Distinct patterns of monocular advantage for facial emotions in social anxiety.

Individuals with social anxiety often exhibit atypical processing of facial expressions. Previous research in social anxiety has primarily emphasized cognitive bias associated with face processing and the corresponding abnormalities in cortico-limbic circuitry, yet whether social anxiety influences early perceptual processing of emotional faces remains largely unknown. We used a psychophysical method to investigate the monocular advantage for face perception (i.e., face stimuli are better recognized when presented to the same eye compared to different eyes), an effect that is indicative of early, subcortical processing of face stimuli. We compared the monocular advantage for different emotional expressions (neutral, angry and sad) in three groups (N = 24 per group): individuals clinically diagnosed with social anxiety disorder (SAD), individuals with high social anxiety in subclinical populations (SSA), and a healthy control (HC) group of individuals matched for age and gender. Compared to SSA and HC groups, we found that individuals with SAD exhibited a greater monocular advantage when processing neutral and sad faces. While the magnitudes of monocular advantages were similar across three groups when processing angry faces, individuals with SAD performed better in this condition when the faces were presented to different eye. The former findings suggest that social anxiety leads to an enhanced role of subcortical structures in processing nonthreatening expressions. The latter findings, on the other hand, likely reflect an enhanced cortical processing of threatening expressions in SAD group. These distinct patterns of monocular advantage indicate that social anxiety altered representation of emotional faces at various stages of information processing, starting at an early stage of the visual system.

Huaier enhances the tumor-killing effect and reverses gemcitabine-induced stemness by suppressing FoxM1.

BACKGROUND: Gemcitabine is the first-line chemotherapy drug that can easily cause chemotherapy resistance. Huaier is a traditional Chinese medicine and shows an antitumor effect in pancreatic cancer, but whether it can enhance the gemcitabine chemotherapeutic response and the potential mechanism remain unknown. PURPOSE: This study was performed to explore the effect of Huaier in promoting the tumor-killing effect of gemcitabine and elucidate the possible mechanism in pancreatic cancer. METHODS: Cell Counting Kit-8 assays and colony formation assays were used to detect proliferation after different treatments. Protein coimmunoprecipitation was applied to demonstrate protein interactions. Nuclear protein extraction and immunofluorescence were used to confirm the intracellular localization of the proteins. Western blotting was performed to detect cell proliferation-related protein expression or cancer stem cell-associated protein expression. Sphere formation assays and flow cytometry were used to assess the stemness of pancreatic cancer cells. The in vivo xenograft model was used to confirm the inhibitory effect under physiological conditions, and immunohistochemistry was used to detect protein expression. RESULTS: Huaier suppressed the proliferation and stem cell-like properties of pancreatic cancer cells. We found that Huaier suppressed the expression of forkhead box protein M1 (FoxM1). In addition, Huaier inhibited FoxM1 function by blocking its nuclear translocation. Treatment with Huaier reversed the stemness induced by gemcitabine in a FoxM1-dependent manner. Furthermore, we verified the above results by an in vivo study, which reached the same conclusion as those in vitro. CONCLUSION: Overall, this study illustrates that Huaier augments the tumor-killing effect of gemcitabine through suppressing the stemness induced by gemcitabine in a FoxM1-dependent way. These results indicate that Huaier can be applied to overcome gemcitabine resistance.

Reward history modulates attention based on feature relationship.

Prioritizing attention to reward-predictive items is critical for survival, but challenging because these items rarely appear in the same feature or within the same environment. However, whether attention selection can be adaptively tuned to items that matched the context-dependent, relative feature of previously rewarded items remains largely unknown. In four experiments (N = 40 per experiment), we trained participants to learn the color-reward association and then adopted visual search tasks in which the color of a singleton distractor matched either the feature value (e.g., red or yellow) or feature relationship (i.e., redder or yellower) of previously rewarded colors. We consistently found enhanced attentional capture by a singleton distractor when it was relationally matched to the high reward compared with the low reward relationship, in addition to observing the typical effect of learned value on singletons matching the previously rewarded colors. Our findings provide novel evidence for the flexibility of value-driven attention via feature relationship, which is particularly useful given the changeable sensory inputs in real-world searches. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Mutant p53 driven-LINC00857, a protein scaffold between FOXM1 and deubiquitinase OTUB1, promotes the metastasis of pancreatic cancer.

Tumour metastasis is the major adverse factor for recurrence and death in pancreatic cancer (PC) patients. P53 mutations are considered to be the second most common type of mutation in PC and significantly promote PC metastasis. However, the molecular mechanisms underlying the effects of p53 mutations, especially the regulatory relationship of the protein with long noncoding RNAs (lncRNAs), remain unclear. In the present study, we demonstrated that the lncRNA LINC00857 exhibits a significantly elevated level in PC and that it is associated with poor prognosis; furthermore, TCGA data showed that LINC00857 expression was significantly upregulated in the mutant p53 group compared with the wild-type p53 group. Gain- and loss-of-function experiments showed that LINC00857 promotes the metastasis of PC cells. We further found that LINC00857 upregulates FOXM1 protein expression and thus accelerates metastasis in vitro and in vivo. Mechanistically, LINC00857 bound simultaneously to FOXM1 and to the deubiquitinase OTUB1, thereby serving as a protein scaffold and enhancing the interaction between FOXM1 and OTUB1, which inhibits FOXM1 degradation through the ubiquitin-proteasome pathway. Interestingly, we found that mutant p53 promotes LINC00857 transcription by binding to its promoter region. Finally, atorvastatin, a commonly prescribe lipid-lowering drug, appeared to inhibit PC metastasis by inhibiting the mutant p53-LINC00857 axis. Taken together, our results provide new insights into the biology driving PC metastasis and indicate that the mutant p53-LINC00857 axis might represent a novel therapeutic target for PC metastasis.

Preparatory attention to visual features primarily relies on non-sensory representation.

Prior knowledge of behaviorally relevant information promotes preparatory attention before the appearance of stimuli. A key question is how our brain represents the attended information during preparation. A sensory template hypothesis assumes that preparatory signals evoke neural activity patterns that resembled the perception of the attended stimuli, whereas a non-sensory, abstract template hypothesis assumes that preparatory signals reflect the abstraction of attended stimuli. To test these hypotheses, we used fMRI and multivariate analysis to characterize neural activity patterns when human participants were prepared to attend a feature and then select it from a compound stimulus. In an fMRI experiment using basic visual feature (motion direction), we observed reliable decoding of the to-be-attended feature from the preparatory activity in both visual and frontoparietal areas. However, while the neural patterns constructed by a single feature from a baseline task generalized to the activity patterns during stimulus selection, they could not generalize to the activity patterns during preparation. Our findings thus suggest that neural signals during attentional preparation are predominantly non-sensory in nature that may reflect an abstraction of the attended feature. Such a representation could provide efficient and stable guidance of attention.

Piezo1 act as a potential oncogene in pancreatic cancer progression.

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer related death. A growing number of studies believe that matrix stiffness plays an important role in the development of pancreatic disease. As one of the famous mechanically activated cation channels, Piezo1 has received more attention recently. Here we tried to describe the role of Piezo1 on PDAC progression. It seemed that Piezo1 was a potential tumor-promoting marker of pancreatic cancer. By using Yoda1, we measured the intracellular calcium flux mediated by Piezo1 which confirmed it did act as an intrinsic cation channel in pancreatic cancer cells. Additionally, we also found the inhibition of Piezo1 could inhibit cancer progression in vitro; however, Piezo1 activation (induced by Yoda1) had an oppositive effect. Moreover, Piezo1 activation may also accelerate pancreatic cancer tumor growth/formation via modulating pancreatic cancer cell-tumor microenvironment interactions in vivo. We concluded that Piezo1 acted as an oncogenic gene in pancreatic cancer progression. It might be one of promising targets for pancreatic cancer therapy.

Huaier suppresses pancreatic cancer progression via activating cell autophagy induced ferroptosis.

Purpose: The anti-tumour effect of Huaier has been demonstrated in a variety of tumours. Ferroptosis is a newly identified type of programmed cell death accompanied by the accumulation of reactive oxygen species (ROS) and iron in cells and plays a key role in the therapeutic process against malignant tumours. We aimed to explore the potential therapeutic role of Huaier in pancreatic cancer and uncover the relationship between Huaier and ferroptosis. Methods: CCK8 and colony formation assays were used to determine the proliferation of pancreatic cancer cells (PCs). The levels of cellular ROS were analysed by a fluorescence probe, and the accumulation of cellular iron was showed by Prussian blue staining. The autophagosomes and mitochondrial morphology were characterised by transmission electron microscopy (TEM). The levels of intracellular glutathione (GSH) and lipid peroxidation were measured by the corresponding kits. Results: The growth inhibitory effect of Huaier on PCs was concentration- and time-dependent, but this effect was significantly attenuated by ferroptosis inhibitors. In addition, Huaier effectively inhibited the GSH-GPX4 antioxidation system and resulted in the massive accumulation of ROS in PCs As shown by TEM, Huaier-treated PCs exhibited a decrease in mitochondrial cristae and a smaller mitochondrion, accompanied by an increase in autophagosomes. Indeed, we found that autophagy can induce ferroptosis in PCs and that Huaier-induced ferroptosis can be suppressed by the autophagosome inhibitor, Wortmannin. Conclusion: Huaier can activate ferroptosis by inducing autophagy in PCs.

Mechanically activated ion channel Piezo1 contributes to melanoma malignant progression through AKT/mTOR signaling.

Melanoma is a highly aggressive cancer that can metastasize at early stage. The aim of this study is to clarify the role of Piezo1 and its potential mechanism in regulating the malignant phenotypes of melanoma. In the present study, we first showed that Piezo1 was abnormally expressed in melanoma, which accelerated the malignant progression by activating AKT/mTOR signaling. Firstly, we found that Piezo1 was upregulated in melanoma and associated with poor survival. Additionally, Piezo1 knockdown significantly weakened intracellular calcium signal and viability of melanoma cells. Furthermore, Piezo1 knockdown inhibited the transendothelial migration and invasion in vitro, as well as metastasis in vivo. Mechanistically, we found that Piezo1 activated AKT/mTOR signaling to maintain malignant phenotypes of melanoma. Therefore, Piezo1 acts as an oncogene in melanoma cells and provides a novel candidate for melanoma diagnosis and treatment.

Thiostrepton induces ferroptosis in pancreatic cancer cells through STAT3/GPX4 signalling.

Ferroptosis is a new form of regulated cell death that is mediated by intracellular iron and ester oxygenase, and glutathione-dependent lipid hydroperoxidase glutathione peroxidase 4 (GPX4) prevents ferroptosis by converting lipid hydroperoxides into nontoxic lipid alcohols. Although thiostrepton (TST) has been reported to exert antitumor effects, its role in pancreatic cancer and the underlying mechanisms remain unclear. In this study, we found that TST reduced the viability and clonogenesis of pancreatic cancer cell lines, along with intracellular iron overload, increasing reactive oxygen species (ROS) accumulation, malondialdehyde (MDA) overexpression, and glutathione peroxidase (GSH-PX) depletion. Mechanistically, chromatin immunoprecipitation (ChIP) and dual luciferase reporter gene assays were used to confirm that signal transducer and activator of transcription 3 (STAT3) binds to the GPX4 promoter region and promotes its transcription, whereas TST blocked GPX4 expression by regulating STAT3. Finally, in vivo experiments revealed that TST inhibited the growth of subcutaneously transplanted tumours and had considerable biosafety. In conclusion, our study identified the mechanism by which TST-induced ferroptosis in pancreatic cancer cells through STAT3/GPX4 signalling.

NNK from tobacco smoking enhances pancreatic cancer cell stemness and chemoresistance by creating a ß2AR-Akt feedback loop that activates autophagy.

Low responsiveness to chemotherapy is an important cause of poor prognosis in pancreatic cancer. Smoking is a high-risk factor for pancreatic cancer and cancer resistance to gemcitabine; however, the underlying mechanisms remain unclear. 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is the main metabolite of tobacco burning and has been shown to be associated with cancer development and chemoresistance. However, in pancreatic cancer, its mechanism remains poorly understood. In this study, we found that NNK promoted stemness and gemcitabine resistance in pancreatic cancer cell lines. Moreover, NNK increased autophagy and elevated the expression levels of the autophagy-related markers autophagy-related gene 5 (ATG5), autophagy-related gene 7 (ATG7), and Beclin1. Furthermore, the results showed that NNK-promoted stemness and gemcitabine resistance was partially dependent on the role of NNK in cell autophagy, which is mediated by the ß2-adrenergic receptor (ß2AR)-Akt axis. Finally, we proved that NNK intervention could not only activate ß2AR, but also increase its expression, making ß2AR and Akt form a feedback loop. Overall, these findings show that the NNK-induced ß2AR-Akt feedback loop promotes stemness and gemcitabine resistance in pancreatic cancer cells.

HGF/c-Met pathway facilitates the perineural invasion of pancreatic cancer by activating the mTOR/NGF axis.

Perineural invasion (PNI) is a pathologic feature of pancreatic cancer and is associated with poor outcomes, metastasis, and recurrence in pancreatic cancer patients. However, the molecular mechanism of PNI remains unclear. The present study aimed to investigate the mechanism that HGF/c-Met pathway facilitates the PNI of pancreatic cancer. In this study, we confirmed that c-Met expression was correlated with PNI in pancreatic cancer tissues. Activating the HGF/c-Met signaling pathway potentiated the expression of nerve growth factor (NGF) to recruit nerves and promote the PNI. Activating the HGF/c-Met signaling pathway also enhanced the migration and invasion ability of cancer cells to facilitate cancer cells invading nerves. Mechanistically, HGF/c-Met signaling pathway can active the mTOR/NGF axis to promote the PNI of pancreatic cancer. Additionally, we found that knocking down c-Met expression inhibited cancer cell migration along the nerve, reduced the damage of the sciatic nerve caused by cancer cells and protected the function of the sciatic nerve in vivo. Taken together, our findings suggest a supportive mechanism of the HGF/c-Met signaling pathway in promoting PNI by activating the mTOR/NGF axis in pancreatic cancer. Blocking the HGF/c-Met signaling pathway may be an effective target for the treatment of PNI.

Honokiol Suppresses Perineural Invasion of Pancreatic Cancer by Inhibiting SMAD2/3 Signaling.

BACKGROUND: Perineural invasion (PNI) is an important pathologic feature of pancreatic cancer, and the incidence of PNI in pancreatic cancer is 70%-100%. PNI is associated with poor outcome, metastasis, and recurrence in pancreatic cancer patients. There are very few treatments for PNI in pancreatic cancer. Honokiol (HNK) is a natural product that is mainly obtained from Magnolia species and has been indicated to have anticancer activity. HNK also has potent neurotrophic activity and may be effective for suppressing PNI. However, the potential role of HNK in the treatment of PNI in pancreatic cancer has not been elucidated. METHODS: In our study, pancreatic cancer cells were treated with vehicle or HNK, and the invasion and migration capacities were assessed by wound scratch assays and Transwell assays. A cancer cell-dorsal root ganglion coculture model was established to evaluate the effect of HNK on the PNI of pancreatic cancer. Western blotting was used to detect markers of EMT and neurotrophic factors in pancreatic tissue. Recombinant TGF-ß1 was used to activate SMAD2/3 to verify the effect of HNK on SMAD2/3 and neurotrophic factors. The subcutaneous tumor model and the sciatic nerve invasion model, which were established in transgenic engineered mice harboring spontaneous pancreatic cancer, were used to investigate the mechanism by which HNK inhibits EMT and PNI in vivo. RESULTS: We found that HNK can inhibit the invasion and migration of pancreatic cancer cells. More importantly, HNK can inhibit the PNI of pancreatic cancer. The HNK-mediated suppression of pancreatic cancer PNI was partially mediated by inhibition of SMAD2/3 phosphorylation. In addition, the inhibitory effect of HNK on PNI can be reversed by activating SMAD2/3. In vivo, we found that HNK can suppress EMT in pancreatic cancer. HNK can also inhibit cancer cell migration along the nerve, reduce the damage to the sciatic nerve caused by tumor cells and protect the function of the sciatic nerve. CONCLUSION: Our results demonstrate that HNK can inhibit the invasion, migration, and PNI of pancreatic cancer by blocking SMAD2/3 phosphorylation, and we conclude that HNK may be a new strategy for suppressing PNI in pancreatic cancer.

Perceptual Learning beyond Perception: Mnemonic Representation in Early Visual Cortex and Intraparietal Sulcus.

The ability to discriminate between stimuli relies on a chain of neural operations associated with perception, memory and decision-making. Accumulating studies show learning-dependent plasticity in perception or decision-making, yet whether perceptual learning modifies mnemonic processing remains unclear. Here, we trained human participants of both sexes in an orientation discrimination task, while using functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) to separately examine training-induced changes in working memory (WM) representation. fMRI decoding revealed orientation-specific neural patterns during the delay period in primary visual cortex (V1) before, but not after, training, whereas neurodisruption of V1 during the delay period led to behavioral deficits in both phases. In contrast, both fMRI decoding and disruptive effect of TMS showed that intraparietal sulcus (IPS) represented WM content after, but not before, training. These results suggest that training does not affect the necessity of sensory area in representing WM information, consistent with the sensory recruitment hypothesis in WM, but likely alters the coding format of the stored stimulus in this region. On the other hand, training can render WM content to be maintained in higher-order parietal areas, complementing sensory area to support more robust maintenance of information.SIGNIFICANCE STATEMENT There has been accumulating progresses regarding experience-dependent plasticity in perception or decision-making, yet how perceptual experience moulds mnemonic processing of visual information remains less explored. Here, we provide novel findings that learning-dependent improvement of discriminability accompanies altered WM representation at different cortical levels. Critically, we suggest a role of training in modulating cortical locus of WM representation, providing a plausible explanation to reconcile the discrepant findings between human and animal studies regarding the recruitment of sensory or higher-order areas in WM.

Biased Neural Representation of Feature-Based Attention in the Human Frontoparietal Network.

Selective attention is a core cognitive function for efficient processing of information. Although it is well known that attention can modulate neural responses in many brain areas, the computational principles underlying attentional modulation remain unclear. Contrary to the prevailing view of a high-dimensional, distributed neural representation, here we show a surprisingly simple, biased neural representation for feature-based attention in a large dataset including five human fMRI studies. We found that when human participants (both sexes) selected one feature from a compound stimulus, voxels in many cortical areas responded consistently higher to one attended feature over the other. This univariate bias was consistent across brain areas within individual subjects. Importantly, this univariate bias showed a progressively stronger magnitude along the cortical hierarchy. In frontoparietal areas, the bias was strongest and contributed largely to pattern-based decoding, whereas early visual areas lacked such a bias. These findings suggest a gradual transition from a more analog to a more abstract representation of attentional priority along the cortical hierarchy. Biased neural responses in high-level areas likely reflect a low-dimensional neural code that can facilitate a robust representation and simple readout of cognitive variables.SIGNIFICANCE STATEMENT It is typically assumed that cognitive variables are represented by distributed population activities. Although this view is rooted in decades of work in the sensory system, it has not been rigorously tested at different levels of cortical hierarchy. Here we show a novel, low-dimensional coding scheme that dominated the representation of feature-based attention in frontoparietal areas. The simplicity of such a biased code may confer a robust representation of cognitive variables, such as attentional selection, working memory, and decision-making.

Continuous and discrete representations of feature-based attentional priority in human frontoparietal network.

Previous studies suggest that human frontoparietal network represents feature-based attentional priority, yet the precise nature of the priority signals remains unclear. Here, we examined whether priority signals vary continuously or discretely as a function of feature similarity. In an fMRI experiment, we presented two superimposed dot fields moving along two linear directions (leftward and rightward) while varying the angular separation between the two directions. Subjects were cued to attend to one of the two dot fields and respond to a possible speed-up in the cued direction. We used multivariate analysis to evaluate how priority representation of the attended direction changes with feature similarity. We found that in early visual areas as well as posterior intraparietal sulcus and inferior frontal junction, the patterns of neural activity became more different as the feature similarity decreased, indicating a continuous representation of the attended feature. In contrast, patterns of neural activity in anterior intraparietal sulcus and frontal eye field remained invariant to changes in feature similarity, indicating a discrete representation of the attended feature. Such distinct neural coding of attentional priority across the frontoparietal network may make complementary contributions to enable flexible attentional control.

Reward differentially interacts with physical salience in feature-based attention.

A visual feature associated with reward can capture attention when it is neither physically salient nor task relevant. Although such findings suggest that reward acts similarly as physical salience, it is unknown whether reward works independently or interactively with physical salience to modulate attentional priority. Here, we first trained participants to associate two motion directions with high and low reward. During the test, we presented superimposed but perceptually separable stimuli that consisted of coherently and randomly moving dot fields, while manipulating the physical salience (low vs. high contrast) and reward history (low vs. high reward) of the coherent stimulus. Participants were instructed to identify speed-up targets on the coherent or random stimulus. We found that reward improved target detection in the coherent stimulus regardless of the physical contrast, whereas reward disrupted target detection in the random stimulus only when the coherent stimulus was of high contrast. Our findings thus suggest that goal-directed, feature-specific selection determines the pattern of interaction between reward and physical salience, such that they contribute either independently or interactively to attentional priority. We propose two possible mechanisms that can account for the intricate patterns of influence among multiple sources of priority.

Neural Determinants of Task Performance during Feature-Based Attention in Human Cortex.

Studies of feature-based attention have associated activity in a dorsal frontoparietal network with putative attentional priority signals. Yet, how this neural activity mediates attentional selection and whether it guides behavior are fundamental questions that require investigation. We reasoned that endogenous fluctuations in the quality of attentional priority should influence task performance. Human subjects detected a speed increment while viewing clockwise (CW) or counterclockwise (CCW) motion (baseline task) or while attending to either direction amid distracters (attention task). In an fMRI experiment, direction-specific neural pattern similarity between the baseline task and the attention task revealed a higher level of similarity for correct than incorrect trials in frontoparietal regions. Using transcranial magnetic stimulation (TMS), we disrupted posterior parietal cortex (PPC) and found a selective deficit in the attention task, but not in the baseline task, demonstrating the necessity of this cortical area during feature-based attention. These results reveal that frontoparietal areas maintain attentional priority that facilitates successful behavioral selection.

Reward learning modulates the attentional processing of faces in children with and without autism spectrum disorder.

The processing of social stimuli, such as human faces, is impaired in individuals with autism spectrum disorder (ASD), which could be accounted for by their lack of social motivation. The current study examined how the attentional processing of faces in children with ASD could be modulated by the learning of face-reward associations. Sixteen high-functioning children with ASD and 20 age- and ability-matched typically developing peers participated in the experiments. All children started with a reward learning task, in which the children were presented with three female faces that were attributed with positive, negative, and neutral values, and were required to remember the faces and their associated values. After this, they were tested on the recognition of the learned faces and a visual search task in which the learned faces served as the distractor. We found a modulatory effect of the face-reward associations on the visual search but not the recognition performance in both groups despite the lower efficacy among children with ASD in learning the face-reward associations. Specifically, both groups responded faster when one of the distractor faces was associated with positive or negative values than when the distractor face was neutral, suggesting an efficient attentional processing of these reward-associated faces. Our findings provide direct evidence for the perceptual-level modulatory effect of reward learning on the attentional processing of faces in individuals with ASD. Autism Res 2017, 10: 1797-1807. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: In our study, we tested whether the face processing of individuals with ASD could be changed when the faces were associated with different social meanings. We found no effect of social meanings on face recognition, but both groups responded faster in the visual search task when one of the distractor faces was associated with positive or negative values than when the neutral face. The findings suggest that children with ASD could efficiently process faces associated with different values like typical children.

Perceptual Competition Promotes Suppression of Reward Salience in Behavioral Selection and Neural Representation.

Visual attentional selection is influenced by the value of objects. Previous studies have demonstrated that reward-associated items lead to rapid distraction and associated behavioral costs, which are difficult to override with top-down control. However, it has not been determined whether a perceptually competitive environment could render the reward-driven distraction more susceptible to top-down suppression. Here, we trained both genders of human subjects to associate two orientations with high and low magnitudes of reward. After training, we collected fMRI data while the subjects performed a categorical visual search task. The item in the reward-associated orientation served as the distractor, and the relative physical salience between the target and distractor was carefully controlled to modulate the degree of perceptual competition. The behavioral results showed faster searches in the presence of high, relative to low, reward-associated distractors. However, this effect was evident only if the physical salience of the distractor was higher than that of the target, indicating a context-dependent suppression effect of reward salience that relied on high perceptual competition. By analyzing the fMRI data in primary visual cortex, we found that the behavioral pattern of results could be predicted by the suppressed channel responses tuned to the reward-associated orientation in the distractor location, accompanied by increased responses in the midbrain dopaminergic region. Our results suggest that the learned salience of a reward plays a flexible role in solving perceptual competition, enabling the neural system to adaptively modulate the perceptual representation for behavioral optimization.SIGNIFICANCE STATEMENT The predictiveness principle in learning theory suggests that the stimulus with high predictability of reward receives priority in attentional selection. This selection bias leads to difficulties in changing approach behaviors, and thus becomes an important factor related to psychiatric disorders with attentional deficits. Here, we demonstrated that such principle is adaptively implemented in attentional suppression in visual search. We showed that the learned salience induced the suppression of the reward-associated distractor if its competition with the target was strong and could not be readily solved. This behavioral pattern was accompanied by increased midbrain fMRI activity and weakened sensory representation of the reward-associated distractor in V1. Our findings provided direct evidence that our brain flexibly uses learned regularities in attentional control.