Evolving topological order in the postnatal visceral pleura.

BACKGROUND: Changes in epithelial cell shape reflects optimal cell packing and the minimization of surface free energy, but also cell-cell interactions, cell proliferation, and cytoskeletal rearrangements. RESULTS: Here, we studied the structure of the rat pleura in the first 15 days after birth. After pleural isolation and image segmentation, the analysis demonstrated a progression of epithelial order from postnatal day 1 (P1) to P15. The cells with the largest surface area and greatest shape variability were observed at P1. In contrast, the cells with the smallest surface area and most shape consistency were observed at P15. A comparison of polygonal cell geometries demonstrated progressive optimization with an increase in the number of hexagons (six-sided) as well as five-sided and seven-sided polygons. Analysis of the epithelial organization with Voronoi tessellations and graphlet motif frequencies demonstrated a developmental path strikingly distinct from mathematical and natural reference paths. Graph Theory analysis of cell connectivity demonstrated a progressive decrease in network heterogeneity and clustering coefficient from P1 to P15. CONCLUSIONS: We conclude that the rat pleura undergoes a striking change in pleural structure from P1 to P15. Further, a geometric and network-based approach can provide a quantitative characterization of these developmental changes.

Differential alterations in brain structural network organization during addiction between adolescents and adults.

BACKGROUND: The adolescent brain may be susceptible to the influences of illicit drug use. While compensatory network reorganization is a unique developmental characteristic that may restore several brain disorders, its association with methamphetamine (MA) use-induced damage during adolescence is unclear. METHODS: Using independent component (IC) analysis on structural magnetic resonance imaging data, spatially ICs described as morphometric networks were extracted to examine the effects of MA use on gray matter (GM) volumes and network module connectivity in adolescents (51 MA users v. 60 controls) and adults (54 MA users v. 60 controls). RESULTS: MA use was related to significant GM volume reductions in the default mode, cognitive control, salience, limbic, sensory and visual network modules in adolescents. GM volumes were also reduced in the limbic and visual network modules of the adult MA group as compared to the adult control group. Differential patterns of structural connectivity between the basal ganglia (BG) and network modules were found between the adolescent and adult MA groups. Specifically, adult MA users exhibited significantly reduced connectivity of the BG with the default network modules compared to control adults, while adolescent MA users, despite the greater extent of network GM volume reductions, did not show alterations in network connectivity relative to control adolescents. CONCLUSIONS: Our findings suggest the potential of compensatory network reorganization in adolescent brains in response to MA use. The developmental characteristic to compensate for MA-induced brain damage can be considered as an age-specific therapeutic target for adolescent MA users.

Reorganization of the Neurobiology of Language After Sentence Overlearning.

It is assumed that there are a static set of "language regions" in the brain. Yet, language comprehension engages regions well beyond these, and patients regularly produce familiar "formulaic" expressions when language regions are severely damaged. These suggest that the neurobiology of language is not fixed but varies with experiences, like the extent of word sequence learning. We hypothesized that perceiving overlearned sentences is supported by speech production and not putative language regions. Participants underwent 2 sessions of behavioral testing and functional magnetic resonance imaging (fMRI). During the intervening 15 days, they repeated 2 sentences 30 times each, twice a day. In both fMRI sessions, they "passively" listened to those sentences, novel sentences, and produced sentences. Behaviorally, evidence for overlearning included a 2.1-s decrease in reaction times to predict the final word in overlearned sentences. This corresponded to the recruitment of sensorimotor regions involved in sentence production, inactivation of temporal and inferior frontal regions involved in novel sentence listening, and a 45% change in global network organization. Thus, there was a profound whole-brain reorganization following sentence overlearning, out of "language" and into sensorimotor regions. The latter are generally preserved in aphasia and Alzheimer's disease, perhaps explaining residual abilities with formulaic expressions in both.

Global Network Organization of the Fetal Functional Connectome.

Recent advances in brain imaging have enabled non-invasive in vivo assessment of the fetal brain. Characterizing brain development in healthy fetuses provides baseline measures for identifying deviations in brain function in high-risk clinical groups. We examined 110 resting state MRI data sets from fetuses at 19 to 40 weeks' gestation. Using graph-theoretic techniques, we characterized global organizational features of the fetal functional connectome and their prenatal trajectories. Topological features related to network integration (i.e., global efficiency) and segregation (i.e., clustering) were assessed. Fetal networks exhibited small-world topology, showing high clustering and short average path length relative to reference networks. Likewise, fetal networks' quantitative small world indices met criteria for small-worldness (σ > 1, ω = [-0.5 0.5]). Along with this, fetal networks demonstrated global and local efficiency, economy, and modularity. A right-tailed degree distribution, suggesting the presence of central areas that are more highly connected to other regions, was also observed. Metrics, however, were not static during gestation; measures associated with segregation-local efficiency and modularity-decreased with advancing gestational age. Altogether, these suggest that the neural circuitry underpinning the brain's ability to segregate and integrate information exists as early as the late 2nd trimester of pregnancy and reorganizes during the prenatal period. Significance statement. Mounting evidence for the fetal origins of some neurodevelopmental disorders underscores the importance of identifying features of healthy fetal brain functional development. Alterations in prenatal brain connectomics may serve as early markers for identifying fetal-onset neurodevelopmental disorders, which in turn provide improved surveillance of at-risk fetuses and support the initiation of early interventions.

GEVI cell-type specific labelling and a manifold learning approach provide evidence for lateral inhibition at the population level in the mouse hippocampal CA1 area.

The CA1 area in the mammalian hippocampus is essential for spatial learning. Pyramidal cells are the hippocampus output neurons and their activities are regulated by inhibition exerted by a diversified population of interneurons. Lateral inhibition has been suggested as the mechanism enabling the reconfiguration of pyramidal cell assembly activity observed during spatial learning tasks in rodents. However, lateral inhibition in the CA1 lacks the overwhelming evidence reported in other hippocampal areas such as the CA3 and the dentate gyrus. The use of genetically encoded voltage indicators and fast optical recordings permits the construction of cell-type specific response maps of neuronal activity. Here, we labelled mouse CA1 pyramidal neurons with the genetically encoded voltage indicator ArcLight and optically recorded their response to Schaffer Collaterals stimulation in vitro. By undertaking a manifold learning approach, we report a hyperpolarization-dominated area focused in the perisomatic region of pyramidal cells receiving late excitatory synaptic input. Functional network organization metrics revealed that information transfer was higher in this area. The localized hyperpolarization disappeared when GABAA receptors were pharmacologically blocked. This is the first report where the spatiotemporal pattern of lateral inhibition is visualized in the CA1 by expressing a genetically encoded voltage indicator selectively in principal neurons. Our analysis suggests a fundamental role of lateral inhibition in CA1 information processing.

Functional brain network organization measured with magnetoencephalography predicts cognitive decline in multiple sclerosis.

BACKGROUND: Cognitive decline remains difficult to predict as structural brain damage cannot fully explain the extensive heterogeneity found between MS patients. OBJECTIVE: To investigate whether functional brain network organization measured with magnetoencephalography (MEG) predicts cognitive decline in MS patients after 5 years and to explore its value beyond structural pathology. METHODS: Resting-state MEG recordings, structural MRI, and neuropsychological assessments were analyzed of 146 MS patients, and 100 patients had a 5-year follow-up neuropsychological assessment. Network properties of the minimum spanning tree (i.e. backbone of the functional brain network) indicating network integration and overload were related to baseline and longitudinal cognition, correcting for structural damage. RESULTS: A more integrated beta band network (i.e. smaller diameter) and a less integrated delta band network (i.e. lower leaf fraction) predicted cognitive decline after 5 years (Radj2=15%), independent of structural damage. Cross-sectional analyses showed that a less integrated network (e.g. lower tree hierarchy) related to worse cognition, independent of frequency band. CONCLUSIONS: The level of functional brain network integration was an independent predictive marker of cognitive decline, in addition to the severity of structural damage. This work thereby indicates the promise of MEG-derived network measures in predicting disease progression in MS.

Enhanced accuracy and reduced delay in diagnosing bone tumors within an expert sarcoma network: A nationwide study.

INTRODUCTION: Primary bone tumors encompass a range of rare and diverse lesions. Pathological diagnosis poses significant challenges, with histological discrepancies extensively studied in soft tissue sarcomas but lacking specific investigation in bone lesions. This study aimed to determine the rate of major diagnostic discrepancies in primary bone tumors, assessing whether initial histological analysis within an expert referral center network reduces this rate and final diagnostic delay. Additionally, we examined the impact of mandatory systematic re-reading by expert pathologists on diagnostic variation and readjustment. METHODS: Our study cohort comprised patients with primary bone tumors, drawn from the national prospective French sarcoma network database. A total of 1075 patients were included from 2018 to 2019. RESULTS: The cohort exhibited a major discrepancy rate of 24%. Within the expert referral centers network, 49 cases (7%) showed major diagnostic discrepancies in the initial analysis, compared to 207 cases (57%) outside the network (p < 0.001). Regarding the final diagnostic delay, a mean of 2.8 weeks (±4.9) was observed within the network, contrasting with 6.5 weeks (±9.1) outside the network (p < 0.001). Systematic re-reading by an expert pathologist facilitated diagnosis readjustment in 75% of the 256 cases, with 68% of all diagnostic variations occurring preoperatively. CONCLUSION: Early management within the expert network significantly reduced major diagnostic discrepancies and shortened the diagnosis delay by approximately a month. Expert pathologist systematic re-readings were responsible for diagnosis readjustments in three-quarters of cases, with two-thirds of all diagnostic variations occurring preoperatively, thereby mitigating the consequences of mistreatment.

Role of middle managers in dealing with hierarchy and network logics: exploration in the context of Sino-Foreign Cooperative University.

While organizations tend to introduce network mechanism to activate the potential of members in the hierarchical dominated context, it is not clear how individual members deal with the complexity caused by two logics of hierarchy and network. To address this gap, this study focuses on the role of middle managers in collaborating with others in the multiple-logic complexity. We identify three types of collaboration scenarios, top-down, bottom-up, and horizontal, through 27 semi-structured interviews within a Sino-Foreign Cooperative University from 2021 to 2023. Guided by the grounded theory approach, we conceptualize the composite role of middle managers as the translucent hand of explicit and implicit connections, which help us to interpret middle managers' tangibly and intangibly impact under a hybrid organization context. The empirical results also reveal that the boundary perception of authority and responsibility as an important factor determines middle managers' awareness of power involvement in cooperation. The findings extend the understanding of middle managers in network organizations in the higher education context and provide suggestions for the dynamic role of middle managers and hybrid university management in the information age.

Neighborhood poverty during childhood prospectively predicts adolescent functional brain network architecture.

Family poverty has been associated with altered brain structure, function, and connectivity in youth. However, few studies have examined how disadvantage within the broader neighborhood may influence functional brain network organization. The present study leveraged a longitudinal community sample of 538 twins living in low-income neighborhoods to evaluate the prospective association between exposure to neighborhood poverty during childhood (6-10 y) with functional network architecture during adolescence (8-19 y). Using resting-state and task-based fMRI, we generated two latent measures that captured intrinsic brain organization across the whole-brain and network levels - network segregation and network segregation-integration balance. While age was positively associated with network segregation and network balance overall across the sample, these associations were moderated by exposure to neighborhood poverty. Specifically, these positive associations were observed only in youth from more, but not less, disadvantaged neighborhoods. Moreover, greater exposure to neighborhood poverty predicted reduced network segregation and network balance in early, but not middle or late, adolescence. These effects were detected both across the whole-brain system as well as specific functional networks, including fronto-parietal, default mode, salience, and subcortical systems. These findings indicate that where children live may exert long-reaching effects on the organization and development of the adolescent brain.

Associations between psychotropic drugs and rsEEG connectivity and network characteristics: a cross-sectional study in hospital-admitted psychiatric patients.

Introduction: Resting-state EEG (rsEEG) characteristics, such as functional connectivity and network topology, are studied as potential biomarkers in psychiatric research. However, the presence of psychopharmacological treatment in study participants poses a potential confounding factor in biomarker research. To address this concern, our study aims to explore the impact of both single and multi-class psychotropic treatments on aforementioned rsEEG characteristics in a psychiatric population. Methods: RsEEG was analyzed in a real-world cross-sectional sample of 900 hospital-admitted psychiatric patients. Patients were clustered into eight psychopharmacological groups: unmedicated, single-class treatment with antipsychotics (AP), antidepressants (AD) or benzodiazepines (BDZ), and multi-class combinations of these treatments. To assess the associations between psychotropic treatments and the macroscale rsEEG characteristics mentioned above, we employed a general linear model with post-hoc tests. Additionally, Spearman's rank correlation analyses were performed to explore potential dosage effects. Results: Compared to unmedicated patients, single-class use of AD was associated with lower functional connectivity in the delta band, while AP was associated with lower functional connectivity in both the delta and alpha bands. Single-class use of BDZ was associated with widespread rsEEG differences, including lower functional connectivity across frequency bands and a different network topology within the beta band relative to unmedicated patients. All of the multi-class groups showed associations with functional connectivity or topology measures, but effects were most pronounced for concomitant use of all three classes of psychotropics. Differences were not only observed in comparison with unmedicated patients, but were also evident in comparisons between single-class, multi-class, and single/multi-class groups. Importantly, multi-class associations with rsEEG characteristics were found even in the absence of single-class associations, suggesting potential cumulative or interaction effects of different classes of psychotropics. Dosage correlations were only found for antipsychotics. Conclusion: Our exploratory, cross-sectional study suggests small but significant associations between single and multi-class use of antidepressants, antipsychotics and benzodiazepines and macroscale rsEEG functional connectivity and network topology characteristics. These findings highlight the importance of considering the effects of specific psychotropics, as well as their interactions, when investigating rsEEG biomarkers in a medicated psychiatric population.

Mechanistic decomposition and reduction in complex, context-sensitive systems.

Standard arguments in philosophy of science infer from the complexity of biological and neural systems to the presence of emergence and failure of mechanistic/reductionist explanation for those systems. I argue against this kind of argument, specifically focusing on the notion of context-sensitivity. Context-sensitivity is standardly taken to be incompatible with reductionistic explanation, because it shows that larger-scale factors influence the functioning of lower-level parts. I argue that this argument can be overcome if there are mechanisms underlying those context-specific reorganizations. I argue that such mechanisms are frequently discovered in neuroscience.

Dissociation of categorical and coordinate spatial relations on dynamic network organization states.

Humans can flexibly represent both categorical and coordinate spatial relations. Previous research has mainly focused on hemisphere lateralization in representing these two types of spatial relations, but little is known about how distinct network organization states support representations of the two. Here we used dynamic resting-state functional connectivity (FC) to explore this question. To do this, we separated a meta-identified navigation network into a ventral and two other subnetworks. We revealed a Weak State and a Strong State within the ventral subnetwork and a Negative State and a Positive State between the ventral and other subnetworks. Further, we found the Weak State (i.e., weak but positive FC) within the ventral subnetwork was related to the ability of categorical relation recognition, suggesting that the representation of categorical spatial relations was related to weak integration among focal regions in the navigation network. In contrast, the Negative State (i.e., negative FC) between the ventral and other subnetworks was associated with the ability of coordinate relation processing, suggesting that the representation of coordinate spatial relations may require competitive interactions among widely distributed regions. In sum, our study provides the first empirical evidence revealing different focal and distributed organizations of the navigation network in representing different types of spatial information.

Molecular Layer Interneurons: Key Elements of Cerebellar Network Computation and Behavior.

Molecular layer interneurons (MLIs) play an important role in cerebellar information processing by controlling Purkinje cell (PC) activity via inhibitory synaptic transmission. A local MLI network, constructed from both chemical and electrical synapses, is organized into spatially structured clusters that amplify feedforward and lateral inhibition to shape the temporal and spatial patterns of PC activity. Several recent in vivo studies indicate that such MLI circuits contribute not only to sensorimotor information processing, but also to precise motor coordination and cognitive processes. Here, we review current understanding of the organization of MLI circuits and their roles in the function of the mammalian cerebellum.

Analyzing the relationship between managers' working pressure and creative behavior from the social network perspective.

BACKGROUND: With the social environment requirements for innovation and creativity, requirements for enterprises' innovation and creativity are also higher. However, research on the working pressure and innovation behavior of enterprise managers is rare. OBJECTIVE: To explore the relationship between the working pressure of managers and creative organizational behavior, provide a reference for the development of corporate innovation activities, thereby improving corporate organizational creativity. METHODS: Managers in enterprises under social networks' background are selected as research objects to study the relationship between their working pressure and creative organizational behavior. First, the theory of pressure cognition activation is elaborated. The challenge pressure, hindrance pressure, and organizational creativity are selected as the basis, and the reliability and validity of the corresponding scale tools are analyzed and tested. Second, based on the relationship among challenging working pressure, hindrance working pressure, and organizational, creative behavior activities, two hypotheses are proposed, which are expressed as Hypothesis 1 and Hypothesis 2, respectively. Finally, according to the managerial working pressure in organizational, creative behavioral activities, two kinds of hypotheses are proposed, which are represented by Hypothesis 3 and Hypothesis 4, respectively. RESULTS: The results show: The selected scale tools have good reliability and validity. The Cronbach's Alpha reliability coefficients corresponding to challenge pressure, hindrance pressure, and organizational, creative behavior activities are all above 0.85. The challenge pressure has a significantly positive impact on organizational creativity (P < 0.01), while the hindrance pressure has a significantly negative impact on organizational creativity (P < 0.01); therefore, Hypothesis 1 and Hypothesis 2 are verified. The organizational support for creative behavior activities has a dual adjustment impact. In addition to negatively regulating the positive path of managers' working pressure on work engagement, organizational support also positively regulates the positive path of managers' work engagement on organizational creativity. Therefore, Hypothesis 3 and Hypothesis 4 are verified. CONCLUSIONS: The above results provide a theoretical reference for a profound understanding of the relationship between working pressure and creative behavior and the improvement of the creative ability of enterprises.

Long-term stability of avalanche scaling and integrative network organization in prefrontal and premotor cortex.

Ongoing neuronal activity in the brain establishes functional networks that reflect normal and pathological brain function. Most estimates of these functional networks suffer from low spatiotemporal resolution and indirect measures of neuronal population activity, limiting the accuracy and reliability in their reconstruction over time. Here, we studied the stability of neuronal avalanche dynamics and corresponding reconstructed functional networks in the adult brain. Using chronically implanted high-density microelectrode arrays, the local field potential (LFP) of resting-state activity was recorded in prefrontal and premotor cortex of awake nonhuman primates. Avalanche dynamics revealed stable scaling exhibiting an inverted parabolic profile and collapse exponent of 2 in line with a critical branching process over many days and weeks. Functional networks were based on a Bayesian-derived estimator and demonstrated stable integrative properties characterized by nontrivial high neighborhood overlap between strongly connected nodes and robustness to weak-link pruning. Entropy-based mixing analysis revealed significant changes in strong link weights over weeks. The long-term stability in avalanche scaling and integrative network organization in the face of individual link weight changes should support the development of noninvasive biomarkers to characterize normal and abnormal brain states in the adult brain.

High School Sports-Related Concussion and the Effect of a Jugular Vein Compression Collar: A Prospective Longitudinal Investigation of Neuroimaging and Neurofunctional Outcomes.

Sports-related concussion (SRC) can exert serious acute and long-term consequences on brain microstructure, function, and behavioral outcomes. We aimed to quantify the alterations in white matter (WM) microstructure and global network organization, and the decrements in behavioral and cognitive outcomes from pre-season to post-concussion in youth athletes who experienced SRC. We also aimed to evaluate whether wearing a jugular compression neck collar, a device designed to mitigate brain "slosh" injury, would mitigate the pre-season to post-concussion alterations in neuroimaging, behavioral, and cognitive outcomes. A total of 488 high school football and soccer athletes (14-18 years old) were prospectively enrolled and assigned to the non-collar group (n = 237) or the collar group (n = 251). The outcomes of the study were the pre-season to post-concussion neuroimaging, behavioral, and cognitive alterations. Forty-six participants (non-collar: n = 24; collar: n = 22) were diagnosed with a SRC during the season. Forty of these 46 athletes (non-collar: n = 20; collar: n = 20) completed neuroimaging assessment. Significant pre-season to post-concussion alterations in WM microstructural integrity and brain network organization were found in these athletes (corrected p < 0.05). The alterations were significantly reduced in collar-wearing athletes compared to non-collar-wearing athletes (corrected p < 0.05). Concussion and collar main effects were identified for some of the behavioral and cognitive outcomes, but no collar by SRC interaction effects were observed in any outcomes. In summary, young athletes exhibited significant WM microstructural and network organizational, and cognitive alterations following SRC. The use of the jugular vein compression collar showed promising evidence to reduce these alterations in high school contact sport athletes.

Brain networks reorganization and functional disability in glaucoma.

Glaucoma is an optic neuropathy characterized by progressive loss of retinal ganglion cells with associated structural and functional changes of the optic nerve head and retinal nerve fiber layer. However, recent studies employing advanced neuroimaging techniques confirmed that glaucomatous damage is not limited to the eye but extends to the brain, affecting it also beyond the central visual pathways and disrupting brain network organization. We therefore posit that, while visual field changes play an important role in glaucoma-induced disability, central nervous pathways and mechanisms may play an important role in sustaining functional and daily living disability caused by the disease. Here we to summarize the current state of the art on the involvement of central brain circuits and possibly related disabilities in patients with glaucoma.

Alterations of neural network organization during REM sleep in women: implication for sex differences in vulnerability to mood disorders.

BACKGROUND: Sleep plays an important role in vulnerability to mood disorders. However, despite the existence of sex differences in vulnerability to mood disorders, no study has yet investigated the sex effect on sleep network organization and its potential involvement in vulnerability to mood disorders. The aim of our study was to empirically investigate the sex effect on network organization during REM and slow-wave sleep using the effective connectivity measured by Granger causality. METHODS: Polysomnographic data from 44 healthy individuals (28 men and 16 women) recruited prospectively were analysed. To obtain the 19 × 19 connectivity matrix of all possible pairwise combinations of electrodes by Granger causality method from our EEG data, we used the Toolbox MVGC multivariate Granger causality. The computation of the network measures was realized by importing these connectivity matrices into EEGNET Toolbox. RESULTS: In men and women, all small-world coefficients obtained are compatible with a small-world network organization during REM and slow-wave sleep. However, compared to men, women present greater small-world coefficients during REM sleep as well as for all EEG bands during this sleep stage, which indicates the presence of a small-world network organization less marked during REM sleep as well as for all EEG bands during this sleep stage in women. In addition, in women, these small-world coefficients during REM sleep as well as for all EEG bands during this sleep stage are positively correlated with the presence of subclinical symptoms of depression. CONCLUSIONS: Thus, the highlighting of these sex differences in network organization during REM sleep indicates the presence of differences in the global and local processing of information during sleep between women and men. In addition, this small-world network organization less marked during REM sleep appears to be a marker of vulnerability to mood disorders specific to women, which opens up new perspectives in understanding sex differences in the occurrence of mood disorders.

The sleep network organization during slow-wave sleep is more stable with age and has small-world characteristics more marked than during REM sleep in healthy men.

Sleep plays an important role in cognitive functioning. However, few studies have investigated the sleep network organization. The aim of our study was to empirically investigate the presence and the stability with age of a small-world network organization during REM and slow-wave sleep using the effective connectivity measured by the Granger causality. Polysomnographic data from 30 healthy men recruited prospectively were analysed. To obtain the 19 × 19 connectivity matrix of all possible pairwise combinations of electrodes by the Granger causality method from our EEG data, we used the Toolbox MVGC multivariate Granger causality. The computation of the network measures was realised by importing these connectivity matrices into the EEGNET Toolbox. Even if all small-world coefficients obtained are compatible with a small-world network organization during REM and slow-wave sleep, slow-wave sleep seems to have a small-world network organization more marked than REM sleep. Moreover, the sleep network organization is affected greater by age during REM sleep than during slow-wave sleep. In healthy individuals, the highlighting of a sleep network organization during slow-wave sleep more stable with age and with small-world characteristics more marked than during REM sleep may help to better understand the global and local processing of information during sleep.

Nonsocial and social cognition in schizophrenia: current evidence and future directions.

Cognitive impairment in schizophrenia involves a broad array of nonsocial and social cognitive domains. It is a core feature of the illness, and one with substantial implications for treatment and prognosis. Our understanding of the causes, consequences and interventions for cognitive impairment in schizophrenia has grown substantially in recent years. Here we review a range of topics, including: a) the types of nonsocial cognitive, social cognitive, and perceptual deficits in schizophrenia; b) how deficits in schizophrenia are similar or different from those in other disorders; c) cognitive impairments in the prodromal period and over the lifespan in schizophrenia; d) neuroimaging of the neural substrates of nonsocial and social cognition, and e) relationships of nonsocial and social cognition to functional outcome. The paper also reviews the considerable efforts that have been directed to improve cognitive impairments in schizophrenia through novel psychopharmacology, cognitive remediation, social cognitive training, and alternative approaches. In the final section, we consider areas that are emerging and have the potential to provide future insights, including the interface of motivation and cognition, the influence of childhood adversity, metacognition, the role of neuroinflammation, computational modelling, the application of remote digital technology, and novel methods to evaluate brain network organization. The study of cognitive impairment has provided a way to approach, examine and comprehend a wide range of features of schizophrenia, and it may ultimately affect how we define and diagnose this complex disorder.