The Anatomy and Physiology of Claustrum-Cortex Interactions.

The claustrum is one of the most widely connected regions of the forebrain, yet its function has remained obscure, largely due to the experimentally challenging nature of targeting this small, thin, and elongated brain area. However, recent advances in molecular techniques have enabled the anatomy and physiology of the claustrum to be studied with the spatiotemporal and cell type-specific precision required to eventually converge on what this area does. Here we review early anatomical and electrophysiological results from cats and primates, as well as recent work in the rodent, identifying the connectivity, cell types, and physiological circuit mechanisms underlying the communication between the claustrum and the cortex. The emerging picture is one in which the rodent claustrum is closely tied to frontal/limbic regions and plays a role in processes, such as attention, that are associated with these areas.

Deriving the number of salience maps an observer has from the number and quality of concurrent centroid judgments.

[C. Koch, S. Ullman, Hum. Neurobiol.4, 219-227 (1985)] proposed a 2D topographical salience map that took feature-map outputs as its input and represented the importance "saliency" of the feature inputs at each location as a real number. The computation on the map, "winner-take-all," was used to predict action priority. We propose that the same or a similar map is used to compute centroid judgments, the center of a cloud of diverse items. [P. Sun, V. Chu, G. Sperling, Atten. Percept. Psychophys.83, 934-955 (2021)] demonstrated that following a 250-msec exposure of a 24-dot array of 3 intermixed colors, subjects could accurately report the centroid of each dot color, thereby indicating that these subjects had at least three salience maps. Here, we use a postcue, partial-report paradigm to determine how many more salience maps subjects might have. In 11 experiments, subjects viewed 0.3-s flashes of 28 to 32 item arrays composed of M, M = 3,...,8, different features followed by a cue to mouse-click the centroid of items of just the post-cued feature. Ideal detector response analyses show that subjects utilized at least 12 to 17 stimulus items. By determining whether a subject's performance in (M-1)-feature experiments could/could-not predict performance in M-feature experiments, we conclude that one subject has at least 7 and the other two have at least five salience maps. A computational model shows that the primary performance-limiting factors are channel capacity for representing so many concurrently presented groups of items and working-memory capacity for so many computed centroids.

Neuronal Ensembles in the Amygdala Allow Social Information to Motivate Later Decisions.

Social experiences carry tremendous weight in our decision-making, even when social partners are not present. To determine mechanisms, we trained female mice to respond for two food reinforcers. Then, one food was paired with a novel conspecific. Mice later favored the conspecific-associated food, even in the absence of the conspecific. Chemogenetically silencing projections from the prelimbic subregion (PL) of the medial prefrontal cortex to the basolateral amygdala (BLA) obstructed this preference while leaving social discrimination intact, indicating that these projections are necessary for socially driven choice. Further, mice that performed the task had greater densities of dendritic spines on excitatory BLA neurons relative to mice that did not. We next induced chemogenetic receptors in cells active during social interactions-when mice were encoding information that impacted later behavior. BLA neurons stimulated by social experience were necessary for mice to later favor rewards associated with social conspecifics but not make other choices. This profile contrasted with that of PL neurons stimulated by social experience, which were necessary for choice behavior in social and nonsocial contexts alike. The PL may convey a generalized signal allowing mice to favor particular rewards, while units in the BLA process more specialized information, together supporting choice motivated by social information.

Re-examining the Mysterious Role of the Cerebellum in Pain.

Pain is considered a multidimensional experience that embodies not merely sensation, but also emotion and perception. As is appropriate for this complexity, pain is represented and processed by an extensive matrix of cortical and subcortical structures. Of these structures, the cerebellum is gaining increasing attention. Although association between the cerebellum and both acute and chronic pain have been extensively detailed in electrophysiological and neuroimaging studies, a deep understanding of what functions are mediated by these associations is lacking. Nevertheless, the available evidence implies that lobules IV-VI and Crus I are especially pertinent to pain processing, and anatomical studies reveal that these regions connect with higher-order structures of sensorimotor, emotional, and cognitive function. Therefore, we speculate that the cerebellum exerts a modulatory role in pain via its communication with sites of sensorimotor, executive, reward, and limbic function. On this basis, in this review, we propose numerous ways in which the cerebellum might contribute to both acute and chronic pain, drawing particular attention to emotional and cognitive elements of pain. In addition, we emphasise the importance of advancing our knowledge about the relationship between the cerebellum and pain by discussing novel therapeutic opportunities that capitalize on this association.

Auditory Competition and Coding of Relative Stimulus Strength across Midbrain Space Maps of Barn Owls.

The natural environment challenges the brain to prioritize the processing of salient stimuli. The barn owl, a sound localization specialist, exhibits a circuit called the midbrain stimulus selection network, dedicated to representing locations of the most salient stimulus in circumstances of concurrent stimuli. Previous competition studies using unimodal (visual) and bimodal (visual and auditory) stimuli have shown that relative strength is encoded in spike response rates. However, open questions remain concerning auditory-auditory competition on coding. To this end, we present diverse auditory competitors (concurrent flat noise and amplitude-modulated noise) and record neural responses of awake barn owls of both sexes in subsequent midbrain space maps, the external nucleus of the inferior colliculus (ICx) and optic tectum (OT). While both ICx and OT exhibit a topographic map of auditory space, OT also integrates visual input and is part of the global-inhibitory midbrain stimulus selection network. Through comparative investigation of these regions, we show that while increasing strength of a competitor sound decreases spike response rates of spatially distant neurons in both regions, relative strength determines spike train synchrony of nearby units only in the OT. Furthermore, changes in synchrony by sound competition in the OT are correlated to gamma range oscillations of local field potentials associated with input from the midbrain stimulus selection network. The results of this investigation suggest that modulations in spiking synchrony between units by gamma oscillations are an emergent coding scheme representing relative strength of concurrent stimuli, which may have relevant implications for downstream readout.

Putaminal dopamine modulates movement motivation in Parkinson's disease.

The relative inability to produce effortful movements is the most specific motor sign of Parkinson's disease, which is primarily characterized by loss of dopaminergic terminals in the putamen. The motor motivation hypothesis suggests that this motor deficit may not reflect a deficiency in motor control per se, but a deficiency in cost-benefit considerations for motor effort. For the first time, we investigated the quantitative effect of dopamine depletion on the motivation of motor effort in Parkinson's disease. A total of 21 early-stage, unmedicated patients with Parkinson's disease and 26 healthy controls were included. An incentivized force task was used to capture the amount of effort participants were willing to invest for different monetary incentive levels and dopamine transporter depletion in the bilateral putamen was assessed. Our results demonstrate that patients with Parkinson's disease applied significantly less grip force than healthy controls, especially for low incentive levels. Congruously, decrease of motor effort with greater loss of putaminal dopaminergic terminals was most pronounced for low incentive levels. This signifies that putaminal dopamine is most critical to motor effort when the trade-off with the benefit is poor. Taken together, we provide direct evidence that the reduction of effortful movements in Parkinson's disease depends on motivation and that this effect is associated with putaminal dopaminergic degeneration.

Action video games and posterior parietal cortex neuromodulation enhance both attention and reading in adults with developmental dyslexia.

The impact of action video games on reading performance has been already demonstrated in individuals with and without neurodevelopmental disorders. The combination of action video games and posterior parietal cortex neuromodulation by a transcranial random noise stimulation could enhance brain plasticity, improving attentional control and reading skills also in adults with developmental dyslexia. In a double blind randomized controlled trial, 20 young adult nonaction video game players with developmental dyslexia were trained for 15 h with action video games. Half of the participants were stimulated with bilateral transcranial random noise stimulation on the posterior parietal cortex during the action video game training, whereas the others were in the placebo (i.e. sham) condition. Word text reading, pseudowords decoding, and temporal attention (attentional blink), as well as electroencephalographic activity during the attentional blink, were measured before and after the training. The action video game + transcranial random noise stimulation group showed temporal attention, word text reading, and pseudoword decoding enhancements and P300 amplitude brain potential changes. The enhancement in temporal attention performance was related with the efficiency in pseudoword decoding improvement. Our results demonstrate that the combination of action video game training with parietal neuromodulation increases the efficiency of visual attention deployment, probably reshaping goal-directed and stimulus-driven fronto-parietal attentional networks interplay in young adults with neurodevelopmental conditions.

Infants' reorienting efficiency depends on parental autistic traits and predicts future socio-communicative behaviors.

Attentional reorienting is dysfunctional not only in children with autism spectrum disorder (ASD), but also in infants who will develop ASD, thus constituting a potential causal factor of future social interaction and communication abilities. Following the research domain criteria framework, we hypothesized that the presence of subclinical autistic traits in parents should lead to atypical infants' attentional reorienting, which in turn should impact on their future socio-communication behavior in toddlerhood. During an attentional cueing task, we measured the saccadic latencies in a large sample (total enrolled n = 89; final sample n = 71) of 8-month-old infants from the general population as a proxy for their stimulus-driven attention. Infants were grouped in a high parental traits (HPT; n = 23) or in a low parental traits (LPT; n = 48) group, according to the degree of autistic traits self-reported by their parents. Infants (n = 33) were then longitudinally followed to test their socio-communicative behaviors at 21 months. Results show a sluggish reorienting system, which was a longitudinal predictor of future socio-communicative skills at 21 months. Our combined transgenerational and longitudinal findings suggest that the early functionality of the stimulus-driven attentional network-redirecting attention from one event to another-could be directly connected to future social and communication development.

The mediating role of trait impulsivity in the relation between cue-induced craving and functional connectivity within the salience network among abstinent patients with methamphetamine use disorder.

Given the widespread use and relapse of methamphetamine (METH), it has caused serious public health burdens globally. However, the neurobiological basis of METH addiction remains poorly understood. Therefore, this study aimed to use magnetic resonance imaging (MRI) to investigate changes in brain networks and their connection to impulsivity and drug craving in abstinent individuals with METH use disorder (MUDs). A total of 110 MUDs and 55 age- and gender-matched healthy controls (HCs) underwent resting-state functional MRI and T1-weighted imaging scans, and completed impulsivity and cue-induced craving measurements. We applied independent component analysis to construct functional brain networks and multivariate analysis of covariance to investigate group differences in network connectivity. Mediation analyses were conducted to explore the relationships among brain-network functional connectivity (FC), impulsivity, and drug craving in the patients. MUDs showed increased connectivity in the salience network (SN) and decreased connectivity in the default mode network compared to HCs. Impulsivity was positively correlated with FC within the SN and played a completely mediating role between METH craving and FC within the SN in MUDs. These findings suggest alterations in functional brain networks underlying METH dependence, with SN potentially acting as a core neural substrate for impulse control disorders.

Basolateral amygdala activation enhances object recognition memory by inhibiting anterior insular cortex activity.

Noradrenergic activation of the basolateral amygdala (BLA) by emotional arousal enhances different forms of recognition memory via functional interactions with the insular cortex (IC). Human neuroimaging studies have revealed that the anterior IC (aIC), as part of the salience network, is dynamically regulated during arousing situations. Emotional stimulation first rapidly increases aIC activity but suppresses it in a delayed fashion. Here, we investigated in male Sprague-Dawley rats whether the BLA influence on recognition memory is associated with an increase or suppression of aIC activity during the postlearning consolidation period. We first employed anterograde and retrograde viral tracing and found that the BLA sends dense monosynaptic projections to the aIC. Memory-enhancing norepinephrine administration into the BLA following an object training experience suppressed aIC activity 1 h later, as determined by a reduced expression of the phosphorylated form of the transcription factor cAMP response element-binding (pCREB) protein and neuronal activity marker c-Fos. In contrast, the number of perisomatic γ-aminobutyric acid (GABA)ergic inhibitory synapses per pCREB-positive neuron was significantly increased, suggesting a dynamic up-regulation of GABAergic tone. In support of this possibility, pharmacological inhibition of aIC activity with a GABAergic agonist during consolidation enhanced object recognition memory. Norepinephrine administration into the BLA did not affect neuronal activity within the posterior IC, which receives sparse innervation from the BLA. The evidence that noradrenergic activation of the BLA enhances the consolidation of object recognition memory via a mechanism involving a suppression of aIC activity provides insight into the broader brain network dynamics underlying emotional regulation of memory.

Minority salience and the overestimation of individuals from minority groups in perception and memory.

Our cognitive system is tuned toward spotting the uncommon and unexpected. We propose that individuals coming from minority groups are, by definition, just that­uncommon and often unexpected. Consequently, they are psychologically salient in perception, memory, and visual awareness. This minority salience creates a tendency to overestimate the prevalence of minorities, leading to an erroneous picture of our social environments­an illusion of diversity. In 12 experiments with 942 participants, we found evidence that the presence of minority group members is indeed overestimated in memory and perception and that masked images of minority group members are prioritized for visual awareness. These findings were consistent when participants were members of both the majority group and the minority group. Moreover, this overestimated prevalence of minorities led to decreased support for diversity-promoting policies. We discuss the theoretical implications of the illusion of diversity and how it may inform more equitable and inclusive decision-making.

Molecular pathways underlying lung-brain axis signaling in asthma: Relevance for psychopathology and neuroinflammation.

BACKGROUND: Accumulating evidence indicates that asthma has systemic effects and affects brain function. Although airway inflammation is proposed to initiate afferent communications with the brain, the signaling pathways have not been established. OBJECTIVE: We sought to identify the cellular and molecular pathways involved in afferent lung-brain communication during airway inflammation in asthma. METHODS: In 23 adults with mild asthma, segmental bronchial provocation with allergen (SBP-Ag) was used to provoke airway inflammation and retrieve bronchoalveolar lavage fluid for targeted protein analysis and RNA sequencing to determine gene expression profiles. Neural responses to emotional cues in nodes of the salience network were assessed with functional magnetic resonance imaging at baseline and 48 hours after SBP-Ag. RESULTS: Cell deconvolution and gene coexpression network analysis identified 11 cell-associated gene modules that changed in response to SBP-Ag. SBP-Ag increased bronchoalveolar lavage eosinophils and expression of an eosinophil-associated module enriched for genes related to TH17-type inflammation (eg, IL17A), as well as cell proliferation in lung and brain (eg, NOTCH1, VEGFA, and LIF). Increased expression of genes in this module, as well as several TH17-type inflammation-related proteins, was associated with an increase from baseline in salience network reactivity. CONCLUSIONS: Our results identify a specific inflammatory pathway linking asthma-related airway inflammation and emotion-related neural function. Systemically, TH17-type inflammation has been implicated in both depression and neuroinflammation, with impacts on long-term brain health. Thus, our data emphasize that inflammation in the lung in asthma may have profound effects outside of the lung that may be targetable with novel therapeutic approaches.

Feature-Specific Salience Maps in Human Cortex.

Priority map theory is a leading framework for understanding how various aspects of stimulus displays and task demands guide visual attention. Per this theory, the visual system computes a priority map, which is a representation of visual space indexing the relative importance, or priority, of locations in the environment. Priority is computed based on both salience, defined based on image-computable properties; and relevance, defined by an individual's current goals, and is used to direct attention to the highest-priority locations for further processing. Computational theories suggest that priority maps identify salient locations based on individual feature dimensions (e.g., color, motion), which are integrated into an aggregate priority map. While widely accepted, a core assumption of this framework, the existence of independent feature dimension maps in visual cortex, remains untested. Here, we tested the hypothesis that retinotopic regions selective for specific feature dimensions (color or motion) in human cortex act as neural feature dimension maps, indexing salient locations based on their preferred feature. We used fMRI activation patterns to reconstruct spatial maps while male and female human participants viewed stimuli with salient regions defined by relative color or motion direction. Activation in reconstructed spatial maps was localized to the salient stimulus position in the display. Moreover, the strength of the stimulus representation was strongest in the ROI selective for the salience-defining feature. Together, these results suggest that feature-selective extrastriate visual regions highlight salient locations based on local feature contrast within their preferred feature dimensions, supporting their role as neural feature dimension maps.SIGNIFICANCE STATEMENT Identifying salient information is important for navigating the world. For example, it is critical to detect a quickly approaching car when crossing the street. Leading models of computer vision and visual search rely on compartmentalized salience computations based on individual features; however, there has been no direct empirical demonstration identifying neural regions as responsible for performing these dissociable operations. Here, we provide evidence of a critical double dissociation that neural activation patterns from color-selective regions prioritize the location of color-defined salience while minimally representing motion-defined salience, whereas motion-selective regions show the complementary result. These findings reveal that specialized cortical regions act as neural "feature dimension maps" that are used to index salient locations based on specific features to guide attention.

Suppressive Control of Incentive Salience in Real-World Human Vision.

Reward-related activity in the dopaminergic midbrain is thought to guide animal behavior, in part by boosting the perceptual and attentional processing of reward-predictive environmental stimuli. In line with this incentive salience hypothesis, studies of human visual search have shown that simple synthetic stimuli, such as lines, shapes, or Gabor patches, capture attention to their location when they are characterized by reward-associated visual features, such as color. In the real world, however, we commonly search for members of a category of visually heterogeneous objects, such as people, cars, or trees, where category examples do not share low-level features. Is attention captured to examples of a reward-associated real-world object category? Here, we have human participants search for targets in photographs of city and landscapes that contain task-irrelevant examples of a reward-associated category. We use the temporal precision of EEG machine learning and ERPs to show that these distractors acquire incentive salience and draw attention, but do not capture it. Instead, we find evidence of rapid, stimulus-triggered attentional suppression, such that the neural encoding of these objects is degraded relative to neutral objects. Humans appear able to suppress the incentive salience of reward-associated objects when they know these objects will be irrelevant, supporting the rapid deployment of attention to other objects that might be more useful. Incentive salience is thought to underlie key behaviors in eating disorders and addiction, among other conditions, and the kind of suppression identified here likely plays a role in mediating the attentional biases that emerge in these circumstances.Significance Statement Like other animals, humans are prone to notice and interact with environmental objects that have proven rewarding in earlier experience. However, it is common that such objects have no immediate strategic use and are therefore distracting. Do these reward-associated real-world objects capture our attention, despite our strategic efforts otherwise? Or are we able to strategically control the impulse to notice them? Here we use machine learning classification of human electrical brain activity to show that we can establish strategic control over the salience of naturalistic reward-associated objects. These objects draw our attention, but do not necessarily capture it, and this kind of control may play an important role in mediating conditions like eating disorder and addiction.

Inhibition of Dopamine Neurons Prevents Incentive Value Encoding of a Reward Cue: With Revelations from Deep Phenotyping.

The survival of an organism is dependent on its ability to respond to cues in the environment. Such cues can attain control over behavior as a function of the value ascribed to them. Some individuals have an inherent tendency to attribute reward-paired cues with incentive motivational value, or incentive salience. For these individuals, termed sign-trackers, a discrete cue that precedes reward delivery becomes attractive and desirable in its own right. Prior work suggests that the behavior of sign-trackers is dopamine-dependent, and cue-elicited dopamine in the NAc is believed to encode the incentive value of reward cues. Here we exploited the temporal resolution of optogenetics to determine whether selective inhibition of ventral tegmental area (VTA) dopamine neurons during cue presentation attenuates the propensity to sign-track. Using male tyrosine hydroxylase (TH)-Cre Long Evans rats, it was found that, under baseline conditions, ∼84% of TH-Cre rats tend to sign-track. Laser-induced inhibition of VTA dopamine neurons during cue presentation prevented the development of sign-tracking behavior, without affecting goal-tracking behavior. When laser inhibition was terminated, these same rats developed a sign-tracking response. Video analysis using DeepLabCutTM revealed that, relative to rats that received laser inhibition, rats in the control group spent more time near the location of the reward cue even when it was not present and were more likely to orient toward and approach the cue during its presentation. These findings demonstrate that cue-elicited dopamine release is critical for the attribution of incentive salience to reward cues.SIGNIFICANCE STATEMENT Activity of dopamine neurons in the ventral tegmental area (VTA) during cue presentation is necessary for the development of a sign-tracking, but not a goal-tracking, conditioned response in a Pavlovian task. We capitalized on the temporal precision of optogenetics to pair cue presentation with inhibition of VTA dopamine neurons. A detailed behavioral analysis with DeepLabCutTM revealed that cue-directed behaviors do not emerge without dopamine neuron activity in the VTA. Importantly, however, when optogenetic inhibition is lifted, cue-directed behaviors increase, and a sign-tracking response develops. These findings confirm the necessity of dopamine neuron activity in the VTA during cue presentation to encode the incentive value of reward cues.

Reward-Mediated, Model-Free Reinforcement-Learning Mechanisms in Pavlovian and Instrumental Tasks Are Related.

Model-free and model-based computations are argued to distinctly update action values that guide decision-making processes. It is not known, however, if these model-free and model-based reinforcement learning mechanisms recruited in operationally based instrumental tasks parallel those engaged by pavlovian-based behavioral procedures. Recently, computational work has suggested that individual differences in the attribution of incentive salience to reward predictive cues, that is, sign- and goal-tracking behaviors, are also governed by variations in model-free and model-based value representations that guide behavior. Moreover, it is not appreciated if these systems that are characterized computationally using model-free and model-based algorithms are conserved across tasks for individual animals. In the current study, we used a within-subject design to assess sign-tracking and goal-tracking behaviors using a pavlovian conditioned approach task and then characterized behavior using an instrumental multistage decision-making (MSDM) task in male rats. We hypothesized that both pavlovian and instrumental learning processes may be driven by common reinforcement-learning mechanisms. Our data confirm that sign-tracking behavior was associated with greater reward-mediated, model-free reinforcement learning and that it was also linked to model-free reinforcement learning in the MSDM task. Computational analyses revealed that pavlovian model-free updating was correlated with model-free reinforcement learning in the MSDM task. These data provide key insights into the computational mechanisms mediating associative learning that could have important implications for normal and abnormal states.SIGNIFICANCE STATEMENT Model-free and model-based computations that guide instrumental decision-making processes may also be recruited in pavlovian-based behavioral procedures. Here, we used a within-subject design to test the hypothesis that both pavlovian and instrumental learning processes were driven by common reinforcement-learning mechanisms. Sign-tracking and goal-tracking behaviors were assessed in rats using a pavlovian conditioned approach task, and then instrumental behavior was characterized using an MSDM task. We report that sign-tracking behavior was associated with greater model-free, but not model-based, learning in the MSDM task. These data suggest that pavlovian and instrumental behaviors may be driven by conserved reinforcement-learning mechanisms.

Towards a unified medical microbiome ecology of the OMU for metagenomes and the OTU for microbes.

BACKGROUND: Metagenomic sequencing technologies offered unprecedented opportunities and also challenges to microbiology and microbial ecology particularly. The technology has revolutionized the studies of microbes and enabled the high-profile human microbiome and earth microbiome projects. The terminology-change from microbes to microbiomes signals that our capability to count and classify microbes (microbiomes) has achieved the same or similar level as we can for the biomes (macrobiomes) of plants and animals (macrobes). While the traditional investigations of macrobiomes have usually been conducted through naturalists' (Linnaeus & Darwin) naked eyes, and aerial and satellite images (remote-sensing), the large-scale investigations of microbiomes have been made possible by DNA-sequencing-based metagenomic technologies. Two major types of metagenomic sequencing technologies-amplicon sequencing and whole-genome (shotgun sequencing)-respectively generate two contrastingly different categories of metagenomic reads (data)-OTU (operational taxonomic unit) tables representing microorganisms and OMU (operational metagenomic unit), a new term coined in this article to represent various cluster units of metagenomic genes. RESULTS: The ecological science of microbiomes based on the OTU representing microbes has been unified with the classic ecology of macrobes (macrobiomes), but the unification based on OMU representing metagenomes has been rather limited. In a previous series of studies, we have demonstrated the applications of several classic ecological theories (diversity, composition, heterogeneity, and biogeography) to the studies of metagenomes. Here I push the envelope for the unification of OTU and OMU again by demonstrating the applications of metacommunity assembly and ecological networks to the metagenomes of human gut microbiomes. Specifically, the neutral theory of biodiversity (Sloan's near neutral model), Ning et al.stochasticity framework, core-periphery network, high-salience skeleton network, special trio-motif, and positive-to-negative ratio are applied to analyze the OMU tables from whole-genome sequencing technologies, and demonstrated with seven human gut metagenome datasets from the human microbiome project. CONCLUSIONS: All of the ecological theories demonstrated previously and in this article, including diversity, composition, heterogeneity, stochasticity, and complex network analyses, are equally applicable to OMU metagenomic analyses, just as to OTU analyses. Consequently, I strongly advocate the unification of OTU/OMU (microbiomes) with classic ecology of plants and animals (macrobiomes) in the context of medical ecology.

The dynamics of statistical learning in visual search and its interaction with salience processing: An EEG study.

Visual attention can be guided by statistical regularities in the environment, that people implicitly learn from past experiences (statistical learning, SL). Moreover, a perceptually salient element can automatically capture attention, gaining processing priority through a bottom-up attentional control mechanism. The aim of our study was to investigate the dynamics of SL and if it shapes attentional target selection additively with salience processing, or whether these mechanisms interact, e.g. one gates the other. In a visual search task, we therefore manipulated target frequency (high vs. low) across locations while, in some trials, the target was salient in terms of colour. Additionally, halfway through the experiment, the high-frequency location changed to the opposite hemifield. EEG activity was simultaneously recorded, with a specific interest in two markers related to target selection and post-selection processing, respectively: N2pc and SPCN. Our results revealed that both SL and saliency significantly enhanced behavioural performance, but also interacted with each other, with an attenuated saliency effect at the high-frequency target location, and a smaller SL effect for salient targets. Concerning processing dynamics, the benefit of salience processing was more evident during the early stage of target selection and processing, as indexed by a larger N2pc and early-SPCN, whereas SL modulated the underlying neural activity particularly later on, as revealed by larger late-SPCN. Furthermore, we showed that SL was rapidly acquired and adjusted when the spatial imbalance changed. Overall, our findings suggest that SL is flexible to changes and, combined with salience processing, jointly contributes to establishing attentional priority.

Impaired olfactory identification in dementia-free individuals is associated with the functional abnormality of the precuneus.

OBJECTIVE: Olfactory dysfunction indicates a higher risk of developing dementia. However, the potential structural and functional changes are still largely unknown. METHODS: A total of 236 participants were enrolled, including 45 Alzheimer's disease (AD) individuals and 191dementia-free individuals. Detailed study methods, comprising neuropsychological assessment and olfactory identification test (University of Pennsylvania smell identification test, UPSIT), as well as structural and functional magnetic resonance imaging (MRI) were applied in this research. The dementia-free individuals were divided into two sub-groups based on olfactory score: dementia-free with olfactory dysfunction (DF-OD) sub-group and dementia-free without olfactory dysfunction (DF-NOD) sub-group. The results were analyzed for subsequent intergroup comparisons and correlations. The cognitive assessment was conducted again three years later. RESULTS: (i) At dementia-free stage, there was a positive correlation between olfactory score and cognitive function. (ii) In dementia-free group, the volume of crucial brain structures involved in olfactory recognition and processing (such as amygdala, entorhinal cortex and basal forebrain volumes) are positively associated with olfactory score. (iii) Compared to the DF-NOD group, the DF-OD group showed a significant reduction in olfactory network (ON) function. (iv) Compared to DF-NOD group, there were significant functional connectivity (FC) decline between PCun_L(R)_4_1 in the precuneus of posterior default mode network (pDMN) and the salience network (SN) in DF-OD group, and the FC values decreased with falling olfactory scores. Moreover, in DF-OD group, the noteworthy reduction in FC were observed between PCun_L(R)_4_1 and amygdala, which was a crucial component of ON. (v) The AD conversion rate of DF-OD was 29.41%, while the DF-NOD group was 12.50%. The structural and functional changes in the precuneus were also observed in AD and were more severe. CONCLUSIONS: In addition to the olfactory circuit, the precuneus is a critical structure in the odor identification process, whose abnormal function underlies the olfactory identification impairment of dementia-free individuals.

Role of dopamine neurons in familiarity.

Dopamine neurons signal the salience of environmental stimuli and influence learning, although it is less clear if these neurons also determine the salience of memories. Ventral tegmental area (VTA) dopamine neurons increase their firing in the presence of new objects and reduce it upon repeated, inconsequential exposures, marking the shift from novelty to familiarity. This study investigates how dopamine neuron activity during repeated familiar object exposure affects an animal's preference for new objects in a subsequent novel object recognition (NOR) test. We hypothesize that a single familiarization session will not sufficiently lower dopamine activity, such that the memory of a familiar object remains salient, leading to equal exploration of familiar and novel objects and weaker NOR discrimination. In contrast, multiple familiarization sessions likely suppress dopamine activity more effectively, reducing the salience of the familiar object and enhancing subsequent novelty discrimination. Our experiments in mice indicated that multiple familiarization sessions reduce VTA dopamine neuron activation, as measured by c-Fos expression, and enhance novelty discrimination compared with a single familiarization session. Dopamine neurons that show responsiveness to novelty were primarily located in the paranigral nucleus of the VTA and expressed vesicular glutamate transporter 2 transcripts, marking them as dopamine-glutamate neurons. Chemogenetic inhibition of dopamine neurons during a single session paralleled the effects of multiple sessions, improving NOR. These findings suggest that a critical role of dopamine neurons during the transition from novelty to familiarity is to modulate the salience of an object's memory.