The Brain Salience Network at the Intersection of Pain and Substance use Disorders: Insights from Functional Neuroimaging Research.

Purpose of Review: The brain's salience network (SN), primarily comprising the anterior insula and anterior cingulate cortex, plays a key role in detecting salient stimuli and processing physical and socioemotional pain (e.g., social rejection). Mounting evidence underscores an altered SN in the etiology and maintenance of substance use disorders (SUDs). This paper aims to synthesize recent functional neuroimaging research emphasizing the SN's involvement in SUDs and physical/socioemotional pain and explore the therapeutic prospects of targeting the SN for SUD treatment. Recent Findings: The SN is repeatedly activated during the experience of both physical and socioemotional pain. Altered activation within the SN is associated with both SUDs and chronic pain conditions, characterized by aberrant activity and connectivity patterns as well as structural changes. Among individuals with SUDs, functional and structural alterations in the SN have been linked to abnormal salience attribution (e.g., heightened responsiveness to drug-related cues), impaired cognitive control (e.g., impulsivity), and compromised decision-making processes. The high prevalence of physical and socioemotional pain in the SUD population may further exacerbate SN alterations, thus contributing to hindered recovery progress and treatment failure. Interventions targeting the restoration of SN functioning, such as real-time functional MRI feedback, neuromodulation, and psychotherapeutic approaches, hold promise as innovative SUD treatments. Summary: The review highlights the significance of alterations in the structure and function of the SN as potential mechanisms underlying the co-occurrence of SUDs and physical/socioemotional pain. Future work that integrates neuroimaging with other research methodologies will provide novel insights into the mechanistic role of the SN in SUDs and inform the development of next-generation treatment modalities.

Wanting to matter and learning to care: A neurodevelopmental window of opportunity for (Pro) social learning?

Wanting to matter-to feel socially recognized, appreciated, and capable of actions that benefit others-represents a fundamental motivation in human development. The motivational salience of mattering appears to increase in adolescence. Evidence suggests this is related to pubertal increases in the incentive salience for gaining social value and personal agency. This can provide a useful heuristic for understanding motivational proclivities (i.e. wanting to matter) that influence action-outcome learning as young adolescents are exploring and learning how to navigate increasingly complex social and relational environments. Adolescence also brings new capacities, motives, and opportunities for learning to care about and contribute to the benefit of others. Together, these create a window of opportunity: a sensitive period for learning to gain salient feelings of mattering through caring prosocial actions and valued societal contributions. Successfully discovering ways of mattering by doing things that matter to others may contribute to formative socio-emotional learning about self/other. Advances in understanding these social and relational learning processes and their neurodevelopmental underpinnings can inform strategies to improve developmental trajectories of social competence and wellbeing among adolescents growing up in a rapidly changing and increasingly techno-centric world.

Amygdala fMRI-A Critical Appraisal of the Extant Literature.

Even before the advent of fMRI, the amygdala occupied a central space in the affective neurosciences. Yet this amygdala-centred view on emotion processing gained even wider acceptance after the inception of fMRI in the early 1990s, a landmark that triggered a goldrush of fMRI studies targeting the amygdala in vivo. Initially, this amygdala fMRI research was mostly confined to task-activation studies measuring the magnitude of the amygdala's response to emotional stimuli. Later, interest began to shift more towards the study of the amygdala's resting-state functional connectivity and task-based psychophysiological interactions. Later still, the test-retest reliability of amygdala fMRI came under closer scrutiny, while at the same time, amygdala-based real-time fMRI neurofeedback gained widespread popularity. Each of these major subdomains of amygdala fMRI research has left its marks on the field of affective neuroscience at large. The purpose of this review is to provide a critical assessment of this literature. By integrating the insights garnered by these research branches, we aim to answer the question: What part (if any) can amygdala fMRI still play within the current landscape of affective neuroscience? Our findings show that serious questions can be raised with regard to both the reliability and validity of amygdala fMRI. These conclusions force us to cast doubt on the continued viability of amygdala fMRI as a core pilar of the affective neurosciences.

Mortality Salience and Death Anxiety: The Moderating Roles of Self-Esteem and Religiosity.

The purpose of this study was to investigate the relationship between mortality salience, death anxiety, and two moderating variables: self-esteem and religiosity. A total of 174 undergraduate students from the Mindanao State University-Main Campus in the Philippines were selected via convenience sampling. Specifically, the study was carried out to determine if both self-esteem and religiosity moderate the relationship between mortality salience and death anxiety. The results revealed that mortality salience was positively correlated with death anxiety among undergraduate students. Moreover, self-esteem significantly moderated the relationship between mortality salience and death anxiety, with low self-esteem enhancing this relationship. However, religiosity was found to be a non-significant moderator of the link between mortality salience and death anxiety. Overall, the findings of this study have implications for understanding these relationships and offer recommendations for further research.

Corrigendum: Where's Wally: the influence of visual salience on referring expression generation.

[This corrects the article DOI: 10.3389/fpsyg.2013.00329.].

Salience network resting state functional connectivity during airway inflammation in asthma: A feature of mental health resilience?

BACKGROUND: Inflammation is an established contributor to the pathophysiology of depression and the prevalence of depression in those with chronic inflammatory disease is two- to four-fold higher than the general population. Yet little is known about the neurobiological changes that confer depression or resilience to depression, that occur when episodes of heightened inflammation are frequent or span many years. METHODS: We used an innovative combination of longitudinal resting state functional magnetic resonance imaging coupled to segmental bronchial provocation with allergen (SBP-Ag) to assess changes in resting state functional connectivity (rsFC) of the salience network (SN) caused by an acute inflammatory exacerbation in twenty-six adults (15 female) with asthma and varying levels of depressive symptoms. Eosinophils measured in bronchoalveolar lavage fluid and blood provided an index of allergic inflammation and the Beck Depression Inventory provided an index of depressive symptoms. RESULTS: We found that in those with the highest symptoms of depression at baseline, SN rsFC declined most from pre- to post-SBP-Ag in the context of a robust eosinophilic response to challenge, but in those with low depressive symptoms SN rsFC was maintained or increased, even in those with the most pronounced SBP-Ag response. CONCLUSIONS: Thus, the maintenance of SN rsFC during inflammation may be a biomarker of resilience to depression, perhaps via more effective orchestration of large-scale brain network dynamics by the SN. These findings advance our understanding of the functional role of the SN during inflammation and inform treatment recommendations for those with comorbid inflammatory disease and depression.

Emotional text messages affect the early processing of emoticons depending on their emotional congruence: evidence from the N170 and EPN event related potentials.

Emoticons have been considered pragmatic cues that enhance emotional expressivity during computer-mediated communication. Yet, it is unclear how emoticons are processed in ambiguous text-based communication due to incongruences between the emoticon's emotional valence and its context. In this study, we investigated the electrophysiological correlates of contextual influence on the early emotional processing of emoticons, during an emotional congruence judgment task. Participants were instructed to judge the congruence between a text message expressing an emotional situation (positive or negative), and a subsequent emoticon expressing positive or negative emotions. We analyzed early event-related potentials elicited by emoticons related to face processing (N170) and emotional salience in visual perception processing (Early Posterior Negativity, EPN). Our results show that accuracy and Reaction Times depend on the interaction between the emotional valence of the context and the emoticon. Negative emoticons elicited a larger N170, suggesting that the emotional information of the emoticon is integrated at the early stages of the perceptual process. During emoticon processing, a valence effect was observed with enhanced EPN amplitudes in occipital areas for emoticons representing negative valences. Moreover, we observed a congruence effect in parieto-temporal sites within the same time-window, with larger amplitudes for the congruent condition. We conclude that, similar to face processing, emoticons are processed differently according to their emotional content and the context in which they are embedded. A congruent context might enhance the emotional salience of the emoticon (and therefore, its emotional expression) during the early stages of their processing.

Similarities and differences in dynamic properties of brain networks between internet gaming disorder and tobacco use disorder.

BACKGROUND: Internet gaming disorder (IGD) and tobacco use disorder (TUD) are two major addiction disorders that result in substantial financial loss. Identifying the similarities and differences between these two disorders is important to understand substance addiction and behavioral addiction. The current study was designed to compare these two disorders utilizing dynamic analysis. METHOD: Resting-state data were collected from 35 individuals with IGD, 35 individuals with TUD and 35 healthy controls (HCs). Dynamic coactivation pattern analysis was employed to decipher their dynamic patterns. RESULTS: IGD participants showed decreased coactivation patterns within the default mode network (DMN) and between the DMN and the salience network (SN). The SN showed reduced coactivation patterns with the executive control network (ECN) and DMN, and the ECN showed decreased coactivation patterns with the DMN. In the TUD group, the DMN exhibited decreased coactivation patterns with the SN, the SN exhibited reduced coactivation patterns with the DMN and ECN, and the ECN showed decreased coactivation patterns with the DMN and within the ECN. Furthermore, the triple network model was fitted to the dynamic properties of the two addiction disorders. Decoding analysis results indicated that addiction-related memory and memory retrieval displayed similar dysfunctions in both addictions. CONCLUSION: The dynamic characteristics of IGD and TUD suggest that there are similarities in the dynamic features between the SN and DMN and differences in the dynamic features between the DMN and ECN. Our results revealed that the two addiction disorders have dissociable brain mechanisms, indicating that future studies should consider these two addiction disorders as having two separate mechanisms to achieve precise treatment for their individualized targets.

Emotional salience modulates the forward-flow of memory.

As we navigate our day-to-day lives, we regularly adapt our behaviour according to what we predict may happen next in a given context. When an unexpected event occurs, our predictions about the world are disrupted and must be updated. Unexpected, isolated events, particularly with high emotionality, are also better recalled. In the present work, we investigated how oddballs affect recall dynamics. Seventy young, healthy participants encoded word lists containing either emotional or perceptual oddballs at varying stimulus onset asynchronies followed by free recall. It is well established that after recalling an item, we have a higher probability of recalling items encoded nearby, particularly those that were encoded after the item was recalled, a phenomenon known as forward contiguity of recall. We tested how novelty (oddballs versus control words) modulated forward contiguity as a function of salience type (emotional versus perceptual). The present results provide empirical evidence of forward contiguity modulation selectively by emotional salience and suggest that recall patterns after presenting emotional and perceptual oddballs are mediated by different mechanisms.

Holocaust centrality, anxiety, and other risk factors associated with terror threat salience among descendants of Holocaust survivors.

The study examined risk factors for sensitivity to terror threats among descendants of Holocaust survivors (Holocaust G1) during a significant rise in terrorist attacks in Israel. We examined the association of the number of familial Holocaust G1, trauma exposure, probable posttraumatic stress disorder (PTSD), anxiety symptoms, and Holocaust centrality with terror threat salience (TTS) in children and grandchildren of Holocaust G1 (Holocaust G2; G3). A web-based national sample included 297 Holocaust G2 (Mage=62.95, SD=10.25), 224 comparison G2 (Mage=61.79, SD=10.13), 379 Holocaust G3 (Mage=34.02, SD=8.65) and 171 comparison G3 (Mage=33.55, SD=8.26). Participants completed questionnaires on background characteristics, Holocaust background, trauma exposure, probable PTSD, anxiety symptoms, Holocaust centrality, and TTS. Findings showed that Holocaust G2 and G3 reported higher Holocaust centrality and TTS relative to comparisons, and Holocaust G3 reported higher levels of anxiety than comparison G3. The number of Holocaust G1, background characteristics, Holocaust centrality, and anxiety symptoms were associated with TTS in G2 and G3. Probable PTSD and trauma exposure were also associated with TTS in G2 and G3, respectively. Results highlight Holocaust centrality and anxiety among the factors associated with an increased preoccupation with terror threats in Holocaust descendants. Practitioners should implement interventions focusing on these factors, particularly at times of increased terrorism.

Corrigendum: Giving good directions: order of mention reflects visual salience.

[This corrects the article DOI: 10.3389/fpsyg.2015.01793.].

Identifying neurofunctional domains across substance use disorders.

Background: Substance use disorders (SUDs) are heterogeneous across multiple functional domains. Various frameworks posit that domains (e.g., executive function) contribute to the persistence of SUDs; however, the domains identified in different studies vary.Objectives: We used factor analysis to identify the underlying latent domains present in a large sample (N = 5,244, 55.8% male) with a variety of SUDs to yield findings more generalizable than studies with a narrower focus.Method: Participants (1,384 controls and 3,860 participants with one or more SUDs including alcohol, cocaine, cannabis, and/or opioid use disorders) completed the Semi-Structured Assessment for Drug Dependence and Alcoholism, the NEO Personality Inventory, and the Wisconsin Card Sorting Test. Exploratory factor analysis (EFA) and fit indices (root mean-squared error of approximation (RMSEA), Comparative Fit Index (CFI), and Tucker-Lewis Index (TLI)) were used to examine different latent variable models. A multiple indicators, multiple causes (MIMIC) approach-tested associations of the latent variables with sociodemographics, substance use, and a history of abuse/neglect.Results: A six-factor model (predominant alcohol, predominant cocaine, predominant opioid, externalizing, personality, and executive function) provided the best fit [RMSEA = 0.063 (90% CI 0.060, 0.066), CFI = 0.98, TLI = 0.96]. All factors were moderately correlated (coefficient = 0.25-0.55, p < .05) with the exception of executive function. MIMIC analysis revealed different patterns of associations (all p < .0001) with sociodemographics, substance use, and a history of abuse/neglect among the factors.Conclusions: The domains identified, particularly executive function, were parallel to those observed previously. These factors underscore the heterogeneous nature of SUDs and may be useful in developing more targeted clinical interventions.

"Blocking-like" effects in attentional set-shifting: Redundant cues facilitate shifting in male rats with medial prefrontal cortex inactivation.

Without a functioning prefrontal cortex, humans and other animals are impaired in measures of cognitive control and behavioral flexibility, including attentional set-shifting. However, the reason for this is unclear with evidence suggesting both impaired and enhanced attentional shifting. We inhibited the medial prefrontal cortex (mPFC) of rats while they performed a modified version of an attentional set-shifting task to explore the nature of this apparent contradiction. Twelve adult male Lister hooded rats received AAV5-CaMKIIa-hM4D(Gi)-mCherry viral vector bilaterally into mPFC to express inhibitory 'Designer Receptors Exclusively Activated by Designer Drugs' (iDREADDs). The receptors were activated by systemic clozapine N-oxide (CNO) to inhibit mPFC function. The rats were tested in the standard attentional set-shifting task four times: twice after i.p. administration and twice after oral administration of vehicle or CNO (10 mg/kg). They were then tested twice in a modified task, with or without oral CNO. The modified task had an extra stage before the extradimensional shift, in which the relevant exemplars remained relevant and new exemplars that were fully predictive but redundant replaced the previous irrelevant exemplars. These exemplars then became relevant at the subsequent ED stage. In the standard task, mPFC inactivation impaired attentional set-shifting, consistent with previous findings. However, in the modified task, mPFC inactivation abolished ED shift-costs. The results support the suggestion that the mPFC is needed for the downregulation of attention that prevents learning about redundant and irrelevant stimuli. With mPFC inactivated, the rat learns more rapidly when previously redundant exemplars become the only relevant information.

From brain connectivity to cognitive function: Dissecting the salience network in pediatric BECTS-ESES.

BACKGROUND: Benign childhood epilepsy with centrotemporal spikes (BECTS), a common pediatric epilepsy, may lead to cognitive decline when compounded by Electrical Status Epilepticus during Sleep (ESES). Emerging evidence suggests that disruptions in the Salience Network (SN) contribute significantly to the cognitive deficits observed in BECTS-ESES. Our study rigorously investigates the dynamic functional connectivity (dFC) within the SN and its correlation with cognitive impairments in BECTS-ESES, employing advanced neuroimaging and neuropsychological assessments. METHODS: In this research, 45 patients diagnosed with BECTS-ESES and 55 age-matched healthy controls (HCs) participated. We utilized resting-state functional magnetic resonance imaging (fMRI) and Independent Component Analysis (ICA) to identify three fundamental SN nodes: the right Anterior Insula (rAI), left Anterior Insula (lAI), and the Anterior Cingulate Cortex (ACC). A two-sample t-test facilitated the comparison of dFC between these pivotal regions and other brain areas. RESULTS: Significantly, the BECTS-ESES group demonstrated increased dFC, particularly between the ACC and the right Middle Occipital Gyrus, and from the rAI to the right Superior Parietal Gyrus and Cerebellum, and from the lAI to the left Postcentral Gyrus. Such dFC augmentations provide neural insights potentially explaining the neuropsychological deficits in BECTS-ESES children. Employing comprehensive neuropsychological evaluations, we mapped these dFC disruptions to specific cognitive impairments encompassing memory, executive functioning, language, and attention. Through multiple regression analysis and path analysis, a preliminary but compelling association was discovered linking dFC disturbances directly to cognitive impairments. These findings underscore the critical role of SN disruptions in BECTS-ESES cognitive dysfunctions. LIMITATION: Our cross-sectional design and analytic methods preclude definitive mediation models and causal inferences, leaving the precise nature of dFC's mediating role and its direct impact by BECTS-ESES partially unresolved. Future longitudinal and confirmatory studies are needed to comprehensively delineate these associations. CONCLUSION: Our study heralds dFC within the SN as a vital biomarker for cognitive impairment in pediatric epilepsy, advocating for targeted cognitive-specific interventions in managing BECTS-ESES. The preliminary nature of our findings invites further studies to substantiate these associations, offering profound implications for the prognosis and therapeutic strategies in BECTS-ESES, thereby underlining the importance of this research in the field of pediatric neurology and epilepsy management.

Climate change effects and their implications for the financial markets: Evidence from the United Kingdom.

This study aims to examine how the climate affects the behaviour of the stock market. To achieve this, we have drawn on daily data from Jan 2005 to Jan 31, 2023 and several environmental factors (e.g., temperature, humidity, cloud cover and visibility) to account for extreme weather conditions using the 21-day moving average and its standard deviation. The empirical analysis has revealed three key findings regarding the impact of weather on the stock market's behaviour. First, various forms of extreme weather conditions consistently lead to influence stock behaviour. Second, results provide valuable insights into market behaviour and help investors to make more informed investment decisions. Third, the weather conditions have new information about the climate risk and investors should react to it swiftly in light of our findings. The saliency theory can help reconcile the theoretical conflicts between the real options and risk-shifting theories when it comes to investing in uncertain and extreme climate conditions.

Salient semantics.

Semantic features are components of concepts. In philosophy, there is a predominant focus on those features that are necessary (and jointly sufficient) for the application of a concept. Consequently, the method of cases has been the paradigm tool among philosophers, including experimental philosophers. However, whether a feature is salient is often far more important for cognitive processes like memory, categorization, recognition and even decision-making than whether it is necessary. The primary objective of this paper is to emphasize the significance of researching salient features of concepts. I thereby advocate the use of semantic feature production tasks, which not only enable researchers to determine whether a feature is salient, but also provide a complementary method for studying ordinary language use. I will discuss empirical data on three concepts, conspiracy theory, female/male professor, and life, to illustrate that semantic feature production tasks can help philosophers (a) identify those salient features that play a central role in our reasoning about and with concepts, (b) examine socially relevant stereotypes, and (c) investigate the structure of concepts.

Effect of Antiseizure Medication on the Salience Network in Patients with Epilepsy with Generalized Tonic-Clonic Seizures Alone.

This study aimed to investigate the effects of antiepileptic drugs on salience network regions in patients with epilepsy with generalized tonic-clonic seizures alone (EGTCSa). A retrospective observational case-control study was performed on 40 patients diagnosed with epilepsy with EGTCSa and 40 healthy age-matched controls. In LORETA, a voxel-by-voxel analysis between regions from the salience network was performed for both hemispheres, specifically between the anterior cingulate (BA 32 and BA 24) and the sublobar insula (BA 13). Subsequently, a Wilcoxon rank-sum test (the Mann-Whitney U test) was conducted for the equality of medians in the transformation matrix. A comparison was then made between each region of interest as defined by the salience network and the controls. Marked differences were found in the brain regions assessed in patients with EGTCSa treated with valproic acid and carbamazepine compared to the control group; few differences in patients treated with levetiracetam; and no difference was found in the group without treatment compared with those in the control group. These results suggest that ASMs can influence cognitive processes, which provide novel insights toward understanding the neural mechanisms underlying the effects of ASMs administration.

Frontoparietal and salience network synchronizations during nonsymbolic magnitude processing predict brain age and mathematical performance in youth.

The development and refinement of functional brain circuits crucial to human cognition is a continuous process that spans from childhood to adulthood. Research increasingly focuses on mapping these evolving configurations, with the aim to identify markers for functional impairments and atypical development. Among human cognitive systems, nonsymbolic magnitude representations serve as a foundational building block for future success in mathematical learning and achievement for individuals. Using task-based frontoparietal (FPN) and salience network (SN) features during nonsymbolic magnitude processing alongside machine learning algorithms, we developed a framework to construct brain age prediction models for participants aged 7-30. Our study revealed differential developmental profiles in the synchronization within and between FPN and SN networks. Specifically, we observed a linear increase in FPN connectivity, concomitant with a decline in SN connectivity across the age span. A nonlinear U-shaped trajectory in the connectivity between the FPN and SN was discerned, revealing reduced FPN-SN synchronization among adolescents compared to both pediatric and adult cohorts. Leveraging the Gradient Boosting machine learning algorithm and nested fivefold stratified cross-validation with independent training datasets, we demonstrated that functional connectivity measures of the FPN and SN nodes predict chronological age, with a correlation coefficient of .727 and a mean absolute error of 2.944 between actual and predicted ages. Notably, connectivity within the FPN emerged as the most contributing feature for age prediction. Critically, a more matured brain age estimate is associated with better arithmetic performance. Our findings shed light on the intricate developmental changes occurring in the neural networks supporting magnitude representations. We emphasize brain age estimation as a potent tool for understanding cognitive development and its relationship to mathematical abilities across the critical developmental period of youth. PRACTITIONER POINTS: This study investigated the prolonged changes in the brain's architecture across childhood, adolescence, and adulthood, with a focus on task-state frontoparietal and salience networks. Distinct developmental pathways were identified: frontoparietal synchronization strengthens consistently throughout development, while salience network connectivity diminishes with age. Furthermore, adolescents show a unique dip in connectivity between these networks. Leveraging advanced machine learning methods, we accurately predicted individuals' ages based on these brain circuits, with a more mature estimated brain age correlating with better math skills.

A connectome-based model of delusion in schizophrenia using functional connectivity under working memory task.

Delusion is an important feature of schizophrenia, which may stem from cognitive biases. Working memory (WM) is the core foundation of cognition, closely related to delusion. However, the knowledge of neural mechanisms underlying the relationship between WM and delusion in schizophrenia is poorly investigated. Two hundred and thirty patients with schizophrenia (dataset 1: n = 130; dataset 2: n = 100) were enrolled and scanned for an N-back WM task. We constructed the WM-related whole-brain functional connectome and conducted Connectome-based Predictive Modelling (CPM) to detect the delusion-related networks and built the correlation model in dataset 1. The correlation between identified networks and delusion severity was tested in a separate, heterogeneous sample of dataset 2 that mainly includes early-onset schizophrenia. The identified delusion-related network has a strong correlation with delusion severity measured by the NO.20 item of SAPS in dataset 1 (r = 0.433, p = 2.7 × 10-7, permutation-p = 0.035), and can be validated in the same dataset by using another delusion measurement, that is, the P1 item of PANSS (r = 0.362, p = 0.0005). It can be validated in another independent dataset 2 (NO.20 item of SAPS for r = 0.31, p = 0.0024, P1 item of PANSS for r = 0.27, p = 0.0074). The delusion-related network comprises the connections between the default mode network (DMN), cingulo-opercular network (CON), salience network (SN), subcortical, sensory-somatomotor network (SMN), and visual networks. We successfully established correlation models of individualized delusion based on the WM-related functional connectome and showed a strong correlation between delusion severity and connections within the DMN, CON, SMN, and subcortical network.

Predicting Clinical Improvement in Early Psychosis Using Circuit-Based Resting-State Functional Magnetic Resonance Imaging.

BACKGROUND AND HYPOTHESIS: Identifying biomarkers that predict treatment response in early psychosis (EP) is a priority for psychiatry research. Previous work suggests that resting-state connectivity biomarkers may have promise as predictive measures, although prior results vary considerably in direction and magnitude. Here, we evaluated the relationship between intrinsic functional connectivity of the attention, default mode, and salience resting-state networks and 12-month clinical improvement in EP. STUDY DESIGN: Fifty-eight individuals with EP (less than 2 years from illness onset, 35 males, average age 20 years) had baseline and follow-up clinical data and were included in the final sample. Of these, 30 EPs showed greater than 20% improvement in Brief Psychiatric Rating Scale (BPRS) total score at follow-up and were classified as "Improvers." STUDY RESULTS: The overall logistic regression predicting Improver status was significant (χ2 = 23.66, Nagelkerke's R2 = 0.45, P < .001, with 85% concordance). Significant individual predictors of Improver status included higher default mode within-network connectivity, higher attention-default mode between-network connectivity, and higher attention-salience between-network connectivity. Including baseline BPRS as a predictor increased model significance and concordance to 92%, and the model was not significantly influenced by the dose of antipsychotic medication (chlorpromazine equivalents). Linear regression models predicting percent change in BPRS were also significant. CONCLUSIONS: Overall, these results suggest that resting-state functional magnetic resonance imaging connectivity may serve as a useful biomarker of clinical outcomes in recent-onset psychosis.