglycan insertion, penicillin-binding protein 2 (PBP 2) delocalization, and reduced membrane amounts of PBP 2a, despite the increased transcription of mecA through mec regulatory elements. We have found that the VraSR sensor-regulator is a key component of DAP resistance, triggering mutated mprF-mediated cell membrane (CM) modifications that result in impairment of PrsA location and chaperone functions, both of which are essential for PBP 2a maturation, the key determinant of ß-lactam resistance. These observations provide for the first time evidence that synergistic effects between DAP and ß-lactams involve PrsA posttranscriptional regulation of CM-associated PBP 2a.

Generation and Evaluation of a Cortical Area Parcellation from Resting-State Correlations.

The cortical surface is organized into a large number of cortical areas; however, these areas have not been comprehensively mapped in the human. Abrupt transitions in resting-state functional connectivity (RSFC) patterns can noninvasively identify locations of putative borders between cortical areas (RSFC-boundary mapping; Cohen et al. 2008). Here we describe a technique for using RSFC-boundary maps to define parcels that represent putative cortical areas. These parcels had highly homogenous RSFC patterns, indicating that they contained one unique RSFC signal; furthermore, the parcels were much more homogenous than a null model matched for parcel size when tested in two separate datasets. Several alternative parcellation schemes were tested this way, and no other parcellation was as homogenous as or had as large a difference compared with its null model. The boundary map-derived parcellation contained parcels that overlapped with architectonic mapping of areas 17, 2, 3, and 4. These parcels had a network structure similar to the known network structure of the brain, and their connectivity patterns were reliable across individual subjects. These observations suggest that RSFC-boundary map-derived parcels provide information about the location and extent of human cortical areas. A parcellation generated using this method is available at http://www.nil.wustl.edu/labs/petersen/Resources.html.

Individual Differences in Reward and Somatosensory-Motor Brain Regions Correlate with Adiposity in Adolescents.

The prevalence of adolescent obesity has increased dramatically over the past three decades, and research has documented that the number of television shows viewed during childhood is associated with greater risk for obesity. In particular, considerable evidence suggests that exposure to food marketing promotes eating habits that contribute to obesity. The present study examines neural responses to dynamic food commercials in overweight and healthy-weight adolescents using functional magnetic resonance imaging (fMRI). Compared with non-food commercials, food commercials more strongly engaged regions involved in attention and saliency detection (occipital lobe, precuneus, superior temporal gyri, and right insula) and in processing rewards [left and right nucleus accumbens (NAcc) and left orbitofrontal cortex (OFC)]. Activity in the left OFC and right insula further correlated with subjects' percent body fat at the time of the scan. Interestingly, this reward-related activity to food commercials was accompanied by the additional recruitment of mouth-specific somatosensory-motor cortices-a finding that suggests the intriguing possibility that higher-adiposity adolescents mentally simulate eating behaviors and offers a potential neural mechanism for the formation and reinforcement of unhealthy eating habits that may hamper an individual's ability lose weight later in life.

Rifampin Resistance rpoB Alleles or Multicopy Thioredoxin/Thioredoxin Reductase Suppresses the Lethality of Disruption of the Global Stress Regulator spx in Staphylococcus aureus.

UNLABELLED: Staphylococcus aureus is capable of causing a remarkable spectrum of disease, ranging from mild skin eruptions to life-threatening infections. The survival and pathogenic potential of S. aureus depend partly on its ability to sense and respond to changes in its environment. Spx is a thiol/oxidative stress sensor that interacts with the C-terminal domain of the RNA polymerase RpoA subunit, leading to changes in gene expression that help sustain viability under various conditions. Using genetic and deep-sequencing methods, we show that spx is essential in S. aureus and that a previously reported Δspx strain harbored suppressor mutations that allowed it to grow without spx One of these mutations is a single missense mutation in rpoB (a P-to-L change at position 519 encoded by rpoB [rpoB-P519L]) that conferred high-level resistance to rifampin. This mutation alone was found to be sufficient to bypass the requirement for spx The generation of rifampin resistance libraries led to the discovery of an additional rpoB mutation, R484H, which supported strains with the spx disruption. Other rifampin resistance mutations either failed to support the Δspx mutant or were recovered at unexpectedly low frequencies in genetic transduction experiments. The amino acid residues encoded by rpoB-P519L and -R484H map in close spatial proximity and comprise a highly conserved region of RpoB. We also discovered that multicopy expression of either trxA (encoding thioredoxin) or trxB (encoding thioredoxin reductase) supports strains with the deletion of spx Our results reveal intriguing properties, especially of RNA polymerase, that compensate for the loss of an essential gene that is a key mediator of diverse processes in S. aureus, including redox and thiol homeostasis, antibiotic resistance, growth, and metabolism. IMPORTANCE: The survival and pathogenicity of S. aureus depend on complex genetic programs. An objective for combating this insidious organism entails dissecting genetic regulatory circuits and discovering promising new targets for therapeutic intervention. In this study, we discovered that Spx, an RNA polymerase-interacting stress regulator implicated in many stress responses in S. aureus, including responses to oxidative and cell wall antibiotics, is essential. We describe two mechanisms that suppress the lethality of spx disruption. One mechanism highlights how only certain rifampin resistance-encoding alleles of RpoB confer new properties on RNA polymerase, with important mechanistic implications. We describe additional stress conditions where the loss of spx is deleterious, thereby highlighting Spx as a multifaceted regulator and attractive drug discovery target.

Striatal Associative Learning Signals Are Tuned to In-groups.

An important feature of adaptive social behavior is the ability to flexibly modify future actions based on the successes or failures of past experiences. The ventral striatum (VS) occupies a central role in shaping behavior by using feedback to evaluate actions and guide learning. The current studies tested whether feedback indicating the need to update social knowledge would engage the VS, thereby facilitating subsequent learning. We also examined the sensitivity of these striatal signals to the value associated with social group membership. Across two fMRI studies, participants answered questions testing their knowledge about the preferences of personally relevant social groups who were high (in-group) or low (out-group) in social value. Participants received feedback indicating whether their responses were correct or incorrect on a trial-by-trial basis. After scanning, participants were given a surprise memory test examining memory for the different types of feedback. VS activity in response to social feedback correlated with subsequent memory, specifying a role for the VS in encoding and updating social knowledge. This effect was more robust in response to in-group than out-group feedback, indicating that the VS tracks variations in social value. These results provide novel evidence of a neurobiological mechanism adaptively tuned to the motivational relevance of the surrounding social environment that focuses learning efforts on the most valuable social outcomes and triggers adjustments in behavior when necessary.

Missense mutations in PBP2A Affecting ceftaroline susceptibility detected in epidemic hospital-acquired methicillin-resistant Staphylococcus aureus clonotypes ST228 and ST247 in Western Switzerland archived since 1998.

The development and maintenance of an arsenal of antibiotics is a major health care challenge. Ceftaroline is a new cephalosporin with activity against methicillin-resistant Staphylococcus aureus (MRSA); however, no reports concerning MRSA ceftaroline susceptibility have been reported in Switzerland. We tested the in vitro activity of ceftaroline against an archived set of 60 MRSA strains from the University Hospital of Geneva collected from 1994 to 2003. Our results surprisingly revealed ceftaroline-resistant strains (MIC, >1 µg/ml in 40/60 strains; EUCAST breakpoints, susceptible [S], ≤1 µg/ml; resistant [R], >1 µg/ml) were present from 1998 to 2003. The detected resistant strains predominantly belonged to sequence type 228 (ST228) (South German clonotype) but also to ST247 (Iberian clonotype). A sequence analysis of these strains revealed missense mutations in the penicillin-binding protein 2A (PBP2A) allosteric domain (N146K or E239K and N146K-E150K-G246E). The majority of our ST228 PBP2A mutations (N146K or E150K) were distinct from ST228 PBP2A allosteric domain mutations (primarily E239K) recently described for MRSA strains collected in Thailand and Spain during the 2010 Assessing Worldwide Antimicrobial Resistance Evaluation (AWARE) global surveillance program. We also found that similar allosteric domain PBP2A mutations (N146K) correlated with ceftaroline resistance in an independent external ST228 MRSA set obtained from the nearby University Hospital of Lausanne, Lausanne, Switzerland, collected from 2003 to 2008. Thus, ceftaroline resistance was observed in our archived strains (including two examples of an MIC of 4 µg/ml for the Iberian ST247 clonotype with the triple mutation N146K/E150K/G246E), at least as far back as 1998, considerably predating the commercial introduction of ceftaroline. Our results reinforce the notion that unknown parameters can potentially exert selective pressure on PBP2A that can subsequently modulate ceftaroline resistance.

The Staphylococcus aureus Chaperone PrsA Is a New Auxiliary Factor of Oxacillin Resistance Affecting Penicillin-Binding Protein 2A.

Expression of the methicillin-resistant S. aureus (MRSA) phenotype results from the expression of the extra penicillin-binding protein 2A (PBP2A), which is encoded by mecA and acquired horizontally on part of the SCCmec cassette. PBP2A can catalyze dd-transpeptidation of peptidoglycan (PG) because of its low affinity for ß-lactam antibiotics and can functionally cooperate with the PBP2 transglycosylase in the biosynthesis of PG. Here, we focus upon the role of the membrane-bound PrsA foldase protein as a regulator of ß-lactam resistance expression. Deletion of prsA altered oxacillin resistance in three different SCCmec backgrounds and, more importantly, caused a decrease in PBP2A membrane amounts without affecting mecA mRNA levels. The N- and C-terminal domains of PrsA were found to be critical features for PBP2A protein membrane levels and oxacillin resistance. We propose that PrsA has a role in posttranscriptional maturation of PBP2A, possibly in the export and/or folding of newly synthesized PBP2A. This additional level of control in the expression of the mecA-dependent MRSA phenotype constitutes an opportunity to expand the strategies to design anti-infective agents.

Neural predictors of giving in to temptation in daily life.

The ability to control desires, whether for food, sex, or drugs, enables people to function successfully within society. Yet, in tempting situations, strong impulses often result in self-control failure. Although many triggers of self-control failure have been identified, the question remains as to why some individuals are more likely than others to give in to temptation. In this study, we combined functional neuroimaging and experience sampling to determine if there are brain markers that predict whether people act on their food desires in daily life. We examined food-cue-related activity in the nucleus accumbens (NAcc), as well as activity associated with response inhibition in the inferior frontal gyrus (IFG). Greater NAcc activity was associated with greater likelihood of self-control failures, whereas IFG activity supported successful resistance to temptations. These findings demonstrate an important role for the neural mechanisms underlying desire and self-control in people's real-world experiences of temptations.

Interactions between transient and sustained neural signals support the generation and regulation of anxious emotion.

Anxious emotion can manifest on brief (threat response) and/or persistent (chronic apprehension and arousal) timescales, and prior work has suggested that these signals are supported by separable neural circuitries. This fMRI study utilized a mixed block-event-related emotional provocation paradigm in 55 healthy participants to simultaneously measure brief and persistent anxious emotional responses, testing the specificity of, and interactions between, these potentially distinct systems. Results indicated that components of emotional processing networks were uniquely sensitive to transient and sustained anxious emotion. Whereas the amygdala and midbrain showed only transient responses, the ventral basal forebrain and anterior insula showed sustained activity during extended emotional contexts that tracked positively with task-evoked anxiety. States of lesser anxiety were associated with greater sustained activity in the ventromedial prefrontal cortex. Furthermore, ventromedial prefrontal recruitment was lower in individuals with higher scores on intolerance of uncertainty measures, and this hyporecruitment predicted greater transient amygdala responding to potential threat cues. This work demonstrates how brain circuitries interact across temporal scales to support brief and persistent anxious emotion and suggests potentially divergent mechanisms of dysregulation in clinical syndromes marked by brief versus persistent symptoms of anxiety.

BOOSTING SKULL-STRIPPING PERFORMANCE FOR PEDIATRIC BRAIN IMAGES.

Skull-stripping is the removal of background and non-brain anatomical features from brain images. While many skull-stripping tools exist, few target pediatric populations. With the emergence of multi-institutional pediatric data acquisition efforts to broaden the understanding of perinatal brain development, it is essential to develop robust and well-tested tools ready for the relevant data processing. However, the broad range of neuroanatomical variation in the developing brain, combined with additional challenges such as high motion levels, as well as shoulder and chest signal in the images, leaves many adult-specific tools ill-suited for pediatric skull-stripping. Building on an existing framework for robust and accurate skull-stripping, we propose developmental SynthStrip (d-SynthStrip), a skull-stripping model tailored to pediatric images. This framework exposes networks to highly variable images synthesized from label maps. Our model substantially outperforms pediatric baselines across scan types and age cohorts. In addition, the <1-minute runtime of our tool compares favorably to the fastest baselines. We distribute our model at https://w3id.org/synthstrip.