Anomalous static and dynamic functional connectivity of amygdala subregions in individuals with high trait anxiety.

BACKGROUND: Trait anxiety is considered a susceptible factor for stress-related disorders, and is characterized by abnormal brain activity and connectivity in the regions related to emotional processing (e.g., the amygdala). However, only a few studies have examined the static and dynamic changes of functional connectivity in trait anxiety. METHOD: We compared the resting-state static and dynamic functional connectivity (sFC/dFC) in individuals with high trait anxiety (HTA, n = 257) and low trait anxiety (LTA, n = 264) using bilateral amygdala subregions as the seeds, that is, the centromedial amygdala (CMA), basolateral amygdala (BLA), and superficial amygdala (SFA). RESULTS: The CMA, BLA, and SFA all showed reduced sFC with the executive control network (ECN) and anomalous dFC with the default mode network (DMN) in individuals with HTA. The CMA only showed reduced sFC with the ECN and reduced dFC with the DMN in individuals with HTA. The BLA showed reduced sFC with the salience network (mainly in the anterior and median cingulate), and increased dFC between the BLA and the DMN in individuals with HTA compared to those with LTA. Notably, HTA showed widespread anomalous functional connectivity in the SFA, including the visual network, mainly in the calcarine fissure, limbic system (olfactory cortex), and basal ganglia (putamen). CONCLUSION: The anomalous sFC and dFC in individuals with HTA may reflect altered mechanisms in prefrontal control, salient stimuli processing, and amygdaloidal responsivity to potential threats, leading to alterations in associative, attentional, interpretative, and regulating processes that sustain a threat-related processing bias in HTA individuals.

Subgenual anterior cingulate-insula resting-state connectivity as a neural correlate to trait and state stress resilience.

Accumulating evidence indicates important roles of the subgenual anterior cingulate cortex and rostral limbic regions such as the anterior insula, in regulating stress-related affective responses and negative affect states in general. However, research is lacking in simultaneously assessing the inter-relations between trait and state affective responses to stress, and the functional connectivity between the subgenual anterior cingulate and anterior insula. This preliminary research involved matched healthy participants with high (N = 10) and low (N = 10) self-reported trait stress resilience, and assessed their affective and subgenual anterior cingulate-anterior insula resting-state functional connectivity patterns before and after a psychosocial stress task. We found that while the low-resilience group displayed higher trait negative affect and perceived greater task-related stress, only the high-resilience group showed increase of negative affect, along with greater decrease of left subgenual anterior cingulate-right anterior insula connectivity, following stress induction. Moreover, the functional connectivity change mediated group difference in affect change following stress task. We speculate that the contingent increase of negative affect, and the associated temporary decoupling of subgenual anterior cingulate-insula circuitry, may represent a normative and adaptive stress response underpinned by adaptive and dynamic interplay between the default mode and salience networks. Such findings, if consolidated, have important implications for promoting stress resilience and reducing risk for stress-related affective disorders.

Mediating roles of sleep quality and resilience in the relationships between chronotypes and mental health symptoms.

Sleep and mental health are intrinsically intertwined, but not every individual with problems sleeping develops a mental health disorder. This study examined the association among chronotypes, resilience, sleep quality and mental health symptoms amongst otherwise healthy individuals. Two hundred adults (Mage = 27.75 ± 5.11, 68% female) with no previous diagnosis of mental illness were recruited and filled in a set of questionnaires measuring chronotypes, sleep quality, depression and anxiety symptoms. The findings from the path analysis showed that the morning type had a statistically significant direct effect on a range of sleep quality indices. These included better subjective sleep quality, shortened sleep latency, and fewer daytime dysfunctions, as well as a higher level of resilience. However, it did not significantly affect depression and anxiety symptoms. In addition, the morning type had statistically significant indirect effects on a higher level of resilience and fewer depression and anxiety symptoms through the mediating effect of sleep quality indices. Findings from this study support that morning type is associated with better resilience and psychological health, which is mediated through better sleep quality.

Conceptualizing psychological resilience through resting-state functional MRI in a mentally healthy population: a systematic review.

Conceptualizations and operational definitions of psychological resilience vary across resilience neuroimaging studies. Data on the neural features of resilience among healthy individuals has been scarce. Furthermore, findings from resting-state functional magnetic resonance imaging (fMRI) studies were inconsistent across studies. This systematic review summarized resting-state fMRI findings in different modalities from various operationally defined resilience in a mentally healthy population. The PubMed and MEDLINE databases were searched. Articles that focused on resting-state fMRI in relation to resilience, and published before 2022, were targeted. Orbitofrontal cortex, anterior cingulate cortex, insula and amygdala, were reported the most from the 19 included studies. Regions in emotional network was reported the most from the included studies. The involvement of regions like amygdala and orbitofrontal cortex indicated the relationships between emotional processing and resilience. No common brain regions or neural pathways were identified across studies. The emotional network appears to be studied the most in association with resilience. Matching fMRI modalities and operational definitions of resilience across studies are essential for meta-analysis.

The role of resilience in depression and anxiety symptoms: A three-wave cross-lagged study.

Cultivation of resilience is believed to ameliorate mental health problems. The impact of mental health problems on resilience is however rarely discussed. This study investigated the reciprocal relationship of resilience with depression and anxiety symptoms using a three-wave cross-lagged design. Resilience level, depression, and anxiety symptoms were assessed at baseline, the third and the sixth month in 125 university students without psychiatric disorders (62 females). No significant changes in resilience levels were observed across the 6 months. Depressive symptoms, but not anxiety symptoms significantly increased at the third and sixth months compared with baseline. The three-wave cross-lagged models revealed an unstable reciprocal relationship of resilience with depression and a stable reciprocal relationship between resilience and anxiety symptoms over time. The reciprocal relationship between resilience and mental health problems indicates the importance of cultivating resilience for the prevention of mental illness as well as the importance of managing mental health symptoms at non-clinical levels for monitoring resilience. The unstable reciprocal relationship between resilience and depression symptoms across time suggests the existence of potential moderators that impact the relationship between resilience and depression. Our findings further support the notion that resilience is conceptualized as a dynamic process.

Hyperconnectivity between the posterior cingulate and middle frontal and temporal gyrus in depression: Based on functional connectivity meta-analyses.

Disrupted whole-brain resting-state functional connectivity (RSFC) of the posterior cingulate (PCC) has been highlighted to associate with cognitive and affective dysfunction in major depressive disorder (MDD). However, prior findings showed certain inconsistency about the RSFC of the PCC in MDD. This study aims to investigate the aberrant RSFC of the PCC in MDD using anisotropic effect-size version of seed-based d mapping (AES-SDM). Web of Science and PubMed were searched for studies investigating PCC-based RSFC in MDD. A total of 17 studies, involving 804 patients and 724 healthy controls (HCs), fit our selection criteria. Additionally, to seek for the link between functional and structural differences, we did a meta-analysis on the studies in conjunction with voxel-based morphology (VBM) analysis. The PCC showed higher RSFC with the left middle temporal gyrus (MTG) and the right middle frontal gyrus (MFG), and lower RSFC with the left superior frontal gyrus (SFG) and the left precuneus in patients with MDD than HCs. Moreover, the meta-regression analysis revealed a negative correlation between the FC alteration of the right MFG with the PCC and depression severity. Notably, the left MTG and the left MFG demonstrated gray matter deviations in conjunction analysis. Our results indicated that the aberrant RSFC between the PCC and brain regions sub-serving cognitive control and emotional regulation in patients with MDD. And such functional alterations may have structural basis. These findings may underlie the mechanisms of deficits in cognitive control and emotional regulation of MDD.

A Comparative Multimodal Meta-analysis of Anisotropy and Volume Abnormalities in White Matter in People Suffering From Bipolar Disorder or Schizophrenia.

Schizophrenia (SZ) and bipolar disorder (BD) share some similarities in terms of genetic-risk genes and abnormalities of gray-matter structure in the brain, but white matter (WM) abnormalities have not been studied in depth. We undertook a comparative multimodal meta-analysis to identify common and disorder-specific abnormalities in WM structure between SZ and BD. Anisotropic effect size-signed differential mapping software was used to conduct a comparative meta-analysis of 68 diffusion tensor imaging (DTI) and 34 voxel-based morphometry (VBM) studies comparing fractional anisotropy (FA) and white matter volume (WMV), respectively, between patients with SZ (DTI: N = 1543; VBM: N = 1068) and BD (DTI: N = 983; VBM: N = 518) and healthy controls (HCs). The bilateral corpus callosum (extending to the anterior and superior corona radiata) showed shared decreased WMV and FA in SZ and BD. Compared with BD patients, SZ patients showed remarkable disorder-specific WM abnormalities: decreased FA and increased WMV in the left cingulum, and increased FA plus decreased WMV in the right anterior limb of the internal capsule. SZ patients showed more extensive alterations in WM than BD cases, which may be the pathophysiological basis for the clinical continuity of both disorders. The disorder-specific regions in the left cingulum and right anterior limb of the internal capsule provided novel insights into both disorders. Our study adds value to further understanding of the pathophysiology, classification, and differential diagnosis of SZ and BD.

Charting the neural circuits disruption in inhibitory control and its subcomponents across psychiatric disorders: A neuroimaging meta-analysis.

BACKGROUND: Inhibitory control, comprising cognitive inhibition and response inhibition, showed consistent deficits among several major psychiatric disorders. We aim to identify the trans-diagnostic convergence of neuroimaging abnormalities underlying inhibitory control across psychiatric disorders. METHODS: Inhibitory control tasks neuroimaging, including functional magnetic resonance imaging, single-photon emission computed tomography, and positron emission tomography articles published in PubMed and Web of Science before April 2020 comparing healthy controls with patients with several psychiatric disorders were searched. RESULTS: 146 experiments on 2653 patients with different disorders and 2764 control participants were included. Coordinates of case-control differences coded by diagnosis and inhibitory control components were analyzed using activation likelihood estimation. A robust trans-diagnostic pattern of aberrant brain activation in the bilateral cingulate gyri extending to medial frontal gyri, right insula, bilateral lentiform nuclei, right inferior frontal gyrus, right precuneus extending to inferior parietal lobule, and right supplementary motor area were detected. Frontostriatal pathways are the commonly disrupted neural circuits in the inhibitory control across psychiatric disorders. Furthermore, Patients showed aberrant activation in the dorsal frontal inhibitory system in cognitive inhibition, while in the frontostriatal system in response inhibition across disorders. CONCLUSION: Consistent with the Research Domain Criteria initiative, current findings show that psychiatric disorders may be productively formulated as a phenotype of trans-diagnostic neurocircuit disruption. Our results provide new insights for future research into mental disorders with inhibition-related dysfunctions.

Integrative psycho-biophysiological markers in predicting psychological resilience.

The hypothalamic-pituitary-adrenal (HPA) and parasympathetic nervous systems have been reported to play important roles in emotion regulation and stress coping. Yet, their direct relationship with psychological resilience remains unclear. These biophysiological features should be considered together with the traditional psychometric properties in studying resilience more comprehensively. The current study aimed to examine the role of these systems during a laboratory stress task and to determine the prediction power of resilience by combining psychological and biophysiological features. One hundred and seven (52 females) university students without psychiatric disorders underwent the Trier Social Stress Task (TSST). Psychometric properties of resilience were measured at rest; vagal heart rate variability (HRV), salivary cortisol, and dehydroepiandrosterone (DHEA) levels were captured at baseline, during, and after TSST. Multivariate linear regression as well as support vector regression machine-learning analyses were performed to investigate significant predictors and the prediction power of resilience. Results showed that positive and negative affects, HRV during the anticipatory phase of stress, and the ratio of cortisol/DHEA at the first recovery time point were significant predictors of resilience. The addition of biophysiological features increased the prediction power of resilience by 1.2-fold compared to psychological features alone. Results from machine learning analyses further demonstrated that the increased prediction power of resilience by adding the ratio of cortisol/DHEA was significant in "cortisol responders"; whereas a trend level was observed in "cortisol non-responders". Our findings extend the knowledge from the literature that high vagal activity during the anticipating phase of stress and the ability to restore the balance between cortisol and DHEA after a stress event could be an important feature in predicting resilience. Our findings also further support the need of combining psychological and biophysiological features in studying/predicting resilience.

Hypofunctional connectivity between the posterior cingulate cortex and ventromedial prefrontal cortex in autism: Evidence from coordinate-based imaging meta-analysis.

BACKGROUND: Underconnectivity in the posterior cingulate cortex (PCC) may be associated with a weakened ability to interpret social signals in autism spectrum disorder (ASD) and result in cognitive inflexibility - a hallmark feature of ASD. However, previous neuroimaging studies using resting-state functional magnetic resonance imaging in ASD reported inconsistent findings on functional connectivity of the PCC. This study investigated the aberrant resting-state functional connectivity of the PCC in ASD using multilevel kernel density analysis. METHODS: Online databases (MEDLINE/PubMed) were searched for PCC-based functional connectivity in ASD. Ten studies (501 subjects; 161 reported foci) met the inclusion criteria of this meta-analysis. RESULTS: We found one consistent and strong abnormal functional connectivity of ASD during the resting state, which was the hypoconnectivity between the PCC and ventromedial prefrontal cortex (VMPFC). Importantly, the Jackknife sensitivity analysis revealed that the VMPFC cluster was stably hypoconnected with the PCC in ASD (maximum spatial overlap rate: 100%). CONCLUSIONS: The reduced PCC-VMPFC functional coupling may provide an early insight into the effects of ASD on multiple dimensions of functioning, including higher-order cognitive and complex social functions.

Impaired left amygdala resting state functional connectivity in subthreshold depression individuals.

Subthreshold depression (StD) affects people who experience clinically relevant depressive symptoms, which does not meet the diagnostic criteria for major depressive disorder (MDD). StD represents an ideal model for understanding the pathophysiological mechanisms of depression. Impaired emotion processing is a core feature of depression; careful investigation is required to better understand the neural correlates of emotion processing in depressed populations. In the current study, we explored whether the resting-state functional connectivity of the amygdala, a hub that taps a wide range of brain areas involved in emotion processing, is altered in individuals with StD when compared with healthy controls. Resting-state imaging data was collected from 59 individuals with StD and 59 age- and gender-matched controls. We found that the resting-state functional connectivity of the left amygdala with the cognitive control network and the left insula was significantly lower in people with StD than that in healthy controls. Such association was not observed in the right amygdala. Furthermore, functional connectivity strength between the left amygdala and the left precuneus was positively associated with depressive symptoms in individuals with StD. Our findings are in line with those reported in subjects with MDD, which may assist in further elucidating the pathophysiological mechanisms of depression, and contribute to the development of tailored treatments for individuals with StD who are at high risk of developing MDD.

Resting-state abnormalities in Autism Spectrum Disorders: A meta-analysis.

The gold standard for clinical assessment of Autism Spectrum Disorders (ASD) relies on assessing behavior via semi-structured play-based interviews and parent interviews. Although these methods show good sensitivity and specificity in diagnosing ASD cases, behavioral assessments alone may hinder the identification of asymptomatic at-risk group. Resting-state functional magnetic resonance imaging (rs-fMRI) could be an appropriate approach to produce objective neural markers to supplement behavioral assessments due to its non-invasive and task-free nature. Previous neuroimaging studies reported inconsistent resting-state abnormalities in ASD, which may be explained by small sample sizes and phenotypic heterogeneity in ASD subjects, and/or the use of different analytical methods across studies. The current study aims to investigate the local resting-state abnormalities of ASD regardless of subject age, IQ, gender, disease severity and methodological differences, using activation likelihood estimation (ALE). MEDLINE/PubMed databases were searched for whole-brain rs-fMRI studies on ASD published until Feb 2018. Eight experiments involving 424 subjects were included in the ALE meta-analysis. We demonstrate two ASD-related resting-state findings: local underconnectivity in the dorsal posterior cingulate cortex (PCC) and in the right medial paracentral lobule. This study contributes to uncovering a consistent pattern of resting-state local abnormalities that may serve as potential neurobiological markers for ASD.

Potential Mechanisms of Mindfulness in Improving Sleep and Distress.

The mechanisms of mindfulness-improved sleep quality are not extensively studied. Recently, attention monitoring/awareness and acceptance in mindfulness have been proposed to be the underlying mechanisms that tackle distress and related disorders. The current study tested if acceptance moderated the relationship of awareness with psychological distress and sleep quality, and verified that psychological distress mediated the relationship between mindfulness and sleep quality in a group of community-dwelling healthy adults. Three hundred and sixty-four healthy Chinese non-meditators (age 18-65, 59% female) completed a set of online self-reported questionnaires in Chinese via SurveyMonkey. Awareness and acceptance were measured by Observe and Nonreact facets in the Five Facet Mindfulness Questionnaire (FFMQ), respectively. General psychological distress levels and sleep quality were reflected in the global score of the Depression Anxiety and Stress Scales (DASS) and the Pittsburgh Sleep Quality Index (PSQI), respectively. Model 1 and model 8 in the PROCESS macro for SPSS were used to assess the moderation and moderated mediation effects. Increased level of acceptance (Nonreact) weakened the positive relationship between awareness (Observe) and poor sleep quality (ß = -0.0154, p = 0.0123), which was partially mediated through perceived psychological distress (ß = -0.0065, 95% bias-corrected bootstrap CI = -0.0128, -0.0004) in a group of community-dwelling healthy adults. Our findings suggested that awareness and acceptance could be the mechanisms of mindfulness interventions in improving sleep quality, partly via reducing psychological stress.

Meditation-induced neuroplastic changes in amygdala activity during negative affective processing.

Recent evidence suggests that the effects of meditation practice on affective processing and resilience have the potential to induce neuroplastic changes within the amygdala. Notably, literature speculates that meditation training may reduce amygdala activity during negative affective processing. Nonetheless, studies have thus far not verified this speculation. In this longitudinal study, participants (N = 21, 9 men) were trained in awareness-based compassion meditation (ABCM) or matched relaxation training. The effects of meditation training on amygdala activity were examined during passive viewing of affective and neutral stimuli in a non-meditative state. We found that the ABCM group exhibited significantly reduced anxiety and right amygdala activity during negative emotion processing than the relaxation group. Furthermore, ABCM participants who performed more compassion practice had stronger right amygdala activity reduction during negative emotion processing. The lower right amygdala activity after ABCM training may be associated with a general reduction in reactivity and distress. As all participants performed the emotion processing task in a non-meditative state, it appears likely that the changes in right amygdala activity are carried over from the meditation practice into the non-meditative state. These findings suggest that the distress-reducing effects of meditation practice on affective processing may transfer to ordinary states, which have important implications on stress management.

Moderating Effects of Cortisol on Neural-Cognitive Association in Cognitively Normal Elderly Subjects.

Cortisol homeostasis is important for healthy brain and cognitive aging. The aim of the current study is to investigate the role of serum cortisol levels in the relationship between regional brain volumes and cognitive processing speed in a group of cognitively normal elderly subjects. Forty-one healthy elderly participants were from a parallel longitudinal study. The reported data in this study reflects baseline measurements. Whole-brain anatomical scanning was performed using a 3.0 Tesla Philips Medical Systems Achieva scanner. Cognitive processing speed was assessed by the digit-symbol and symbol search tests, from the Chinese version of the Wechsler Adult Intelligence Scale-third edition (WAIS-III). Serum cortisol levels (sampled in the late morning) were measured by ELISA kits. Whole-brain regression analysis revealed that serum cortisol levels positively predicted the white matter volumes (WMV) of the right thalamus, the gray matter volumes (GMV) of the left thalamus and right cerebellar tonsil, and negatively predicted the WMV and GMV of the left middle temporal gyrus (MTG) in 41 healthy elderly participants. Furthermore, serum cortisol significantly moderated the relationship between the GMV of the left MTG and processing speed, as well as the GMV of the left thalamus and processing speed. This study provided the first piece of evidence supporting serum cortisol levels in moderating the relationship between regional brain volumes and processing speed in healthy elderly subjects. This observation enriches our understanding of the role of cortisol in brain morphology and cognitive functioning.

PM2.5 Exposure Suppresses Dendritic Maturation in Subgranular Zone in Aged Rats.

Detrimental effects of long-term inhalation of fine particulate matter (PM2.5) on the pulmonary and cardiovascular systems have been widely reported. Recent studies have shown that exposure to PM2.5 also causes adverse neurocognitive effects. This study investigates the effects of inhaled ammonium sulfate, which is a major compound of inorganic air pollutants in PM2.5, on adult neurogenesis in aged Sprague-Dawley rats. A total of 20 rats were randomly assigned to experimental (n = 10) and control (n = 10) conditions, wherein they were exposed to either ammonium sulfate or sham air for 2 h per day and for 28 consecutive days. It was observed that ammonium sulfate inhibited the maturation process and diminished dendritic complexity of immature neurons in the subgranular zone (SGZ) of the hippocampus significantly, although the number of neural stem cells or the rates of differentiation were comparable between the two groups. Our findings provide clear evidence on the direct relationship between air quality and advantageous neurogenesis. Exposure to PM leads to specific adverse effects on the maturation process during neurogenesis.

Can the neural-cortisol association be moderated by experience-induced changes in awareness?

Cortisol homeostasis is important for cognitive and affective functions that depend on cortisol-sensitive brain regions including the hippocampus and prefrontal cortex. Recent studies have shown that training induces changes in the brain. We report the findings of a longitudinal study that verified the moderation effect of experience-induced changes in awareness on the neural-cortisol association in cortisol-sensitive brain regions. These findings provide the first piece of evidence that planned behavioral experience can moderate the neural-cortisol association. A range of changes in awareness was achieved in a sample of 21 Chinese participants, divided into two groups: Awareness-based compassion meditation (ABCM) (n = 10) and relaxation (n = 11). We observed that changes in awareness were significant moderators of hippocampal-cortisol changes. Furthermore, a significant negative association between changes in plasma cortisol level and the resting-state synchrony of the right hippocampal and insular-frontal-operculum regions was observed. These novel findings shed light on the inter-relationships between changes in hippocampal-cortisol levels and changes in awareness and preliminarily identify the neural underpinnings of interventions for cortisol-related abnormal functioning for further study.

The role of circulating serotonin in the development of chronic obstructive pulmonary disease.

BACKGROUND: Cigarette smoking is a major risk factor in the development of age-related chronic obstructive pulmonary disease (COPD). The serotonin transporter (SERT) gene polymorphism has been reported to be associated with COPD, and the degree of cigarette smoking has been shown to be a significant mediator in this relationship. The interrelation between circulating serotonin (5-hydroxytyptamine, 5-HT), cigarette smoking and COPD is however largely unknown. The current study aimed at investigating the mediation effects of plasma 5-HT on cigarette smoking-induced COPD and the relation between plasma 5-HT levels and age. METHODS: The association between plasma 5-HT, age and COPD was analyzed in a total of 62 COPD patients (ever-smokers) and 117 control subjects (healthy non-smokers and ever-smokers). Plasma 5-HT levels were measured by enzyme-linked immuno assay (EIA). RESULTS: The elevated plasma 5-HT levels were significantly associated with increased odds for COPD (OR = 1.221, 95% CI = 1.123 to 1.319, p<0.0001). The effect remained significant after being adjusted for age and pack-years smoked (OR = 1.271, 95% CI = 1.134 to 1.408, p = 0.0003). Furthermore, plasma 5-HT was found to mediate the relation between pack-years smoked and COPD. A positive correlation (r = 0.303, p = 0.017) was found between plasma 5-HT levels and age in COPD, but not in the control subjects (r = -0.149, p = 0.108). CONCLUSION: Our results suggest that cigarette smoke-induced COPD is partially mediated by the plasma levels of 5-HT, and that these become elevated with increased age in COPD. The elevated plasma 5-HT levels in COPD might contribute to the pathogenesis of this disease.