Activity In Anterior Insula Research Articles

Pain Catastrophizing and Functional Activation During Occlusion in TMD Patients-An Interventional Study.

In temporomandibular disorder (TMD), the effects of standard interventions such as using an occlusal splint and its impact on pain relief and pain catastrophizing are poorly understood. Earlier work pointed to a crucial role of insula activation with changes in pain relief by occlusal splint treatment. We performed a functional imaging study using specially developed splint systems to allow for a placebo-controlled longitudinal design. Using functional MRI we examined 20 TMD patients during repetitive occlusal movements at baseline and over the course of splint therapy and also collected self-reported pain catastrophizing. For balancing performance between baseline and after intervention we used occlusion force measures in an individualized fMRI-splint system. Splint therapy lasted for approximately 7 weeks with one group selected by randomization wearing a palatine placebo splint over the first 3 weeks (delayed start; 11 individuals). As expected, fMRI activation in areas involved in pain processing (insula, primary and secondary somatosensory cortex) decreased with intervention. At baseline a positive correlation between activation of the left anterior insula and pain catastrophizing was present. Both parameters decreased over intervention while associations were primarily observable for patients with rather mild TMD.

Effects of intranasal oxytocin on fear extinction learning.

Once a threat no longer exists, extinction of conditioned fear becomes adaptive in order to reduce allotted resources towards cues that no longer predict the threat. In anxiety and stress disorders, fear extinction learning may be affected. Animal findings suggest that the administration of oxytocin (OT) modulates extinction learning in a timepoint-dependent manner, facilitating extinction when administered prior to fear conditioning, but impairing it when administered prior to extinction learning. The aim of the present study was to examine if these findings translate into human research. Using a randomized, double-blind, placebo-controlled, 2-day fear conditioning and extinction learning design, behavioral (self-reported anxiety), physiological (skin conductance response), neuronal (task-based and resting-state functional magnetic resonance imaging), and hormonal (cortisol) data were collected from 124 naturally cycling (taking no hormonal contraceptives) healthy females. When administered prior to conditioning (Day 1), OT, similar to rodent findings, did not affect fear conditioning, but modulated the intrinsic functional connectivity of the anterior insula immediately after fear conditioning. In contrast to animal findings, OT impaired, not facilitated, extinction learning on the next day and increased anterior insula activity. When administered prior to extinction learning (day 2), OT increased the activity in the bilateral middle temporal gyrus, and similar to animal findings, reduced extinction learning. The current findings suggest that intranasal OT impedes fear extinction learning in humans regardless of the timepoint of administration, providing new insights and directions for future translational research and clinical applications.

Neural processing of audiovisual and painful analogue trauma and its relationship with subsequent audiovisual and pain intrusions

ABSTRACT Background: Posttraumatic stress disorder and medically unexplained pain frequently co-occur. While pain is common during traumatic events, the processing of pain during trauma and its relation to audiovisual and pain intrusions is poorly understood. Objective: Here we investigate neural activations during painful analogue trauma, focusing on areas that have been related to threat and pain processing, and how they predict intrusion formation. We also examine the moderating role of cumulative lifetime adversity. Methods: Sixty-five healthy women were assessed using functional magnetic resonance imaging. An analogue trauma was induced by an adaptation of the trauma-film paradigm extended by painful electrical stimulation in a 2 (film: aversive, neutral) x 2 (pain: pain, no-pain) design, followed by 7-day audiovisual and pain intrusion assessment using event-based ecological momentary assessment. Intrusions were fitted with Bayesian multilevel regression and a hurdle lognormal distribution. Results: Conjunction analysis confirmed a wide network including anterior insula (AI) and dorsal anterior cingulate cortex (dACC) being active both, during aversive films and pain. Pain resulted in activation in areas amongst posterior insula and deactivation in a network around ventromedial prefrontal cortex (VMPFC). Higher AI and dACC activity during aversive>neutral film predicted greater audiovisual intrusion probability over time and predicted greater audiovisual intrusion frequency particularly for participants with high lifetime adversity. Lower AI, dACC, hippocampus, and VMPFC activity during pain>no-pain predicted greater pain intrusion probability particularly for participants with high lifetime adversity. Weak regulatory VMPFC activation was associated with both increased audiovisual and pain intrusion frequency. Conclusions: Enhanced AI and dACC processing during aversive films, poor pain vs. no-pain discrimination in AI and dACC, as well as weak regulatory VMPFC processing may be driving factors for intrusion formation, particularly in combination with high lifetime adversity. Results shed light on a potential path for the etiology of PTSD and medically unexplained pain.

Neural correlates of proactive avoidance deficits and alcohol use motives in problem drinking

Physical pain and negative emotions represent two distinct drinking motives that contribute to harmful alcohol use. Proactive avoidance, in contrast, can reduce consumption in response to these motives but appears to be impaired in those with problem drinking. Despite such evidence, proactive avoidance and its underlying neural deficits have not been assessed experimentally. How these deficits inter-relate with drinking motives to influence alcohol use also remains unclear. The current study leveraged neuroimaging data in forty-one problem and forty-one social drinkers who performed a probabilistic learning go/nogo task featuring proactive avoidance of painful outcomes. We identified the brain responses to proactive avoidance and contrasted the neural correlates of drinking to avoid negative emotions vs. physical pain. Behavioral results confirmed proactive avoidance deficits in problem drinking individuals’ learning rate and performance accuracy, both which were associated with greater alcohol use. Imaging findings in the problem drinking group showed that negative emotions as a drinking motive predicted attenuated right anterior insula activation during proactive avoidance. In contrast, physical pain motive predicted reduced right putamen response. These regions’ activations as well as functional connectivity with the somatomotor cortex also demonstrated a negative relationship with drinking severity and positive relationship with proactive avoidance performance. Path modeling further delineated the pathways through which physical pain and negative emotions influenced the neural and behavioral measures of proactive avoidance. Taken together, the current findings provide experimental evidence for proactive avoidance deficits in alcohol misuse and establish the link between their neural underpinnings and drinking behavior.

Loss, gain and choice difficulty in gambling patients: Neural and behavioural processes.

Impaired decision-making is often displayed by individuals suffering from gambling disorder (GD). Since there are a variety of different phenomena influencing decision-making, we focused in this study on the effects of GD on neural and behavioural processes related to loss aversion and choice difficulty. Behavioural responses as well as brain images of 23 patients with GD and 20 controls were recorded while they completed a mixed gambles task, where they had to decide to either accept or reject gambles with different amounts of potential gain and loss. We found no behavioural loss aversion in either group and no group differences regarding loss and gain-related choice behaviour, but there was a weaker relation between choice difficulty and decision time in patients with GD. Similarly, we observed no group differences in processing of losses or gains, but choice difficulty was weaker associated with brain activity in the right anterior insula and anterior cingulate cortex in patients with GD. Our results showed for the first time the effects of GD on neural processes related to choice difficulty. In addition, our findings on choice difficulty give new insights on the psychopathology of GD and on neural processes related to impaired decision-making in GD.

Exploring the impact of immersive virtual reality on depression knowledge and stigma reduction: a cross-over RCT fMRI study

The stigma of mental illness is a form of negative judgmental knowledge and is a barrier to individual seeking treatment. Contact-based educational interventions with first-person perspective (1PP) combined with immersive virtual reality (IVR) is promising as an anti-stigma intervention. This study aims to investigate the effectiveness of 1PP anti-stigma IVR intervention compared to video in enhancing depression knowledge and reducing stigma, as well as to examine the corresponding depression knowledge brain activity change using functional magnetic resonance imaging (fMRI). Participants engaged in a 1PP anti-stigma intervention using both IVR and conventional video, focusing on the daily life and recovery of a patient with mild depression. The change in depression knowledge, stigma-related behavioral, and brain activity using fMRI were measured at pre- and post-interventions. Depression knowledge improved for both interventions; however, only the IVR intervention reduced stigma. In the IVR intervention, depression knowledge score was positively associated with neural response in the right superior frontal gyrus activation, indicative of empathic concern. Conversely, the video intervention correlated with increased activity in the right anterior insula, suggesting a distress-related response. The findings demonstrate that the immersive nature of IVR can reduce stigma more effectively than video intervention. This effectiveness is underpinned by the change in depression knowledge on neural activity, with IVR fostering empathy-related behavioral responses. The results highlight the potential of IVR in enhancing empathic understanding and reducing stigma towards mental illness, emphasizing the need for further exploration into immersive technologies for mental health education.

Neuronal correlates of intensification and acceptance of symptoms during exposure therapy in patients with obsessive-compulsive disorder.

Cognitive behaviour therapy with exposure and response prevention is efficient in treating patients with obsessive-compulsive disorder (OCD). Nevertheless, it would be helpful for many patients to complement the therapeutic treatment with acceptance strategies to further increase the therapeutic benefit. The aim of the present study was to examine neurobiological responses to acceptance and intensification strategies during symptom provocation alongside the psychotherapeutic process. A total of 23 patients diagnosed with OCD (subtype: washing/contamination fear) was instructed to utilise either an acceptance strategy (ACS) or an intensification strategy (INS) to cope with their emotional and cognitive reactions to personalised symptom-triggering and neutral pictures. Fourteen patients participated twice: at the beginning [T1] and at the end [T2] of an inpatient multimodal treatment including cognitive behaviour therapy with response prevention to assess functional variations. For the contrast of T1 and T2, ACS showed increased brain activity in the left inferior frontal gyrus (IFG), left caudate body, and posterior cingulate gyrus (PCC). They also showed decreased activity in the left anterior insula. INS showed decreased activation in right lingual gyrus and right caudate body. At T2, ACS showed increased activation compared to INS in the left cerebrum: IFG, caudate nucleus, middle and superior temporal gyrus, and PCC/cuneus. For the comparison of T1 and T2, the ACS revealed increased brain activity in the left IFG, left caudate body, and right inferior parietal lobe. It showed decreased activity in the left anterior insula. The INS revealed decreased activity in right lingual gyrus and right caudate body.The psychometric questionnaires suggested that patients were able to reduce obsession, compulsion, and depression symptoms. Furthermore, patients rated the ACS as more useful for themselves compared with the INS. The increased left IFG activity using ACS (T1 vs. T2) could be interpreted as a better inhibitory top-down process, while the increased PCC response might be due to a better reappraisal strategy after therapy. ACS seems to mobilise neuronal activations under therapy, especially in the left hemisphere. Both strategies showed reductions in emotional networks as a neuronal correlate of therapy success. Overall, ACS may be more efficient than INS, as rated by the patients and as in accordance with neurobiological findings.

Neural Mechanisms Underlying the Impact of Psychological Resilience on Psychosocial Stress Responses

Background: High psychological resilience (HR) could protect individuals from psychosocial stress and thereby make individuals less vulnerable to depression and anxiety; however, the underlying neural mechanism remains to be investigated.Methods: The Montreal Imaging Stress Task (MIST) was administered to participants of 59 healthy individuals with HR and 56 individuals with low psychological resilience (LR) during functional magnetic resonance imaging (fMRI) scanning. Cortisol concentrations and subjective stress levels were collected across the MIST. Repeated measures analyses of variance were conducted to measure the group differences in subjective and cortisol stress responses. Two‐sample t‐tests were conducted to detect the group differences in stress‐related brain activation and functional connectivity (FC).Results: The LR group exhibited an increase in cortisol concentration after the MIST, whereas the HR group exhibited a decrease in cortisol concentration after the MIST. The LR group exhibited higher activation in the left anterior insula and lower FC between the left orbitofrontal cortex (OFC) and the right temporal pole (TP) (all pFWE < 0.05). Mediation analyses revealed that the left anterior insula mediates the relationship between psychological resilience and depression and the left OFC–right TP FC mediates the relationship between psychological resilience and anxiety.Conclusions: Findings highlight that the anterior insula and OFC–TP FC could be the critical neural mechanism underlying the interaction between psychological resilience and psychosocial stress. Moreover, higher anterior insula activation and lower OFC–TP FC could be the crucial neural mechanism of individuals with low psychological resilience developing into depression/anxiety when experiencing daily psychosocial stressors.

Heart rate and insula activity increase in response to music in individuals with high interoceptive sensitivity.

Interoception plays an important role in emotion processing. However, the neurobiological substrates of the relationship between visceral responses and emotional experiences remain unclear. In the present study, we measured interoceptive sensitivity using the heartbeat discrimination task and investigated the effects of individual differences in interoceptive sensitivity on changes in pulse rate and insula activity in response to subjective emotional intensity. We found a positive correlation between heart rate and valence level when listening to music only in the high interoceptive sensitivity group. The valence level was also positively correlated with music-elicited anterior insula activity. Furthermore, a region of interest analysis of insula subregions revealed significant activity in the left dorsal dysgranular insula for individuals with high interoceptive sensitivity relative to individuals with low interoceptive sensitivity while listening to the high-valence music pieces. Our results suggest that individuals with high interoceptive sensitivity use their physiological responses to assess their emotional level when listening to music. In addition, insula activity may reflect the use of interoceptive signals to estimate emotions.

The impact of past childhood adversity and recent life events on neural responses during fear conditioning.

Many studies have shown that exposure to life events can have a negative impact on mental health. Life events like the death of a spouse or the birth of a child pose a challenge and require temporal or permanent adjustments. Meta-analyses on brain stress responses found bilateral anterior insula activation in response to acute stress. Fear conditioning is assumed a crucial mechanism for the development of anxiety disorders associated with increased activation in the bilateral amygdala. Empirical evidence is lacking regarding the relationship of exposure to recent life events and past childhood adversity with neural processing during fear conditioning. In the present study, we analyzed data from 103 young, healthy participants. Multiple linear regressions were performed on functional magnetic resonance imaging activation during fear conditioning with the Life Events Scale for Students and the Childhood Trauma questionnaire included as covariates in two separate models. We found a positive relationship between the number of life events in the last year and left amygdala activation to the conditioned stimulus. A second finding was a positive relationship between childhood adversity and right anterior insula response to the unconditioned stimulus. Many studies have shown increased amygdala activity after stressful life events. In addition, the anterior insula is activated during acute stress. The present study points to stressor-induced increased salience processing during fear conditioning. We suggest that this could be a potential mechanism for resilience versus mental illness.

“Listen to your heart”: A novel interoceptive strategy for real-time fMRI neurofeedback training of anterior insula activity

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.

Ketamine’s acute effects on negative brain states are mediated through distinct altered states of consciousness in humans

Ketamine commonly and rapidly induces dissociative and other altered states of consciousness (ASCs) in humans. However, the neural mechanisms that contribute to these experiences remain unknown. We used functional neuroimaging to engage key regions of the brain’s affective circuits during acute ketamine-induced ASCs within a randomized, multi-modal, placebo-controlled design examining placebo, 0.05 mg/kg ketamine, and 0.5 mg/kg ketamine in nonclinical adult participants (NCT03475277). Licensed clinicians monitored infusions for safety. Linear mixed effects models, analysis of variance, t-tests, and mediation models were used for statistical analyses. Our design enabled us to test our pre-specified primary and secondary endpoints, which were met: effects of ketamine across dose conditions on (1) emotional task-evoked brain activity, and (2) sub-components of dissociation and other ASCs. With this design, we also could disentangle which ketamine-induced affective brain states are dependent upon specific aspects of ASCs. Differently valenced ketamine-induced ASCs mediated opposing effects on right anterior insula activity. Participants experiencing relatively higher depersonalization induced by 0.5 mg/kg of ketamine showed relief from negative brain states (reduced task-evoked right anterior insula activity, 0.39 SD). In contrast, participants experiencing dissociative amnesia showed an exacerbation of insula activity (0.32 SD). These results in nonclinical participants may shed light on the mechanisms by which specific dissociative states predict response to ketamine in depressed individuals.

On difference between direct-response method and strategy method in decision-making: behavioural and neural evidence in a reward-punishment game

Decision-makers may follow either the direct-response method or strategy method. While the two elicitation methods are theoretically equivalent, it is uncertain whether they lead to the same outcomes in practice. To explore this issue, we conduct an experiment based on a reward-punishment game under both methods, in which functional magnetic resonance imaging (fMRI) is used to provide neural evidence for uncovering the underlying behavioural mechanisms. The results show that both the reward and punishment rates are significantly higher under the strategy method compared to the direct-response method. We develop behavioural models to explain these differences and identify the ownership effect, strategic thinking, and counterfactual thinking as potential drivers. Comparison of neural activity between the two treatments demonstrates that during reward/no-reward decisions, the direct-response treatment accrues stronger activation in the bilateral anterior insula, indicating that decision-makers overweigh reward cost due to ownership effect, which consequently leads to reduced willingness to impose rewards. Conversely, during punishment/no-punishment decisions, the strategy treatment causes stronger activations in the bilateral anterior insula and inferior parietal lobule, implying that decision-makers perceive strong unfairness due to counterfactual thinking, which further results in more punishment decisions. Moreover, our findings reveal that strategic thinking influences decision-making during long-term interactions.

Stress-Induced Sensitization of Insula Activation Predicts Alcohol Craving and Alcohol Use in Alcohol Use Disorder

BackgroundStress and alcohol cues trigger alcohol consumption and relapse in alcohol use disorder. However, the neurobiological processes underlying their interaction are not well understood. Thus, we conducted a randomized, controlled neuroimaging study to investigate the effects of psychosocial stress on neural cue reactivity and addictive behaviors. MethodsNeural alcohol cue reactivity was assessed in 91 individuals with alcohol use disorder using a validated functional magnetic resonance imaging (fMRI) task. Activation patterns were measured twice, at baseline and during a second fMRI session, prior to which participants were assigned to psychosocial stress (experimental condition) or a matched control condition or physical exercise (control conditions). Together with fMRI data, alcohol craving and cortisol levels were assessed, and alcohol use data were collected during a 12-month follow-up. Analyses tested the effects of psychosocial stress on neural cue reactivity and associations with cortisol levels, craving, and alcohol use. ResultsCompared with both control conditions, psychosocial stress elicited higher alcohol cue–induced activation in the left anterior insula (familywise error–corrected p < .05) and a stress- and cue-specific dynamic increase in insula activation over time (F22,968 = 2.143, p = .007), which was predicted by higher cortisol levels during the experimental intervention (r = 0.310, false discovery rate–corrected p = .016). Cue-induced insula activation was positively correlated with alcohol craving during fMRI (r = 0.262, false discovery rate–corrected p = .032) and alcohol use during follow-up (r = 0.218, false discovery rate–corrected p = .046). ConclusionsResults indicate a stress-induced sensitization of cue-induced activation in the left insula as a neurobiological correlate of the effects of psychosocial stress on alcohol craving and alcohol use in alcohol use disorder, which likely reflects changes in salience attribution and goal-directed behavior.

Healthcare experience affects pain-specific responses to others' suffering in the anterior insula.

Medical students and professional healthcare providers often underestimate patients' pain, together with decreased neural responses to pain information in the anterior insula (AI), a brain region implicated in self-pain processing and negative affect. However, the functional significance and specificity of these neural changes remains debated. Across two experiments, we recruited university medical students and emergency nurses to test the role of healthcare experience on the brain reactivity to other's pain, emotions, and beliefs, using both pictorial and verbal cues. Brain responses to self-pain was also assessed and compared with those to observed pain. Our results confirmed that healthcare experience decreased the activity in AI in response to others' suffering. This effect was independent from stimulus modality (pictures or texts), but specific for pain, as it did not generalize to inferences about other mental or affective states. Furthermore, representational similarity and multivariate pattern analysis revealed that healthcare experience impacted specifically a component of the neural representation of others' pain that is shared with that of first-hand nociception, and related more to AI than to other pain-responsive regions. Taken together, our study suggests a decreased propensity to appraise others' suffering as one's own, associated with a reduced recruitment of pain-specific information in AI. These findings provide new insights into neural mechanisms leading to pain underestimation by caregivers in clinical settings.

Blunted Neurobehavioral Loss Anticipation Predicts Relapse to Stimulant Drug Use

BackgroundPatients with stimulant use disorder experience high rates of relapse. While neurobehavioral mechanisms involved in initiating drug use have been studied extensively, less research has focused on relapse. MethodsTo assess motivational processes involved in relapse and diagnosis, we acquired functional magnetic resonance imaging responses to nondrug (monetary) gains and losses in detoxified patients with stimulant use disorder (n = 68) and community control participants (n = 42). In a prospective multimodal design, we combined imaging of brain function, brain structure, and behavior to longitudinally track subsequent risk for relapse. ResultsAt the 6-month follow-up assessment, 27 patients remained abstinent, but 33 had relapsed. Patients with blunted anterior insula (AIns) activity during loss anticipation were more likely to relapse, an association that remained robust after controlling for potential confounds (i.e., craving, negative mood, years of use, age, and gender). Lower AIns activity during loss anticipation was associated with lower self-reported negative arousal to loss cues and slower behavioral responses to avoid losses, which also independently predicted relapse. Furthermore, AIns activity during loss anticipation was associated with the structural coherence of a tract connecting the AIns and the nucleus accumbens, as was functional connectivity between the AIns and nucleus accumbens during loss processing. However, these neurobehavioral responses did not differ between patients and control participants. ConclusionsTaken together, the results of the current study show that neurobehavioral markers predicted relapse above and beyond conventional self-report measures, with a cross-validated accuracy of 72.7%. These findings offer convergent multimodal evidence that implicates blunted avoidance motivation in relapse to stimulant use and may therefore guide interventions targeting individuals who are most vulnerable to relapse.

Stress and reward in the maternal brain of mothers with borderline personality disorder: a script-based fMRI study

Borderline personality disorder (BPD) is associated with altered neural activity in regions of salience and emotion regulation. An exaggerated sensitization to emotionally salient situations, increased experience of emotions, and dysfunctional regulative abilities could be reasons for increased distress also during parenting. Mothers with BPD tend to have less reciprocal mother–child interactions (MCI) and reveal altered cortisol and oxytocin reactivity in the interaction with their child, which could indicate altered processing of stress and reward. Here, we studied underlying neural mechanisms of disrupted MCI in BPD. Twenty-five mothers with BPD and 28 healthy mothers participated in a script-driven imagery functional magnetic resonance imaging (fMRI)-paradigm. Scripts described stressful or rewarding MCI with the own child, or situations in which the mother was alone. Mothers with BPD showed larger activities in the bilateral insula and anterior cingulate cortex (ACC) compared to healthy mothers during the imagination of MCI and non-MCI. Already in the precursory phase while listening to the scripts, a similar pattern emerged with stronger activity in the left anterior insula (AINS), but not in the ACC. This AINS activity correlated negatively with the quality of real-life MCI for mothers with BPD. Mothers with BPD reported lower affect and higher arousal. An exaggerated sensitization to different, emotionally salient situations together with dysfunctional emotion regulation abilities, as reflected by increased insula and ACC activity, might hinder sensitive maternal behavior in mothers with BPD. These results underline the importance for psychotherapeutic interventions to improve emotional hyperarousal and emotion regulation in patients with BPD, especially in affected mothers caring for young children.

Neural activation to peer acceptance and rejection in relation to concurrent and prospective depression risk in adolescent and pre-adolescent girls

Neurobiological sensitivity to peer interactions is a proposed marker of risk for adolescent depression. We investigated neural response to peer rejection and acceptance in relation to concurrent and prospective depression risk in adolescent and pre-adolescent girls. Participants were 76 girls (Mage=13, 45% racial/ethnic minorities) varying in depression risk: 22 with current major depressive disorder (MDD), 30 at High Risk for MDD based on parental history, and 24 at Low Risk with no psychiatric history. Girls participated in the Chatroom-Interact task—involving rejection and acceptance feedback from fictitious peers—while undergoing functional magnetic resonance neuroimaging. Activation in response to peer rejection and acceptance was extracted from regions of interest. Depressive symptoms were assessed at 6- and 12-month follow-up. Girls with MDD showed blunted left subgenual anterior cingulate response to acceptance versus girls in High and Low Risk groups. Girls in the High Risk group showed greater right temporo-parietal junction (rTPJ) and right anterior insula (AI) activation to both acceptance and rejection versus girls in the MDD (rTPJ) and Low Risk (rTPJ, AI) groups. Greater rTPJ response to rejection was associated with fewer depressive symptoms at 12-months and mediated the association between High Risk group status and 12-month depressive symptoms; greater rTPJ response to acceptance mediated the association between High Risk and increased 12-month depressive symptoms. Our finding of associations between altered neural response to peer interactions and concurrent and prospective depression risk/resilience highlights the importance of neural underpinnings of social cognition as risk and compensatory adaptations along the pathway to depression.

Interoceptive Awareness of the Breath Preserves Attention and Language Networks amidst Widespread Cortical Deactivation: A Within-Participant Neuroimaging Study.

Interoception, the representation of the body's internal state, serves as a foundation for emotion, motivation, and wellbeing. Yet despite its centrality in human experience, the neural mechanisms of interoceptive attention are poorly understood. The Interoceptive/Exteroceptive Attention Task (IEAT) is a novel neuroimaging paradigm that compares behavioral tracking of the respiratory cycle (Active Interoception) to tracking of a visual stimulus (Active Exteroception). Twenty-two healthy participants completed the IEAT during two separate scanning sessions (N = 44) as part of a randomized control trial of Mindful Awareness in Body-oriented Therapy (MABT). Compared to Active Exteroception, Active Interoception deactivated somatomotor and prefrontal regions. Greater self-reported interoceptive sensibility (MAIA scale) predicted sparing from deactivation within the anterior cingulate cortex (ACC) and left-lateralized language regions. The right insula-typically described as a primary interoceptive cortex-was only specifically implicated by its deactivation during an exogenously paced respiration condition (Active Matching) relative to self-paced Active Interoception. Psychophysiological interaction (PPI) analysis characterized Active Interoception as promoting greater ACC connectivity with lateral prefrontal and parietal regions commonly referred to as the Dorsal Attention Network (DAN). In contrast to evidence relating accurate detection of liminal interoceptive signals such as the heartbeat to anterior insula activity, interoceptive attention towards salient signals such as the respiratory cycle may involve reduced cortical activity but greater ACC-DAN connectivity, with greater sensibility linked to reduced deactivation within the ACC and language-processing regions.Significance StatementInteroception, the representation of the body's internal state, is poorly understood compared to the external senses, with existing neuroimaging studies failing to match task difficulty between interoceptive and exteroceptive tasks. The present study used a novel fMRI task to compare interoceptive and exteroceptive attention and explore whether this distinction was moderated by self-reported interoceptive awareness. The results implicate three novel interoceptive mechanisms: interoceptive attention reduces widespread cortical activity while increasing prefrontal connectivity, wherein greater self-reported interoceptive awareness is linked to preserved activation of the anterior cingulate cortex and language regions. Rather than increasing activation of interoceptive cortex, interoceptive attention to the breath may involve attending to body representations typically ignored in favor of exteroceptive information and other forms of cognition.

0162 The neural bases of emotion dysregulation in rotating shift workers

Abstract Introduction Shift work is known to be associated with sleep disturbance and circadian misalignment and may contribute to alterations in the brain implicated in emotion dysregulation. In this study, we examined 1) neural correlates of emotion dysregulation, including emotional reactivity and regulation in shift workers and 2) relationships between neural correlates of emotion dysregulation, sleep disturbance, and circadian misalignment. Methods Fifty-six rotating shift workers (SW, 42 females, 30.80 ± 6.94 years old) who had non-standard shift schedules and 52 healthy controls (HC, 36 females, 31.69 ± 7.86 years old) who did not work as shift schedules participated in this study. Both SW and HC completed self-reported measures of sleep and mood problems, and wrote sleep diary and wore actigraphy to assess sleep quality and circadian rhythms. They also underwent one night polysomnography and were scanned while they were performing the emotion regulation task. We analyzed group differences in mood, sleep, circadian rhythms, and neural bases of emotional reactivity and regulation, and examined relationships between these variables. Results SW showed significant differences in actigraphy-estimated sleep (i.e., lower sleep efficiency) and circadian rhythms (e.g., greater motor activity [M10] and lower interdaily stability) compared to HC. SW also exhibited increased anterior insula (AI) activation in response to negative pictures, but reduced activation in the dorsomedial prefrontal cortex (dMPFC) and AI-dMPFC functional connectivity during emotion regulation compared to HC. AI activation and AI-dMPFC functional connectivity were significantly associated with sleep disturbance (i.e., sleep diary-estimated sleep onset latency) and circadian misalignment (e.g., M10 and interdaily stability). Furthermore, a mediation analysis revealed that shift work was associated with increased motor activity during the most active 10-hour period, which then contributed to increased AI activation in response to negative pictures. Conclusion Our findings suggest that shift work may contribute to sleep disturbance and circadian misalignment, and neural alterations associated with emotional reactivity and regulation. Furthermore, the mediation result suggests that increased motor activity along with misaligned circadian rhythm may serve as a pathway, through shift work contributes to heightened emotional reactivity to negative information. Support (if any) National Research Foundation (No. 2022R1A2C2008417, NRF-2022R1A2C1008209) and Korea Institute for Advancement of Technology (No. 20009210).