Search

Humans constantly make predictions and such predictions allow us to prepare for future events. Yet, such benefits may come with drawbacks as premature predictions may potentially bias subsequent judgments. Here we examined how prediction influences our perceptual decisions and subsequent confidence judgments, on scenarios where the predictions were arbitrary and independent of the identity of the upcoming stimuli. We defined them as invalid and non-informative predictions. Behavioral results showed that, such non-informative predictions biased perceptual decisions in favor of the predicted choice, and such prediction-induced perceptual bias further increased the metacognitive efficiency. The functional MRI results showed that activities in the medial prefrontal cortex (mPFC) and subgenual anterior cingulate cortex (sgACC) encoded the response consistency between predictions and perceptual decisions. Activity in mPFC predicted the strength of this congruency bias across individuals. Moreover, the parametric encoding of confidence in putamen was modulated by prediction-choice consistency, such that activity in putamen was negatively correlated with confidence rating after inconsistent responses. These findings suggest that predictions, while made arbitrarily, orchestrate the neural representations of choice and confidence judgment.

Humans anticipate and evaluate both obtained and counterfactual outcomes – outcomes that could have been had an alternate decision been taken – and experience associated emotions of regret and relief. Although many functional magnetic resonance imaging (fMRI) studies have examined the neural correlates of these emotions, there is substantial heterogeneity in their results. We conducted coordinate-based ALE and network-based ANM meta-analysis of fMRI studies of experienced regret and relief to examine commonalities and differences in their neural correlates. Regionally, we observed that the experience of both regret and relief was associated with greater activation in the right ventral striatum (VS), which is implicated in tracking reward prediction error. At the network level, regret and relief shared the reward-sensitive mesocorticolimbic network with preferential activation of the medial orbitofrontal cortex (mOFC) for regret processing and medial cingulate cortex (MCC) for relief processing. Our research identified shared and separable brain systems subserving regret and relief experience, which may inform the treatment of regret-related mood disorders.

The hippocampus has long been considered a pivotal region implicated in both stress susceptibility and resilience. A wealth of evidence from animal and human studies underscores the significance of hippocampal functional connectivity with the ventromedial prefrontal cortex (vmPFC) in these stress-related processes. However, there remains a scarcity of research that explores and contrasts the roles of hippocampus-vmPFC connectivity in stress susceptibility and resilience when facing a real-life traumatic event from a prospective standpoint. In the present study, we investigated the contributions of undirected and directed connectivity between the hippocampus and vmPFC to stress susceptibility and resilience within the context of the COVID-19 pandemic. Our findings revealed that the left hippocampus-left vmPFC connectivity prior to the pandemic exhibited a negative correlation with both stress susceptibility and resilience. Specifically, individuals with stronger left hippocampus-left vmPFC connectivity reported experiencing fewer stress-related feelings during the outbreak period of the epidemic but displayed lower levels of stress resilience five months later. Our application of spectral dynamic causal modeling unveiled an additional inhibitory connectivity pathway from the left hippocampus to the left vmPFC in the context of stress susceptibility, which was notably absent in stress resilience. Furthermore, we observed a noteworthy positive association between self-inhibition of the vmPFC and stress susceptibility, with this effect proving substantial enough to predict an individual's susceptibility to stress; conversely, these patterns did not manifest in the realm of stress resilience. These findings enrich our comprehension of stress susceptibility and stress resilience and might have implications for innovative approaches to managing stress-related disorders.

Reward outcomes associated with costs like time delay and effort investment are generally discounted in decision-making. Standard economic models predict rewards associated with different types of costs are devalued in a similar manner. However, our review of rodent lesion studies indicated partial dissociations between brain regions supporting temporal- and effort-based decision-making. Another debate is whether options involving low and high costs are processed in different brain substrates (dual-system) or in the same regions (single-system). This research addressed these issues using coordinate-based, connectivity-based, and activation network-based meta-analyses to identify overlapping and separable neural systems supporting temporal (39 studies) and effort (20 studies) discounting. Coordinate-based activation likelihood estimation and resting-state connectivity analyses showed immediate-small reward and delayed-large reward choices engaged distinct regions with unique connectivity profiles, but their activation network mapping was found to engage the default mode network. For effort discounting, salience and sensorimotor networks supported low-effort choices, while the frontoparietal network supported high-effort choices. There was little overlap between the temporal and effort networks. Our findings underscore the importance of differentiating different types of costs in decision-making and understanding discounting at both regional and network levels.

Humans adjust their behavioral strategies based on feedback, a process that may depend on intrinsic preferences and contextual factors such as visual salience. In this study, we hypothesized that decision-making based on visual salience is influenced by habitual and goal-directed processes, which can be evidenced by changes in attention and subjective valuation systems. To test this hypothesis, we conducted a series of studies to investigate the behavioral and neural mechanisms underlying visual salience-driven decision-making. We first established the baseline behavioral strategy without salience in Experiment 1 (n = 21). We then highlighted the utility or performance dimension of the chosen outcome using colors in Experiment 2 (n = 30). We demonstrated that the difference in staying frequency increased along the salient dimension, confirming a salience effect. Furthermore, the salience effect was abolished when directional information was removed in Experiment 3 (n = 28), suggesting that the salience effect is feedback-specific. To generalize our findings, we replicated the feedback-specific salience effects using eye-tracking and text emphasis. The fixation differences between the chosen and unchosen values were enhanced along the feedback-specific salient dimension in Experiment 4 (n = 48) but unchanged after removing feedback-specific information in Experiment 5 (n = 32). Moreover, the staying frequency was correlated with fixation properties, confirming that salience guides attention deployment. Lastly, our neuroimaging study (Experiment 6, n = 25) showed that the striatum subregions encoded salience-based outcome evaluation, while the vmPFC encoded salience-based behavioral adjustments. The connectivity of the vmPFC-ventral striatum accounted for individual differences in utility-driven, whereas the vmPFC-dmPFC for performance-driven behavioral adjustments. Together, our results provide a neurocognitive account of how task-irrelevant visual salience drives decision-making by involving attention and the frontal-striatal valuation systems. Public significance statement: Humans may use the current outcome to make behavior adjustments. How this occurs may depend on stable individual preferences and contextual factors, such as visual salience. Under the hypothesis that visual salience determines attention and subsequently modulates subjective valuation, we investigated the underlying behavioral and neural bases of visual-context-guided outcome evaluation and behavioral adjustments. Our findings suggest that the reward system is orchestrated by visual context and highlight the critical role of attention and the frontal-striatal neural circuit in visual-context-guided decision-making that may involve habitual and goal-directed processes.

When faced with uncertainty, individuals’ value-based decisions are influenced by the expected rewards and risks. Understanding how reward and risk are processed and integrated at the behavioral and neural levels is essential for building up utility theories. Using a modified monetary incentive delay task in which the mean of two possible outcomes (expected reward) and the standard deviation (SD) of the possible outcomes (risk) were parametrically manipulated and orthogonalized, we measured eye movements, response times (RTs), and brain activity when participants seek to secure a reward. We found that RTs varied as a function of the mean but not the SD of the potential reward, suggesting that expected rewards are the main driver of RTs. Moreover, the difference between gazes focused on high vs. low value rewards became smaller when the magnitude of the potential reward (mean of possible outcomes) was larger and when risk (SD of possible outcomes) became smaller, highlighting that reward and risk have different effects on attention deployment. Processing the mean reward activated the striatum. The positive striatal connectivity to the amygdala and negative striatal connectivity to the superior frontal gyrus were correlated with individuals’ sensitivity to the expected reward. In contrast, processing risk activated the anterior insula. Its positive connectivity to the ventromedial prefrontal cortex and negative connectivity to the anterior midcingulate cortex were correlated with individual differences in risk sensitivity, further suggesting the functional dissociation of reward and risk at the neural level. Our findings, based on several different measures, delineate the distinct representations of reward and risk in non-decision contexts and provide insight into how these utility parameters modulate attention, motivation, and brain networks.

Human decision-making can be influenced by whether the option is framed as positive or negative, known as the framing effect. Neuroeconomic studies have shown the engagement of the amygdala underlies the framing effect by automatically incorporating emotional (or intuitive) information into the decision process, thus leading to ''irrational'' decisions or decision biases (De Martino et al. 2006). However, these studies focus only on the gain domain in which the initial state is appetitive, leaving the mechanisms of the framing effect in the loss or aversive domain less understood, which could be equally important or even more dominant for human survival. In the present study, we first replicated De Martino et al.’s research on the framing effect in the gain domain. We then checked the commonality and distinctiveness of the framing effect across gain and loss domains using a similar experimental design combined with functional magnetic resonance imaging (fMRI). Behaviorally, participants showed comparable framing effects in both domains, suggesting a domain-general decision bias. Neuronally, the amygdala represented the framing effect for the gain domain, and its connectivity to vmPFC was positively modulated by framing bias, consistently shown in De Martino et al.’s study. Moreover, the striatum represented the framing effect for the loss domain, and its connectivity to dmPFC was subject to framing bias, suggesting distinctive neural substrates across two domains. Our study accentuates the importance of distinguishing decision processes across appetitive or aversive domains and highlights the role of the cortical-striatal-limbic network underlying the framing effect.

A major caveat with investigations on schizophrenic patients is the difficulty to control for medication usage across samples as disease-related neural differences may be confounded by medication usage. Following a thorough literature search (632 records identified), we included 37 studies with a total of 740 medicated schizophrenia patients and 367 unmedicated schizophrenia patients. Here, we perform several meta-analyses to assess the neurofunctional differences between medicated and unmedicated schizophrenic patients across fMRI studies to determine systematic regions associated with medication usage. Several clusters identified by the meta-analysis on the medicated group include three right lateralized frontal clusters and a left lateralized parietal cluster, whereas the unmedicated group yielded concordant activity among right lateralized frontal-parietal regions. We further explored the prevalence of activity within these regions across illness duration and task type. These findings suggest a neural compensatory mechanism across these regions both spatially and chronically, offering new insight into the spatial and temporal dynamic neural differences among medicated and unmedicated schizophrenia patients.

Risk and ambiguity are inherent in virtually all human decision-making. Risk refers to a situation in which we know the precise probability of potential outcomes of each option, whereas ambiguity refers to a situation in which outcome probabilities are not known. A large body of research has shown that individuals prefer known risks to ambiguity, a phenomenon known as ambiguity aversion. One heated debate concerns whether risky and ambiguous decisions rely on the same or distinct neural circuits. In the current meta-analyses, we integrated the results of neuroimaging research on decision-making under risk (n = 69) and ambiguity (n = 31). Our results showed that both processing of risk and ambiguity showed convergence in anterior insula, indicating a key role of anterior insula in encoding uncertainty. Risk additionally engaged dorsomedial prefrontal cortex (dmPFC) and ventral striatum, whereas ambiguity specifically recruited the dorsolateral prefrontal cortex (dlPFC), inferior parietal lobe (IPL) and right anterior insula. Our findings demonstrate overlapping and distinct neural substrates underlying different types of uncertainty, guiding future neuroimaging research on risk-taking and ambiguity aversion.

Although many studies have explored the neural mechanism of the feeling of stress, to date, no effort has been made to establish a model capable of predicting the feeling of stress at the individual level using the resting-state functional connectome. Although individuals may be confronted with multidimensional stressors during the coronavirus disease 2019 (COVID-19) pandemic, their appraisal of the impact and severity of these events might vary. In this study, connectome-based predictive modeling (CPM) with leave-one-out cross-validation was conducted to predict individual perceived stress (PS) from whole-brain functional connectivity data from 817 participants. The results showed that the feeling of stress could be predicted by the interaction between the default model network and salience network, which are involved in emotion regulation and salience attribution, respectively. Key nodes that contributed to the prediction model comprised regions mainly located in the limbic systems and temporal lobe. Critically, the CPM model of PS based on regular days can be generalized to predict individual PS levels during the COVID-19 pandemic, which is a multidimensional, uncontrollable stressful situation. The stability of the results was demonstrated by two independent datasets. The present work not only expands existing knowledge regarding the neural mechanism of PS but also may help identify high-risk individuals in healthy populations.

Neural networks involved in placebo analgesia and nocebo hyperalgesia processes have been widely investigated with neuroimaging methods. However, few studies have directly compared these two processes and it remains unclear whether common or distinct neural circuits are involved. To address this issue, we implemented a coordinate-based meta-analysis and compared neural representations of placebo analgesia (30 studies; 205 foci; 677 subjects) and nocebo hyperalgesia (22 studies; 301 foci; 401 subjects). Contrast analyses confirmed placebo-specific concordance in the right ventral striatum, and nocebo-specific concordance in the dorsal anterior cingulate cortex (dACC), left posterior insula and left parietal operculum during combined pain anticipation and administration stages. Importantly, no overlapping regions were found for these two processes in conjunction analyses, even when the threshold was low. Meta-analytic connectivity modeling (MACM) and resting-state functional connectivity (RSFC) analyses on key regions further confirmed the distinct brain networks underlying placebo analgesia and nocebo hyperalgesia. Together, these findings indicate that the placebo analgesia and nocebo hyperalgesia processes involve distinct neural circuits, which supports the view that the two phenomena may operate via different neuropsychological processes.

The ability to adopt the perspectives of others is fundamental to effective communication in social interactions. However, the neural correlates of allocentric thinking in communicative signaling remain unclear. We adapted a novel signaling task in which the signaler was given the target word and must choose a one-word signal to help the receiver guess the target. Behavioral results suggest that speakers can use allocentric thinking to choose signals that are salient from the perspective of the receiver rather than their own point of view. At the neural level, functional magnetic resonance imaging (fMRI) data reveal that the medial prefrontal cortex (mPFC), ventral striatum, and temporal-parietal junction are more activated when signalers engage in allocentric than egocentric thinking. Moreover, functional connectivity between the mPFC and ventral striatum predicted individuals’ perspective-taking ability during successful communication. These findings reveal that neural representations in the mPFC-striatum network support perspective-taking in complex social decision making, providing a new perspective on how the brain arbitrates between allocentric thinking and egocentric thinking in communication and social coordination.

Background: Working memory (WM) is an executive ability that allows one to hold and manipulate information for a short period of time. Schizophrenia and mood disorders are severe psychiatric conditions with overlapping genetic and clinical symptoms. Whilst WM has been suggested as meeting the criteria for being an endophenotype for schizophrenia and mood disorders, it still unclear whether they share overlapping neural circuitry. Objective: The n-back task has been widely used to measure WM capacity, such as maintenance, flexible updating, and interference control. Here we compiled studies that included psychiatric populations, i.e., schizophrenia, bipolar disorder and major depressive disorder. Methods: We performed a coordinate-based meta-analysis that combined 34 BOLD-fMRI studies comparing activity associated with n-back working memory between psychiatric patients and healthy controls. We specifically focused our search using the n-back task to diminish study heterogeneity. Results: All patient groups showed blunted activity in the striatum, anterior insula and frontal lobe. The same brain networks related to WM were compromised in schizophrenia, major depressive disorder and bipolar disorder. Conclusion: Our findings support the suggestion of commonal functional abnormalities across schizophrenia and mood disorders related to WM.

Humans inevitably go through various stressful events, which initiates a chain of neuroendocrine reactions that may affect brain functions and lead to psychopathological symptoms. Previous studies have shown stress-induced changes in activation of individual brain regions or pairwise inter-regional connectivity. However, it remains unclear how large-scale brain network is reconfigured in response to stress. Using a within-subjects design, we combined the Trier Social Stress Test and graph theoretical method to characterize stress-induced topological alterations of brain functional network. Modularity analysis revealed that the brain network can be divided into frontoparietal, default mode, occipital, subcortical, and central-opercular modules under control and stress conditions, corresponding to several well-known functional systems underpinning cognitive control, self-referential mental processing, visual, salience processing, sensory and motor functions. While the frontoparietal module functioned as a connector module under stress, its within-module connectivity was weakened. The default mode module lost its connector function and its within-module connectivity was enhanced under stress. Moreover, stress altered the capacity to control over information flow in a few regions important for salience processing and self-referential metal processing. Furthermore, there was a trend of negative correlation between modularity and stress response magnitude. These findings demonstrate that acute stress prompts large-scale brain-wide reconfiguration involving multiple functional modules.

Human decision-making is mainly driven by two fundamental learning processes: a slow, deliberative, goal-directed model-based process that maps out the potential outcomes of all options and a rapid habitual model-free process that enables reflexive repetition of previously successful choices. Although many model-informed neuroimaging studies have examined the neural correlates of model-based and model-free learning, the concordant activity among these two processes remains unclear. We used quantitative meta-analyses of functional magnetic resonance imaging experiments to identify the concordant activity pertaining to model-based and model-free learning over a range of reward-related paradigms. We found that: 1) both processes yielded concordant ventral striatum activity, 2) model-based learning activated the medial prefrontal cortex and orbital frontal cortex, and 3) model-free learning specifically activated the left globus pallidus and right caudate head. Our findings suggest that model-free and model-based decision making engage overlapping yet distinct neural regions. These stereotaxic maps improve our understanding of how deliberative goal-directed and reflexive habitual learning are implemented in the brain.

Background: Functional near infrared spectroscopy (fNIRS) provides a direct and quantitative assessment of cortical haemodynamic function during a cognitive task. This functional neuroimaging modality may be used to elucidate the pathophysiology of psychiatric disorders, and identify neurophysiological differences between co-occurring psychiatric disorders. However, fNIRS research on borderline personality disorder (BPD) has been limited. Hence, this study aimed to compare cerebral haemodynamic function in healthy controls (HC), patients with major depressive disorder (MDD) and patients with BPD. Methods: fNIRS signals during a verbal fluency task designed for clinical assessment was recorded for all participants. Demographics, clinical history and symptom severity were also noted. Findings: Compared to HCs (n = 31), both patient groups (MDD, n = 31; BPD, n = 31) displayed diminished haemodynamic response in the frontal, temporal and parietal cortices. Moreover, haemodynamic response in the right frontal cortex is markedly lower in patients with MDD compared to patients with BPD. Interpretation: Normal cortical function in patients with BPD is disrupted, but not as extensively as in patients with MDD. These results provide further neurophysiological evidence for the distinction of patients with MDD from patients with BPD. Keywords: Near-infrared spectroscopy, Verbal fluency task, Prefrontal cortex, Haemodynamic response, Borderline personality disorder, Major depressive disorder

Life stress has been shown to impact cognitive functions, including inhibitory control. However, the immediate effects of acute stress on inhibitory control and the underlying neural mechanisms remain unclear. In a behavioral pilot study (N = 30) and a within-subject functional magnetic resonance imaging study (N = 30), we examined how acute stress induced by Trier Social Stress Test influenced inhibitory control in a stop signal task. Behavioral results across two studies showed that stress consistently improved inhibitory control. Shorter stop signal reaction time (SSRT) in stress as compared with control condition was associated with stronger connectivity between the superior/middle frontal gyrus (SFG/MFG) and striatum. Dynamic causal modeling revealed distinct best models under stress and control condition, with an enhanced interaction between the SFG/MFG and the striatum after stress exposure. This research identified the SFG/MFG-striatum network as a key circuit underlying acute stress-elicited enhancement of inhibitory control in a stop signal task.

The amygdala has long been considered a vital region involved in acute and chronic stress responses. Extensive evidences from animal and human studies suggest that the functional connectivity of amygdalar subnuclei (basolateral amygdala (BLA), centromedial amygdala (CMA) and superficial amygdala (SFA)) undergo specific alterations in stress-related psychopathology. However, whether and how intrinsic functional connectivity within the amygdalar subcomponents is differently altered in the aftermath of an acute stressor remains unknown. In the present study, using a within-subject design, we examined the impact of acute psychological social stress on the functional connectivity of amygdalar subregions at rest. Results showed that stress mainly affected the connectivity pattern of CMA. In particular, in the stress condition compared with the control, the connectivity of CMA to left posterior cingulate cortex and right thalamus was decreased under stress, while the connectivity of CMA to left caudate connectivity was increased at rest post-stressor. The findings suggest that healthy individuals may adapt to threatening surroundings by reducing threatening information input, and shifting to well-learned procedural behaviors. Keywords: Stress, Amygdala, Functional connectivity, Subregions

People often make decisions in the face of ambiguous information, but it remains unclear how ambiguity is represented in the brain. We used three types of ambiguous stimuli and combined EEG and fMRI to examine the neural representation of perceptual decisions under ambiguity. We identified a late positive potential, the LPP, which differentiated levels of ambiguity, and which was specifically associated with behavioral judgments about choices that were ambiguous, rather than passive perception of ambiguous stimuli. Mediation analyses together with two further control experiments confirmed that the LPP was generated only when decisions are made (not during mere perception of ambiguous stimuli), and only when those decisions involved choices on a dimension that is ambiguous. A further control experiment showed that a stronger LPP arose in the presence of ambiguous stimuli compared to when only unambiguous stimuli were present. Source modeling suggested that the LPP originated from multiple loci in cingulate cortex, a finding we further confirmed using fMRI and fMRI-guided ERP source prediction. Taken together, our findings argue for a role of an LPP originating from cingulate cortex in encoding decisions based on task-relevant perceptual ambiguity, a process that may in turn influence confidence judgment, response conflict, and error correction.

The hippocampus is a core brain region that responds to stress. Previous studies have found a dysconnectivity between hippocampus and other brain regions under acute and chronic stress. However, whether and how acute social stress influences the directed connectivity patterns from and to the hippocampus remains unclear. In this study, using a within-subject design and Granger causal analysis (GCA), we investigated the alterations of resting state effective connectivity from and to hippocampal subregions after an acute social stressor (the Trier Social Stress Test). Participants were engaged in stress and control conditions spaced approximately one month apart. Our findings showed that stress altered the information flows in the thalamus-hippocampus-insula/midbrain circuit. The changes in this circuit could also predict with high accuracy the stress and control conditions at the subject level. These hippocampus-related brain networks have been documented to be involved in emotional information processing and storage, as well as habitual responses. We speculate that alterations of the effective connectivity between these brain regions may be associated with the registering and encoding of threatening stimuli under stress. Our investigation of hippocampal functional connectivity at a subregional level may help elucidate the functional neurobiology of stress-related psychiatric disorders. Keywords: Stress, Hippocampus, Granger causal analysis, Insula, Midbrain, Thalamus

Humans often make decisions in stressful situations, for example when the stakes are high and the potential consequences severe, or when the clock is ticking and the task demand is overwhelming. In response, a whole train of biological responses to stress has evolved to allow organisms to make a fight-or-flight response. When under stress, fast and effortless heuristics may dominate over slow and demanding deliberation in making decisions under uncertainty. Here, I review evidence from behavioral studies and neuroimaging research on decision making under stress and propose that stress elicits a switch from an analytic reasoning system to intuitive processes, and predict that this switch is associated with diminished activity in the prefrontal executive control regions and exaggerated activity in subcortical reactive emotion brain areas. Previous studies have shown that when stressed, individuals tend to make more habitual responses than goal-directed choices, be less likely to adjust their initial judgment, and rely more on gut feelings in social situations. It is possible that stress influences the arbitration between the emotion responses in subcortical regions and deliberative processes in the prefrontal cortex, so that final decisions are based on unexamined innate responses. Future research may further test this ‘stress induced deliberation-to-intuition’ (SIDI) model and examine its underlying neural mechanisms.

Chronic low back pain is a common neurological disorder. The periaqueductal gray (PAG) plays a key role in the descending modulation of pain. In this study, we investigated brain resting state PAG functional connectivity (FC) differences between patients with chronic low back pain (cLBP) in low pain or high pain condition and matched healthy controls (HCs). PAG seed based functional connectivity (FC) analysis of the functional MR imaging data was performed to investigate the difference among the connectivity maps in the cLBP in the low or high pain condition and HC groups as well as within the cLBP at differing endogenous back pain intensities. Results showed that FC between the PAG and the ventral medial prefrontal cortex (vmPFC)/rostral anterior cingulate cortex (rACC) increased in cLBP patients compared to matched controls. In addition, we also found significant negative correlations between pain ratings and PAG–vmPFC/rACC FC in cLBP patients after pain-inducing maneuver. The duration of cLBP was negatively correlated with PAG–insula and PAG–amygdala FC before pain-inducing maneuver in the patient group. These findings are in line with the impairments of the descending pain modulation reported in patients with cLBP. Our results provide evidence showing that cLBP patients have abnormal FC in PAG centered pain modulation network during rest.