Amygdala Volume Research Articles

A Longitudinal Study of Medial Temporal Lobe Volumes in Graves Disease.

Context Neuropsychiatric symptoms are common features of Graves disease (GD) in hyperthyroidism and after treatment. The mechanism behind these symptoms is unknown, but reduced hippocampal volumes have been observed in association with increased thyroid hormone levels.ObjectiveThis work aimed at investigating GD influence on regional medial temporal lobe (MTL) volumes.MethodsSixty-two women with newly diagnosed GD underwent assessment including magnetic resonance (MR) imaging in hyperthyroidism and 48 of them were followed up after a mean of 16.4 ± 4.2 SD months of treatment. Matched thyroid-healthy controls were also assessed twice at a 15-month interval. MR images were automatically segmented using multiatlas propagation with enhanced registration. Regional medial temporal lobe (MTL) volumes for amygdalae and hippocampi were compared with clinical data and data from symptom questionnaires and neuropsychological tests.ResultsPatients had smaller MTL regions than controls at inclusion. At follow-up, all 4 MTL regions had increased volumes and only the volume of the left amygdala remained reduced compared to controls. There were significant correlations between the level of thyrotropin receptor antibodies (TRAb) and MTL volumes at inclusion and also between the longitudinal difference in the levels of free 3,5,3′-triiodothyronine and TRAb and the difference in MTL volumes. There were no significant correlations between symptoms or test scores and any of the 4 MTL volumes.ConclusionDynamic alterations in the amygdalae and hippocampi in GD reflect a previously unknown level of brain involvement both in the hyperthyroid state of the condition and after treatment. The clinical significance, as well as the mechanisms behind these novel findings, warrant further study of the neurological consequences of GD.

Birth order and prosociality in the early adolescent brain

Birth order is a crucial environmental factor for child development. For example, later-born children are relatively unlikely to feel secure due to sibling competition or diluted parental resources. The positive effect of being earlier-born on cognitive intelligence is well-established. However, whether birth order is linked to social behavior remains controversial, and the neural correlates of birth order effects in adolescence when social cognition develops remain unknown. Here, we explored the birth order effect on prosociality using a large-scale population-based adolescent cohort. Next, since the amygdala is a key region for sociality and environmental stress, we examined amygdala substrates of the association between birth order and prosociality using a subset neuroimaging cohort. We found enhanced prosociality in later-born adolescents (N = 3160), and observed the mediating role of larger amygdala volume (N = 208) and amygdala-prefrontal functional connectivity with sex-selective effects (N = 183). We found that birth order, a non-genetic environmental factor, affects adolescent social development via different neural substrates. Our findings may indicate the later-born people’s adaptive survival strategy in stressful environments.

Charting the human amygdala development across childhood and adolescence: Manual and automatic segmentation

The developmental pattern of the amygdala throughout childhood and adolescence has been inconsistently reported in previous neuroimaging studies. Given the relatively small size of the amygdala on full brain MRI scans, discrepancies may be partly due to methodological differences in amygdalar segmentation. To investigate the impact of volume extraction methods on amygdala volume, we compared FreeSurfer, FSL and volBrain segmentation measurements with those obtained by manual tracing. The manual tracing method, which we used as the ‘gold standard’, exhibited almost perfect intra- and inter-rater reliability. We observed systematic differences in amygdala volumes between automatic (FreeSurfer and volBrain) and manual methods. Specifically, compared with the manual tracing, FreeSurfer estimated larger amygdalae, and volBrain produced smaller amygdalae while FSL demonstrated a mixed pattern. The tracing bias was not uniform, but higher for smaller amygdalae. We further modeled amygdalar growth curves using accelerated longitudinal cohort data from the Chinese Color Nest Project (http://deepneuro.bnu.edu.cn/?p=163). Trajectory modeling and statistical assessments of the manually traced amygdalae revealed linearly increasing and parallel developmental patterns for both girls and boys, although the amygdalae of boys were larger than those of girls. Compared to these trajectories, the shapes of developmental curves were similar when using the volBrain derived volumes. FreeSurfer derived trajectories had more nonlinearities and appeared flatter. FSL derived trajectories demonstrated an inverted U shape and were significantly different from those derived from manual tracing method. The use of amygdala volumes adjusted for total gray-matter volumes, but not intracranial volumes, resolved the shape discrepancies and led to reproducible growth curves between manual tracing and the automatic methods (except FSL). Our findings revealed steady growth of the human amygdala, mirroring its functional development across the school age. Methodological improvements are warranted for current automatic tools to achieve more accurate amygdala structure at school age, calling for next generation tools.

Examining Associations Between Amygdala Volumes and Anxiety Symptoms in Autism Spectrum Disorder

BackgroundAnxiety is one of the most common co-occurring conditions in people with autism spectrum disorder. The amygdala has been identified as being associated with anxiety in populations with and without autism, yet associations in autism were based on relatively small or developmentally constrained samples, leaving questions as to whether these results hold at different developmental ages and in a larger, more robust sample. MethodsStructural neuroimaging and parent report of anxiety symptoms of children ages 5–13 years with (n = 123) and without (n = 171) a diagnosis of autism were collected from the University of Maryland and three sites from the Autism Brain Imaging Data Exchange. Standardized residuals for bilateral amygdala volumes were computed adjusting for site, hemispheric volumes, and covariates (age, sex, Full Scale IQ). ResultsClinically significant anxiety symptoms did not differentiate amygdala volumes between groups (i.e., autism and anxiety, autism without anxiety, without autism or anxiety). No significant association between left or right amygdala volumes and anxiety scores was observed among the sample of individuals with autism. Meta-analytic and Bayes factor estimations provided additional support for the null hypothesis. Age, sex, and autism severity did not moderate associations between anxiety and amygdala volumes. ConclusionsNo relation between amygdala volumes and anxiety symptoms in children with autism was observed in the largest sample to investigate this question. We discuss directions for future research to determine whether additional factors including age or method of assessment may contribute to this lack of association.

Baseline MRI atrophy predicts 2-year cognitive outcomes in early-onset Alzheimer's disease.

MRI atrophy predicts cognitive status in AD. However, this relationship has not been investigated in early-onset AD (EOAD, < 65years) patients with a biomarker-based diagnosis. Forty eight EOAD (MMSE ≥ 15; A + T + N +) and forty two age-matched healthy controls (HC; A-T-N-) from a prospective cohort underwent full neuropsychological assessment, 3T-MRI scan and lumbar puncture at baseline. Participants repeated the cognitive assessment annually. We used linear mixed models to investigate whether baseline cortical thickness (CTh) or subcortical volume predicts two-year cognitive outcomes in the EOAD group. In EOAD, hemispheric CTh and ventricular volume at baseline were associated with global cognition, language and attentional/executive functioning 2years later (p < 0.0028). Regional CTh was related to most cognitive outcomes (p < 0.0028), except verbal/visual memory subtests. Amygdalar volume was associated with letter fluency test (p < 0.0028). Hippocampal volume did not show significant associations. Baseline hemispheric/regional CTh, ventricular and amygdalar volume, but not the hippocampus, predict two-year cognitive outcomes in EOAD.

Association of subcortical gray-matter volumes with life-course-persistent antisocial behavior in a population-representative longitudinal birth cohort.

Neuropsychological evidence supports the developmental taxonomy theory of antisocial behavior, suggesting that abnormal brain development distinguishes life-course-persistent from adolescence-limited antisocial behavior. Recent neuroimaging work confirmed that prospectively-measured life-course-persistent antisocial behavior is associated with differences in cortical brain structure. Whether this extends to subcortical brain structures remains uninvestigated. This study compared subcortical gray-matter volumes between 672 members of the Dunedin Study previously defined as exhibiting life-course-persistent, adolescence-limited or low-level antisocial behavior based on repeated assessments at ages 7-26 years. Gray-matter volumes of 10 subcortical structures were compared across groups. The life-course-persistent group had lower volumes of amygdala, brain stem, cerebellum, hippocampus, pallidum, thalamus, and ventral diencephalon compared to the low-antisocial group. Differences between life-course-persistent and adolescence-limited individuals were comparable in effect size to differences between life-course-persistent and low-antisocial individuals, but were not statistically significant due to less statistical power. Gray-matter volumes in adolescence-limited individuals were near the norm in this population-representative cohort and similar to volumes in low-antisocial individuals. Although this study could not establish causal links between brain volume and antisocial behavior, it constitutes new biological evidence that all people with antisocial behavior are not the same, supporting a need for greater developmental and diagnostic precision in clinical, forensic, and policy-based interventions.

Social Networks and Cognitive Reserve: Network Structure Moderates the Association Between Amygdalar Volume and Cognitive Outcomes.

The cognitive reserve hypothesis has been proposed as a key mechanism explaining the link between social networks and cognitive function but has rarely been empirically tested using neuroimaging data. This study examines whether social network attributes moderate the association between amygdalar volume and cognitive function. Data were from the Social Networks in Alzheimer Disease study (N = 154) and Indiana Alzheimer's Disease Research Center. Social networks were measured using the PhenX Social Network Battery. Regional data from magnetic resonance imaging (amygdalar volume [AV]) were analyzed using FreeSurfer software. Cognitive function was measured using the Montreal Cognitive Assessment (MoCA) and consensus diagnosis. Linear regression analyses were conducted to test the moderating role of social networks on the association between AV and cognitive function. Participants with greater ability to span multiple social roles and subgroups within their networks scored higher on the MoCA after adjusting for sociodemographic variables, depression, frequency of contact, and AV. Social networks moderated the association between AV and cognitive function. Among participants who engaged in diverse and loosely connected social networks, the expected adverse cognitive effects of brain volume in regions implicated in socioemotional processing were attenuated. These findings suggest that cognitive stimulation achieved through social interaction with a diverse array of social relationships across multiple contexts may help promote cognitive reserve.

The evolutionary trajectories of the individual amygdala nuclei in the common shrew, guinea pig, rabbit, fox and pig: A consequence of embryological fate and mosaic-like evolution.

The amygdala primarily evolved as a danger detector that regulates emotional behaviours and learning. However, it is also engaged in stress responses as well as olfactory/pheromonal and reproductive functions. All of these functions are processed by a set of nuclei which are derived from different telencephalic sources (pallial and subpallial) and have a unique cellular structure and specific connections. It is unclear how these individual anatomical and functional units evolved to fit the amygdala to the specific needs of various mammals. Thus, this study provides quantitative data regarding volumes, neuron density and neuron numbers in the main amygdala nuclei of the common shrew, guinea pig, rabbit, fox and pig - species from across the mammalian phylogeny which differ in brain complexity and ecology. The results show that the volume of the amygdala and its individual nuclei scale with negative allometry relative to brain mass (an allometric coefficient below one). However, in relation to the whole amygdala volume, volumes and volumetric percentages of the lateral (LA) and basomedial (BM) nuclei scale with positive allometry, for the medial (ME) and lateral olfactory tract (NLOT) nuclei these parameters scale with negative allometry while the values of these parameters for the basolateral (BL), central (CE) and cortical (CO) nuclei scale with isometry. Moreover, density of neurons scales with strong negative allometry relative to both brain mass and amygdala volume with values of allometric coefficient below zero across studied species. This value for BL is significantly lower than that for the whole amygdala, for ME it is significantly higher while values for NLOT, CE, CO, LA and BM are quite similar to the value for whole amygdala. Finally, neuron numbers in the whole amygdala and its individual nuclei scale with negative allometry in relation to brain mass. However, in relation to the number of neurons in the whole amygdala, neuron numbers and percentages of neurons for LA and BM scale with positive allometry, for BL and NLOT they scale with negative allometry while the values of these parameters for CE, CO and ME scale with isometry. In conclusion, all of these results indicate that each of the nuclei studied displays a different and unique pattern of evolution in relation to brain mass or the whole amygdala volume. These patterns do not match with the various classical concepts of amygdala parcellation; however, in some way, they reflect diversity revealed by the expression of homeobox genes in various embryological studies.

Structural abnormalities in adolescents with conduct disorder and high versus low callous unemotional traits.

There may be distinct conduct disorder (CD) etiologies and neural morphologies in adolescents with high callous unemotional (CU) traits versus low CU traits. Here, we employed surface-based morphometry methods to investigate morphological differences in adolescents diagnosed with CD [42 with high CU traits (CD-HCU) and 40 with low CU traits (CD-LCU)] and healthy controls (HCs, N = 115) in China. Whole-brain analyses revealed significantly increased cortical surface area (SA) in the left inferior temporal cortex and the right precuneus, but decreased SA in the left superior temporal cortex in the CD-LCU group, compared with the HC group. There were no significant cortical SA differences between the CD-HCU and the HC groups. Compared to the CD-HCU group, the CD-LCU group had a greater cortical thickness (CT) in the left rostral middle frontal cortex. Region-of-interest analyses revealed significant group differences in the right hippocampus, with CD-HCU group having lower righthippocampal volumes than HCs. We did not detect significant group differences in the amygdalar volume, however, the right amygdalar volume was found to be a significant moderator of the correlation between CU traits and the proactive aggression in CD patients. The present results suggested that the manifestations of CD differ between those with high CU traits versus low CU traits, and underscore the importance of sample characteristics in understanding the neural substrates of CD.

Maternal Childhood Maltreatment Is Associated With Lower Infant Gray Matter Volume and Amygdala Volume During the First Two Years of Life

BackgroundChildhood maltreatment affects approximately 25% of the world’s population. Importantly, the children of mothers who have been maltreated are at increased risk of behavioral problems. Thus, one important priority is to identify child neurobiological processes associated with maternal childhood maltreatment (MCM) that might contribute to such intergenerational transmission. This study assessed the impact of MCM on infant gray and white matter volumes and infant amygdala and hippocampal volumes during the first 2 years of life. MethodsFifty-seven mothers with 4-month-old infants were assessed for MCM, using both the brief Adverse Childhood Experiences screening questionnaire and the more detailed Maltreatment and Abuse Chronology of Exposure scale. A total of 58% had experienced childhood maltreatment. Between 4 and 24 months (age in months: mean = 12.28, SD = 5.99), under natural sleep, infants completed a magnetic resonance imaging scan using a 3T Siemens scanner. Total brain volume, gray matter volume, white matter volume, and amygdala and hippocampal volumes were extracted via automated segmentation. ResultsMCM on the Adverse Childhood Experiences and Maltreatment and Abuse Chronology of Exposure scales were associated with lower infant total brain volume and gray matter volume, with no moderation by infant age. However, infant age moderated the association between MCM and right amygdala volume, such that MCM was associated with lower volume at older ages. ConclusionsMCM is associated with alterations in infant brain volumes, calling for further identification of the prenatal and postnatal mechanisms contributing to such intergenerational transmission. Furthermore, the brief Adverse Childhood Experiences questionnaire predicted these alterations, suggesting the potential utility of early screening for infant risk.

The role of glucocorticoid receptor gene in the association between attention deficit-hyperactivity disorder and smaller brain structures.

ADHD is associated with smaller subcortical brain volumes and cortical surface area, with greater effects observed in children than adults. It is also associated with dysregulation of the HPA axis. Considering the effects of the glucocorticoid receptor (NR3C1) in neurophysiology, we hypothesize that the blurred relationships between brain structures and ADHD in adults could be partly explained byNR3C1gene variation.Structural T1-weighted images were acquired on a 3T scanner (N = 166). Large-scale genotyping was performed, and it was followed by quality control and pruning procedures, which resulted in 48 independent NR3C1 gene variants analyzed.After a stringent Bonferroni correction, two SNPs (rs2398631 and rs72801070) moderated the association between ADHD and accumbens and amygdala volumes in adults. The significant SNPs that interacted with ADHD appear to have a role in gene expression regulation, and they are in linkage disequilibrium withNR3C1variants that present well-characterized physiological functions.The literature-reported associations of ADHD with accumbens and amygdala were only observed for specificNR3C1genotypes. Our findings reinforce the influence of the NR3C1 gene on subcortical volumes and ADHD. They suggest a genetic modulation of the effects of a pivotal HPA axis component in the neuroanatomical features of ADHD.

UNDERSTANDING SEX DIFFERENCES IN AUTISM SPECTRUM DISORDER

Autism spectrum disorder (ASD) is diagnosed more frequently in boys than in girls, at ratios of approximately 3-4:1. There is increasing appreciation that behavioral features, genetic risk factors, developmental paths, and treatment response differ across sexes, and girls with ASD remain an understudied group. Clare Harrop, PhD, examined sex-specific performance in visual attention. Christine Nordahl, PhD, employed fMRI to evaluate sex differences in amygdala structure and function. Dorothy Grice, MD, carried out deep phenotyping of DDX3X syndrome, a major cause of ASD in girls. Donna Werling, PhD, analyzed RNA-sequence data from prenatal and postnatal human prefrontal cortex in males and females. Dr. Harrop showed that visual interactive paradigms produced the largest differences in total attention between the ASD and typically developing (TD) groups; attention was greater when the sex of the subjects and gender of the objects were congruent. Dr. Nordahl demonstrated that global patterns of amygdala functional connectivity show robust sex differences in TD participants, but differences were attenuated in children with ASD; amygdala volume was positively correlated with internalizing behaviors in girls with ASD, but not in boys. Dr. Grice showed that 80% of individuals with DDX3X syndrome met the criteria for intellectual disability, 60% for ASD, and 53% for ADHD. Dr. Werling demonstrated that ASD risk genes were more likely to show female-skewed expression; however, the magnitude of the shifts was minimal. Male-biased expression was enriched for ASD-upregulated immune function–associated genes and for markers of endothelial cells and microglia. Studies of visual attention support the importance of reevaluating prior studies conducted with majority-male samples to consider biological sex and gender. Sex-specific patterns of amygdala development in ASD suggest differing etiologies and may be predictive of differential outcomes and treatment approaches. DDX3X syndrome provides an opportunity to examine genetic pathways to ASD and related phenotypes in girls. Transcriptome analyses indicate that sex effects act downstream from ASD risk genes via interacting pathways. Studies that delineate sex differences in ASD provide deeper understanding of risk pathways and trajectories and opportunities for more specific interventions. The discussants are Meng-Chuan Lai, MD, PhD, and Allison Jack, PhD, who will contextualize the talks to the larger field.

Disrupted Association Between Empathy and Brain Structure in Attention-Deficit/Hyperactivity Disorder.

ObjectivesTo investigate the relationship between brain structure and empathy in early adolescents with attention-deficit/hyperactivity disorder (ADHD).MethodsNineteen early adolescents with ADHD and 20 healthy controls underwent 3T MRI. All the participants were assessed for different aspects of empathy using measures including the Interpersonal Reactivity Index and Empathy Quotient. Cortical thickness and subcortical structural volume based on T1-weighted scans were analyzed using FreeSurfer.ResultsCognitive empathy (t=-2.52, p=0.016) and perspective taking (t=-2.10, p=0.043) were impaired in the ADHD group compared with the control group. The cluster encompassing the left posterior insular, supramarginal, and transverse temporal cortices [cluster-wise p-value (CWP)=0.001], which are associated with emotional empathy, was significantly smaller in the ADHD group, and the volume of the left nucleus accumbens was greater than that of the control group (F=10.12, p=0.003, effect size=0.22). In the control group, the left superior temporal (CWP=0.002) and lingual cortical (CWP=0.035) thicknesses were positively associated with cognitive empathy, while the right amygdala volume was positively associated with empathic concern (Coef=14.26, t=3.92, p=0.001). However, there was no significant correlation between empathy and brain structure in the ADHD group.ConclusionThe ADHD group had a smaller volume of the cortical area associated with emotional empathy than the control group, and there was no brain region showing significant correlation with empathy, unlike in the control group.

Transcriptome-based polygenic score links depression-related corticolimbic gene expression changes to sex-specific brain morphology and depression risk.

Studies in post-mortem human brain tissue have associated major depressive disorder (MDD) with cortical transcriptomic changes, whose potential in vivo impact remains unexplored. To address this translational gap, we recently developed a transcriptome-based polygenic risk score (T-PRS) based on common functional variants capturing 'depression-like' shifts in cortical gene expression. Here, we used a non-clinical sample of young adults (n = 482, Duke Neurogenetics Study: 53% women; aged 19.8 ± 1.2 years) to map T-PRS onto brain morphology measures, including Freesurfer-derived subcortical volume, cortical thickness, surface area, and local gyrification index, as well as broad MDD risk, indexed by self-reported family history of depression. We conducted side-by-side comparisons with a PRS independently derived from a Psychiatric Genomics Consortium (PGC) MDD GWAS (PGC-PRS), and sought to link T-PRS with diagnosis and symptom severity directly in PGC-MDD participants (n = 29,340, 59% women; 12,923 MDD cases, 16,417 controls). T-PRS was associated with smaller amygdala volume in women (t = -3.478, p = 0.001) and lower prefrontal gyrification across sexes. In men, T-PRS was associated with hypergyrification in temporal and occipital regions. Prefrontal hypogyrification mediated a male-specific indirect link between T-PRS and familial depression (b = 0.005, p = 0.029). PGC-PRS was similarly associated with lower amygdala volume and cortical gyrification; however, both effects were male-specific and hypogyrification emerged in distinct parietal and temporo-occipital regions, unassociated with familial depression. In PGC-MDD, T-PRS did not predict diagnosis (OR = 1.007, 95% CI = [0.997-1.018]) but correlated with symptom severity in men (rho = 0.175, p = 7.957 × 10-4) in one cohort (N = 762, 48% men). Depression-like shifts in cortical gene expression have sex-specific effects on brain morphology and may contribute to broad depression vulnerability in men.

Alterations of brain structural MRI are associated with outcome of surgical treatment in trigeminal neuralgia.

To assess magnetic resonance imaging (MRI) alterations occurring in patients with trigeminal neuralgia (TN) and to explore the predictive ability of MRI for initial surgical outcome and long-term pain relief/recurrence after Gamma Knife radiosurgery (GKS). Thirty patients with idiopathic or classic TN, who underwent GKS and were followed for at least 24months, were retrospectively included. Pre-treatment structural MRI and pre- and serial, postoperative clinical features were investigated. Fifteen age- and sex-matched healthy controls were also enrolled. Cortical thickness and gray matter (GM) volumes were assessed in TN patients relative to controls, as well as between patient subgroups according to treatment outcomes (initial responders/non-responders, patients with pain recurrence/long-lasting pain relief at the last follow-up). Clinical and MRI predictors of treatment outcomes were explored. Cortical thinning of temporal, prefrontal, cingulate, somatosensory and occipital areas bilaterally was found in TN patients relative to controls. No cortical thickness and GM volume differences were observed when TN initial responders and non-responders were compared. Patients who experienced TN recurrence after initial pain relief were characterized by thicker parahippocampal and temporal cortices bilaterally and greater volume of right amygdala and hippocampus compared to patients with long-lasting pain relief. In TN patients, disease duration and baseline cortical thinning of right parahippocampal, left fusiform and middle temporal cortices were associated with poor outcome after GKS at the last follow-up (R2 =0.57, p<0.001). The study provides novel insights into structural brain alterations of TN patients, which might contribute to disease development and pain maintenance.

Sex differences in the aging brain? A voxel-based morphometry analysis of the hippocampus and the amygdala.

Volumetric reductions in the hippocampus and the amygdala are considered a hallmark for many psychiatric and neurodegenerative disorders. Because brain atrophy is often observed in disorders that have a higher prevalence in females than males, it has been proposed that sex differences in the aging brain represent a vulnerability factor for developing more severe psychiatric conditions. Sexual dimorphism was assessed in the amygdala volume and hippocampal volume in a large sample (N = 554) of healthy individuals ranging from 20 to 79 years old, using structural brain data available from a public dataset. In both the hippocampus and the amygdala, a quadratic association was found between age and brain volume. Using uncorrected data for head size [total intracranial volume (TIV)], males clearly demonstrated larger amygdala and hippocampal volume across all ages, and an interaction between age and sex in the hippocampus supported the hypothesis of accelerated atrophy in the hippocampus in later life (60-79 years old). However, when volumetric data adjusted for TIV were used, sex differences were not observed in the hippocampus nor the amygdala. These findings support the extensive series of studies suggesting that sex differences in brain volume are likely related to the confounding effect of head size. While continued effort is allocated to identify sex-related biomarkers, increasing evidence suggests that sexual dimorphism in the hippocampus or the amygdala does not appear to be the primary candidates for precision medicine to identify sex-related biomarkers that index potential vulnerabilities.

Timing-specific associations between income-to-needs ratio and hippocampal and amygdala volumes in middle childhood: A preliminary study.

It is well known that financial disadvantage is associated with alterations in brain development in regions critical to socioemotional well-being such as the hippocampus and the amygdala. Yet little is known about whether family income at different points in development is differentially associated with these structures. Furthermore, little is known about which environmental factors statistically mediate associations between income and subcortical structure. Using a longitudinal birth cohort and linear mixed-effects models, we identified associations between income-to-needs ratio (INR) at 6 timepoints throughout childhood and hippocampal and amygdala volumes at age 7-9 years (n=41; 236 INR measurements; 41 brain measurements). Mediation analysis identified environmental sequelae of income that statistically accounted for INR-brain associations. Lower INR prior to age 4 was associated with smaller hippocampal volumes, whereas lower INR prior to age 2 was associated with smaller right amygdala volume. These associations were mediated by unmet basic needs (e.g., food, housing). These findings delineate the temporal specificity of associations between income and hippocampal and amygdala structures.

Leveraging high-resolution 7-tesla MRI to derive quantitative metrics for the trigeminal nerve and subnuclei of limbic structures in trigeminal neuralgia

BackgroundTrigeminal Neuralgia (TN) is a chronic neurological disease that is strongly associated with neurovascular compression (NVC) of the trigeminal nerve near its root entry zone. The trigeminal nerve at the site of NVC has been extensively studied but limbic structures that are potentially involved in TN have not been adequately characterized. Specifically, the hippocampus is a stress-sensitive region which may be structurally impacted by chronic TN pain. As the center of the emotion-related network, the amygdala is closely related to stress regulation and may be associated with TN pain as well. The thalamus, which is involved in the trigeminal sensory pathway and nociception, may play a role in pain processing of TN. The objective of this study was to assess structural alterations in the trigeminal nerve and subregions of the hippocampus, amygdala, and thalamus in TN patients using ultra-high field MRI and examine quantitative differences in these structures compared with healthy controls.MethodsThirteen TN patients and 13 matched controls were scanned at 7-Tesla MRI with high resolution, T1-weighted imaging. Nerve cross sectional area (CSA) was measured and an automated algorithm was used to segment hippocampal, amygdaloid, and thalamic subregions. Nerve CSA and limbic structure subnuclei volumes were compared between TN patients and controls.ResultsCSA of the posterior cisternal nerve on the symptomatic side was smaller in patients (3.75 mm2) compared with side-matched controls (5.77 mm2, p = 0.006). In TN patients, basal subnucleus amygdala volume (0.347 mm3) was reduced on the symptomatic side compared with controls (0.401 mm3, p = 0.025) and the paralaminar subnucleus volume (0.04 mm3) was also reduced on the symptomatic side compared with controls (0.05 mm3, p = 0.009). The central lateral thalamic subnucleus was larger in TN patients on both the symptomatic side (0.033 mm3) and asymptomatic side (0.035 mm3), compared with the corresponding sides in controls (0.025 mm3 on both sides, p = 0.048 and p = 0.003 respectively). The inferior and lateral pulvinar thalamic subnuclei were both reduced in TN patients on the symptomatic side (0.2 mm3 and 0.17 mm3 respectively) compared to controls (0.23 mm3, p = 0.04 and 0.18 mm3, p = 0.04 respectively). No significant findings were found in the hippocampal subfields analyzed.ConclusionsThese findings, generated through a highly sensitive 7 T MRI protocol, provide compelling support for the theory that TN neurobiology is a complex amalgamation of local structural changes within the trigeminal nerve and structural alterations in subnuclei of limbic structures directly and indirectly involved in nociception and pain processing.

Sociability, but not spatial memory, is correlated with regional brain volume variation in the striped mouse Rhabdomys spp.

Local environmental conditions associated with different geographic areas may elicit variations in behavioural responses in animals, leading to concomitant differences in functional brain region volumes. We investigated the behavioural correlates of hippocampus and amygdala volumes in three sister taxa of the murid rodent genus Rhabdomys, occurring in different environments. We used a Barnes maze to test spatial memory, dyadic encounters to test social behaviour, and histological brain sections to calculate hippocampus and amygdala volumes. Arid-occurring R. pumilio made fewer errors and had shorter latencies in locating the escape tunnel compared to moist grassland-occurring R. d. dilectus and R. d. chakae in two probe trials, 48 and 96 h after the last learning trial. R. pumilio was more amicable than the R. dilectus subspecies in intra-specific dyadic encounters. R. pumilio had larger hippocampus and amygdala volumes than the other species. Smaller amygdala volumes were correlated with longer latencies in females for probe trial 1, but males showed similar latencies regardless of taxon. Higher amicability scores were correlated with larger amygdala volumes in all taxa. Higher amicability scores were correlated with larger hippocampus volumes in R. pumilio and R. d. chakae but smaller hippocampus volumes in R. d. dilectus. Correlative relationships between spatial memory and amygdala volume appeared 48 h, but not 96 h, after the last learning trial. Local environmental conditions may influence spatial navigation, but social correlates drive regional brain size within cryptic striped mouse taxa.

Long-term global and focal cerebral atrophy in perimesencephalic subarachnoid hemorrhage-a case-control study.

Non-aneurysmal perimesencephalic subarachnoid hemorrhage (PmSAH) represents 6.8% of spontaneous subarachnoid hemorrhage, and usually has a benign clinical course. However, patients might have early cerebral ischemic lesions and long-term neurocognitive complaints. Cerebral atrophy has been described in patients after aneurysmal SAH, but not in PmSAH. We aimed to investigate if PmSAH associates with increased brain volume loss. In this prospective study, we included consecutive patients with PmSAH that performed MR in the first 10days after hemorrhage, and follow-up MR 6-7years later. Automated volumetric measurements of intracranial, white matter, gray matter, whole brain, lateral ventricles, hippocampus, and amygdala volumes were performed. Volumes were compared to a normal population, matched for age. Eight patients with PmSAH were included, with a mean age of 51.5 (SE 3.6) at baseline. The control group included 22 patients with a mean age of 56.3 (SE 2.0). A relative reduction of all volumes was found in both groups; however, PmSAH patients had significant reductions in intracranial, white and gray matter, whole brain, and hippocampal volumes when compared to controls. These changes had a higher magnitude in whole brain volume, with a significant absolute decrease of 6.5% in PmSAH patients (versus 1.9% in controls), and a trend for an increase in lateral ventricle volume (absolute 21.3% increase, versus 3.9% in controls). Our cohort of PmSAH patients showed significant long-term parenchymal atrophy, and higher global and focal parenchymal volume loss rates when compared to a non-SAH population.