Superficial Amygdala Research Articles

Aberrant functional connectivity of amygdala subregions in temporal lobe epilepsy with ictal panic.

The amygdala joins the model of fear neurocircuitry for its subregional roles in processing and mediating panic. This study aims to explore the underlying neuromechanisms of temporal lobe epilepsy (TLE) patients with ictal panic (IP) by investigating the amygdala subregions functional connectivity (FC) alteration. 18 TLE patients with IP (TLE-IP group), 23 TLE patients without IP (TLE-none-IP group) and 22 age- and sex- matched healthy controls (HC) were enrolled and required to take resting-state functional magnetic resonance imaging (rs-fMRI) scanning. The basolateral (BLA), centromedial (CMA), and superficial(SFA) amygdala subregions were extracted from Juelich histological atlas. The amygdala subregions-based FC was computed and compared among three groups. The TLE-IP group demonstrated stronger FC between the left BLA and right middle frontal gyrus (MFG) than the TLE-none-IP group and HC. Compared with the TLE-none-IP group and HC, the TLE-IP group showed increased FC between the right BLA and right postcentral gyrus. The FC between the left BLA/SFA and the orbital part of right MFG increased in the TLE-IP group. Furthermore, the TLE-IP group exhibited decreased FC between the left CMA and pons. Further analysis indicated altered FC between the amygdala subregions and the pons, precuneus and thalamus in the left-sided TLE-IP group, but the MFG, inferior parietal gyrus, supplementary motor area and cerebellum in the right-sided TLE-IP group. The present study revealed aberrant amygdala subregions-based FC in TLE patients with IP. These findings offer unique insights into the understanding of fear neurocircuitry in TLE patients with IP.

Functional connectivity of the amygdala subregions and the antidepressant effects of repeated ketamine infusions in major depressive disorder.

Amygdala subregion-based network dysfunction has been determined to be centrally implicated in major depressive disorder (MDD). Little is known about whether ketamine modulates amygdala subarea-related networks. We aimed to investigate the relationships between changes in the resting-state functional connectivity (RSFC) of amygdala subregions and ketamine treatment and to identify important neuroimaging predictors of treatment outcomes. Thirty-nine MDD patients received six doses of ketamine (0.5mg/kg). Depressive symptoms were assessed, and magnetic resonance imaging (MRI) scans were performed before and after treatment. Forty-five healthy controls underwent one MRI scan. Seed-to-voxel RSFC analyses were performed on the amygdala subregions, including the centromedial amygdala (CMA), laterobasal amygdala (LBA), and superficial amygdala subregions. Abnormal RSFC between the left LBA and the left precuneus in MDD patients is related to the therapeutic efficacy of ketamine. There were significant differences in changes in bilateral CMA RSFC with the left orbital part superior frontal gyrus and in changes in the left LBA with the right middle frontal gyrus between responders and nonresponders following ketamine treatment. Moreover, there was a difference in the RSFC of left LBA and the right superior temporal gyrus/middle temporal gyrus (STG/MTG) between responders and nonresponders at baseline, which could predict the antidepressant effect of ketamine on Day 13. The mechanism by which ketamine improves depressive symptoms may be related to its regulation of RSFC in the amygdala subregion. The RSFC between the left LBA and right STG/MTG may predict the response to the antidepressant effect of ketamine.

Amygdala subdivisions exhibit aberrant whole-brain functional connectivity in relation to stress intolerance and psychotic symptoms in 22q11.2DS

The amygdala is a key region in emotional regulation, which is often impaired in psychosis. However, it is unclear if amygdala dysfunction directly contributes to psychosis, or whether it contributes to psychosis through symptoms of emotional dysregulation. We studied the functional connectivity of amygdala subdivisions in patients with 22q11.2DS, a known genetic model for psychosis susceptibility. We investigated how dysmaturation of each subdivision’s connectivity contributes to positive psychotic symptoms and impaired tolerance to stress in deletion carriers. Longitudinally-repeated MRI scans from 105 patients with 22q11.2DS (64 at high-risk for psychosis and 37 with impaired tolerance to stress) and 120 healthy controls between the ages of 5 to 30 years were included. We calculated seed-based whole-brain functional connectivity for amygdalar subdivisions and employed a longitudinal multivariate approach to evaluate the developmental trajectory of functional connectivity across groups. Patients with 22q11.2DS presented a multivariate pattern of decreased basolateral amygdala (BLA)-frontal connectivity alongside increased BLA-hippocampal connectivity. Moreover, associations between developmental drops in centro-medial amygdala (CMA)-frontal connectivity to both impaired tolerance to stress and positive psychotic symptoms in deletion carriers were detected. Superficial amygdala hyperconnectivity to the striatum was revealed as a specific pattern arising in patients who develop mild to moderate positive psychotic symptoms. Overall, CMA-frontal dysconnectivity was found as a mutual neurobiological substrate in both impaired tolerance to stress and psychosis, suggesting a role in prodromal dysregulation of emotions in psychosis. While BLA dysconnectivity was found to be an early finding in patients with 22q11.2DS, which contributes to impaired tolerance to stress.

Increased functional connectivity of amygdala subregions in patients with drug-naïve panic disorder and without comorbidities.

Amygdala plays an important role in the neurobiological basis of panic disorder (PD), and the amygdala contains different subregions, which may play different roles in PD. The aim of the present study was to examine whether there are common or distinct patterns of functional connectivity of the amygdala subregions in PD using resting-state functional magnetic resonance imaging and to explore the relationship between the abnormal spontaneous functional connectivity patterns of the regions of interest (ROIs) and the clinical symptoms of PD patients. Fifty-three drug-naïve, non-comorbid PD patients and 70 healthy controls (HCs) were recruited. Seed-based resting-state functional connectivity (rsFC) analyses were conducted using the bilateral amygdalae and its subregions as the ROI seed. Two samples t test was performed for the seed-based Fisher's z -transformed correlation maps. The relationship between the abnormal spontaneous functional connectivity patterns of the ROIs and the clinical symptoms of PD patients was investigated by Pearson correlation analysis. PD patients showed increased rsFC of the bilateral amygdalae and almost all the amygdala subregions with the precuneus/posterior cingulate gyrus compared with the HC group (left amygdala [lAMY]: t = 4.84, P <0.001; right amygdala [rAMY]: t = 4.55, P <0.001; left centromedial amygdala [lCMA]: t = 3.87, P <0.001; right centromedial amygdala [rCMA]: t = 3.82, P = 0.002; left laterobasal amygdala [lBLA]: t = 4.33, P <0.001; right laterobasal amygdala [rBLA]: t = 4.97, P <0.001; left superficial amygdala [lSFA]: t = 3.26, P = 0.006). The rsFC of the lBLA with the left angular gyrus/inferior parietal lobule remarkably increased in the PD group ( t = 3.70, P = 0.003). And most of the altered rsFCs were located in the default mode network (DMN). A significant positive correlation was observed between the severity of anxiety and the rsFC between the lSFA and the left precuneus in PD patients ( r = 0.285, P = 0.039). Our research suggested that the increased rsFC of amygdala subregions with DMN plays an important role in the pathogenesis of PD. Future studies may further explore whether the rsFC of amygdala subregions, especially with the regions in DMN, can be used as a biological marker of PD.

Regional superficial amygdala resting-state functional connectivity in adults infers childhood maltreatment severity.

Childhood maltreatment (CM) is a potential risk factor for some neuropsychiatric disorders in adulthood (e.g. depression and anxiety) and alters trajectories of brain development. Accumulating evidence suggests that functional connectivity of the limbic system, especially the amygdala, is highly associated with childhood maltreatment, although not all studies have found this. These inconsistent results may be due to differential alterations of amygdala resting-state functional connectivity (rsFC) following childhood maltreatment. Our aim was to investigate the relationship between the rsFC of amygdala subregions and CM severity, as well as to develop a stable rsFC-based model for inferring the severity of CM. In this study, we employed the Childhood Trauma Questionnaire (CTQ) to assess CM severity in each individual. We explored the relationship between the rsFC of amygdala subregions (i.e. centromedial -CMA, basolateral -BLA, superficial-SFA amygdala) and CM experience in a discovery dataset of n=110 healthy Chinese participants by linear multiple regression analysis. Subsequent dimensional and categorical approach were performed to elucidate the relationship between rsFCs and CM severity and CM subtypes, respectively. A support vector regression model was then conducted to validate the associations between rsFCs and total CTQ scores. Moreover, we also verified the model into another independent replication dataset (n=38). Our findings suggested that childhood maltreatment was negatively associated with rsFC between the right superficial amygdala and perigenual anterior cingulate cortex (pgACC)/postcentral gyrus (PCG) but not the other two amygdala subregions. Moreover, SFA-pgACC coupling was more associated with physical neglect whereas the SFA-PCG was more related to emotional neglect. In addition, supervised machine learning confirmed that using these two rsFCs as predictors could stably estimate continuous maltreatment severity in both discovery and replication datasets. The current study supports that the rsFCs of superficial amygdala are related to childhood maltreatment and which may be a potential biomarker for the effects of childhood maltreatment-related psychiatric disorders (i.e. depression and anxiety).

Common and distinct roles of amygdala subregional functional connectivity in non-motor symptoms of Parkinson’s disease

Neuroimaging studies suggest a pivotal role of amygdala dysfunction in non-motor symptoms (NMS) of Parkinson’s disease (PD). However, the relationship between amygdala subregions (the centromedial (CMA), basolateral (BLA) and superficial amygdala (SFA)) and NMS has not been delineated. We used resting-state functional MRI to examine the PD-related alterations in functional connectivity for amygdala subregions. The left three subregions and right BLA exhibited between-group differences, and were commonly hypo-connected with the frontal, temporal, insular cortex, and putamen in PD. Each subregion displayed distinct hypoconnectivity with the limbic systems. Partial least-squares analysis revealed distinct amygdala subregional involvement in diverse NMS. Hypo-connectivity of all four subregions was associated with emotion, pain, olfaction, and cognition. Hypo-connectivity of the left SFA was associated with sleepiness. Our findings highlight the hypofunction of the amygdala subregions in PD and their preliminary associations with NMS, providing new insights into the pathogenesis of NMS.

Functional Connectivity Between Basal Forebrain and Superficial Amygdala Negatively Correlates with Social Fearfulness

Social anxiety is characterized by an intense fear of evaluation from others and/or withdrawal from social situations. Extreme social anxiety can lead to social anxiety disorder. There remains an urgent need to investigate the neural substrates of subclinical social anxiety for early diagnosis and intervention to reduce the risk to develop social anxiety disorder. Twenty-nine young adults were recruited (10 males/19 females; mean age (SD) = 20.34 (2.29)). Trait-like social anxiety was assessed by Liebowitz Social Anxiety Scale. Functional magnetic resonance imaging was used with an emotional face-matching paradigm to probe brain activation in response to emotional stimuli including angry, fearful, and happy faces, with shape-matching as a control condition. Behavioral results showed positive correlations between Liebowitz Social Anxiety Scale scores and the reaction time in both angry and fearful conditions. The activation of superficial amygdala and the deactivation of basal forebrain in response to angry condition showed positive correlations with the level of social anxiety. In addition, the resting-state functional connectivity between these two regions was negatively correlated with the level of social anxiety. These results may help to understand the individual difference and corresponding neural underpinnings of social anxiety in the subclinical population, and might provide some insight to develop strategies for early diagnosis and interventions of social anxiety to reduce the risk of deterioration from subclinical to clinical level of social anxiety.

Functional connectivity differences in the amygdala are related to the antidepressant efficacy of ketamine in patients with anxious depression

BackgroundThe antidepressant effects of ketamine in patients with anxious depression (AD) remain unclear. Functional connectivity (FC) differences in the amygdala have been linked to depression improvement after ketamine treatment in depressed patients, but their role in AD patients is uncertain. We investigated the correlation between depression improvement after ketamine treatment and amygdala FC in AD patients. MethodsThirty-one AD patients and 18 non-anxious depression (NAD) patients received six intravenous ketamine infusions (0.5 mg/kg) over two weeks. AD patients were further divided into responders (defined as a ≥50% MADRS total score reduction on day 13) and non-responders. The FC of the amygdala subregions, including the laterobasal amygdala (LBA), centromedial amygdala (CMA), and superficial amygdala, were compared between the groups. Receiver operating characteristic curves were used to predict treatment response after ketamine infusions. ResultsThe baseline FC difference in the left LBA and the left precuneus between responders and non-responders among AD patients was found to be associated with depression improvement and was a significant predictor of treatment response to ketamine. A marked reduction in baseline LBA-precuneus FC after ketamine infusion was observed in responders. Unlike in patients with NAD, a lower right CMA-right middle temporal gyrus FC was found in AD patients. LimitationsThe sample size is rather small. ConclusionsOur findings may suggest that amygdala FC is a significant predictor of treatment response to ketamine infusions in patients with AD. Further studies exploring the potential antidepressant mechanisms of ketamine may aid in the treatment of AD patients.

Sleep deprivation altered encoding of basolateral amygdala on fear acquisition.

Sleep deprivation (SD) may lead to the development of fear- and anxiety-related emotional disorders. However, the neural mechanisms underlying the effects of SD on fear acquisition are unclear. Here, we tested whether and how SD influences the behavioral and neural manifestations of fear acquisition. We found that subjective fear ratings and objective fear indices (skin conductance response [SCR]) in the SD group were greater than those in the control group during fear acquisition, suggesting that SD facilitated fear acquisition (nSD = 18 and ncontrol = 23 for self-reported rating analysis; nSD = 10 and ncontrol = 10 for SCR analysis). Neuroimaging data showed that the SD group exhibited stronger activity in the left basolateral amygdala (BLA) and left superficial amygdala (SFA). Moreover, the left BLA activity, which positively correlated with the objective fear indices, significantly mediated the effect of SD on fear acquisition. Together, the present findings indicate that SD facilitates fear acquisition by augmenting threat-specific encoding in the BLA, which may be a potential biomarker of the risk of developing fear-related disorders under traumatic and distressing situations.

An exploratory study of resting-state functional connectivity of amygdala subregions in posttraumatic stress disorder following trauma in adulthood

We carried out an exploratory study aimed at identifying differences in resting-state functional connectivity for the amygdala and its subregions, right and left basolateral, centromedial and superficial nuclei, in patients with Posttraumatic Stress Disorder (PTSD), relative to controls. The study included 10 participants with PTSD following trauma in adulthood (9 females), and 10 controls (9 females). The results suggest PTSD was associated with a decreased (negative) functional connectivity between the superficial amygdala and posterior brain regions relative to controls. The differences were observed between right superficial amygdala and right fusiform gyrus, and between left superficial amygdala and left lingual and left middle occipital gyri. The results suggest that among PTSD patients, the worse the PTSD symptoms, the lower the connectivity. The results corroborate the fMRI literature that shows PTSD is associated with weaker amygdala functional connectivity with areas of the brain involved in sensory and perceptual processes. The results also suggest that though the patients traumatic experience occured in adulthood, the presence of early traumatic experiences were associated with negative connectivity between the centromedial amygdala and sensory and perceptual regions. We argue that the understanding of the mechanisms of PTSD symptoms, its behaviors and the effects on quality of life of patients may benefit from the investigation of brain function that underpins sensory and perceptual symptoms associated with the disorder.

Structural covariance of amygdala subregions is associated with trait aggression and endogenous testosterone in healthy individuals

Many studies point toward volume reductions in the amygdala as a potential neurostructural marker for trait aggression. However, most of these findings stem from clinical samples, rendering unclear whether the findings generalize to non-clinical populations. Furthermore, the notion of neural networks suggests that interregional correlations in gray matter volume (i.e., structural covariance) can explain individual differences in aggressive behavior beyond local univariate associations. Here, we tested whether structural covariance between amygdala subregions and the rest of the brain is associated with self-reported aggression in a large sample of healthy young students (n = 263; 49% women). Salivary testosterone concentrations were measured for a subset of n = 40 male and n = 36 female subjects, allowing us to investigate the influence of endogenous testosterone on structural covariance. Aggressive individuals showed enhanced covariance between left superficial amygdala (SFA) and left dorsal anterior insula (dAI), but lower covariance between right laterobasal amygdala (LBA) and right dorsolateral prefrontal cortex (dlPFC). These structural patterns overlap with functional networks involved in the genesis and regulation of aggressive behavior, respectively. With increasing endogenous testosterone, we observed stronger structural covariance between right centromedial amygdala (CMA) and right medial prefrontal cortex in men and between left CMA and bilateral orbitofrontal cortex in women. These results speak for structural covariance of amygdala subregions as a robust correlate of trait aggression in healthy individuals. Moreover, regions that showed structural covariance with the amygdala modulated by either testosterone or aggression did not overlap, suggesting a complex role of testosterone in human social behavior beyond facilitating aggressiveness.

Distinct alterations of amygdala subregional functional connectivity in early- and late-onset obsessive-compulsive disorder

BackgroundAge of onset may be an important feature associated with distinct subtypes of obsessive-compulsive disorder (OCD). The amygdala joined neurocircuitry models of OCD for its role in mediating fear and regulating anxiety. The present study aims to identify the underlying pathophysiological specifics in OCD with different onset times by assessing amygdala subregional functional connectivity (FC) alterations in early-onset OCD (EO-OCD) and late-onset OCD (LO-OCD). MethodsResting-state functional magnetic resonance imaging data were acquired from 88 medication-free OCD patients (including 30 EO-OCD and 58 LO-OCD) and age- and sex-matched healthy controls (HC) for each patient group. Onset-by-diagnosis interactions were examined and comparisons between each OCD group and the corresponding HC group were performed regarding the FC of amygdala subregions including the basolateral amygdala (BLA), centromedial amygdala (CMA), superficial amygdala (SFA) and amygdalostriatal transition area (Astr). ResultsSignificant onset-by-diagnosis interactions were found in FC between bilateral SFA, right CMA, left Astr and the cerebellum. EO-OCD patients showed abnormally increased BLA/SFA-cerebellum, BLA-precuneus and BLA/SFA-fusiform connectivity in addition to decreased BLA/SFA-orbitofrontal cortex connectivity. In contrast, LO-OCD patients exhibited increased CMA/Astr-precentral/postcentral gyrus and CMA-cuneus connectivity as well as decreased CMA/Astr-cerebellum and BLA-striatum connectivity. LimitationsThe exclusion of comorbidity may reduce the generalizability of our results. ConclusionsThese findings emphasized the different patterns of amygdala subregional connectivity alterations associated with EO-OCD and LO-OCD patients. These results provide unique insights into constructing evidence-based distinct OCD subtypes based on brain intrinsic connectivity and point to the need of specified management for EO-OCD and LO-OCD in clinical setting.

Resting-state functional connectivity of the amygdala subregions in unmedicated patients with obsessive-compulsive disorder before and after cognitive behavioural therapy.

Background:Cognitive behavioural therapy (CBT) is considered an effective first-line treatment for obsessive–compulsive disorder (OCD). However, the neural basis of CBT for OCD has not yet been elucidated. The role of the amygdala in OCD and its functional coupling with the cerebral cortex have received increasing attention, and may provide new understanding of the neural basis of CBT for OCD.Methods:We acquired baseline resting-state functional MRI (fMRI) scans from 45 unmedicated patients with OCD and 40 healthy controls; we then acquired another wave of resting-state fMRI scans from the patients with OCD after 12 weeks of CBT. We performed seed-based resting-state functional connectivity analyses of the amygdala subregions to examine changes in patients with OCD as a result of CBT.Results:Compared to healthy controls, patients with OCD showed significantly increased resting-state functional connectivity at baseline between the left basolateral amygdala and the right middle frontal gyrus, and between the superficial amygdala and the right cuneus. In patients with OCD who responded to CBT, we found decreased resting-state functional connectivity after CBT between the amygdala subregions and the visual association cortices and increased resting-state functional connectivity between the amygdala subregions and the right inferior parietal lobe. Furthermore, these changes in resting-state functional connectivity were positively associated with changes in scores on the compulsion or obsession subscales of the Yale–Brown Obsessive–Compulsive Scale.Limitations:Because of the lack of a second scan for healthy controls after 12 weeks, our results may have been confounded by other variables.Conclusion:Our findings yield insights into the pathophysiology of OCD; they also reveal the potential neural changes elicited by CBT, and thus have implications for guiding effective treatment strategies with CBT for OCD.

Functional connectivity of amygdala subregions predicts vulnerability to depression following the COVID-19 pandemic

BackgroundThe amygdala is vital in processing psychological stress and predicting vulnerability or resilience to stress-related disorders. This study aimed to build the link between functional magnetic resonance imaging data obtained before the stress event and the subsequent stress-related depressive symptoms. MethodsNeuroimaging data obtained before the coronavirus disease 2019 pandemic from 39 patients with major depressive disorder (MDD) and 61 health controls (HCs) were used in this study. The participants were divided retrospectively into four groups in accordance with the severity of depressive symptoms during the pandemic: remitted patients, non-remitted patients, depressed HCs (HCd) and non-depressed HCs (HCnd). Seed-based resting-state functional connectivity (rsFC) analyses of the amygdala and its subregions, including the centromedial (CM), the basolateral and the superficial (SF), were performed. ResultsVulnerability to depression was suggested by decreased rsFC between the left CM amygdala and the bilateral lingual gyrus in the HCd group compared with the HCnd group, and decreased rsFC of the left CM or right SF amygdala with the precuneus and the postcentral gyrus in the HCd group compared with patients with MDD. No evidence supported the rsFC of the amygdala or its subregions as a biomarker for the resilience of patients with MDD to stress under antidepressant treatment. LimitationsSmaller sample size and no longitudinal neuroimaging data. ConclusionsOur findings suggested that the rsFC of amygdala subregions may represent a neurobiological marker of vulnerability to depression following stress.

Dynamic Functional Connectivity Reveals Abnormal Variability in the Amygdala Subregions of Children With Attention-Deficit/Hyperactivity Disorder

Objective: This study investigates whether the dynamic functional connectivity (dFC) of the amygdala subregions is altered in children with attention-deficit/hyperactivity disorder (ADHD).Methods: The dFC of the amygdala subregions was systematically calculated using a sliding time window method, for 75 children with ADHD and 20 healthy control (HC) children.Results: Compared with the HC group, the right superficial amygdala exhibited significantly higher dFC with the right prefrontal cortex, the left precuneus, and the left post-central gyrus for children in the ADHD group. The dFC of the amygdala subregions showed a negative association with the cognitive functions of children in the ADHD group.Conclusion: Functional connectivity of the amygdala subregions is more unstable among children with ADHD. In demonstrating an association between the stability of functional connectivity of the amygdala and cognitive functions, this study may contribute by providing a new direction for investigating the internal mechanism of ADHD.

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

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. 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). 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). 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.

Common and Specific Alterations of Amygdala Subregions in Major Depressive Disorder With and Without Anxiety: A Combined Structural and Resting-State Functional MRI Study.

Anxious major depressive disorder is a common subtype of major depressive disorder; however, its unique neural mechanism is not well-understood currently. Using multimodal MRI data, this study examined common and specific alterations of amygdala subregions between patients with and without anxiety. No alterations were observed in the gray matter volume or intra-region functional integration in either patient group. Compared with the controls, both patient groups showed decreased functional connectivity between the left superficial amygdala and the left putamen, and between the right superficial amygdala and the bilateral anterior cingulate cortex and medial orbitofrontal cortex, while only patients with anxiety exhibited decreased activity in the bilateral laterobasal and superficial amygdala. Moreover, the decreased activity correlated negatively with the Hamilton depression scale scores in the patients with anxiety. These findings provided insights into the pathophysiologic processes of anxious major depressive disorder and may help to develop new and effective treatment programs.

Effective connectivity between bed nucleus of the stria terminalis and amygdala: Reproducibility and relation to anxiety.

In a previous study, we investigated the resting‐state fMRI effective connectivity (EC) between the bed nucleus of the stria terminalis (BNST) and the laterobasal (LB), centromedial (CM), and superficial (SF) amygdala. We found strong negative EC from all amygdala nuclei to the BNST, while the BNST showed positive EC to the amygdala. However, the validity of these findings remains unclear, since a reproduction in different samples has not been done. Moreover, the association of EC with measures of anxiety offers deeper insight, due to the known role of the BNST and amygdala in fear and anxiety. Here, we aimed to reproduce our previous results in three additional samples. We used spectral Dynamic Causal Modeling to estimate the EC between the BNST, the LB, CM, and SF, and its association with two measures of self‐reported anxiety. Our results revealed consistency over samples with regard to the negative EC from the amygdala nuclei to the BNST, while the positive EC from BNST to the amygdala was also found, but weaker and more heterogenic. Moreover, we found the BNST‐BNST EC showing a positive and the CM‐BNST EC, showing a negative association with anxiety. Our study suggests a reproducible pattern of negative EC from the amygdala to the BNST along with weaker positive EC from the BNST to the amygdala. Moreover, less BNST self‐inhibition and more inhibitory influence from the CM to the BNST seems to be a pattern of EC that is related to higher anxiety.

Altered amygdala-based functional connectivity in individuals with attenuated psychosis syndrome and first-episode schizophrenia

Altered resting-state functional connectivity (FC) of the amygdala (AMY) has been demonstrated to be implicated in schizophrenia (SZ) and attenuated psychosis syndrome (APS). Specifically, no prior work has investigated FC in individuals with APS using subregions of the AMY as seed regions of interest. The present study examined AMY subregion-based FC in individuals with APS and first-episode schizophrenia (FES) and healthy controls (HCs). The resting state FC maps of the three AMY subregions were computed and compared across the three groups. Correlation analysis was also performed to examine the relationship between the Z-values of regions showing significant group differences and symptom rating scores. Individuals with APS showed hyperconnectivity between the right centromedial AMY (CMA) and left frontal pole cortex (FPC) and between the laterobasal AMY and brain stem and right inferior lateral occipital cortex compared to HCs. Patients with FES showed hyperconnectivity between the right superficial AMY and left occipital pole cortex and between the left CMA and left thalamus compared to the APS and HCs respectively. A negative relationship was observed between the connectivity strength of the CMA with the FPC and negative-others score of the Brief Core Schema Scales in the APS group. We observed different altered FC with subregions of the AMY in individuals with APS and FES compared to HCs. These results shed light on the pathogenetic mechanisms underpinning the development of APS and SZ.

Altered effective connectivity from the pregenual anterior cingulate cortex to the laterobasal amygdala mediates the relationship between internet gaming disorder and loneliness.

Individual with internet gaming disorder (IGD) often experience a high level of loneliness, and neuroimaging studies have demonstrated that amygdala function is associated with both IGD and loneliness. However, the neurobiological basis underlying these relationships remains unclear. In the current study, Granger causal analysis was performed to investigate amygdalar subdivision-based resting-state effective connectivity differences between 111 IGD subjects and 120 matched participants with recreational game use (RGUs). We further correlated neuroimaging findings with clinical measures. Mediation analysis was conducted to explore whether amygdalar subdivision-based effective connectivity mediated the relationship between IGD severity and loneliness. Compared with RGUs, IGD subjects showed inhibitory effective connections from the left pregenual anterior cingulate cortex (pACC) to the left laterobasal amygdala (LBA) and from the right medial prefrontal cortex (mPFC) to the left LBA, as well as an excitatory effective connection from the left middle prefrontal gyrus (MFG) to the right superficial amygdala. Further analyses demonstrated that the left pACC-left LBA effective connection was negatively correlated with both Internet Addiction Test and UCLA Loneliness scores, and it mediated the relationship between the two. IGD subjects and RGUs showed different connectivity patterns involving amygdalar subdivisions. These findings support a neurobiological mechanism for the relationship between IGD and loneliness, and suggest targets for therapeutic approaches that could be used to treat IGD.