Amygdala Functional Connectivity Research Articles

Negative family and interpersonal relationship are associated with centromedial amygdala functional connectivity alterations in adolescent depression.

The amygdala, known for its functional heterogeneity, plays a critical role in the neural mechanism of adolescent major depressive disorder (aMDD). However, changes in its subregional functional networks in relation to stressful factors remain unclear. We recruited 78 comorbidity-free, medication-naive aMDD patients and 40 matched healthy controls (HC) to explore changes in resting-state functional connectivity (FC) across four amygdala subregions: the centromedial nucleus (CM), the basolateral nucleus (LB), the superficial nucleus (SF), and the amygdalostriatal transition area (Astr). Then, we performed partial correlation analysis to investigate the relationship between amygdala subregional FC and stressful factors as measured by the Chinese Version of Family Environment Scale (FES-CV) and the Adolescent Self-Rated Life Events Scale (ASLEC). Compared to HC, aMDD patients demonstrated significantly decreased functional connectivity between the left CM and left precentral gyrus, as well as between left SF and left precentral gyrus, and between left LB and posterior cingulate gyrus (PCC)/precuneus. In aMDD group, left CM-precentral gyrus FC exhibited negative correlation with interpersonal relationship and punishment, and positive correlation with family cohesion and expressiveness. This study reveals distinct patterns of abnormal functional connectivity among amygdala subregions in aMDD. Our findings suggest that the CM network, in particular, may be involved in stress-related factors in aMDD, which provide a potential target for the prevention and treatment of adolescent depression.

Amygdala functional connectivity in borderline personality disorder

Borderline personality disorder (BPD) is characterised by structural and functional brain alterations. Yet, there is little data on functional connectivity (FC) across different levels of brain networks and parameters. In this study, we applied a multi-level approach to analyse abnormal functional connectivity. We analysed resting-state functional magnetic resonance imaging (fMRI) data sets of 69 subjects: 17 female BPD patients and 51 age-matched psychiatrically healthy female controls. fMRI was analysed using CONN toolbox including: a) seed-based FC analysis of amygdala connectivity, b) independent component analysis (ICA) based network analysis of intra- and inter-network FC of selected resting-state networks (DMN, SN, FPN), as well as c) graph-theory based measures of network-level characteristics. We show group-level seed FC differences with higher amygdala to contralateral (superior) occipital cortex connectivity in BPD, which correlated with schema-therapy derived measures of symptoms/traits across the entire cohort. While there was no significant group effect on DMN, SN, or FPN intra-network or inter-network FC, we show a significant group difference for local efficiency and cluster coefficient for a DMN-linked cerebellum cluster. Our findings demonstrate BPD-linked changes in FC across multiple levels of observation, which supports a multi-level analysis for future studies to consider different aspects of functional connectome alterations.

Sex differences in alcohol's effects on fronto-amygdalar functional connectivity during processing of emotional stimuli.

Amygdala function underlying emotion processing has been shown to vary with an individuals' biological sex. Expanding upon functional magnetic resonance imaging (fMRI) findings reported previously where a low level of response was the focus, we examined alcohol and sex effects on functional connectivity between the amygdala and other brain regions. The central hypothesis predicted that sex would influence alcohol's effects on frontal-limbic functional circuits underlying the processing of negative and positive facial emotions. Secondary analyses were conducted on data from a double-blind, placebo controlled, within-subjects, cross-over study in 54 sex-matched pairs (N = 108) of 18- to 25-year-old individuals without an alcohol use disorder at baseline. Participants performed an emotional faces fMRI processing task after placebo or approximately 0.7 mL/kg of ethanol. Psychophysiological interaction analyses examined functional connectivity between the amygdala with other brain regions. There were significant alcohol-by-sex interactions when processing negatively valenced faces. Whereas intoxicated men exhibited decreased functional connectivity between the amygdala and ventral and dorsal anterior cingulate, angular gyrus, and middle frontal gyrus connectivity was increased in intoxicated women. There was also a main sex effect where women exhibited less functional connectivity in the middle insula than men regardless of whether they received alcohol or placebo. For happy faces, main effects of both sex and alcohol were observed. Women exhibited less amygdala functional connectivity in the right inferior frontal gyrus than men. Both men and women exhibited greater functional connectivity in the superior frontal gyrus in response to alcohol than placebo. Alcohol's effects on amygdala functional circuits that underlying emotional processing vary by sex. Women had higher functional connectivity than men following exposure to a moderate dose of alcohol which could indicate that women arebetter than men at processing affectively laden stimuli when intoxicated.

The effectiveness of using escitalopram in pediatric generalized anxiety disorder and the methods to predict the treatment response: A systematic review and meta-analysis

Background Generalized Anxiety Disorder (GAD) affects approximately 10–15% of children and adolescents. Selective Serotonin Reuptake Inhibitors (SSRIs) are among the main treatment options. Escitalopram, an SSRI for adult anxiety, is being studied for pediatric use. Predicting the treatment response could optimize interventions. This systematic review aimed to understand the safety and efficacy of escitalopram in the treatment of pediatric GAD and to determine potential treatment response indicators. Methods Searches for randomized controlled trials (RCTs) on escitalopram’s effectiveness in pediatric GAD were conducted across six databases. Two reviewers selected the trials, extracted data, and evaluated the trial quality independently. A third reviewer resolved the discrepancies. Outcomes were presented as mean differences (MDs) with 95% confidence intervals (CIs), while the Cochrane risk of bias tool was used to gauge evidence quality. Results Five RCTs including 401 patients were analyzed. Escitalopram showed a greater reduction in The Pediatric Anxiety Rating Scale PARS score than placebo (MD -6.1, 95% CI [-8.75 to -3.44] (P = 0.09, I2 = 65%)). Multiple methods have been used to predict escitalopram treatment responses, such as reaction time changes, executive functions, and Amygdala Functional Connectivity, including the CYP2C19 metabolizer phenotype. The data indicated that neuroimaging was the most effective predictor of the treatment response. Conclusion Escitalopram notably reduced PARS scores in pediatric patients with GAD. Neuroimaging, as a biomarker, is a valuable predictor of treatment response and provides insights into the neurological aspects of anxiety disorders, offering the potential for groundbreaking treatment advancements.

Basolateral Amygdala Functional Connectivity in Alexithymia: Linking Interoceptive Sensibility and Cognitive Empathy

Emotions rely on bodily states, and perceiving the emotions of others depends on awareness of one’s own emotional state. However, the intercorrelations among interoception, alexithymia, and empathy are not well understood, and the neural mechanisms behind this connection are also largely unknown. To address these issues, 297 college students participated in this study, completing measures of interoceptive sensibility (IS), empathy and alexithymia and undergoing resting-state fMRI scans. The functional connectivity of the amygdala was analysed to identify the neural substrates of alexithymia, and mediation analyses were conducted to examine the mediation effect of alexithymia and alexithymia-specific amygdala functional connectivity on the relationship between IS and empathy. The results showed that higher levels of IS were associated with increased cognitive empathy through weakened alexithymia. Functional connectivity analysis indicated that right basolateral amygdala (BLA)-left precuneus connectivity was negatively related to alexithymia, while right BLA-left precentral gyrus connectivity was positively related to alexithymia. Furthermore, right BLA-left precuneus connectivity was found to mediate the impact of interoception on cognitive empathy. In conclusion, this study provides valuable insights into the relationships among IS, alexithymia, and empathy. The right BLA-left precuneus connectivity may serve as a shared neural substrate between interoception and cognitive empathy.

Neighborhood Perceptions Are Associated With Intrinsic Amygdala Activity and Resting-State Connectivity With Salience Network Nodes Among Older Adults.

Neighborhood perceptions are associated with physical and mental health outcomes; however, the biological associates of this relationship remain to be fully understood. Here, we evaluate the relationship between neighborhood perceptions and amygdala activity and connectivity with salience network (i.e., insula, anterior cingulate, thalamus) nodes. Forty-eight older adults (mean age = 68 [7] years, 52% female, 47% non-Hispanic Black, 2% Hispanic) without dementia or depression completed the Perceptions of Neighborhood Environment Scale. Lower scores indicated less favorable perceptions of aesthetic quality, walking environment, availability of healthy food, safety, violence (i.e., more perceived violence), social cohesion, and participation in activities with neighbors. Participants separately underwent resting-state functional magnetic resonance imaging. Less favorable perceived safety ( β = -0.33, pFDR = .04) and participation in activities with neighbors ( β = -0.35, pFDR = .02) were associated with higher left amygdala activity, independent of covariates including psychosocial factors. Less favorable safety perceptions were also associated with enhanced left amygdala functional connectivity with the bilateral insular cortices and the left anterior insula ( β = -0.34, pFDR = .04). Less favorable perceived social cohesion was associated with enhanced left amygdala functional connectivity with the right thalamus ( β = -0.42, pFDR = .04), and less favorable perceptions about healthy food availability were associated with enhanced left amygdala functional connectivity with the bilateral anterior insula (right: β = -0.39, pFDR = .04; left: β = -0.42, pFDR = .02) and anterior cingulate gyrus ( β = -0.37, pFDR = .04). Taken together, our findings document relationships between select neighborhood perceptions and amygdala activity as well as connectivity with salience network nodes; if confirmed, targeted community-level interventions and existing community strengths may promote brain-behavior relationships.

Decreased amygdala-sensorimotor connectivity mediates the association between prenatal stress and broad autism phenotype in young adults: Project Ice Storm

Studies show that prenatal maternal stress (PNMS) is related to risk for child autism, and to atypical amygdala functional connectivity in the autistic child. Yet, it remains unclear whether amygdala functional connectivity mediates the association between PNMS and autistic traits, particularly in young adult offspring. We recruited women who were pregnant during, or within 3 months of, the 1998 Quebec ice storm crisis, and assessed three aspects of PNMS: objective hardship (events experienced during the ice storm), subjective distress (post-traumatic stress symptoms experienced as a result of the ice storm) and cognitive appraisal. At age 19, 32 young adults (21 females) self-reported their autistic-like traits (i.e., aloof personality, pragmatic language impairment and rigid personality), and underwent structural MRI and resting-state functional MRI scans. Seed-to-voxel analyses were conducted to map the amygdala functional connectivity network. Mediation analyses were implemented with bootstrapping of 20,000 resamplings. We found that greater maternal objective hardship was associated with weaker functional connectivity between the left amygdala and the right postcentral gyrus, which was then associated with more pragmatic language impairment. Greater maternal subjective distress was associated with weaker functional connectivity between the right amygdala and the left precentral gyrus, which was then associated with more aloof personality. Our results demonstrate that the long-lasting effect of PNMS on offspring autistic-like traits may be mediated by decreased amygdala-sensorimotor circuits. The differences between amygdala-sensory and amygdala-motor pathways mediating different aspects of PNMS on different autism phenotypes need to be studied further.

Patterns of Neural Network Functional Connectivity Associated With Mania/Hypomania and Depression Risk in 3 Independent Young Adult Samples

Mania/hypomania is the pathognomonic feature of bipolar disorder (BD). Established, reliable neural markers denoting mania/hypomania risk to help with early risk detection and diagnosis and guide the targeting of pathophysiologically informed interventions are lacking. To identify patterns of neural responses associated with lifetime mania/hypomania risk, the specificity of such neural responses to mania/hypomania risk vs depression risk, and the extent of replication of findings in 2 independent test samples. This cross-sectional study included 3 independent samples of young adults aged 18 to 30 years without BD or active substance use disorder within the past 3 months who were recruited from the community through advertising. Of 603 approached, 299 were ultimately included and underwent functional magnetic resonance imaging at the University of Pittsburgh, Pittsburgh, Pennsylvania, from July 2014 to May 2023. Activity and functional connectivity to approach-related emotions were examined using a region-of-interest mask supporting emotion processing and emotional regulation. The Mood Spectrum Self-Report assessed lifetime mania/hypomania risk and depression risk. In the discovery sample, elastic net regression models identified neural variables associated with mania/hypomania and depression risk; multivariable regression models identified the extent to which selected variables were significantly associated with each risk measure. Multivariable regression models then determined whether associations in the discovery sample replicated in both test samples. A total of 299 participants were included. The discovery sample included 114 individuals (mean [SD] age, 21.60 [1.91] years; 80 female and 34 male); test sample 1, 103 individuals (mean [SD] age, 21.57 [2.09] years; 30 male and 73 female); and test sample 2, 82 individuals (mean [SD] age, 23.43 [2.86] years; 48 female, 29 male, and 5 nonbinary). Associations between neuroimaging variables and Mood Spectrum Self-Report measures were consistent across all 3 samples. Bilateral amygdala-left amygdala functional connectivity and bilateral ventrolateral prefrontal cortex-right dorsolateral prefrontal cortex functional connectivity were positively associated with mania/hypomania risk: discovery omnibus χ2 = 1671.7 (P < .001); test sample 1 omnibus χ2 = 1790.6 (P < .001); test sample 2 omnibus χ2 = 632.7 (P < .001). Bilateral amygdala-left amygdala functional connectivity and right caudate activity were positively associated and negatively associated with depression risk, respectively: discovery omnibus χ2 = 2566.2 (P < .001); test sample 1 omnibus χ2 = 2935.9 (P < .001); test sample 2 omnibus χ2 = 1004.5 (P < .001). In this study of young adults, greater interamygdala functional connectivity was associated with greater risk of both mania/hypomania and depression. By contrast, greater functional connectivity between ventral attention or salience and central executive networks and greater caudate deactivation were reliably associated with greater risk of mania/hypomania and depression, respectively. These replicated findings indicate promising neural markers distinguishing mania/hypomania-specific risk from depression-specific risk and may provide neural targets to guide and monitor interventions for mania/hypomania and depression in at-risk individuals.

Developmental changes in functional connectivity between the prefrontal cortex and amygdala following fear extinction

The amygdala and prefrontal cortex (PFC) undergo dramatic changes in structure, function, and regional connectivity in early life, ultimately stabilizing in early adulthood. Pathways between these two structures underlie many forms of emotional learning, including the extinction of conditioned fear. Here we sought to characterize changes in extinction-related medial PFC (mPFC) → amygdala functional connectivity across development that might explain adolescent impairments in extinction. The retrograde tracer Fluorogold was infused into the amygdala of postnatal day (P)22–23 (juvenile), P31-32 (adolescent), or ≥ P69 (adult) rats, which were then exposed to fear conditioning and extinction training. Brains were collected following extinction or context exposure and processed for expression of pMAPK (as a marker of learning-dependent plasticity) in prelimbic (PL) and infralimbic (IL) amygdala-projecting neurons. Consistent with previous findings, amygdala-projecting mPFC neurons were located primarily in layers (L)II/III and V of the mPFC. We noted that mPFC LII/III projected predominantly to the ipsilateral basolateral amygdala, whereas LV projected bilaterally and targeted multiple amygdalar nuclei. Extinction was not associated with changes in extinction-related plasticity in the PL-amygdala pathways in any age group. No changes were seen in LII/III of the IL, but extinction-related plasticity in LV amygdala-projecting IL neurons decreased linearly across development. These findings suggest that extinction-related functional connectivity between the IL and the amygdala undergoes fundamental changes across development that may contribute to alterations in fear suppression across development.

Testosterone and the Amygdala's Functional Connectivity in Women and Men.

The amygdala contains androgen receptors and is involved in various affective and social functions. An interaction between testosterone and the amygdala's functioning is likely. We investigated the amygdala's resting-state functional connectivity (rsFC) network in association with testosterone in 94 healthy young adult women and men (final data available for analysis from 42 women and 39 men). Across the whole sample, testosterone was positively associated with the rsFC between the right amygdala and the right middle occipital gyrus, and it further predicted lower agreeableness scores. Significant sex differences appeared for testosterone and the functional connectivity between the right amygdala and the right superior frontal gyrus (SFG), showing higher testosterone levels with lower connectivity in women. Sex further predicted the openness and agreeableness scores. Our results show that testosterone modulates the rsFC between brain areas involved in affective processing and executive functions. The data indicate that the cognitive control of the amygdala via the frontal cortex is dependent on the testosterone levels in a sex-specific manner. Testosterone seems to express sex-specific patterns (1) in networks processing affect and cognition, and (2) in the frontal down-regulation of the amygdala. The sex-specific coupling between the amygdala and the frontal cortex in interaction with the hormone levels may drive sex-specific differences in a variety of behavioral phenomena that are further associated with psychiatric illnesses that show sex-specific prevalence rates.

At the Head and Heart of Oxytocin’s Stress-Regulatory Neural and Cardiac Effects: A Chronic Administration RCT in Children with Autism

Introduction: Intranasal administration of oxytocin presents a promising new approach to reduce disability associated with an autism spectrum disorder diagnosis. Previous investigations have emphasized the amygdala as the neural foundation for oxytocin’s acute effects. However, to fully understand oxytocin’s therapeutic potential, it is crucial to gain insight into the neuroplastic changes in amygdala circuitry induced from chronic oxytocin administrations, particularly in pediatric populations. Objective: We aimed to examine the impact of a 4-week course of intranasal oxytocin on amygdala functional connectivity in children with autism, compared to placebo. Additionally, we investigated whether oxytocin improves cardiac autonomic arousal, as indexed by high-frequency heart rate variability. Methods: Fifty-seven children with autism aged 8–12 years (45 boys, 12 girls) participated in a double-blind, randomized pharmaco-neuroimaging trial involving twice-daily administrations of intranasal oxytocin or placebo. Resting-state fMRI scans and simultaneous, in-scanner heart rate recordings were obtained before, immediately after, and 4 weeks after the nasal spray administration period. Results: Significant reductions in intrinsic amygdala-orbitofrontal connectivity were observed, particularly at the 4-week follow-up session. These reductions were correlated with improved social symptoms and lower cardiac autonomic arousal. Further, oxytocin’s neural and cardiac autonomic effects were modulated by epigenetic modifications of the oxytocin receptor gene. The effects were more pronounced in children with reduced epigenetic methylation, signifying heightened expression of the oxytocin receptor. Conclusion: These findings underscore that a 4-week oxytocin administration course decreases amygdala connectivity and improves cardiac autonomic balance. Epigenetic modulators may explain inter-individual variation in responses to oxytocin.

Links between brain neuroimaging and blood inflammatory markers in urological chronic pelvic pain syndrome

Urological chronic pelvic pain syndrome (UCPPS) is a debilitating painful condition with unclear etiology. Prior researchers have indicated that compared to healthy controls, patients with UCPPS demonstrated altered brain activity. Researchers have also shown that in UCPPS, several blood inflammatory markers relate to clinical variables of pain, fatigue, and pain widespreadness. However, how altered brain function in patients with UCPPS relates to blood inflammation remains unknown. To extend and connect prior findings of altered brain function and inflammatory factors in UCPPS, we conducted a secondary analysis of data from a cohort of UCPPS patients (N = 29) and healthy controls (N = 31) who provided both neuroimaging and blood data (National Institute of Health MAPP Research Network publicly available dataset). In our present study, we aimed to evaluate relationships between a priori-defined brain neuroimaging markers and inflammatory factors of interest and their relationships to pain-psychological variables. We hypothesized that two brain alterations of interest (i.e., PCC – left hippocampus functional connectivity and PCC – bilateral amygdala functional connectivity) would be correlated with four cytokine markers of interest: interleukin (IL) – 6, tumor necrosis factor-alpha (TNF-a), IL-8, and granulocyte-macrophage colony-stimulating factor (GM-CSF). In the UCPPS cohort, we identified a significant PCC - left hippocampus functional connectivity relationship with IL-6 (p = 0.0044). Additionally, in the UCPPS cohort, we identified a PCC - amygdala functional connectivity relationship with GM-CSF which did not meet our model's threshold for statistical significance (p = 0.0665). While these data are preliminary and cross-sectional, our findings suggest connections between brain function and levels of low-grade systemic inflammation in UCPPS. Thus, while further study is needed, our data indicate the potential for advancing the understanding of how brain functional circuits may relate to clinical symptoms and systemic inflammation.

Exploring the association between early exposure to material hardship and psychopathology through indirect effects of fronto-limbic functional connectivity during fear learning.

Experiencing family material hardship has been shown to be associated with disruptions in physical and psychological development. However, the association between material hardship and functional connectivity in the fronto-limbic circuit during fear learning is unclear. A total of 161 healthy young adults aged 17-28 were recruited in our brain imaging study, using the Fear Conditioning Task to test the associations between material hardship and connectivity in fronto-limbic circuit and psychopathology. The results showed that family material hardship was linked to higher positive connectivity between the left amygdala and bilateral dorsal anterior cingulate cortex, as well as higher negative connectivity between the left hippocampus and right ventromedial prefrontal cortex. A mediation analysis showed that material hardship was associated with depression via amygdala functional connectivity (indirect effect = 0.228, P = 0.016), and also indirectly associated with aggression and anger-hostility symptoms through hippocampal connections (aggression: indirect effect = 0.057, P = 0.001; anger-hostility: indirect effect = 0.169, P = 0.048). That is, family material hardship appears to affect fronto-limbic circuits through changes in specific connectivity, and these specific changes, in turn, could lead to specific psychological symptoms. The findings have implications for designing developmentally sensitive interventions to mitigate the emergence of psychopathological symptoms.

Maternal Perinatal Stress Trajectories and Negative Affect and Amygdala Development in Offspring.

Maternal psychological stress during pregnancy is a common risk factor for psychiatric disorders in offspring, but little is known about how heterogeneity of stress trajectories during pregnancy affect brain systems and behavioral phenotypes in infancy. This study was designed to address this gap in knowledge. Maternal anxiety, stress, and depression were assessed at multiple time points during pregnancy in two independent low-risk mother-infant cohorts (N=115 and N=2,156). Trajectories in maternal stress levels in relation to infant negative affect were examined in both cohorts. Neonatal amygdala resting-state functional connectivity MRI was examined in a subset of one cohort (N=60) to explore the potential relationship between maternal stress trajectories and brain systems in infants relevant to negative affect. Four distinct trajectory clusters, characterized by changing patterns of stress over time, and two magnitude clusters, characterized by severity of stress, were identified in the original mother-infant cohort (N=115). The magnitude clusters were not associated with infant outcomes. The trajectory characterized by increasing stress in late pregnancy was associated with blunted development of infant negative affect. This relationship was replicated in the second, larger cohort (N=2,156). In addition, the trajectories that included increasing or peak maternal stress in late pregnancy were related to stronger neonatal amygdala functional connectivity to the anterior insula and the ventromedial prefrontal cortex in the exploratory analysis. The trajectory of maternal stress appears to be important for offspring brain and behavioral development. Understanding heterogeneity in trajectories of maternal stress and their influence on infant brain and behavioral development is critical to developing targeted interventions.

Civilian Moral Injury and Amygdala Functional Connectivity During Attention to Threat

BackgroundMoral injury references emotional and spiritual/existential suffering that may emerge following psychological trauma. Despite being linked to adverse mental health outcomes, little is known about the neurophysiological mechanisms of this phenomenon. In this study, we examined neural correlates of moral injury exposure and distress using the Moral Injury Exposure and Symptom Scale for Civilians. We also examined potential moderation of these effects by race (Black vs. White individuals) given the likely intersection of race-related stress with moral injury. MethodsForty-eight adults ages 18 to 65 years (mean age = 30.56, SD = 11.93) completed the Moral Injury Exposure and Symptom Scale for Civilians and an affective attentional control measure, the affective Stroop task (AS), during functional magnetic resonance imaging; the AS includes presentation of threat-relevant and neutral distractor stimuli. Voxelwise functional connectivity of the bilateral amygdala was examined in response to threat-relevant versus neutral AS distractor trials. ResultsFunctional connectivity between the right amygdala and left postcentral gyrus/primary somatosensory cortex was positively correlated with the Moral Injury Exposure and Symptom Scale for Civilians exposure score (voxelwise p < .001, cluster false discovery rate–corrected p < .05) in response to threat versus neutral AS distractor trials. Follow-up analyses revealed significant effects of race; Black but not White participants demonstrated this significant pattern of amygdala–left somatosensory cortex connectivity. ConclusionsIncreased exposure to potentially morally injurious events may lead to emotion-somatosensory pathway disruptions during attention to threat-relevant stimuli. These effects may be most potent for individuals who have experienced multilayered exposure to morally injurious events, including racial trauma. Moral injury appears to have a distinct neurobiological signature that involves abnormalities in connectivity of emotion-somatosensory paths, which may be amplified by race-related stress.

Associations between infant amygdala functional connectivity and social engagement following a stressor: A preliminary investigation.

Functional architecture of the infant brain, especially functional connectivity (FC) within the amygdala network and between the amygdala and other networks (i.e., default-mode [DMN] and salience [SAL] networks), provides a neural basis for infant socioemotional functioning. Yet, little is known about the extent to which early within- and between-network amygdala FC are related to infant stress recovery across the first year of life. In this study, we examined associations between amygdala FC (i.e., within-network amygdala connectivity, and between-network amygdala connectivity with the DMN and SAL) at 3 months and infant recovery from a mild social stressor at 3, 6 and 9 months. At 3 months, thirty-five infants (13 girls) underwent resting-state functional magnetic resonance imaging during natural sleep. Infants and their mothers completed the still-face paradigm at 3, 6, and 9 months, and infant stress recovery was assessed at each time point as the proportion of infant social engagement during the reunion episode. Bivariate correlations indicated that greater positive within-network amygdala FC and greater positive amygdala-SAL FC, but not amygdala-DMN FC, at 3 months predicted lower levels of stress recovery at 3 and 6 months, but were nonsignificant at 9 months. These findings provide preliminary evidence that early functional synchronization within the amygdala network, as well as segregation between the amygdala and the SAL, may contribute to infant stress recovery in the context of infant-mother interaction.

Altered amygdala functional connectivity after real-time functional MRI emotion self-regulation training.

Real-time functional MRI neurofeedback (rtfMRI-NF) is a noninvasive technique that extracts concurrent brain states and provides feedback to subjects in an online method. Our study aims to investigate the effect of rtfMRI-NF on amygdala-based emotion self-regulation by analyzing resting-state functional connectivity. We conducted a task experiment to train subjects in self-regulating amygdala activity in response to emotional stimuli. Twenty subjects were divided into two groups. The up-regulate group (URG) viewed positive stimulus, while the down-regulate group (DRG) viewed negative stimulus. The rtfMRI-NF experiment paradigm consisted of three conditions. The URG's percent amplitude fluctuation (PerAF) scores are significant, indicating that positive emotions may be a partial side effect, with increased activity in the left hemisphere. Resting-state functional connectivity was analyzed via a paired-sample t-test before and after neurofeedback training. Brain network properties and functional connectivity analysis showed a significant difference between the default mode network (DMN) and the brain region associated with the limbic system. These results reveal to some extent the mechanism of neurofeedback training to improve individuals' emotional regulate regulation ability. Our study has shown that rtfMRI-neurofeedback training can effectively enhance the ability to voluntarily control brain responses. Furthermore, the results of the functional analysis have revealed distinct changes in the amygdala functional connectivity circuits following rtfMRI-neurofeedback training. These findings may suggest the potential clinical applications of rtfMRI-neurofeedback as a new therapy for emotionally related mental disorders.

Intergenerational Transmission of Maternal Childhood Maltreatment Prior to Birth: Effects on Human Fetal Amygdala Functional Connectivity

Childhood maltreatment (CM) is a potent risk factor for developing psychopathology later in life. Accumulating research suggests that the influence is not limited to the exposed individual but may also be transmitted across generations. In this study, we examine the effect of CM in pregnant women on fetal amygdala-cortical function, prior to postnatal influences. Healthy pregnant women (N= 89) completed fetal resting-state functional magnetic resonance imaging (rsfMRI) scans between the late second trimester and birth. Women were primarily from low socioeconomic status households with relatively high CM. Mothers completed questionnaires prospectively evaluating prenatal psychosocial health and retrospectively evaluating trauma from their own childhood. Voxelwise functional connectivity was calculated from bilateral amygdala masks. Connectivity of the amygdala network was relatively higher to left frontal areas (prefrontal cortex and premotor) and relatively lower to right premotor area and brainstem areas in fetuses of mothers exposed to higher CM. These associations persisted after controlling for maternal socioeconomic status, maternal prenatal distress, measures of fetal motion, and gestational age at the time of scan and at birth. Pregnant women's experiences of CM are associated with offspring brain development in utero. The strongest effects were found in the left hemisphere, potentially indicating lateralization of the effects of maternal CM on the fetal brain. This study suggests that the time frame of the Developmental Origins of Health and Disease research should be extended to exposures from mothers' childhood, and indicates that the intergenerational transmission of trauma may occur prior to birth.

Altered functional connectivity of the amygdala across variants of callous-unemotional traits: A resting-state fMRI study in children and adolescents

Over the past years, research has shown that primary (high callousness and low anxiety) and secondary (high callousness and anxiety) variants of CU traits may be associated with opposite amygdala activity (hypo- and hyper-reactivity, respectively). However, their differences in amygdala functional connectivity remains largely unexplored. We conducted a Latent Profile Analysis on a large sample of adolescents (n = 1416) to identify homogeneous subgroups with different levels of callousness and anxiety. We then performed a seed-to-voxel connectivity analysis on resting-state fMRI data to compare subgroups on connectivity patterns of the amygdala. We examined the results in relation to conduct problems to identify potential neural risk factors. The Latent Profile Analysis revealed four subgroups, including the primary and secondary variants, anxious, and typically developing adolescents. The seed-to-voxel analyses showed that the primary variant was mainly characterized by increased connectivity between the left amygdala and left thalamus. The secondary variant exhibited deficient connectivity between the amygdala and the dorsomedial prefrontal cortex, temporo-parietal junction, premotor, and postcentral gyrus. Both variants showed increased connectivity between the left amygdala and the right thalamus but exhibited opposite functional connectivity between the left amygdala and the parahippocampal gyrus. Dimensional analyses indicated that conduct problems may play a mediating role between callousness and amygdala-dmPFC functional connectivity across youths with already high levels of callousness. Our study highlights that both variants differ in the functional connectivity of the amygdala. Our results support the importance of disentangling the heterogeneity of adolescents at risk for conduct problems in neuroimaging.

Altered functional connectivity within the brain fear circuit in Parkinson's disease with anxiety: A seed-based functional connectivity study

ObjectivesAimed to investigate whether there are abnormal changes in the functional connectivity (FC) between the amygdala with other brain areas, in Parkinson's disease (PD) patients with anxiety. MethodsParticipants were enrolled prospectively, and the Hamilton Anxiety Rating (HAMA) Scale was used to quantify anxiety disorder. Rest-state functional MRI (rs-fMRI) was applied to analyze the amygdala FC patterns among anxious PD patients, non-anxious PD patients, and healthy controls. ResultsThirty-three PD patients were recruited, 13 with anxiety, 20 without anxiety, and 19 non-anxious healthy controls. In anxious PD patients, FC between the amygdala with the hippocampus, putamen, intraparietal sulcus, and precuneus showed abnormal alterations compared with non-anxious PD patients and healthy controls. In particular, FC between the amygdala and hippocampus negatively correlated with the HAMA score (r = −0.459, p = 0.007). ConclusionOur results support the role of the fear circuit in emotional regulation in PD with anxiety. Also, the abnormal FC patterns of the amygdala could preliminarily explain the neural mechanisms of anxiety in PD.