Home alone: A population neuroscience investigation of brain morphology substrates.

As a social species, ready exchange with peers is a pivotal asset - our "social capital". Yet, single-person households have come to pervade metropolitan cities worldwide, with unknown consequences in the long run. Here, we systematically explore the morphological manifestations associated with singular living in ∼40,000 UK Biobank participants. The uncovered population-level signature spotlights the highly associative default mode network, in addition to findings such as in the amygdala central, cortical and corticoamygdaloid nuclei groups, as well as the hippocampal fimbria and dentate gyrus. Both positive effects, equating to greater gray matter volume associated with living alone, and negative effects, which can be interpreted as greater gray matter associations with not living alone, were found across the cortex and subcortical structures Sex-stratified analyses revealed male-specific neural substrates, including somatomotor, saliency and visual systems, while female-specific neural substrates centered on the dorsomedial prefrontal cortex. In line with our demographic profiling results, the discovered neural pattern of living alone is potentially linked to alcohol and tobacco consumption, anxiety, sleep quality as well as daily TV watching. The persistent trend for solitary living will require new answers from public-health decision makers. SIGNIFICANCE STATEMENT: Living alone has profound consequences for mental and physical health. Despite this, there has been a rapid increase in single-person households worldwide, with the long-term consequences yet unknown. In the largest study of its kind, we investigate how the objective lack of everyday social interaction, through living alone, manifests in the brain. Our population neuroscience approach uncovered a gray matter signature that converged on the 'default network', alongside targeted subcortical, sex and demographic profiling analyses. The human urge for social relationships is highlighted by the evolving COVID-19 pandemic. Better understanding of how social isolation relates to the brain will influence health and social policy decision-making of pandemic planning, as well as social interventions in light of global shifts in houseful structures.

Differential alterations of amygdala nuclei volumes in acutely ill patients with anorexia nervosa and their associations with leptin levels.

BACKGROUND: The amygdala is a subcortical limbic structure consisting of histologically and functionally distinct subregions. New automated structural magnetic resonance imaging (MRI) segmentation tools facilitate the in vivo study of individual amygdala nuclei in clinical populations such as patients with anorexia nervosa (AN) who show symptoms indicative of limbic dysregulation. This study is the first to investigate amygdala nuclei volumes in AN, their relationships with leptin, a key indicator of AN-related neuroendocrine alterations, and further clinical measures. METHODS: T1-weighted MRI scans were subsegmented and multi-stage quality controlled using FreeSurfer. Left/right hemispheric amygdala nuclei volumes were cross-sectionally compared between females with AN (n = 168, 12-29 years) and age-matched healthy females (n = 168) applying general linear models. Associations with plasma leptin, body mass index (BMI), illness duration, and psychiatric symptoms were analyzed via robust linear regression. RESULTS: Globally, most amygdala nuclei volumes in both hemispheres were reduced in AN v. healthy control participants. Importantly, four specific nuclei (accessory basal, cortical, medial nuclei, corticoamygdaloid transition in the rostral-medial amygdala) showed greater volumetric reduction even relative to reductions of whole amygdala and total subcortical gray matter volumes, whereas basal, lateral, and paralaminar nuclei were less reduced. All rostral-medially clustered nuclei were positively associated with leptin in AN independent of BMI. Amygdala nuclei volumes were not associated with illness duration or psychiatric symptom severity in AN. CONCLUSIONS: In AN, amygdala nuclei are altered to different degrees. Severe volume loss in rostral-medially clustered nuclei, collectively involved in olfactory/food-related reward processing, may represent a structural correlate of AN-related symptoms. Hypoleptinemia might be linked to rostral-medial amygdala alterations.

Explicating the role of amygdala substructure alterations in the link between hypoleptinemia and rumination in anorexia nervosa.

OBJECTIVE: The amygdaloid complex plays a pivotal role in emotion processing and has been associated with rumination transdiagnostically. In anorexia nervosa (AN), we previously observed differential reductions of amygdala nuclei volumes (rostral-medial cluster substantially affected) and, in another study, elevated food-/weight-related rumination. Both amygdala volumes and rumination frequency correlated with characteristically suppressed leptin levels in AN. Thus, we hypothesized that amygdala nuclei alterations might be associated with AN-related rumination and potentially mediate the leptin-rumination relationship in AN. METHODS: Rumination (food-/weight-related) was assessed using ecological momentary assessment for a 14-day period. We employed frequentist and Bayesian linear mixed effects models in females with AN (n = 51, 12-29 years, majority admitted to inpatient treatment) and age-matched healthy females (n = 51) to investigate associations between rostral-medial amygdala nuclei volume alterations (accessory basal, cortical, medial nuclei, corticoamygdaloid transitions) and rumination. We analyzed mediation effects using multi-level structural equation models. RESULTS: Reduced right accessory basal and cortical nuclei volumes predicted more frequent weight-related rumination in AN; both nuclei fully mediated the effect of leptin on weight-related rumination. In contrast, we found robust evidence for the absence of amygdala nuclei volume effects on rumination in healthy females. CONCLUSION: This study provides first evidence for the relevance of specific amygdala substructure reductions regarding cognitive symptom severity in AN and points toward novel mechanistic insight into the relationship between hypoleptinemia and rumination, which might involve the amygdaloid complex. Our findings in AN may have important clinical value with respect to understanding the beneficial neuropsychiatric effects of leptin (treatment) in AN and potentially other psychiatric conditions such as depression.

Neurite density imaging in amygdala nuclei reveals interindividual differences in neuroticism.

Neuroticism is known to have significant health implications. While previous research revealed that interindividual differences in the amygdala function are associated with interindividual differences in neuroticism, the impact of the amygdala's structure and especially microstructure on variations in neuroticism remains unclear. Here, we present the first study using NODDI to examine the association between the in vivo microstructural architecture of the amygdala and neuroticism at the level of neurites. We, therefore, acquired brain images from 221 healthy participants using advanced multi-shell diffusion-weighted imaging. Because the amygdala comprises several nuclei, we, moreover, used a high-resolution T1 image to automatically segment the amygdala into eight different nuclei. Neuroticism and its facets have been assessed using the NEO-PI-R. Finally, we associated neuroticism and its facets with the volume and microstructure of the amygdala nuclei. Statistical analysis revealed that lower neurite density in the lateral amygdala nucleus (La) was significantly associated with higher scores in depression, one of the six neuroticism facets. The La is the sensory relay of the amygdala, filtering incoming information based on previous experiences. Reduced neurite density and related changes in the dendritic structure of the La could impair its filtering function. This again might cause harmless sensory information to be misevaluated as threatening and lead to the altered amygdala responsivity as reported in previous studies investigating the functional correlates of neuroticism and neuroticism-related disorders like depression.

Differential spatial patterns of structural connectivity of amygdala nuclei with orbitofrontal cortex.

The orbitofrontal cortex (OFC)-amygdala circuit is critical to goal-directed behavior, learning, and valuation. However, our understanding of the OFC-amygdala connections that support these emergent processes is hampered by our reliance on the primate literature and insufficient knowledge regarding the connectivity patterns between regions of OFC and amygdala nuclei, each of which is differentially involved in these processes in humans. Thus, we examined structural connectivity between different OFC regions and four amygdala nuclei in healthy adults (n = 1,053) using diffusion-based anatomical networks and probabilistic tractography in four conceptually distinct ways. First, we identified the OFC regions that connect with each nucleus. Second, we identified the OFC regions that were more likely to connect with a given nucleus than the others. Finally, we developed probabilistic and rank-order maps of OFC (one for each nucleus) based upon the likelihood of each OFC voxel exhibiting preferential connectivity with each nucleus and the relative density of connectivity between each OFC voxel and each nucleus, respectively. The first analyses revealed that the connections of each nucleus spanned all of OFC, reflecting widespread overall amygdala linkage with OFC. Analysis of preferential connectivity and probabilistic and rank-order maps of OFC converged to reveal differential patterns of connectivity between OFC and each nucleus. Present findings illustrate the importance of accounting for spatial specificity when examining links between OFC and amygdala. This fine-grained examination of OFC-amygdala connectivity can be applied to understand how such connectivity patterns support a range of emergent functions including affective and motivational processes.

Subcortical Volume Correlates of Psychological Distress in Early Adolescence.

The hippocampus and amygdala have justifiably been the focus of much mental health research due to their putative roles in top-down processing control of emotion, fear, and anxiety. However, understanding the causal relationship between these regions and mental illness has been limited as current literature is lacking in the observation of neuro-structural changes preceding first episodes. Here, we report whole and sub-structural hippocampal and amygdala volume correlates of psychological distress in early adolescence. Automated hippocampal subfield and amygdala nuclei segmentation was carried out in 32 participants (12-13 years old) recruited for the Longitudinal Adolescent Brain Study (LABS) who had psychological distress scores measured by the Kessler-10. Partial correlation analyses revealed significant negative association between left whole amygdala volume and psychological distress. Sub-structure analysis revealed that smaller left hippocampal CA1 volume and left basal and accessory basal amygdala nuclei volumes were all significantly associated with higher levels of psychological distress. Four-month follow-up analysis also revealed an association between change in K10 and CA1 volume suggesting a continued relationship between this hippocampal substructure and psychological distress. Grey matter volume of subcortical sub-structures involved within the hippocampal-basolateral amygdala-prefrontal cortex loop are highly correlated and are significantly reduced in adolescents with higher levels of psychological distress, indicating these nuclei and subfields play an important role in the emergence of mental illness.

Machine Learning Prediction of Estimated Risk for Bipolar Disorders Using Hippocampal Subfield and Amygdala Nuclei Volumes.

The pathophysiology of bipolar disorder (BD) remains mostly unclear. Yet, a valid biomarker is necessary to improve upon the early detection of this serious disorder. Patients with manifest BD display reduced volumes of the hippocampal subfields and amygdala nuclei. In this pre-registered analysis, we used structural MRI (n = 271, 7 sites) to compare volumes of hippocampus, amygdala and their subfields/nuclei between help-seeking subjects divided into risk groups for BD as estimated by BPSS-P, BARS and EPIbipolar. We performed between-group comparisons using linear mixed effects models for all three risk assessment tools. Additionally, we aimed to differentiate the risk groups using a linear support vector machine. We found no significant volume differences between the risk groups for all limbic structures during the main analysis. However, the SVM could still classify subjects at risk according to BPSS-P criteria with a balanced accuracy of 66.90% (95% CI 59.2-74.6) for 10-fold cross-validation and 61.9% (95% CI 52.0-71.9) for leave-one-site-out. Structural alterations of the hippocampus and amygdala may not be as pronounced in young people at risk; nonetheless, machine learning can predict the estimated risk for BD above chance. This suggests that neural changes may not merely be a consequence of BD and may have prognostic clinical value.

Morphometric analysis of medial temporal lobe subregions in Alzheimer's disease using high-resolution MRI.

The spread pattern of progressive degeneration seen in Alzheimer's disease (AD) to small-scale medial temporal lobe subregions is critical for early diagnosis. In this context, it was aimed to examine the morphometric changes of the hippocampal subfields, amygdala nuclei, entorhinal cortex (ERC), and parahippocampal cortex (PHC) using MRI. MRI data of patients diagnosed with 20 Alzheimer's disease dementia (ADD), 30 amnestic mild cognitive impairment (aMCI), and 30 subjective cognitive impairment (SCI) without demographic differences were used. Segmentation and parcellation were performed using FreeSurfer. The segmentation process obtained volume values of 12 hippocampal subfields and 9 amygdala nuclei. Thickness values of ERC and PHC were calculated with the parcellation process. ANCOVA was performed using age, education and gender as covariates to evaluate the intergroup differences. Linear discriminant analysis was used to investigate whether atrophy predicted groups at an early stage. ERC and PHC thickness decreased significantly throughout the disease continuum, while only ERC was affected in the early stage. When the hippocampal and amygdala subfields were compared volumetrically, significant differences were found in the amygdala between the SCI and aMCI groups. In the early period, only volume reduction in the anterior amygdaloid area of the amygdala nuclei exceeded the significance threshold. Research on AD primarily focuses on original hippocampocentric structures and their main function which is episodic memory. Our results emphasized the significance of so far relatively neglected olfactocentric structures and their functions, such as smell and social cognition in the pre-dementia stages of the AD process.

Automated subfield volumetric analysis of amygdala, hippocampus, and thalamic nuclei in mesial temporal lobe epilepsy.

Purpose: Identifying relationships between clinical features and quantitative characteristics of the amygdala-hippocampal and thalamic subregions in mesial temporal lobe epilepsy (mTLE) may offer insights into pathophysiology and the basis for imaging prognostic markers of treatment outcome. Our aim was to ascertain different patterns of atrophy or hypertrophy in mesial temporal sclerosis (MTS) patients and their associations with post-surgical seizure outcomes. To assess this aim, this study is designed in 2 folds: (1) hemispheric changes within MTS group and (2) association with postsurgical seizure outcomes. Methods and materials: 27 mTLE subjects with mesial temporal sclerosis (MTS) were scanned for conventional 3D T1w MPRAGE images and T2w scans. With respect to 12 months post-surgical seizure outcomes, 15 subjects reported being seizure free (SF) and 12 reported continued seizures. Quantitative automated segmentation and cortical parcellation were performed using Freesurfer. Automatic labeling and volume estimation of hippocampal subfields, amygdala, and thalamic subnuclei were also performed. The volume ratio (VR) for each label was computed and compared between (1) between contralateral and ipsilateral MTS using Wilcoxon rank-sum test and (2) SF and not seizure free (NSF) groups using linear regression analysis. False Discovery rate (FDR) with significant level of 0.05 were used in both analyses to correct for multiple comparisons. Results: Amygdala: The medial nucleus of the amygdala was the most significantly reduced in patients with continued seizures when compared to patients who remained seizure free. Hippocampus: Comparison of ipsilateral and contralateral volumes with seizure outcomes showed volume loss was most evident in the mesial hippocampal regions such as CA4 and hippocampal fissure. Volume loss was also most explicit in the presubiculum body in patients with continued seizures at the time of their follow-up. Ipsilateral MTS compared to contralateral MTS analysis showed the heads of the ipsilateral subiculum, presubiculum, parasubiculum, dentate gyrus, CA4, and CA3 were more significantly affected than their respective bodies. Volume loss was most noted in mesial hippocampal regions. Thalamus: VPL and PuL were the most significantly reduced thalamic nuclei in NSF patients. In all statistically significant areas, volume reduction was observed in the NSF group. No significant volume reductions were noted in the thalamus and amygdala when comparing ipsilateral to contralateral sides in mTLE subjects. Conclusions: Varying degrees of volume loss were demonstrated in the hippocampus, thalamus, and amygdala subregions of MTS, especially between patients who remained seizure-free and those who did not. The results obtained can be used to further understand mTLE pathophysiology. Clinical relevance/application: In the future, we hope these results can be used to deepen the understanding of mTLE pathophysiology, leading to improved patient outcomes and treatments.

Dynamic Amygdala Nuclei Alterations in Relation to Weight Status in Anorexia Nervosa Are Mediated by Leptin.

OBJECTIVE: The amygdaloid complex is a subcortical limbic group of distinct nuclei. In a previous patient-control study, differential amygdala nuclei alterations were found in acute anorexia nervosa (AN); rostral-medial nuclei involved in fear and reward processing were substantially reduced in volume and associated with hypoleptinemia, a key neuroendocrine characteristic of AN. Here, longitudinal amygdala nuclei alterations in AN were investigated in relation to weight status and their associations with leptin levels. METHOD: T1-weighted structural magnetic resonance imaging scans were longitudinally processed with FreeSurfer. Amygdala nuclei volumes in young female patients with acute AN before and after short-term weight restoration (n = 110, >14% body mass index increase over 3 months) and female participants with a history of AN (n = 79, long-term [mean 5 years] weight recovered) were compared with female healthy control participants (n = 271) using linear mixed effects models. RESULTS: Rostral-medially clustered amygdala nuclei volumes, accessory basal, cortical, medial nuclei, and corticoamygdaloid transition, increased during short-term weight restoration (Cohen's d range 0.18-0.30). However, volumetric normalization across nuclei was heterogeneous. Right cortical, medial nuclei, bilateral corticoamygdaloid transitions, and anterior amygdaloid areas were only partially normalized following short-term weight restoration. Right anterior amygdaloid area remained reduced after long-term weight recovery compared with control participants (d = 0.36). Leptin increase, accompanying short-term weight restoration, mediated the effect of weight gain on volumetric increase in left corticoamygdaloid transition and bilateral medial nuclei. CONCLUSION: Rostral-medially clustered amygdala nuclei show pronounced volumetric increase but incomplete normalization in AN during and after short-term weight restoration. Leptin increase may be relevant for the recovery of specific amygdala nuclei in addition to nutritional rehabilitation, indicating links between amygdala substructure and leptin dynamics of potential pathophysiological and clinical relevance in AN. PLAIN LANGUAGE SUMMARY: The amygdala plays a critical role in processing fearful and rewarding stimuli, and alterations in the amygdala are associated with anorexia nervosa. In this study, the authors measured amygdala nuclei volumes in female patients with acute anorexia nervosa undergoing weight-restoration treatment (n = 110), long-term weight-recovered individuals with anorexia (n = 79), and healthy control participants (n = 271). Structural magnetic resonance imaging revealed that volumes of specific nuclei, clustered in the rostral-medial amygdala, were substantially reduced in acute anorexia nervosa and only partially normalized following weight restoration treatment. Residual reductions in volume persisted even after long-term weight-recovery, compared to healthy control participants. Short-term weight restoration was associated with increases in the neurohormone leptin, and increasing leptin levels were found to mediate the positive impact of weight gain on increased amygdala volume over the treatment course. DIVERSITY & INCLUSION STATEMENT: We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. We worked to ensure that the study questionnaires were prepared in an inclusive way. One or more of the authors of this paper received support from a program designed to increase minority representation in science. We actively worked to promote sex and gender balance in our author group. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group. While citing references scientifically relevant for this work, we also actively worked to promote sex and gender balance in our reference list. While citing references scientifically relevant for this work, we also actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our reference list. The author list of this paper includes contributors from the location and/or community where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work.

Neural correlates of disaster-related prenatal maternal stress in young adults from Project Ice Storm: Focus on amygdala, hippocampus, and prefrontal cortex.

Background: Studies have shown that prenatal maternal stress alters volumes of the amygdala and hippocampus, and alters functional connectivity between the amygdala and prefrontal cortex. However, it remains unclear whether prenatal maternal stress (PNMS) affects volumes and functional connectivity of these structures at their subdivision levels. Methods: T1-weighted MRI and resting-state functional MRI were obtained from 19-year-old young adult offspring with (n = 39, 18 male) and without (n = 65, 30 male) exposure to PNMS deriving from the 1998 ice storm. Volumes of amygdala nuclei, hippocampal subfields and prefrontal subregions were computed, and seed-to-seed functional connectivity analyses were conducted. Results: Compared to controls, young adult offspring exposed to disaster-related PNMS had larger volumes of bilateral whole amygdala, driven by the lateral, basal, central, medial, cortical, accessory basal nuclei, and corticoamygdaloid transition; larger volumes of bilateral whole hippocampus, driven by the CA1, HATA, molecular layer, fissure, tail, CA3, CA4, and DG; and larger volume of the prefrontal cortex, driven by the left superior frontal. Inversely, young adult offspring exposed to disaster-related PNMS had lower functional connectivity between the whole amygdala and the prefrontal cortex (driven by bilateral frontal poles, the left superior frontal and left caudal middle frontal); and lower functional connectivity between the hippocampal tail and the prefrontal cortex (driven by the left lateral orbitofrontal). Conclusion: These results suggest the possibility that effects of disaster-related PNMS on structure and function of subdivisions of offspring amygdala, hippocampus and prefrontal cortex could persist into young adulthood.

Corrigendum: Correlation between amygdala nuclei volumes and memory in cognitively normal adults carrying the ApoE ε3/ε3 allele.

[This corrects the article DOI: 10.3389/fnagi.2021.747288.].

Impact of Prenatal Stress on Amygdala Anatomy in Young Adulthood: Timing and Location Matter.

BACKGROUND: Exposure to maternal stress in utero has long-term implications for the developing brain and has been linked with a higher risk of depression. The amygdala, which develops during the early embryonic stage and is critical for emotion processing, might be particularly sensitive. METHODS: Using data from a neuroimaging follow-up of the European Longitudinal Study of Pregnancy and Childhood prenatal birth cohort (n = 129, 47% men, 23-24 years old), we studied the impact of prenatal stress during the first and second halves of pregnancy on the volume of the amygdala and its nuclei in young adult offspring. We further evaluated the relationship between amygdala anatomy and offspring depressive symptomatology. Amygdala nuclei were parcellated using FreeSurfer's automated segmentation pipeline. Depressive symptoms were measured via self-report using the Beck Depression Inventory. RESULTS: Exposure to stress during the first half of pregnancy was associated with smaller accessory basal (Cohen's f2 = 0.27, false discovery rate [FDR]-corrected p [pFDR] = .03) and cortical (Cohen's f2 = 0.29, pFDR = .03) nuclei volumes. This effect remained significant after correcting for sex, stress during the second half of pregnancy, maternal age at birth, birth weight, maternal education, and offspring's age at magnetic resonance imaging. These two nuclei showed a quadratic relationship with Beck Depression Inventory scores in young adulthood, where both smaller and larger volumes were associated with more depressive symptoms (accessory basal nucleus: adj. R2 = 0.05, pFDR = .015; cortical nucleus: adj. R2 = 0.04, pFDR = .015). CONCLUSIONS: We conclude that exposure to stress during the first half of pregnancy might have long-term implications for amygdala anatomy, which may in turn predict the experience of depressive symptoms in young adulthood.

Correlation Between Amygdala Nuclei Volumes and Memory in Cognitively Normal Adults Carrying the ApoE ε3/ε3 Allele.

The amygdala is known to be related to cognitive function. In this study, we used an automated approach to segment the amygdala into nine nuclei and evaluated amygdala and nuclei volumetric changes across the adult lifespan in subjects carrying the apolipoprotein E (ApoE) ε3/ε3 allele, and we related those changes to memory function alteration. We found that except the left medial nucleus (Me), whose volume decreased in the old group compared with the middle-early group, all other nuclei volumes presented a significant decline in the old group compared with the young group. Left accessory basal nucleus (AB) and left cortico-amygdaloid transition area (CAT) volumes were also diminished in the middle-late group. In addition, immediate memory recall is impaired by the process of aging, whereas delayed recall and delayed recognition memory functions were not significantly changed. We found significant positive correlations between immediate recall scores and volumes of the bilateral basal nucleus (Ba), AB, anterior amygdaloid area (AAA), CAT, whole amygdala, left lateral nucleus (La), left paralaminar nucleus (PL), and right cortical nucleus (Co). The results suggest that immediate recall memory decline might be associated with volumetric reduction of the amygdala and its nuclei, and the left AB and left CAT might be considered as potential imaging biomarkers of memory decline in aging.

Brain areas associated with resilience to depression in high-risk young women.

Previous structural brain-imaging studies in first-degree relatives of depressed patients showed alterations that are generally accepted as vulnerability markers for depression. However, only half of the relatives had depression at follow-up, while the other half did not. The aim of this study was to identify the brain areas associated with resilience to depression in high-risk subjects with familial depression. We recruited 59 young women with a history of depressed mothers. Twenty-nine of them (high-risk group [HRG]) had no depression history, while 30 (depressive group) had at least 1 depressive episode in adolescence. The brain structures of the groups were compared through voxel-based morphometry and analysis of cortical thickness. Individual amygdala nuclei and hippocampal subfield volumes were measured. The analysis showed larger amygdala volume, thicker subcallosal cortex and bilateral insula in the women in the HRG compared with those in the depressive group. In addition, we detected more gray matter in the left temporal pole in the HRG. The larger gray matter volume and increased cortical thickness in the key hub regions of the salience network (amygdala and insula) and structurally connected regions in the limbic network (subcallosal area and temporal pole) might prevent women in the HRG from converting to depression.

Within amygdala: Basolateral parts are selectively impaired in premature-born adults.

While it is known that whole amygdala volume is lastingly reduced after premature birth, it is unknown whether different amygdala nuclei are distinctively affected by prematurity. This question is motivated by two points: First, the observation that developmental trajectories of superficial, centromedial and basolateral amygdala nuclei are different. And second, the expectation that these different developmental pathways are distinctively affected by prematurity. Furthermore, we stated the question whether alterations in amygdala nuclei are associated with increased adults' anxiety traits after premature birth. We investigated 101 very premature-born adults (<32 weeks of gestation and/or birth weight below 1500 g) and 108 full-term controls of a prospectively and longitudinally collected cohort at 26 years of age using automated amygdala nuclei segmentation based on structural MRI. We found selectively reduced volumes of bilateral accessory basal nuclei (pertaining to the basolateral amygdala of claustral developmental trajectory) adjusted for whole amygdala volume. Volumes of bilateral accessory basal nuclei were positively associated with gestational age and negatively associated with duration of ventilation. Furthermore, structural covariance within the basolateral amygdala was increased in premature-born adults. We did not find an association between reduced volumes of basolateral amygdala and increased social anxiety in the prematurity group. These results demonstrate specifically altered basolateral amygdala structure in premature-born adults. Data suggest that prematurity has distinct effects on amygdala nuclei.

Amygdala Nuclei Volume and Shape in Military Veterans With Posttraumatic Stress Disorder.

BACKGROUND: The amygdala is a subcortical structure involved in socioemotional and associative fear learning processes relevant for understanding the mechanisms of posttraumatic stress disorder (PTSD). Research in animals indicates that the amygdala is a heterogeneous structure in which the basolateral and centromedial divisions are susceptible to stress. While the amygdala complex is implicated in the pathophysiology of PTSD, little is known about the specific contributions of the individual nuclei that constitute the amygdala complex. METHODS: Military veterans (n = 355), including military veterans with PTSD (n = 149) and trauma-exposed control subjects without PTSD (n = 206), underwent high-resolution T1-weighted anatomical scans. Automated FreeSurfer segmentation of the amygdala yielded 9 structures: basal, lateral, accessory basal, anterior amygdaloid, and central, medial, cortical, and paralaminar nuclei, along with the corticoamygdaloid transition zone. Subregional volumes were compared between groups using ordinary-least-squares regression with relevant demographic and clinical regressors followed by 3-dimensional shape analysis of whole amygdala. RESULTS: PTSD was associated with smaller left and right lateral and paralaminar nuclei, but with larger left and right central, medial, and cortical nuclei (p < .05, false discovery rate corrected). Shape analyses revealed lower radial distance in anterior bilateral amygdala and lower Jacobian determinant in posterior bilateral amygdala in PTSD compared with control subjects. CONCLUSIONS: Alterations in select amygdala subnuclear volumes and regional shape distortions are associated with PTSD in military veterans. Volume differences of the lateral nucleus and the centromedial complex associated with PTSD demonstrate a subregion-specific pattern that is consistent with their functional roles in fear learning and fear expression behaviors.