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Background: Loss of empathy (LoE) is common among stroke survivors, yet often undiagnosed and thus untreated. LoE is related to the loss of a caring marital relationship, higher care burden and poorer quality of life in carers. The present study will evaluate the clinical and MRI correlates of LoE in a cohort of stroke survivors. The secondary objective is to describe the 12-month course of LoE. Methods: The current study is a prospective cohort study. We will recruit 246 subjects. Subjects and carers will receive a detailed assessment at a research clinic at 3, 9, and 15 months after stroke onset (T1/T2/T3). The Chinese version of the Interpersonal Reactivity Index (IRI), a 28-item personality assessment tool, will be completed by a carer for each subject. LoE is defined as an IRI total score of 39 or less. Patients will be examined by MRI including diffusion weighted imaging (DWI) within 1 week after the onset of stroke. A stepwise logistic regression will be performed to assess the importance of lesions in the regions of interest. To examine the predictors of LoE remission, the demographic, clinical and MRI variables of remitters and non-remitters at T2/T3 will be examined by logistic regression. Discussion: This project will be the first longitudinal study on LoE in stroke survivors. The results will shed light on the association between prefrontal cortex and subcortical lesions and LoE risk, symptom severity and outcome. The findings will provide data to advance our understanding of the pathogenesis and clinical course of LoE in stroke as well as other neurological conditions. They are thus likely to be applicable to the large population of neurological patients at risk of LoE and should also stimulate further research in this field. [ABSTRACT FROM AUTHOR]

Arterial spin labelling (ASL) is the only non‐invasive technique that allows absolute quantification of perfusion and is increasingly used in brain activation studies. Contrary to the blood oxygen level‐dependent (BOLD) effect ASL measures the cerebral blood flow (CBF) directly. However, the ASL signal has a lower signal‐to‐noise ratio (SNR), than the BOLD signal, which constrains its utilization in neurofeedback studies. If successful, ASL neurofeedback can be used to aid in the rehabilitation of health conditions with impaired blood flow, for example, stroke. We provide the first ASL‐based neurofeedback study incorporating a double‐blind, sham‐controlled design. A pseudo‐continuous ASL (pCASL) approach with background suppression and 3D GRASE readout was combined with a real‐time post‐processing pipeline. The real‐time pipeline allows to monitor the ASL signal and provides real‐time feedback on the neural activity to the subject. In total 41 healthy adults (19–56 years) divided into three groups underwent a neurofeedback‐based emotion imagery training of the left anterior insula. Two groups differing only in the explicitness level of instruction received real training and a third group received sham feedback. Only those participants receiving real feedback with explicit instruction showed significantly higher absolute CBF values in the trained region during neurofeedback than participants receiving sham feedback. However, responder analyses of percent signal change values show no differences in activation between the three groups. Persisting limitations, such as the lower SNR, confounding effects of arterial transit time and partial volume effects still impact negatively the implementation of ASL neurofeedback. [ABSTRACT FROM AUTHOR]

Simulation theories predict that the observation of other's expressions modulates neural activity in the same centres controlling their production. This hypothesis has been developed by two models, postulating that the visual input is directly projected either to the motor system for action recognition (motor resonance) or to emotional/interoceptive regions for emotional contagion and social synchronization (emotional resonance). Here we investigated the role of frontal/insular regions in the processing of observed emotional expressions by combining intracranial recording, electrical stimulation and effective connectivity. First, we intracranially recorded from prefrontal, premotor or anterior insular regions of 44 patients during the passive observation of emotional expressions, finding widespread modulations in prefrontal/insular regions (anterior cingulate cortex, anterior insula, orbitofrontal cortex and inferior frontal gyrus) and motor territories (Rolandic operculum and inferior frontal junction). Subsequently, we electrically stimulated the activated sites, finding that (i) in the anterior cingulate cortex and anterior insula, the stimulation elicited emotional/interoceptive responses, as predicted by the 'emotional resonance model'; (ii) in the Rolandic operculum it evoked face/mouth sensorimotor responses, in line with the 'motor resonance' model; and (iii) all other regions were unresponsive or revealed functions unrelated to the processing of facial expressions. Finally, we traced the effective connectivity to sketch a network-level description of these regions, finding that the anterior cingulate cortex and the anterior insula are reciprocally interconnected while the Rolandic operculum is part of the parieto-frontal circuits and poorly connected with the former. These results support the hypothesis that the pathways hypothesized by the 'emotional resonance' and the 'motor resonance' models work in parallel, differing in terms of spatio-temporal fingerprints, reactivity to electrical stimulation and connectivity patterns. [ABSTRACT FROM AUTHOR]

IntroductionAnxiety is an emotion necessary for human survival. However, persistent and excessive anxiety can be clinically challenging. Increased anxiety affects daily life and requires early detection and intervention. Therefore, a better understanding of the neural basis of mild anxiety is needed. However, previous studies have focused primarily on resting-state functional magnetic resonance imaging (rs-fMRI) in patients with psychiatric disorders presenting with anxiety. Notably, only a few studies have been conducted on healthy participants, and the relationship between anxiety and functional brain connectivity in the healthy range remains unclear. Therefore, in this study, we aimed to clarify the differences in functional brain connectivity at different degrees of anxiety among healthy participants.MethodsThis study included 48 healthy participants with no history of psychiatric disorders. Participants were administered The General Health Questionnaire (GHQ) 60, a psychological test for assessing anxiety, and the Manifest Anxiety Scale (MAS). The participants then underwent rs-fMRI. Based on the results of each psychological test, the participants were classified into normal and anxiety groups, and the functional connectivity between the two groups was compared using a seed-to-voxel analysis.ResultsComparison of functional brain connectivity between the normal and anxiety groups classified based on the GHQ60 and MAS revealed differences between brain regions comprising the salience network (SN) in both psychological tests. For the GHQ60, the anxiety group showed reduced connectivity between the right supramarginal gyrus and insular cortex compared with the normal group. However, for the MAS, the anxiety group showed reduced connectivity between the right supramarginal and anterior cingulate cortical gyri compared with the normal group.ConclusionFunctional connectivity within the SN was reduced in the group with higher anxiety when functional brain connectivity at different anxiety levels was examined in healthy participants. This suggests that anxiety is involved in changes in the functional brain connectivity associated with emotional processing and cognitive control.

BackgroundLoss of empathy (LoE) is common among stroke survivors, yet often undiagnosed and thus untreated. LoE is related to the loss of a caring marital relationship, higher care burden and poorer quality of life in carers. The present study will evaluate the clinical and MRI correlates of LoE in a cohort of stroke survivors. The secondary objective is to describe the 12-month course of LoE.MethodsThe current study is a prospective cohort study. We will recruit 246 subjects. Subjects and carers will receive a detailed assessment at a research clinic at 3, 9, and 15 months after stroke onset (T1/T2/T3). The Chinese version of the Interpersonal Reactivity Index (IRI), a 28-item personality assessment tool, will be completed by a carer for each subject. LoE is defined as an IRI total score of 39 or less. Patients will be examined by MRI including diffusion weighted imaging (DWI) within 1 week after the onset of stroke. A stepwise logistic regression will be performed to assess the importance of lesions in the regions of interest. To examine the predictors of LoE remission, the demographic, clinical and MRI variables of remitters and non-remitters at T2/T3 will be examined by logistic regression.DiscussionThis project will be the first longitudinal study on LoE in stroke survivors. The results will shed light on the association between prefrontal cortex and subcortical lesions and LoE risk, symptom severity and outcome. The findings will provide data to advance our understanding of the pathogenesis and clinical course of LoE in stroke as well as other neurological conditions. They are thus likely to be applicable to the large population of neurological patients at risk of LoE and should also stimulate further research in this field.

Dynamic interactions between large-scale brain networks underpin human cognitive processes, but their electrophysiological mechanisms remain elusive. The triple network model, encompassing the salience network (SN), default mode network (DMN), and frontoparietal network (FPN), provides a framework for understanding these interactions. We analyzed intracranial electroencephalography (EEG) recordings from 177 participants across four diverse episodic memory experiments, each involving encoding as well as recall phases. Phase transfer entropy analysis revealed consistently higher directed information flow from the anterior insula (AI), a key SN node, to both DMN and FPN nodes. This directed influence was significantly stronger during memory tasks compared to resting state, highlighting the AI’s task-specific role in coordinating large-scale network interactions. This pattern persisted across externally driven memory encoding and internally governed free recall. Control analyses using the inferior frontal gyrus (IFG) showed an inverse pattern, with DMN and FPN exerting higher influence on IFG, underscoring the AI’s unique role. We observed task-specific suppression of high-gamma power in the posterior cingulate cortex/precuneus node of the DMN during memory encoding, but not recall. Crucially, these results were replicated across all four experiments spanning verbal and spatial memory domains with high Bayes replication factors. Our findings advance understanding of how coordinated neural network interactions support memory processes, highlighting the AI’s critical role in orchestrating large-scale brain network dynamics during both memory encoding and retrieval. By elucidating the electrophysiological basis of triple network interactions in episodic memory, our study provides insights into neural circuit dynamics underlying memory function and offer a framework for investigating network disruptions in memory-related disorders.

Background: Neuropathic pain is one of the most common symptoms in neuromyelitis optica spectrum disorder (NMOSD). Notwithstanding, its underlying mechanism remains obscure. Methods: The amplitude of low-frequency fluctuations (ALFF) metric was employed to investigate spontaneous neural activity alterations via restingstate functional magnetic resonance imaging (rs-MRI) data from a 3.0 T MRI scanner, in a sample of 26 patients diagnosed with NMOSD with neuropathic pain (NMOSD-WNP), 20 patients with NMOSD but without neuropathic pain (NMOSD-WoNP), and 38 healthy control (HC) subjects matched for age and sex without the comorbidity of depressive or anxious symptoms. Results: It was observed that patients with NMOSD-WNP displayed a significant ALFF decrease in the left amygdala and right anterior insula, relative to both patients with NMOSD-WoNP and HC subjects. Furthermore, ALFF values in the left amygdala were negatively correlated with the scores of the Douleur Neuropathique en 4 Questions and McGill Pain Questionnaire (both sensory and affective descriptors) in patients with NMOSD-WNP. Additionally, there were negative correlations between the ALFF values in the right anterior insula and the duration of pain and the number of relapses in patients with NMOSD-WNP. Conclusion: The present study characterizes spontaneous neural activity changes in brain regions associated with sensory and affective processing of pain and its modulation, which underscore the central aspects in patients with NMOSD-WNP. These findings might contribute to a better understanding of the pathophysiologic basis of neuropathic pain in NMOSD. [ABSTRACT FROM AUTHOR]

Cross‐situational inconsistency is common in the expression of honesty traits; yet, there is insufficient emphasis on behavioral dishonesty across multiple contexts. The current study aimed to investigate behavioral dishonesty in various contexts and reveal the associations between trait honesty, behavioral dishonesty, and neural patterns of observing others behave honestly or dishonestly in videos (abbr.: (dis)honesty video‐watching). First, the results revealed limitations in using trait honesty to reflect variations in dishonest behaviors and predict behavioral dishonesty. The finding highlights the importance of considering neural patterns in understanding and predicting dishonest behaviors. Second, by comparing the predictive performance of seven types of data across three neural networks, the results showed that functional connectivity in the hypothesis‐driven network during (dis)honesty video‐watching provided the highest predictive power in predicting multitask behavioral dishonesty. Last, by applying the feature elimination method, the midline self‐referential regions (medial prefrontal cortex, posterior cingulate cortex, and anterior cingulate cortex), anterior insula, and striatum were identified as the most informative brain regions in predicting behavioral dishonesty. In summary, the study offered insights into individual differences in deception and the intricate connections among trait honesty, behavioral dishonesty, and neural patterns during (dis)honesty video‐watching. [ABSTRACT FROM AUTHOR]

Childhood maltreatment (CM) causes early deviations in cognitive and affective processes, leading to future adaptation failures and psychopathology. Specifically, CM has been linked to cognitive distortions, and recent studies have focused on the impact of CM on the higher level of metacognitive beliefs. However, only a few studies have revealed the neural mechanisms underlying the association between altered metacognition and CM. Therefore, this functional magnetic resonance imaging (fMRI) study investigated the neural correlates of thought–action fusion (TAF) tendency and CM experiences. Overall, 40 young and healthy adults (21 men) participated in this study and underwent fMRI during the TAF task as well as psychological evaluation for CM, TAF tendency, anxiety, and depressive symptoms. During the TAF task, they were asked to read negative (Neg) or neutral (Neu) statements about neutral or close people (CP). Notably, significant activations were found in regions such as the bilateral anterior insula, dorsal anterior cingulate cortex (dACC), caudate, thalamus, medial prefrontal cortex, precuneus, and right amygdala in the NegCp > NeuCP contrast. Furthermore, anterior insula and dACC activities were significantly correlated with total scores of CM experiences and TAF. Exaggerated TAF tendency in persons with CM experiences was associated with increased response of the anterior insula and dACC, which are two core hubs of the salience network. Our results therefore seem to suggest insights for a better understanding of the neural mechanisms underlying metacognitive beliefs related to CM experiences. [ABSTRACT FROM AUTHOR]

• The insula, a brain region known for its role in pain perception, was the focus of our investigation. • Long-term migraine patients exhibit significant volume changes in parietal, central operculum regions, and entire insular cortex. • We report a novel finding: insular regions are implicated in various clinical presentations that were not previously reported. • This study provides insight into the role of the insula in migraine and offers possibilities for managing migraine processes. This study aimed to assess abnormalities in the insular cortex of individuals suffering from migraines and examine their associations with pain duration, medication usage, and clinical symptoms. We analyzed radiological data from 38 migraine patients who had undergone 3D iso T1-weighted brain MRI at our university hospital between 2019 and 2023. Structured questionnaires were used to collect information on participants' age, migraine type, disease duration, clinical symptoms, and medication use. Volumetric analysis was performed on the insular regions using Volbrain and 3DSlicer. The results were statistically analyzed. Comparing groups with chronic pain to normal groups revealed significant differences in several insular regions, including the posterior insula (p = 0.034), parietal operculum (p = 0.04), and the entire insular cortex (p = 0.023). Further group comparisons (Group 1, 2, and 3) showed significant differences in specific insular regions. For instance, the anterior insula (p = 0.032) was associated with taste changes, the posterior insula (p = 0.010) with smell-related changes, and the central operculum (p = 0.046) with sensations of nausea. Additionally, significant changes were observed in the parietal operculum concerning nausea, photophobia, phonophobia, and changes in smell. To the best of our knowledge, there have been no studies investigating the relationship between clinical manifestations and volumetric correlation. This study provides insights into abnormalities in the insular cortex among migraine patients and their potential relevance to pain duration, severity, and migraine type. The results suggest that understanding alterations in insular regions possibly linked to pain could contribute to the development of innovative approaches to managing chronic pain. [ABSTRACT FROM AUTHOR]

Hormesis is a biological phenomenon where exposure to a low dose of a stressor or toxin induces a beneficial adaptive response, whereas higher doses may have detrimental effects. The concept of hormesis is being increasingly appreciated not only in toxicology and in pharmacology, but also in nutrition, clinical medicine, and in situations involving everyday life. Hormesis is an adaptive response of cells and organisms to a moderate and intermittent stressful stimulation. Following such stimulation, the organism must respond, and it has to make a choice: either treat it as a positive ‘challenge’, adapting to it and increasing its robustness, or treat it as a negative ‘threat’ with detrimental consequences for physiology and health. In clinical and everyday situations it is usually difficult to advise patients on how to determine the strength of such stimulation, and when to decide that each new stimulation is too low (ineffective), moderate (appropriate for health), or excessive (damaging to health). In this paper we argue that it is possible to rely on the subjective feelings of ‘comfort vs discomfort’, for deciding about the strength of the stimulus: if each exposure to a stimulation is felt by the individual as a ’comfortable’ event, then it is likely that its effects are beneficial (a hormetic challenge). If it is felt as an ‘uncomfortable’ event, then it is likely that it is damaging to health (a threat). These feelings take place in the anterior insula which evaluates the state of resources for responding to an external or internal event, and are a result of the integration of signals from the amygdala, hippocampus, and the prefrontal cortex. Digital cognitive stimulation and nutritional hormesis are mentioned as two detailed examples.

Much remains unknown about the etiology of compulsion-like alcohol drinking, where consumption persists despite adverse consequences. The role of the anterior insula (AIC) in emotion, motivation, and interoception makes this brain region a likely candidate to drive challenge-resistant behavior, including compulsive drinking. Indeed, subcortical projections from the AIC promote compulsion-like intake in rats and are recruited in heavy-drinking humans during compulsion for alcohol, highlighting the importance of and need for more information about AIC activity patterns that support aversion-resistant responding. Single-unit activity was recorded in the AIC from 15 male rats during alcohol-only and compulsion-like consumption. We found three sustained firing phenotypes, sustained-increase, sustained-decrease, and drinking-onset cells, as well as several firing patterns synchronized with licking. While many AIC neurons had session-long activity changes, only neurons with firing increases at drinking onset had greater activity under compulsion-like conditions. Further, only cells with persistent firing increases maintained activity during pauses in licking, suggesting roles in maintaining drive for alcohol during breaks. AIC firing was not elevated during saccharin drinking, similar to lack of effect of AIC inhibition on sweet fluid intake in many studies. In addition, we observed subsecond changes in AIC neural activity tightly entrained to licking. One lick-synched firing pattern (determined for all licks in a session) predicted compulsion-like drinking, while a separate lick-associated pattern correlated with greater consumption across alcohol intake conditions. Collectively, these data provide a more integrated model for the role of AIC firing in compulsion-like drinking, with important relevance for how the AIC promotes sustained motivated responding more generally. [ABSTRACT FROM AUTHOR]

Recent studies have suggested that emotional reactivity changes with age, but the neural basis is still unclear. The insula may be critical for the emotional reactivity. The current study examined how ageing affects emotional reactivity using the emotional reactivity task data from a human sample (Cambridge Center for Age and Neuroscience, N = 243, age 18–88 years). The resting‐state magnetic resonance measurements from the same sample were used to investigate the potential mechanisms of the insula. In the initial analysis, we conducted partial correlation assessments to examine the associations between emotional reactivity and age, as well as between the gray matter volume (GMV) of the insula and age. Our results revealed that emotional reactivity, especially positive emotional reactivity, decreased with age and that the GMV of the insula was negatively correlated with age. Subsequently, the bilateral insula was divided into six subregions to calculate the whole brain resting‐state functional connectivity (rsFC). The mediating effect of the rsFC on age and emotional reactivity was then calculated. The results showed that the rsFC of the left anterior insula (AI) with the right hippocampus, and the rsFCs of the right AI with the striatum and the thalamus were mediated the relationship between positive emotional reactivity and age. Our findings suggest that attenuating emotional reactivity with age may be a strategic adaptation fostering emotional stability and diminishing emotional vulnerability. Meanwhile, the findings implicate a key role for the AI in the changes in positive emotional reactivity with age. [ABSTRACT FROM AUTHOR]

Substance use disorders (SUD) have been shown to be associated with gray matter (GM) loss, particularly in the frontal cortex. However, unclear is to what degree these regional GM alterations are substance-specific or shared across different substances, and if these regional GM alterations are independent of each other or the result of system-level processes at the intrinsic connectivity network level. The T1 weighted MRI data of 65 treated patients with alcohol use disorder (AUD), 27 patients with opioid use disorder (OUD) on maintenance therapy, 21 treated patients with stimulant use disorder comorbid with alcohol use disorder (polysubstance use disorder patients, PSU), and 21 healthy controls were examined via data-driven vertex-wise and voxel-wise GM analyses. Then, structural covariance analyses and open-access fMRI database analyses were used to map the cortical thinning patterns found in the three SUD groups onto intrinsic functional systems. Among AUD and OUD, we identified both common cortical thinning in right anterior brain regions as well as SUD-specific regional GM alterations that were not present in the PSU group. Furthermore, AUD patients had not only the most extended regional thinning but also significantly smaller subcortical structures and cerebellum relative to controls, OUD and PSU individuals. The system-level analyses revealed that AUD and OUD showed cortical thinning in several functional systems. In the AUD group the default mode network was clearly most affected, followed by the salience and executive control networks, whereas the salience and somatomotor network were highlighted as critical for understanding OUD. Structural brain alterations in groups with different SUDs are largely unique in their spatial extent and functional network correlates.

Real-time fMRI (rt-fMRI) neurofeedback (NF) training is a novel non-invasive technique for volitional brain modulation. Given the important role of the anterior insula (AI) in human cognitive and affective processes, it has become one of the most investigated regions in rt-fMRI studies. Most rt-fMRI insula studies employed emotional recall/imagery as the regulation strategy, which may be less effective for psychiatric disorders characterized by altered emotional processing. The present study thus aimed to examine the feasibility of a novel interoceptive strategy based on heartbeat detection in rt-fMRI guided AI regulation and its associated behavioral changes using a randomized double-blind, sham feedback-controlled between-subject design. 66 participants were recruited and randomly assigned to receive either NF from the left AI (LAI) or sham feedback from a control region while using the interoceptive strategy. N = 57 participants were included in the final data analyses. Empathic and interoceptive pre-post training changes were collected as behavioral measures of NF training effects. Results showed that participants in the NF group exhibited stronger LAI activity than the control group with LAI activity being positively correlated with interoceptive accuracy following NF training, although there were no significant increases of LAI activity over training sessions. Importantly, ability of LAI regulation could be maintained in a transfer session without feedback. Successful LAI regulation was associated with strengthened functional connectivity of the LAI with cognitive control, memory and learning, and salience/interoceptive networks. The present study demonstrated for the first time the efficacy of a novel regulation strategy based on interoceptive processing in up-regulating LAI activity. Our findings also provide proof of concept for the translational potential of this strategy in rt-fMRI AI regulation of psychiatric disorders characterized by altered emotional processing.

The anterior insula (AI) has the central role in coordinating attention and integrating information from multiple sensory modalities. AI dysfunction may contribute to both sensory and social impairments in autism spectrum disorder (ASD). Little is known regarding the brain mechanisms that guide multisensory integration, and how such neural activity might be affected by autistic‐like symptoms in the general population. In this study, 72 healthy young adults performed an audiovisual speech synchrony judgment (SJ) task during fMRI scanning. We aimed to investigate the SJ‐related brain activations and connectivity, with a focus on the AI. Compared with synchronous speech, asynchrony perception triggered stronger activations in the bilateral AI, and other frontal‐cingulate‐parietal regions. In contrast, synchronous perception resulted in greater involvement of the primary auditory and visual areas, indicating multisensory validation and fusion. Moreover, the AI demonstrated a stronger connection with the anterior cingulate gyrus (ACC) in the audiovisual asynchronous (vs. synchronous) condition. To facilitate asynchrony detection, the AI may integrate auditory and visual speech stimuli, and generate a control signal to the ACC that further supports conflict‐resolving and response selection. Correlation analysis, however, suggested that audiovisual synchrony perception and its related AI activation and connectivity did not significantly vary with different levels of autistic traits. These findings provide novel evidence for the neural mechanisms underlying multisensory temporal processing in healthy people. Future research should examine whether such findings would be extended to ASD patients. [ABSTRACT FROM AUTHOR]

Bullying victimization is a risk factor for suicidal ideation, suicide behaviors, and death by suicide in youth. However, not all victims of bullying report suicidal thoughts and behaviors, suggesting that there may be certain subgroups who are at high risk for suicide. Neuroimaging studies suggest that individual differences in neurobiological threat reactivity may contribute to increased vulnerability to suicide, particularly in the context of repeated exposure to bullying. The purpose of the present study was to examine the unique and interactive effects of past-year bullying victimization and neural reactivity to threat on suicide risk in youth. Ninety-one youth (ages 16–19) completed self-report measures of past-year bullying victimization and current suicide risk. Participants also completed a task designed to probe neural reactivity to threat. Specifically, participants passively viewed negative or neutral images during functional magnetic resonance imaging. Bilateral anterior insula (AIC) and amygdala (AMYG) reactivity to threat/negative images (>neutral images) was used to capture threat sensitivity. Greater bullying victimization was associated with increased suicide risk. There was also a bullying by AIC reactivity interaction such that among individuals with high AIC reactivity, greater bullying was associated with increased suicide risk. Among individuals with low AIC reactivity, there was no association between bullying and suicide risk. Results suggest that youth with increased AIC reactivity to threat may be particularly vulnerable to suicide in the context of bullying. These individuals may represent a high-risk group for subsequent suicide behavior and AIC function may be a promising objective prevention target. • Bullying victimization is a risk factor for suicide. • Threat reactivity may further contribute to vulnerability to suicide. • Anterior insula and amygdala reactivity to negative stimuli are markers of threat sensitivity. • Results revealed that bullying had a main effect on suicide risk. • Those with high, but not low, insula reactivity to threat had increased risk for suicide. [ABSTRACT FROM AUTHOR]

The human anterior insula (aINS) is a topographically organized brain region, in which ventral portions contribute to socio-emotional function through limbic and autonomic connections, whereas the dorsal aINS contributes to cognitive processes through frontal and parietal connections. Open questions remain, however, regarding how aINS connectivity varies over time. We implemented a novel approach combining seed-to-whole-brain sliding-window functional connectivity MRI and k-means clustering to assess time-varying functional connectivity of aINS subregions. We studied three independent large samples of healthy participants and longitudinal datasets to assess inter- and intra-subject stability, and related aINS time-varying functional connectivity profiles to dispositional empathy. We identified four robust aINS time-varying functional connectivity modes that displayed both "state" and "trait" characteristics: while modes featuring connectivity to sensory regions were modulated by eye closure, modes featuring connectivity to higher cognitive and emotional processing regions were stable over time and related to empathy measures.

In real life, it is not unusual that we face potential threats (i.e., physical stimuli and environments that may cause harm or danger) with other individuals together, yet it remains largely unknown how threat-induced anxious feelings influence prosocial behaviors such as resource sharing. In this study, we investigated this question by combining functional magnetic resonance imaging and a novel paradigm. Together with an anonymous partner, each participant faced the possibility of receiving a 10-s noise administration, which had a low or high probability to be a threat (i.e., the intensity of noise can induce a high level of unpleasantness). Each participant first reported her/his immediate feeling of anxiety about the current situation (being threatened by the unpleasant noise), then decided how to split a number of resources (which could relieve the noise) between her/him and the partner. Behavioral results revealed that the participants showed a selfish bias in the threat conditions than in the safe conditions, and that self-reported anxiety feeling significantly predicted this bias. Functional magnetic resonance imaging results revealed that: (1) the activation level of the anterior insula was correlated with self-reported anxiety and (2) the connectivity between the anterior insula and the temporoparietal junction was sensitive to the modulating effect of anxiety on the selfish bias. These findings indicate the neural correlates of the association between threat-induced anxiety and prosocial tendencies in social interactions. [ABSTRACT FROM AUTHOR]

Signals related to uncertainty are frequently observed in regions of the cognitive control network, including anterior cingulate/medial prefrontal cortex (ACC/mPFC), dorsolateral prefrontal cortex (dlPFC), and anterior insular cortex. Uncertainty generally refers to conditions in which decision variables may assume multiple possible values and can arise at multiple points in the perception-action cycle, including sensory input, inferred states of the environment, and the consequences of actions. These sources of uncertainty are frequently correlated: noisy input can lead to unreliable estimates of the state of the environment, with consequential influences on action selection. Given this correlation amongst various sources of uncertainty, dissociating the neural structures underlying their estimation presents an ongoing issue: a region associated with uncertainty related to outcomes may estimate outcome uncertainty itself, or it may reflect a cascade effect of state uncertainty on outcome estimates. In this study, we derive signals of state and outcome uncertainty from mathematical models of risk and observe regions in the cognitive control network whose activity is best explained by signals related to state uncertainty (anterior insula), outcome uncertainty (dlPFC), as well as regions that appear to integrate the two (ACC/mPFC). [ABSTRACT FROM AUTHOR]

Increasing evidence showed that learned control of metabolic activity in selected brain regions can support emotion regulation. Notably, a number of studies demonstrated that neurofeedback‐based regulation of fMRI activity in several emotion‐related areas leads to modifications of emotional behavior along with changes of neural activity in local and distributed networks, in both healthy individuals and individuals with emotional disorders. However, the current understanding of the neural mechanisms underlying self‐regulation of the emotional brain, as well as their relationship with other emotion regulation strategies, is still limited. In this study, we attempted to delineate neuroanatomical regions mediating real‐time fMRI‐based emotion regulation by exploring whole brain GM and WM features predictive of self‐regulation of anterior insula (AI) activity, a neuromodulation procedure that can successfully support emotional brain regulation in healthy individuals and patients. To this aim, we employed a multivariate kernel ridge regression model to assess brain volumetric features, at regional and network level, predictive of real‐time fMRI‐based AI regulation. Our results showed that several GM regions including fronto‐occipital and medial temporal areas and the basal ganglia as well as WM regions including the fronto‐occipital fasciculus, tapetum and fornix significantly predicted learned AI regulation. Remarkably, we observed a substantial contribution of the cerebellum in relation to both the most effective regulation run and average neurofeedback performance. Overall, our findings highlighted specific neurostructural features contributing to individual differences of AI‐guided emotion regulation. Notably, such neuroanatomical topography partially overlaps with the neurofunctional network associated with cognitive emotion regulation strategies, suggesting common neural mechanisms. We delineated neuroanatomical predictors of the ability to self‐regulate anterior insula cortex activity through real‐time fMRI neurofeedback. Notably, we observed a major role of the cerebellum in predicting learned regulation of BOLD activity in the anterior insula. Our findings indicated a specific neuroanatomical topography relevant to emotional brain regulation, partially overlapping with the neurofunctional network associated with cognitive emotion regulation. Our neuroanatomical predictors might be ultimately exploited for designing patient‐tailored interventions in emotional disorders. [ABSTRACT FROM AUTHOR]

Self-conscious emotions, such as shame and guilt, play a fundamental role in regulating moral behaviour and in promoting the welfare of society. Despite their relevance, the neural bases of these emotions are uncertain. In the present meta-analysis, we performed a systematic literature review in order to single out functional neuroimaging studies on healthy individuals specifically investigating the neural substrates of shame, embarrassment, and guilt. Seventeen studies investigating the neural correlates of shame/embarrassment and seventeen studies investigating guilt brain representation met our inclusion criteria. The analyses revealed that both guilt and shame/embarrassment were associated with the activation of the left anterior insula, involved in emotional awareness processing and arousal. Guilt-specific areas were located within the left temporo-parietal junction, which is thought to be involved in social cognitive processes. Moreover, specific activations for shame/embarrassment involved areas related to social pain (dorsal anterior cingulate and thalamus) and behavioural inhibition (premotor cortex) networks. This pattern of results might reflect the distinct action tendencies associated with the two emotions. [ABSTRACT FROM AUTHOR]

Current studies have shown that perception of subject's own name (SON) involves multiple multimodal brain regions, while activities in unimodal sensory regions (i.e., primary auditory cortex) and their interaction with multimodal regions during the self‐processing remain unclear. To answer this, we combined multivariate pattern analysis and dynamic causal modelling analysis to explore the regional activation pattern and inter‐region effective connection during the perception of SON. We found that SON and other names could be decoded from the activation pattern in the primary auditory cortex. In addition, we found an excitatory effect of SON on connections from the anterior insula/inferior frontal gyrus to the primary auditory cortex, and to the temporoparietal junction. Our findings extended the current knowledge of self‐processing by showing that primary auditory cortex could discriminate SON from other names. Furthermore, our findings highlighted the importance of influence of the insula on the primary auditory cortex during self‐processing. [ABSTRACT FROM AUTHOR]

Deficits in social cognition consistently underlie functional disabilities in a wide range of psychiatric disorders. Neuroimaging studies have suggested that the anterior insula is a "common core" brain region that is impaired across neurological and psychiatric disorders, which include social cognition deficits. Nevertheless, neurobiological mechanisms of the anterior insula for social cognition remain elusive. This study aims to fill this knowledge gap. To determine the role of the anterior insula in social cognition, the authors manipulated expression of Cyp26B1, an anterior insula-enriched molecule that is crucial for retinoic acid degradation and is involved in the pathology of neuropsychiatric conditions. Social cognition was mainly assayed using the three-chamber social interaction test. Multimodal analyses were conducted at the molecular, cellular, circuitry, and behavioral levels. At the molecular and cellular level, anterior insula–mediated social novelty recognition is maintained by proper activity of the layer 5 pyramidal neurons, for which retinoic acid–mediated gene transcription can play a role. The authors also demonstrate that oxytocin influences the anterior insula–mediated social novelty recognition, although not by direct projection of oxytocin neurons, nor by direct diffusion of oxytocin to the anterior insula, which contrasts with the modes of oxytocin regulation onto the posterior insula. Instead, oxytocin affects oxytocin receptor–expressing neurons in the dorsal raphe nucleus, where serotonergic neurons are projected to the anterior insula. Furthermore, the authors show that serotonin 5-HT2C receptor expressed in the anterior insula influences social novelty recognition. The anterior insula plays a pivotal role in social novelty recognition that is partly regulated by a local retinoic acid cascade but also remotely regulated by oxytocin via a long-range circuit mechanism. [ABSTRACT FROM AUTHOR]

Every day we constantly observe other people receiving rewards. Theoretical accounts posit that vicarious reward processing might be linked to people's sensitivity to internal body states (interoception) and facilitates a tendency to act prosocially. However, the neural processes underlying the links between vicarious reward processing, interoception, and prosocial behaviour are poorly understood. Previous research has linked vicarious reward processing to the anterior cingulate gyrus (ACCg) and the anterior insula (AI). Can we predict someone's propensity to be prosocial or to be aware of interoceptive signals from variability in how the ACCg and AI process rewards? Here, participants monitored rewards being delivered to themselves or a stranger during functional magnetic resonance imaging. Later, they performed a task measuring their willingness to exert effort to obtain rewards for others, and a task measuring their propensity to be aware and use interoceptive respiratory signals. Using multivariate similarity analysis, we show that people's willingness to be prosocial is predicted by greater similarity between self and other representations in the ACCg. Moreover, greater dissimilarity in self-other representations in the AI is linked to interoceptive propensity. These findings highlight that vicarious reward is linked to bodily signals in AI, and foster prosocial tendencies through the ACCg.

Von Economo neurons (VENs) are rod, stick, or corkscrew cells mostly located in layer V of the frontoinsular and anterior cingulate cortices. VENs are projection neurons related to human-like social cognitive abilities. Post-mortem histological studies found VEN alterations in several neuropsychiatric disorders, including schizophrenia (SZ). This pilot study aimed to evaluate the role of VEN-containing areas in shaping patterns of resting-state brain activation in patients with SZ (n = 20) compared to healthy controls (HCs; n = 20). We performed a functional connectivity analysis seeded in the cortical areas with the highest density of VENs followed by fuzzy clustering. The alterations found in the SZ group were correlated with psychopathological, cognitive, and functioning variables. We found a frontotemporal network that was shared by four clusters overlapping with the salience, superior-frontal, orbitofrontal, and central executive networks. Differences between the HC and SZ groups emerged only in the salience network. The functional connectivity of the right anterior insula and ventral tegmental area within this network were negatively correlated with experiential negative symptoms and positively correlated with functioning. This study provides some evidence to show that in vivo, VEN-enriched cortical areas are associated with an altered resting-state brain activity in people with SZ. [ABSTRACT FROM AUTHOR]

Abnormal reward processing is an important yet understudied risk factor for suicide. Recent neuroimaging studies have found that suicidality is associated with abnormal reward-related neural reactivity and connectivity across a wide range of brain regions and circuits. The varying, and oftentimes discrepant, findings have hindered progress in elucidating the neurobiological link between reward processing dysfunction and suicide risk. Some of this variability is likely related to different reward-related paradigms that are utilized across studies. The primary aim of the current study was to address these issues by comparing neural reactivity between youth with and without a history of suicidal ideation during direct manipulation of reward parameters. A total of 108 unmedicated youth, ages 17–19, were classified into two groups: 1) history of suicidal ideation (n = 39) and 2) no history of suicidal ideation (n = 69). All participants completed a novel reward anticipation task probing anticipation of predictable (P-reward) and unpredictable (U-reward) monetary reward. Results revealed that compared with controls, youth with a history of suicidal ideation exhibited increased neural activation in the dorsal anterior cingulate cortex (dACC) and right anterior insula (aINS) during anticipation of U-reward. There were no group differences during anticipation of P-reward. These findings suggest that propensity for suicidal ideation may be related to specific abnormalities during anticipation of U-reward, but not P-reward. • Reward-related neural dysfunction is an understudied risk factor for suicide. • Neuroimaging studies have yielded mixed findings due to varying reward paradigms. • This study manipulated temporal predictability of reward to isolate abnormalities. • Results revealed suicidality is associated with increased salience network reactivity. • Neural differences were observed during anticipation of unpredictable reward, only. [ABSTRACT FROM AUTHOR]

Individuals with high intolerance of uncertainty (IU) tend to display maladaptive cognitive, behavioral, physiological, and/or neural responses during anticipation of uncertain or ambiguous outcomes, both positive and negative in valence. Importantly, high IU has been proposed as a key transdiagnostic phenotypic risk factor for the onset and maintenance of several psychiatric disorders. Within the context of reward processing, high IU has been related to dysfunctional reward anticipation, which may be mediated by hyperactive anterior insula (AIC) response to uncertainty. The present study further investigated the relationship between the AIC and IU by examining the association between individual differences in IU and task-based functional connectivity of the right AIC using functional magnetic resonance imaging (fMRI). Participants (N = 171) completed a self-report measure of IU and a reward anticipation task during fMRI. Generalized psychophysiological interaction (gPPI) analyses were performed with a seed in the right AIC. In the U-threat model, we found that greater self-reported levels of IU were correlated with increased functional connectivity between the right AIC and the dorsal anterior cingulate cortex (dACC) and the right dorsolateral prefrontal cortex (dlPFC). In the P-threat model, we did not find these associations, perhaps indicating that they may be more robust during uncertainty. These preliminary findings suggest that parts of salience and central executive control networks may be impacted by and underlie the expression of IU. Future studies should examine the generalizability of these findings to clinical populations and investigate how disruption of these functional networks may contribute to psychopathology. • High intolerance of uncertainty (IU) is marked by aversion to uncertain (U) rewards. • IU has been linked to hyperactive anterior insula (AIC) response to U-rewards. • The study assessed AIC functional coupling (FC) during U-rewards as it relates to IU. • The AIC-dACC and the AIC-dlPFC FC during U-reward positively correlated with IU. • AIC coupling during U-reward may be impacted by and underlie the expression of IU. [ABSTRACT FROM AUTHOR]

Several studies suggest a link between acute changes in inflammatory parameters due to an endotoxin or (psychological) stressor and the brain’s stress response. The extent to which basal circulating levels of inflammatory markers are associated with the brain’s stress response has been hardly investigated so far. In the present study, baseline plasma levels of the cytokine interleukin (IL)-6 were obtained and linked to neural markers of psychosocial stress using a modified version of the Montreal Imaging Stress Task in a sample of N = 65 healthy subjects (N = 39 female). Of three a-priori defined regions of interest – the amygdala, anterior insula, and anterior cingulate cortex – baseline IL-6 was significantly and negatively associated with stress-related neural activation in the right amygdala and left anterior insula. Our results suggest that baseline cytokines might be related to differences in the neural stress response and that this relationship could be inverse to that previously reported for induced acute changes in inflammation markers.

Pain feels different in different social contexts, yet the mechanisms behind social pain modulation remain poorly understood. To elucidate the impact of social context on pain processing, we investigated how group membership, one of the most important social context factors, shapes pain relief behaviourally and neurally in humans undergoing functional neuroimaging. Participants repeatedly received pain relief from a member of their own group (ingroup treatment) or a member of a disliked outgroup (outgroup treatment). We observed a decrease in pain ratings and anterior insula (AI) pain responses after outgroup treatment, but not after ingroup treatment. Moreover, path analyses revealed that the outgroup treatment induced a stronger relief learning in the AI, which in turn altered pain processing, in particular if the participant entered the treatment with a negative impression toward the outgroup individual. The finding of enhanced analgesia after outgroup treatment is relevant for intergroup clinical settings. More generally, we found that group membership affects pain responses through neural learning and we thus elucidate one possible mechanism through which social context impacts pain processing.

BackgroundInternalizing symptoms like anxiety and depression are common and impairing in autism spectrum disorder (ASD). Here, we test the hypothesis that aberrant functional connectivity among three brain networks (salience network [SN], default mode network [DMN], and frontoparietal network [FPN]) plays a role in the pathophysiology of internalizing in ASD.MethodsWe examined the association between resting-state functional connectivity and internalizing in 102 adolescents and young adults with ASD (n = 49) or typical development (n = 53). Seed-to-target functional connectivity was contrasted between adolescents and young adults with ASD and typically developing subjects using a recent parcellation of the human cerebral cortex, and connections that were aberrant in ASD were analyzed dimensionally as a function of parent-reported internalizing symptoms.ResultsThree connections demonstrated robust overconnectivity in ASD: 1) the anterior insula to the retrosplenial cortex (i.e., SN-DMN), 2) the anterior insula to the frontal pole (i.e., SN-FPN), and 3) the dorsolateral prefrontal cortex to the retrosplenial cortex (i.e., FPN-DMN). These differences remained significant after controlling for age, and no age-related effects survived correction. The SN-DMN connection was associated with greater internalizing in ASD, mediated by a bigger difference between self- and parent-reported internalizing. Control analyses found that the other two connections were not associated with internalizing, and SN-DMN connectivity was not associated with a well-matched control measure (externalizing symptoms).ConclusionsThe present findings provide novel evidence for a specific link between SN-DMN overconnectivity and internalizing in ASD. Further, the mediation results suggest that intact anterior insula-retrosplenial connectivity may play a role in an individual's generating insight into his or her own psychopathology.

Introduction: Functional connectivity is attracting increasing attention for understanding the pathophysiology of depression and predicting the therapeutic efficacy of antidepressants. In this study, we evaluated effective connectivity using isolated effective coherence (iCoh), an effective functional connectivity analysis method developed from low-resolution brain electromagnetic tomography (LORETA) and estimated its practical usefulness for predicting the reaction to antidepressants in theta and alpha band iCoh values. Methods: We enrolled 25 participants from a depression treatment randomized study (the GUNDAM study) in which electroencephalography was performed before treatment. We conducted iCoh between the rostral anterior cingulate cortex (rACC) and anterior insula (AI), which are associated with the salience network. The patients were divided into responder and nonresponder groups at 4 weeks after the start of treatment, and iCoh values were compared between the two groups. Additionally, the sensitivity and specificity of iCoh were calculated using the receiver-operating characteristic (ROC) curve. Results: The Mann-Whitney U test showed significantly weaker connectivity flow from the rACC to the left AI in the alpha band in the responder group. The ROC curve for the connectivity flow from the rACC to the left AI in the alpha band showed 82% sensitivity and 86% specificity. Discussion/Conclusion: These findings suggest the pathological importance of effective connectivity flow from the rACC to the left AI in the alpha and theta bands and suggest its usefulness as a biomarker to distinguish responders to antidepressants. [ABSTRACT FROM AUTHOR]

Endometriosis is the leading cause of chronic pelvic pain. Alterations in brain functional connectivity have been reported in adult women with endometriosis-associated pain (EAP), however, it is still unknown if similar patterns of changes exist in adolescents. Methods : In this pilot study, resting-state fMRI scans were obtained from 11 adolescent and young women with EAP and 14 healthy female controls. Using a seed-to-voxel approach, we investigated functional connectivity between the anterior insula, medial prefrontal cortex, and the rest of the brain. Furthermore, we explored whether potential functional connectivity differences were correlated with clinical characteristics including disease duration, pain intensity, and different psychosocial factors (pain catastrophizing, fear of pain, functional disability, anxiety, and depression). Results : Our findings revealed that patients with EAP demonstrated significantly decreased connectivity between the right anterior insula and two clusters: one in the right cerebellum, and one in the left middle frontal gyrus compared to controls. Additionally, functional connectivity between the right anterior insula and the right cerebellum was positively associated with pain intensity levels. In patients with EAP, brain changes were also correlated with state anxiety and fear of pain. Conclusions: Our results are relevant not only for understanding the brain characteristics underlying EAP at a younger age, but also in enhancing future pain treatment efforts by supporting the involvement of the central nervous system in endometriosis. • Altered brain function in young patients with endometriosis-associated pain (EAP). • Less functional connectivity between the right anterior insula and pain-related regions. • Anterior insula and cerebellum connectivity was linked to greater pain intensity. • Alterations in the pain regulatory pathways in endometriosis. • Endometriosis management should include centrally mediated treatments. [ABSTRACT FROM AUTHOR]

Sleep deprivation is an important cause of cognitive impairment, and anterior insular subregions are core brain regions linked to cognitive function. However, the relationship between anterior insular subregions functional connectivity (FC) and the cognitive impairment that occurs following total sleep deprivation (TSD) remains unknown. As such, this study was designed to evaluate how such anterior insular subregions FC alterations are linked with impaired cognitive activity after TSD. This study recruited 20 healthy volunteers who underwent two rounds of resting-state functional magnetic resonance imaging (rs-fMRI), with one being conducted while in a state of rested wakefulness (RW) and the other being conducted following 24 h of TSD. These rs-fMRI data were then used to conduct seed-based FC analyses for the bilateral anterior insular subregions, including the dorsal anterior insula (dAI) and the ventral anterior insula (vAI). The Psychomotor Vigilance Test (PVT) was used to gauge cognitive performance, and associations between altered FC in these anterior insular subregions and PVT performance following TSD were measured using Pearson correlation analyses. Significant changes in the FC of these bilateral insular subregions were observed following 24 h of TSD relative to the RW state. Significantly enhanced FC was evident between the left dAI and right superior frontal gyrus (SFG), right dAI and bilateral SFG and right putamen, and right vAI and left medial SFG. Moreover, the observed enhancement of FC between the left vAI and right SFG functional connectivity was positively correlated with worse PVT performance. These data suggest that altered FC in the anterior insular subregions represents a prominent neuroimaging biomarker associated with cognitive impairment following TSD. • TSD alters the functional connectivity of anterior insular subregions. • Anterior insular subregions exhibit distinct functional connectivity alterations following TSD. • Enhanced functional connectivity between the left vAI and right SFG is positively correlated with worse PVT performance. [ABSTRACT FROM AUTHOR]

The present research uncovers the shared genetic underpinnings of fairness norm adaptation capability, its neural correlates, and long-term mental health outcomes. One hundred and eighty-six twins are recruited and played as responders in the Ultimatum Game (UG) while undergoing fMRI scanning in their early adulthood (Study-1) and are measured on depressive symptoms eight years later (Study-2). With computational modeling, the process of norm adaptation is differentiated from that of fairness valuation in UG. The two processes both have moderate levels of heritability. The anterior insula has a significant phenotypic correlation, whereas the Supplementary Motor Area/Medial Frontal Gyrus (SMA/mSFG) shows both a significant phenotypic correlation and a shared genetic influence with the learning rate, an index for norm adaptation. The dopaminergic DRD2 polymorphisms correlate with both the learning rate and the SMA/mSFG encoding of prediction error, constituting of their common genetic basis. Regional gene expression analysis reveals the high expression of dopamine-related genes in the SMA/mSFG. Moreover, the learning rate can predict depressive symptom severity eight years later, with the DRD2 polymorphisms constituting their shared genetic basis. This suggests that heritability is a non-negligible driving force behind norm adaptation, which facilitates the learning of social norms in changing environments and preserves long-term mental health., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Dynamic interactions between large-scale brain networks underpin human cognitive processes, but their electrophysiological mechanisms remain elusive. The triple network model, encompassing the salience network (SN), default mode network (DMN), and frontoparietal network (FPN), provides a framework for understanding these interactions. We analyzed intracranial electroencephalography (EEG) recordings from 177 participants across four diverse episodic memory experiments, each involving encoding as well as recall phases. Phase transfer entropy analysis revealed consistently higher directed information flow from the anterior insula (AI), a key SN node, to both DMN and FPN nodes. This directed influence was significantly stronger during memory tasks compared to resting state, highlighting the AI's task-specific role in coordinating large-scale network interactions. This pattern persisted across externally driven memory encoding and internally governed free recall. Control analyses using the inferior frontal gyrus (IFG) showed an inverse pattern, with DMN and FPN exerting higher influence on IFG, underscoring the AI's unique role. We observed task-specific suppression of high-gamma power in the posterior cingulate cortex/precuneus node of the DMN during memory encoding, but not recall. Crucially, these results were replicated across all four experiments spanning verbal and spatial memory domains with high Bayes replication factors. Our findings advance understanding of how coordinated neural network interactions support memory processes, highlighting the AI's critical role in orchestrating large-scale brain network dynamics during both memory encoding and retrieval. By elucidating the electrophysiological basis of triple network interactions in episodic memory, our study provides insights into neural circuit dynamics underlying memory function and offer a framework for investigating network disruptions in memory-related disorders., Competing Interests: AD, VM No competing interests declared, (© 2024, Das and Menon.)

Social connectedness is fundamental to health and life satisfaction. Empathic capacities that support social connections are commonly impaired following damage to the brain's right hemisphere, but how these acquired socio-emotional deficits correspond to real-world social outcomes remains unclear. Using anatomical brain imaging and behavioral data from a large sample of stroke survivors included in the UK Biobank (n = 209), we link damage to regions of the right hemisphere involved in emotion recognition to lower social relationship satisfaction and higher loneliness. The effect was driven by lesions to the right anterior insula and not explained by stroke extent and motor function; it was further corroborated by an exploratory analysis of social decline in a few participants for whom data were available from before and after a stroke to the right anterior insula (n = 3; comparison n = 13). These correlational findings provide new insight into the role of the right hemisphere in maintaining social connections and bear important implications for treatment and rehabilitation post-stroke., (© 2024. The Author(s).)

The emergence of flow is a situation of high salience because externally oriented attention on the task and access to resources for goal-directed behavior are enhanced, while internally oriented or self-related cognition is decreased. The right anterior insula has been reported as a causal out-flow hub of the salience resting-state network, orchestrating the engagement of the central executive network (CEN) and the disengagement of the default-mode network (DMN) during a functional challenge. In the present study, we employed a combined task-based activation and connectivity analysis to investigate the role of the right anterior insula during the emergence of flow. A sample of 41 healthy male subjects was confronted with a functional challenge that permitted the emergence of flow during BOLD-based functional magnetic resonance imaging. Comparing connectivity changes in the right anterior insula during the flow condition against connectivity changes associated with control conditions of boredom and overload, relatively increased couplings were observed with the left and right dorsolateral prefrontal cortex. Activation data for these regions did, however, not show the flow-typical inverted U-shaped (invU) response pattern. Relatively decreased functional couplings encompassed ventral aspects of the striatum, but neither the amygdala nor the medial prefrontal cortex (MPFC). For the ventral striatum, activation data were consistent with the flow-typical U-shaped activation pattern, which supports the notion that under the high salience of autotelic situations, the anterior insula is much less positively coupled with the ventral striatum than under boundary conditions of boredom and overload. Taken together, present functional connectivity results were in alignment with the assumed role of the right anterior insula under conditions of different salience. However, this particular region does not appear to mediate the most typical flow-associated activation patterns.

Alterations of empathy for others’ pain among patients with chronic pain remained inconsistent. Here, applying a capsaicin-based ongoing pain model on healthy participants, this study investigated how ongoing first-hand pain influences empathic reactions to vicarious pain stimuli. Healthy participants were randomly treated with topical capsaicin cream (capsaicin group) or hand cream (control group) on the left forearm. Video clips showing limbs in painful and non-painful situations were used to induce empathic responses. The capsaicin group showed greater empathic neural responses in the right primary somatosensory cortex (S1) than the control group but smaller responses in the left anterior insula (AI) accompanied with smaller empathic pain-intensity ratings. Notably, the intensity of ongoing pain negatively correlated with empathy-related neural responses in the left AI. Inter-subject phase synchronization analysis was used to assess stimulus-dependent dynamic functional connectivity within or between brain regions engaged in pain empathy. The capsaicin group showed greater empathy-related neural synchronization within S1 and between S1 and AI, but less synchronization within AI and between AI and MCC. Behaviorally, the differential inter-subject pain-intensity rating alignment between painful and non-painful videos was more positive for the capsaicin group than for the control group, and this effect was partially mediated by the inter-subject neural synchronization between S1 and AI. These results suggest that ongoing first-hand pain facilitates neural activation and synchronization within brain regions associated with empathy-related somatosensory resonance at the cost of inhibiting activation and synchronization within brain regions engaged in empathy-related affective sharing.

Background: Amotivation is a typical feature in major depressive disorders and refers to individuals exhibiting reduced willingness to exert effort for rewards. However, the motivation pattern when deciding whether to exert effort for self versus others in people with depression remains unclear. Methods: We conducted a functional magnetic resonance imaging study and employed an adapted Effort‐Expenditure for Rewards Task in subthreshold depressive (SD) participants (n = 33) and healthy controls (HC) (n = 32). This required participants to choose between a fixed low‐effort/low‐reward and a variable high‐effort/high‐reward option, and then immediately exert effort to obtain corresponding rewards for themselves or for unfamiliar people. Results: Compared with the HC group, the SD group showed blunted activity in the left dorsal anterior cingulate cortex/dorsomedial prefrontal cortex, bilateral anterior insula (AI), and right putamen‐left dorsolateral prefrontal cortex functional connectivity when choosing to exert effort for themselves. Additionally, the SD group exhibited increased willingness and greater activation in the bilateral AI when choosing to exert effort for others. Furthermore, these brain activations and functional connectivity were positively related to self‐reported motivation. Conclusions: These findings show altered motivation during effort‐based decision‐making in individuals with the mild depressive state, particularly with higher motivation for others. Thus, this suggests that motivational behaviors and prefrontal–striatal circuitry are altered in individuals with SD, which can be utilized to discover treatment targets and develop strategies to address mental illness caused by motivation disorders. [ABSTRACT FROM AUTHOR]

Background: Rates of alcohol use disorders in individuals with bipolar disorder are 3 to 5 times greater than in the general population and exceed rates of alcohol use disorders reported in other affective and anxiety disorders. Despite this high rate of comorbidity, our understanding of the psychosocial and neural mechanisms that underlie the initiation of alcohol misuse in young adults with bipolar disorder remains limited. Prior work suggests that individuals with bipolar disorder may misuse alcohol as a coping mechanism, yet the neural correlates of coping drinking motives and associated alcohol use have not been previously investigated in this population. Methods: Forty‐eight young adults (22 bipolar disorder type I, 26 typically developing; 71% women; average age ± standard deviation = 22 ± 2 years) completed the Drinking Motives and Daily Drinking Questionnaires, and a Continuous Performance Functional magnetic resonance imaging (fMRI) Task with Emotional and Neutral Distracters. We calculated the relative difference in anterior cingulate cortex (ACC) functional coupling with the anterior insula and amygdala in response to emotional distracters compared with neutral stimuli and investigated the relations with coping drinking motives and alcohol use. Results: Across all participants, coping drinking motives were associated with greater quantity of recent alcohol use. In individuals with bipolar disorder, greater ACC‐anterior insula functional coupling was associated with greater coping drinking motives, and greater quantity and frequency of recent alcohol use. The relative difference in ACC‐anterior insula functional coupling was not associated with coping drinking motives or alcohol use in the typically developing group. Greater ACC‐anterior insula functional coupling in individuals with bipolar disorder was also associated with greater anxiety symptoms and recent perceived psychological stress. Exploratory analyses suggest that the relations between ACC‐anterior insula functional coupling and coping drinking motives may be confounded by anticonvulsant use. Conclusion: Results suggest that a difference in ACC‐anterior insula functional coupling during emotion processing may underlie alcohol use as a maladaptive coping mechanism in young adults with bipolar disorder. [ABSTRACT FROM AUTHOR]

Background: Differentiating between bipolar disorder (BD) and major depressive disorder (MDD) during the depressive episode is an important clinical challenge. Reward system abnormalities have received much attention as one of the biological underpinnings of BD and MDD, but few studies have directly compared these abnormalities in remitted and depressed states. Methods: This was a functional MRI study using the Monetary Incentive Delay task in 65 patients (BD [n = 33], MDD [n = 32]) and 33 healthy controls (HC). Regions of interest (ROI) analysis with 21 ROIs related to reward anticipation and 17 ROIs related to gain outcome were implemented, as well as whole‐brain analysis. The difference in the dimensional effect of depression on brain activation was also examined. Results: Relative to the HC group, BD patients showed significantly decreased activation during reward anticipation in the anterior cingulate cortex, anterior insula (AI), and putamen, and MDD patients showed significantly decreased activation in the AI and brainstem. The dimensional effect of depression severity showed a trend‐level difference between BD and MDD in the right brainstem and left AI. Conclusions: The current study showed a possible differential effect of depression on the reward system between MDD and BD. Further studies on reward systems might offer reliable markers to distinguish between MDD and BD patients in the depressive phase. [ABSTRACT FROM AUTHOR]

ObjectiveIn the current study we investigated neurodevelopmental changes in response to social and non-social reinforcement.MethodsFifty-three healthy participants including 16 early adolescents (age, 10-15 years), 16 late adolescents (age, 15-18 years), and 21 young adults (age, 21-25 years) completed a social/non-social reward learning task while undergoing functional magnetic resonance imaging. Participants responded to fractal image stimuli and received social or non-social reward/non-rewards according to their accuracy. ANOVAs were conducted on both the blood oxygen level dependent response data and the product of a context-dependent psychophysiological interaction (gPPI) analysis involving ventromedial prefrontal cortex (vmPFC) and bilateral insula cortices as seed regions.ResultsEarly adolescents showed significantly increased activation in the amygdala and anterior insula cortex in response to non-social monetary rewards relative to both social reward/non-reward and monetary non-rewards compared to late adolescents and young adults. In addition, early adolescents showed significantly more positive connectivity between the vmPFC/bilateral insula cortices seeds and other regions implicated in reinforcement processing (the amygdala, posterior cingulate cortex, insula cortex, and lentiform nucleus) in response to non-reward and especially social non-reward, compared to late adolescents and young adults.ConclusionIt appears that early adolescence may be marked by: (i) a selective increase in responsiveness to non-social, relative to social, rewards; and (ii) enhanced, integrated functioning of reinforcement circuitry for non-reward, and in particular, with respect to posterior cingulate and insula cortices, for social non-reward.

ObjectivePrioritizing self-transcendent values such as family and friends more than nontranscendent values such as wealth and privilege is associated with lower stress response. In this study, we tested whether having self-transcendent values can reduce specific responses in the brain in the context of potentially threatening health communications.MethodsSedentary adults (N = 67) who would likely feel threatened by health messages that highlight the risk of sedentary behavior were recruited. Participants indicated the degree to which they prioritize self-transcendent values more than nontranscendent values. Using functional magnetic resonance imaging, participants' neural responses to health messages were assessed within neural regions implicated in threat responses, including bilateral amygdala and anterior insula (AI).ResultsA tendency to prioritize self-transcendent more than nontranscendent values was associated with lower reactivity during exposure to health messages within anatomically defined regions of left amygdala (t(55) = -2.66, p = .010, 95% confidence interval [CI] = -0.08 to -0.01), right amygdala (t(55) = -2.22, p = .031, 95% CI = -0.06 to 0.0), and left AI (t(55) = -2.17, p = .034, 95% CI = -0.04 to 0.0), as well as a mask functionally defined to be associated with "threat" using an automated meta-analysis (t(55) = -2.04, p = .046, 95% CI = -0.05 to 0.0). No significant effect was obtained within the right AI (t(55) = -1.38, p = .17, 95% CI = -0.04 to .01). These effects were partially enhanced by reinforcing important values through self-affirmation, remained significant after accounting for self-reported social connection, and were specific to health message processing (versus generic self-related information).ConclusionsAttenuated neural reactivity to potentially threatening health messages may be a novel way that prioritizing self-transcendent values could lead to positive health behaviors.

Development of self-regulatory competencies during adolescence is partially dependent on normative brain maturation. Here, we report that adolescent rats as compared to adults exhibit impulsive and compulsive-like behavioral traits, the latter being associated with lower expression of mRNA levels of the immediate early gene zif268 in the anterior insula cortex (AIC). This suggests that underdeveloped AIC function in adolescent rats could contribute to an immature pattern of interoceptive cue integration in decision making and a compulsive phenotype. In support of this, we report that layer 5 pyramidal neurons in the adolescent rat AIC are hypoexcitable and receive fewer glutamatergic synaptic inputs compared to adults. Chemogenetic activation of the AIC attenuated compulsive traits in adolescent rats supporting the idea that in early stages of AIC maturity there exists a suboptimal integration of sensory and cognitive information that contributes to inflexible behaviors in specific conditions of reward availability. [ABSTRACT FROM AUTHOR]

Abstract: Despite diffuse tenderness, patients with fibromyalgia (FM) have reported a wide range of areas with musculoskeletal pain. This study investigated the neural structures and neuroanatomical networks associated with self-reported widespread pain in FM using magnetic resonance imaging. We collected clinical profiles and brain magnetic resonance imaging data of newly diagnosed patients with FM. A total of 138 patients with FM were divided into 3 subgroups based on the number of pain areas, with 3 to 8, 9 to 12, and 13 to 19 areas, respectively. Using voxel-based morphometry analysis, we first identified the neural structure that showed a trend of volumetric change across the 3 subgroups. We then used it as a candidate seed of interest with a seed-to-voxel analytical approach to explore the structural covariance (SC) networks of the whole brain. Finally, we studied the trend of changes in the distribution and strength of SC networks across subgroups of patients. We found a decreasing trend in the volumes of the right anterior insular cortex (rAIC) across the 3 subgroups that had an increased number of pain areas. An increasing trend in the number of neural substrates over the subcortical regions, especially the basal ganglion, showed SC to the rAIC, and a decreasing trend of SC strength was shown between the rAIC and the precuneus, frontal cortex, anterior and posterior cingulate, and lingual gyri, across the patient subgroups with increased pain areas. The rAIC and its altered connection with specific brain regions indicates widespread pain in patients with FM. [ABSTRACT FROM AUTHOR]

Believing as a fundamental mental process influences other cognitive/affective processes and behavior. However, it is unclear whether believing engages distinct neurocognitive mechanisms in people with different cultural experiences. We addressed this issue by scanning Chinese and Danish adults using functional MRI during believing judgments on personality traits of oneself and a celebrity. Drift diffusion model analyses of behavioral performances revealed that speed/quality of information acquisition varied between believing judgments on positive and negative personality traits in Chinese but not in Danes. Chinese adopted a more conservative strategy of decision-making during celebrity- than self-believing judgments whereas an opposite pattern was observed in Danes. Non-decisional processes were longer for celebrity- than for self-believing in Danes but not in Chinese. Believing judgments activated the medial prefrontal cortex (mPFC) in both cultural groups but elicited stronger left anterior insular and ventral frontal activations in Chinese. Greater mPFC activity in Chinese was associated with longer duration of non-decision processes during believing-judgments, which predicted slower retrieval of self-related information in a memory test. Greater mPFC activity in Danes, however, was associated with a less degree of adopting a conservative strategy during believing judgments, which predicted faster retrieval of self-related information. Our findings highlight different neurocognitive processes engaged in believing between individuals from East Asian and Western cultures.

• Anterior insula (AI) may be related to the trait-like degree of sleep reactivity. • AI activation levels in response to sleep-related stimuli were estimated. • AI activation had moderating effects on the relationship between stress and insomnia. • Right AI activation had moderating effects on the association between insomnia and depression. This study investigated the effects of anterior insula (AI) activation on the association between stress and sleep disturbance as a neurobiological basis of the trait-like degree of sleep reactivity to stress. Additionally, it examined the effects of AI activity on the association between sleep disturbance and depression. The participants were 48 adults. To assess AI activation in response to sleep-related stimuli (SS) compared to neutral stimuli (NS), we extracted mean AI parameter estimates for the SS–NS contrast. We examined whether the interaction between life stress and AI activation would predict sleep disturbance and whether the interaction between sleep disturbance and AI activation would predict depression. At higher levels of bilateral AI activation in response to SS, higher levels of stress were associated with greater sleep disturbance (left AI x stress: b = 1.07, SE = 0.44, p < 0.05; right AI x stress: b = 1.05, SE = 0.48, p < 0.05). In addition, at higher levels of right AI activation, higher levels of sleep disturbance were associated with more severe depressive symptoms (right AI x sleep disturbance: b = 2.55, SE = 1.10, p < 0.05). This study assessed sleep quality and depressive symptoms based on self-reported questionnaires. This study revealed moderating effects of AI activation on the association between negative life stress and sleep disturbance. Additionally, AI activation strengthened the association between sleep disturbance and depression. AI activation may reflect a crucial etiological diathesis for insomnia and stress-related disorders. [ABSTRACT FROM AUTHOR]