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.

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.

Depressed patients with childhood maltreatment display altered intra- and inter-network resting state functional connectivity.

BACKGROUND: Childhood maltreatment (CM) is a major risk factor for the development of major depressive disorder (MDD). To gain more knowledge on how adverse childhood experiences influence the development of brain architecture, we studied functional connectivity (FC) alterations of neural networks of depressed patients with, or without the history of CM. METHODS: Depressed patients with severe childhood maltreatment (n = 18), MDD patients without maltreatment (n = 19), and matched healthy controls (n = 20) were examined with resting state functional MRI. History of maltreatment was assessed with the 28-item Childhood Trauma Questionnaire. Intra- and inter-network FC alterations were evaluated using FMRIB Software Library and CONN toolbox. RESULTS: We found numerous intra- and inter-network FC alterations between the maltreated and the non-maltreated patients. Intra-network FC differences were found in the default mode, visual and auditory networks, and cerebellum. Network modelling revealed several inter-network FC alterations connecting the default mode network with the executive control, salience and cerebellar networks. Increased inter-network FC was found in maltreated patients between the sensory-motor and visual, cerebellar, default mode and salience networks. LIMITATIONS: Relatively small sample size, cross-sectional design, and retrospective self-report questionnaire to assess adverse childhood experiences. CONCLUSIONS: Our findings confirm that severely maltreated depressed patients display numerous alterations of intra- and inter-network FC strengths, not only in their fronto-limbic circuits, but also in sensory-motor, visual, auditory, and cerebellar networks. These functional alterations may explain that maltreated individuals typically display altered perception and are prone to develop functional neurological symptom disorder (conversion disorder) in adulthood.

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

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

Longitudinal neurofunctional changes in medication overuse headache patients after mindfulness practice in a randomized controlled trial (the MIND-CM study).

BACKGROUND: Mindfulness practice has gained interest in the management of Chronic Migraine associated with Medication Overuse Headache (CM-MOH). Mindfulness is characterized by present-moment self-awareness and relies on attention control and emotion regulation, improving headache-related pain management. Mindfulness modulates the Default Mode Network (DMN), Salience Network (SN), and Fronto-Parietal Network (FPN) functional connectivity. However, the neural mechanisms underlying headache-related pain management with mindfulness are still unclear. In this study, we tested neurofunctional changes after mindfulness practice added to pharmacological treatment as usual in CM-MOH patients. METHODS: The present study is a longitudinal phase-III single-blind Randomized Controlled Trial (MIND-CM study; NCT03671681). Patients had a diagnosis of CM-MOH, no history of neurological and severe psychiatric comorbidities, and were attending our specialty headache centre. Patients were divided in Treatment as Usual (TaU) and mindfulness added to TaU (TaU + MIND) groups. Patients underwent a neuroimaging and clinical assessment before the treatment and after one year. Longitudinal comparisons of DMN, SN, and FPN connectivity were performed between groups and correlated with clinical changes. Vertex-wise analysis was performed to assess cortical thickness changes. RESULTS: 177 CM-MOH patients were randomized to either TaU group or TaU + MIND group. Thirty-four patients, divided in 17 TaU and 17 TaU + MIND, completed the neuroimaging follow-up. At the follow-up, both groups showed an improvement in most clinical variables, whereas only TaU + MIND patients showed a significant headache frequency reduction (p = 0.028). After one year, TaU + MIND patients showed greater SN functional connectivity with the left posterior insula (p-FWE = 0.007) and sensorimotor cortex (p-FWE = 0.026). In TaU + MIND patients only, greater SN-insular connectivity was associated with improved depression scores (r = -0.51, p = 0.038). A longitudinal increase in cortical thickness was observed in the insular cluster in these patients (p = 0.015). Increased anterior cingulate cortex thickness was also reported in TaU + MIND group (p-FWE = 0.02). CONCLUSIONS: Increased SN-insular connectivity might modulate chronic pain perception and the management of negative emotions. Enhanced SN-sensorimotor connectivity could reflect improved body-awareness of painful sensations. Expanded cingulate cortex thickness might sustain improved cognitive processing of nociceptive information. Our findings unveil the therapeutic potential of mindfulness and the underlying neural mechanisms in CM-MOH patients. TRIAL REGISTRATION: Name of Registry; MIND-CM study; Registration Number ClinicalTrials.gov identifier: NCT0367168; Registration Date: 14/09/2018.

The interplay between insomnia symptoms and Alzheimer's Disease across three main brain networks.

STUDY OBJECTIVES: Insomnia symptoms are prevalent along the trajectory of Alzheimer's disease (AD), but the neurobiological underpinning of their interaction is poorly understood. Here, we assessed structural and functional brain measures within and between the default mode network (DMN), salience network (SN), and central executive network (CEN). METHODS: We selected 320 subjects from the ADNI database and divided by their diagnosis: cognitively normal (CN), Mild Cognitive Impairment (MCI), and AD, with and without self-reported insomnia symptoms. We measured the gray matter volume (GMV), structural covariance (SC), degrees centrality (DC), and functional connectivity (FC), testing the effect and interaction of insomnia symptoms and diagnosis on each index. Subsequently, we performed a within-group linear regression across each network and ROI. Finally, we correlated observed abnormalities with changes in cognitive and affective scores. RESULTS: Insomnia symptoms were associated with FC alterations across all groups. The AD group also demonstrated an interaction between insomnia and diagnosis. Within-group analyses revealed that in CN and MCI, insomnia symptoms were characterised by within-network hyperconnectivity, while in AD, within- and between-network hypoconnectivity was ubiquitous. SC and GMV alterations were non-significant in the presence of insomnia symptoms, and DC indices only showed network-level alterations in the CEN of AD individuals. Abnormal FC within and between DMN and CEN hubs was additionally associated with reduced cognitive function across all groups, and increased depressive symptoms in AD. CONCLUSIONS: We conclude that patients with clinical AD present with a unique pattern of insomnia-related functional alterations, highlighting the profound interaction between both conditions.

Aberrant Functional Connectivity of the Salience Network in Adult Patients with Tic Disorders: A Resting-State fMRI Study.

Tic disorders (TD) are characterized by the presence of motor and/or vocal tics. Common neurophysiological frameworks suggest dysregulations of the cortico-striatal-thalamo-cortical (CSTC) brain circuit that controls movement execution. Besides common tics, there are other "non-tic" symptoms that are primarily related to sensory perception, sensorimotor integration, attention, and social cognition. The existence of these symptoms, the sensory tic triggers, and the modifying effect of attention and cognitive control mechanisms on tics may indicate the salience network's (SN) involvement in the neurophysiology of TD. Resting-state functional MRI measurements were performed in 26 participants with TD and 25 healthy controls (HC). The group differences in resting-state functional connectivity patterns were measured based on seed-to-voxel connectivity analyses. Compared to HC, patients with TD exhibited altered connectivity between the core regions of the SN (insula, anterior cingulate cortex, and temporoparietal junction) and sensory, associative, and motor-related cortices. Furthermore, connectivity changes were observed in relation to the severity of tics in the TD group. The SN, particularly the insula, is likely to be an important site of dysregulation in TD. Our results provide evidence for large-scale neural deviations in TD beyond the CSTC pathologies. These findings may be relevant for developing treatment targets.

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

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

Cortical and subcortical functional connectivity and cognitive impairment in Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disease with cognitive as well as motor impairments. While much is known about the brain networks leading to motor impairments in PD, less is known about the brain networks contributing to cognitive impairments. Here, we leveraged resting-state functional magnetic resonance imaging (rs-fMRI) data from the Parkinson's Progression Marker Initiative (PPMI) to examine network dysfunction in PD patients with cognitive impairment. We focus on canonical cortical networks linked to cognition, including the salience network (SAL), frontoparietal network (FPN), and default mode network (DMN), as well as a subcortical basal ganglia network (BGN). We used the Montreal Cognitive Assessment (MoCA) as a continuous index of coarse cognitive function in PD. In 82 PD patients, we found that lower MoCA scores were linked with lower intra-network connectivity of the FPN. We also found that lower MoCA scores were linked with lower inter-network connectivity between the SAL and the BGN, the SAL and the DMN, as well as the FPN and the DMN. These data elucidate the relationship of cortical and subcortical functional connectivity with cognitive impairments in PD.

Smoking Progression and Nicotine-Enhanced Reward Sensitivity Predicted by Resting-State Functional Connectivity in Salience and Executive Control Networks.

INTRODUCTION: The neural underpinnings underlying individual differences in nicotine-enhanced reward sensitivity and smoking progression are poorly understood. Thus, we investigated whether brain resting-state functional connectivity (rsFC) during smoking abstinence predicts nicotine-enhanced reward sensitivity and smoking progression in young light smokers. We hypothesized that high rsFC between brain areas with high densities of nicotinic receptors (insula, anterior cingulate cortex [ACC], hippocampus, thalamus) and areas involved in reward-seeking (nucleus accumbens [NAcc], prefrontal cortex [PFC]) would predict nicotine-enhanced reward sensitivity and smoking progression. METHODS: Young light smokers (N=64, age 18-24, M = 1.89 cigarettes/day) participated in the study. These individuals smoked between 5 to 35 cigarettes per week and lifetime use never exceeded 35 cigarettes per week. Their rsFC was assessed using functional magnetic resonance imaging after 14-hour nicotine-deprivation. Subjects also completed a probabilistic reward task after smoking a placebo on one day and a regular cigarette on another day. RESULTS: The probabilistic-reward-task assessed greater nicotine-enhanced reward sensitivity was associated with greater rsFC between the right anterior PFC and right NAcc, but with reduced rsFC between the ACC and left inferior prefrontal gyrus and the insula and ACC. Decreased rsFC within the salience network (ACC and insula) predicted increased smoking progression across 18 months and greater nicotine-enhanced reward sensitivity. CONCLUSIONS: These findings provide the first evidence that differences in rsFCs in young light smokers are associated with nicotine-enhanced reward sensitivity and smoking progression. IMPLICATIONS: Weaker rsFC within the salience network predicted greater nicotine-enhanced reward sensitivity and smoking progression. These findings suggest that salience network rsFC and drug-enhanced reward sensitivity may be useful tools and potential endophenotypes for reward sensitivity and drug-dependence research.

Salience Network Functional Connectivity Mediates Association Between Social Engagement and Cognition in Non-Demented Older Adults: Exploratory Investigation.

Background: Social engagement has beneficial effects during cognitive aging. Large-scale cognitive brain network functions are implicated in both social behaviors and cognition. Objective: We evaluated associations between functional connectivity (FC) of large-scale brain cognitive networks and social engagement, characterized by self-reported social network size and contact frequency. We subsequently tested large-scale brain network FC as a potential mediator of the beneficial relationship between social engagement and cognitive performance. Methods: 112 older adults (70.7±7.3 years, range 54.6-89.7; 84 women) completed the Lubben Social Network Scale 6 (LSNS-6), National Alzheimer's Coordinating Center (NACC) Uniform Data Set 3 (UDS-3) cognitive battery, and resting state fMRI. We completed seed-based correlational analysis in the default mode and salience networks. Significant associations between social engagement scores and cognitive performance, as well as between social engagement and FC of brain networks, informed the construction of mediation models. Results: Social engagement was significantly associated with executive function and global cognition, with greater social engagement associated with better cognitive performance. Social engagement was significantly associated with salience network FC, with greater social engagement associated with higher connectivity. Salience network FC partially mediated associations between social engagement and both executive function and global cognition. Conclusions: Our results suggest that the salience network is a key mediator of the beneficial relationship between social engagement and cognition in older adults.

Intrinsic functional connectivity strength of SuperAgers in the default mode and salience networks: Insights from ADNI.

There exists a group of older individuals who appear to be resistant to age-related memory decline. These "SuperAgers" have been shown to demonstrate preservation of cortical thickness and functional connectivity strength across the cortex which positively correlates with memory performance. Over the last decade, roughly 30 articles have been published regarding SuperAgers; however, to our knowledge, no replications of these studies have been published. The current study sought to conceptually replicate Zhang and colleagues' (2020) findings that SuperAgers demonstrate stronger intrinsic functional connectivity within the default mode (DMN) and salience networks (SN), and that connectivity strength within these networks correlates with memory performance. We identified 20 SuperAgers and 20 matched Normal Agers in the control cohort of the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. We compared the functional connectivity strength of the DMN and SN between these groups, and used the Rey Auditory Verbal Learning Test (RAVLT) to evaluate correlations between functional connectivity and memory performance. Our results did not replicate Zhang and colleagues' (2020) results, as we found negligible differences between SuperAgers and Normal Agers in the DMN and SN, and no significant correlations between functional connectivity and memory performance after accounting for multiple comparisons. More replications are needed to confirm existing work. In addition, more research with larger SuperAger samples and more consistent definitions of SuperAging is needed, so that we can better understand this remarkable group of older adults.

Abnormal functional connectivity of the intrinsic networks in adolescent bipolar I versus bipolar II disorder.

BACKGROUND: The symptoms of pediatric bipolar disorder (PBD)-I and PBD-II differ, but accurate identification at an early stage is difficult and may prevent effective treatment of this disorder. Therefore, it is urgent to elucidate a biological marker based on objective imaging indicators to help distinguish the two. Therefore, this research aims to compare the functional connectivity between PBD-I patient and PBD-II patient in different brain networks. METHODS: Our study enrolled 31 PBD-I and 23 PBD-II patients from 12 to 17 years of age. They were analyzed by resting state-functional connectivity through Independent component analysis (ICA). RESULTS: We found differences between PBD-I and PBD-II in functional connectivity of the default network, frontoparietal network, salience network and limbic system. In addition, the clinical features, cognitive functions are associated with the functional connectivity of the intrinsic networks in PBD-I and PBD-II separately. CONCLUSION: This research is the first to find differences in functional connectivity between PBD-I and PBD-II, suggesting that abnormality of the functional connectivity within large networks may be biomarkers that help differentiate PBD-I from PBD-II in the future.

Towards a Real-Life Understanding of the Altered Functional Behaviour of the Default Mode and Salience Network in Chronic Pain: Are People with Chronic Pain Overthinking the Meaning of Their Pain?

Chronic pain is a source of substantial physical and psychological suffering, yet a clear understanding of the pathogenesis of chronic pain is lacking. Repeated studies have reported an altered behaviour of the salience network (SN) and default mode network (DMN) in people with chronic pain, and a majority of these studies report an altered behaviour of the dorsal ventromedial prefrontal cortex (vmPFC) within the anterior DMN. In this topical review, we therefore focus specifically on the role of the dorsal vmPFC in chronic pain to provide an updated perspective on the cortical mechanisms of chronic pain. We suggest that increased activity in the dorsal vmPFC may reflect maladaptive overthinking about the meaning of pain for oneself and one's actions. We also suggest that such overthinking, if negative, may increase the personal "threat" of a given context, as possibly reflected by increased activity in, and functional connectivity to, the anterior insular cortex within the SN.

Neural correlates of model-based behavior in internet gaming disorder and alcohol use disorder.

Background: An imbalance between model-based and model-free decision-making systems is a common feature in addictive disorders. However, little is known about whether similar decision-making deficits appear in internet gaming disorder (IGD). This study compared neurocognitive features associated with model-based and model-free systems in IGD and alcohol use disorder (AUD). Method: Participants diagnosed with IGD (n = 22) and AUD (n = 22), and healthy controls (n = 30) performed the two-stage task inside the functional magnetic resonance imaging (fMRI) scanner. We used computational modeling and hierarchical Bayesian analysis to provide a mechanistic account of their choice behavior. Then, we performed a model-based fMRI analysis and functional connectivity analysis to identify neural correlates of the decision-making processes in each group. Results: The computational modeling results showed similar levels of model-based behavior in the IGD and AUD groups. However, we observed distinct neural correlates of the model-based reward prediction error (RPE) between the two groups. The IGD group exhibited insula-specific activation associated with model-based RPE, while the AUD group showed prefrontal activation, particularly in the orbitofrontal cortex and superior frontal gyrus. Furthermore, individuals with IGD demonstrated hyper-connectivity between the insula and brain regions in the salience network in the context of model-based RPE. Discussion and Conclusions: The findings suggest potential differences in the neurobiological mechanisms underlying model-based behavior in IGD and AUD, albeit shared cognitive features observed in computational modeling analysis. As the first neuroimaging study to compare IGD and AUD in terms of the model-based system, this study provides novel insights into distinct decision-making processes in IGD.

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

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

Climate change on the brain: Neural correlates of climate anxiety.

Climate change is a global crisis impacting individuals' mental health. Climate anxiety is an emerging area of interest within popular culture and the scientific community. Yet, little is known about the mechanisms underlying climate anxiety. We provide evidence that climate anxiety is related to gray matter volume in the midcingulate cortex as well as its level of functional connectivity with the insula cortex. These neuroanatomical and neurofunctional features of climate anxiety are involved in identifying and anticipating potential threats within the environment and preparing an appropriate action response to such threats. These neural correlates align with those observed in anxiety disorders. Yet, climate anxiety itself as well as the neural correlates of climate anxiety were related to pro-environmental behavior. This may suggest that the midcingulate and insula are part of a network linked to an adaptive aspect of climate anxiety in motivating behavioral engagement.

The insula: Leveraging cellular and systems-level research to better understand its roles in health and schizophrenia.

Schizophrenia is a highly heterogeneous disorder characterized by a multitude of complex and seemingly non-overlapping symptoms. The insular cortex has gained increasing attention in neuroscience and psychiatry due to its involvement in a diverse range of fundamental human experiences and behaviors. This review article provides an overview of the insula's cellular and anatomical organization, functional and structural connectivity, and functional significance. Focusing on specific insula subregions and using knowledge gained from humans and preclinical studies of insular tracings in non-human primates, we review the literature and discuss the functional roles of each subregion, including in somatosensation, interoception, salience processing, emotional processing, and social cognition. Building from this foundation, we then extend these findings to discuss reported abnormalities of these functions in individuals with schizophrenia, implicating insular involvement in schizophrenia pathology. This review underscores the insula's vast role in the human experience and how abnormal insula structure and function could result in the wide-ranging symptoms observed in schizophrenia.

Electrophysiological dynamics of a triple network model of cognitive control: A multi-experiment replication.

Dynamic interactions between large-scale brain networks are thought to underpin human cognitive processes, but their underlying electrophysiological dynamics remain unknown. The triple network model, which highlights the salience, default mode, and frontoparietal networks, provides a fundamental framework for understanding these interactions. To unravel the electrophysiological mechanisms underlying these network dynamics, we utilized intracranial EEG recordings from 177 participants across four distinct memory experiments. Our findings revealed a consistent pattern of directed information flow from the anterior insula, a key node of the salience network, to both the default mode and frontoparietal networks. Notably, this pattern of information transmission was observed regardless of the nature of the tasks, whether they involved externally driven stimuli during encoding or internally governed processes during free recall. Moreover, the directed information flow from the anterior insula to the other networks was present irrespective of the activation or suppression states of individual network nodes. Furthermore, we observed a specific suppression of high-gamma power in the posterior cingulate cortex/precuneus node of the default mode network during memory encoding, but not recall, suggesting a task-specific functional down-regulation of this region. Crucially, these results were reliably replicated across all four experiments, underscoring the robustness and generalizability of our findings. Our study significantly advances the understanding of how coordinated neural network interactions underpin cognitive operations and highlights the critical role of the anterior insula in orchestrating the dynamics of large-scale brain networks. These findings have important implications for elucidating the neural basis of cognitive control and its potential disruptions in various neurological and psychiatric disorders.

Fearful arousals in sleep terrors and sleep-related hypermotor epileptic seizures may involve the salience network and the acute stress response of Cannon and Selye.

We consider the disorders of arousal and sleep-related hypermotor epilepsy as genetic twin-conditions, one without, one with epilepsy. They share an augmented arousal-activity during NREM sleep with sleep-wake dissociations, culminating in sleep terrors and sleep-related hypermotor seizures with similar symptoms. The known mutations underlying the two spectra are different, but there are multifold population-genetic-, family- and even individual (the two conditions occurring in the same person) overlaps supporting common genetic roots. In the episodes of disorders of arousal, the anterior cingulate, anterior insular and pre-frontal cortices (shown to be involved in fear- and emotion processing) are activated within a sleeping brain. These regions overlap with the seizure-onset zones of successfully operated sleep-related hypermotor seizures, and notably, belong to the salience network being consistent with its hubs. The arousal-relatedness and the similar fearful confusion occurring in sleep terrors and hypermotor seizures, make them alike acute stress-responses emerging from sleep; triggered by false alarms. The activation of the anterior cingulate, prefrontal and insular regions in the episodes of both conditions, can easily mobilize the hypothalamo-pituitary-adrenal axis (preparing fight-flight responses in wakefulness); through its direct pathways to and from the salience network. This hypothesis has never been studied.