Structural Magnetic Resonance Imaging Scans Research Articles

Understanding Hippocampal Development in Young Children With Autism Spectrum Disorder

We examined growth trajectories of hippocampal volume (HV) in early childhood in a longitudinal cohort of male and female participants with autism spectrum disorder (ASD) and typically developing (TD) individuals, and investigated HV in those with large brains. Relations between factors potentially associated with hippocampal size and growth were investigated. Participants received 1 to 3 structural magnetic resonance imaging scans between ages 25 and 80 months (unique participants: ASD, n=200; TD, n=110; total longitudinal scans, n= 593). HV growth during this period was examined using mixed-effects linear models. Associations between early HV and growth rates, and IQ and adaptive functioning, were evaluated. After accounting for cerebral hemisphere volume, male participants exhibited larger left and right HV than female participants. Hippocampal growth rates did not differ by sex. In children with larger hemisphere volumes, male and female participants with ASD had relatively larger HV than TD participants of similar hemisphere volume. This effect was present in a broader group than only those with disproportionate megalencephaly (male participants with large cerebral volumes relative to body size). Right hippocampi were larger than left hippocampi in both groups and sexes. Right versus left volume differences were greater for ASD. After adjusting for hemisphere volume, male participants with ASD showed a significant positive association between right hippocampal growth and adaptive behavior. HV was relatively greater in ASD in analyses adjusting for hemisphere volume, whereas only subtle differences were observed in HV and growth between participants with ASD and TD participants in unadjusted analyses, suggesting that ASD involves atypical coupling between HV and brain size.

Arterial Spin Labeling Perfusion Magnetic Resonance Imaging Reveals Resting Cerebral Blood Flow Alterations Specific to Retinitis Pigmentosa Patients

ABSTRACTPurpose: This study aimed to assess resting cerebral blood flow (CBF) changes in retinitis pigmentosa (RP) patients using a pseudo-continuous arterial spin labeling (pCASL) perfusion method.Methods: Forty-nine RP patients and 51 healthy controls (HCs) underwent T1-weighted structural and pCASL sequence magnetic resonance imaging (MRI) scans at rest. Two-sample t-tests were performed to compare CBF differences between groups. Pearson correlation was used to analyze relationships between CBF values and clinical variables in the RP group.Results: Compared with HCs, RP patients had significantly lower CBF values in the bilateral cuneus/lingual gyrus/precuneus/posterior cingulate/middle occipital gyrus. In the RP group, CBF values in the left middle occipital and inferior occipital gyrus were positively correlated with mean retinal nerve fiber layer thickness; furthermore, CBF values in several regions were correlated with duration of disease and age of onset.Conclusions: Our results highlighted that RP patients exhibited decreased CBF values in the visual cortices and vision-related cortices. The results suggest that altered CBF might contribute to trans-synaptic retrograde degeneration of the visual pathway in RP patients.

Cannabis-Associated Psychotic-like Experiences Are Mediated by Developmental Changes in the Parahippocampal Gyrus

Cannabis consumption during adolescence has been reported as a risk factor for psychotic-like experiences (PLEs) and schizophrenia. However, brain developmental processes associated with cannabis-related PLEs are still poorly described. A total of 706 adolescents from the general population who were recruited by the IMAGEN consortium had structural magnetic resonance imaging scans at both 14 and 19 years of age. We used deformation-based morphometry to map voxelwise brain changes between the two time points, using the pairwise algorithm in SPM12b. We used an a priori region-of-interest approach focusing on the hippocampus/parahippocampus to perform voxelwise linear regressions. Lifetime cannabis consumption was assessed using the European School Survey Project on Alcohol and other Drugs (ESPAD), and PLEs were assessed with the Comprehensive Assessment Psychotic-like experiences (CAPE) tool. We first tested whether hippocampus/parahippocampus development was associated with PLEs. Then we formulated and tested an a priori simple mediation model in which uncus development mediates the association between lifetime cannabis consumption and PLEs. We found that PLEs were associated with reduced expansion within a specific region of the right hippocampus/parahippocampus formation, the uncus (p= .002 at the cluster level, p= .018 at the peak level). The partial simple mediation model revealed a significant total effect from lifetime cannabis consumption to PLEs (b= 0.069, 95% CI= 0.04-0.1, p=2× 10-16), as well as a small yet significant, indirect effect of right uncus development (0.004; 95% CI= 0.0004-0.01, p= .026). We show here that the uncus development is involved in the cerebral basis of PLEs in a population-based sample of healthy adolescents.

Classification of Alzheimer's Disease in MRI based on Dictionary Learning and Heavy Tailed Modelling.

Diagnosis of brain diseases is considered one of the most challenging medical tasks to perform, even for medical experts who rely on high-resolution anatomical images to identify signs of abnormalities by visual inspection. However, new computational tools which assist to automate this diagnosis have the potential to significantly improve the speed and accuracy of this process. This work presents a model to aid in the task of classification of structural Magnetic Resonance Imaging scans. The classification is performed using a Support Vector Machine, whilst the features to analyze belong to a dictionary space. Such space was mainly built from a dictionary learning perspective, although a predefined one was also assessed. The results indicate that features learnt from the data of interest lead to improved classification performance. The proposed framework was tested on the ADNI dataset stage I.

Brain age in bipolar disorders: Effects of lithium treatment.

Bipolar disorders increase the risk of dementia and show biological and brain alterations, which resemble accelerated aging. Lithium may counter some of these processes and lower the risk of dementia. However, until now no study has specifically investigated the effects of Li on brain age. We acquired structural magnetic resonance imaging scans from 84 participants with bipolar disorders (41 with and 43 without Li treatment) and 45 controls. We used a machine learning model trained on an independent sample of 504 controls to estimate the individual brain ages of study participants, and calculated BrainAGE by subtracting chronological from the estimated brain age. BrainAGE was significantly greater in non-Li relative to Li or control participants, F(2, 125) = 10.22, p < 0.001, with no differences between the Li treated and control groups. The estimated brain age was significantly higher than the chronological age in the non-Li (4.28 ± 6.33 years, matched t(42) = 4.43, p < 0.001), but not the Li-treated group (0.48 ± 7.60 years, not significant). Even Li-treated participants with partial prophylactic treatment response showed lower BrainAGE than the non-Li group, F(1, 64) = 4.80, p = 0.03. Bipolar disorders were associated with greater, whereas Li treatment with lower discrepancy between brain and chronological age. These findings support the neuroprotective effects of Li, which were sufficiently pronounced to affect a complex, multivariate measure of brain structure. The association between Li treatment and BrainAGE was independent of long-term thymoprophylactic response and thus may generalize beyond bipolar disorders, to neurodegenerative disorders.

Developmental trajectories of the human embryologic brain regions

Vertebrate brains commonly consist of five basic embryologic anatomical regions: telencephalon; diencephalon; mesencephalon; metencephalon; and myelencephalon. The proportions of these regions vary widely across species and developmental stages. Investigation of their growth trajectories, therefore, has the potential to provide an understanding of the substrates of inter-species variation in neuroanatomy and function. To investigate the volumetric growth trajectories, structural magnetic resonance imaging (MRI) scans obtained from 618 healthy children (334 boys, 284 girls; ages 3–17 years old) were parcellated into five regions for the volume quantification. The sex- and region-specific growth trajectories were identified, and the most active growth was seen in the mesencephalon for both boys and girls. Whether similar regional growth patterns are seen in other species, or whether such patterns are related to evolution, are important questions that must be elucidated in the future.

Cortical Excitability Dynamics During Fear Processing.

Background:Little is known about the modulation of cortical excitability in the prefrontal cortex during fear processing in humans. Here, we aimed to transiently modulate and test the cortical excitability during fear processing using transcranial magnetic stimulation (TMS) and brain oscillations in theta and alpha frequency bands with electroencephalography (EEG).Methods:We conducted two separate experiments (no-TMS and TMS). In the no-TMS experiment, EEG recordings were performed during the instructed fear paradigm in which a visual cue (CS+) was paired with an aversive unconditioned stimulus (electric shock), while the other visual cue was unpaired (CS-). In the TMS experiment, in addition the TMS was applied on the right dorsomedial prefrontal cortex (dmPFC). The participants also underwent structural MRI (magnetic resonance imaging) scanning and were assigned pseudo-randomly to both experiments, such that age and gender were matched. The cortical excitability was evaluated by time-frequency analysis and functional connectivity with weighted phase lag index (WPLI). We further linked the excitability patterns with markers of stress coping capability.Results:After visual cue onset, we found increased theta power in the frontal lobe and decreased alpha power in the occipital lobe during CS+ relative to CS- trials. TMS of dmPFC increased theta power in the frontal lobe and reduced alpha power in the occipital lobe during CS+. The TMS pulse increased the information flow from the sensorimotor region to the prefrontal and occipital regions in the theta and alpha bands, respectively during CS+ compared to CS-. Pre-stimulation frontal theta power (0.75–1 s) predicted the magnitude of frontal theta power changes after stimulation (1–1.25 s). Finally, the increased frontal theta power during CS+ compared to CS- was positively correlated with stress coping behavior.Conclusion:Our results show that TMS over dmPFC transiently modulated the regional cortical excitability and the fronto-occipital information flows during fear processing, while the pre-stimulation frontal theta power determined the strength of achieved effects. The frontal theta power may serve as a biomarker for fear processing and stress-coping responses in individuals and could be clinically tested in mental disorders.

Specific nutrient patterns are associated with higher structural brain integrity in dementia-free older adults

Optimal nutrition may play a beneficial role in maintaining a healthy brain. However, the relationship between nutrient intake and brain integrity is largely unknown. We investigated the association of specific nutrient dietary patterns with structural characteristics of the brain. Within the population-based Swedish National study on Aging and Care-Kungsholmen (SNAC-K), a cross-sectional study of 417 dementia-free participants aged ≥60 years who underwent structural magnetic resonance imaging (MRI) scans during 2001–2003, was carried-out. Data on dietary intake were collected using a food frequency questionnaire, from which intake of 21 nutrients was estimated. By principal component analysis, five nutrient patterns were extracted: (1) NP1 was characterized by fiber, vitamin C, E, β-carotene, and folate [Fiber&Antioxidants], (2) NP2 by eicosapentaenoic (EPA, 20:5 ω-3) and docosahexaenoic (DHA, 22:6 ω-3) polyunsaturated fatty acids (PUFAs), proteins, cholesterol, vitamin B3, B12, and D [long chain (LC) ω-3PUFAs&Proteins], (3) NP3 by α-linoleic (18:2 ω-6) and α-linolenic (18:3 ω-3) PUFAs, monounsaturated fatty acids (MUFAs), and vitamin E [MUFAs&ω-3,6PUFAs], (4) NP4 by saturated fatty acids (SFAs), trans fats, MUFAs, and cholesterol [SFAs&Trans fats], (5) NP5 by B-vitamins, retinol, and proteins [B-Vitamins&Retinol]. Nutrient patterns scores were tertiled with the lowest tertile as reference, and were related to total brain volume (TBV) and white matter hyperintensities volume (WMHV) using linear regression models adjusting for potential confounders. In the multi-adjusted model, compared to the lowest intake for each pattern, the highest intake of NP1 (β = 11.11, P = 0.009), NP2 (β = 7.47, P = 0.052), and NP3 (β = 10.54, P = 0.005) was associated with larger TBV whereas NP5 was related to smaller TBV (β = −12.82, P = 0.001). The highest intake of NP1 was associated with lower WMHV (β = −0.32, P = 0.049), whereas NP4 was associated with greater WMHV (β = 0.31, P = 0.036). In sum, our results suggest that the identified brain-health specific nutrient combinations characterized by higher intake of fruit, vegetables, legumes, olive and seed oils, fish, lean red meat, poultry and low in milk and dairy products, cream, butter, processed meat and offal, were strongly associated with greater brain integrity among older adults.

Characterizing the Structural Pattern Predicting Medication Response in Herpes Zoster Patients Using Multivoxel Pattern Analysis.

Herpes zoster (HZ) can cause a blistering skin rash with severe neuropathic pain. Pharmacotherapy is the most common treatment for HZ patients. However, most patients are usually the elderly or those that are immunocompromised, and thus often suffer from side effects or easily get intractable post-herpetic neuralgia (PHN) if medication fails. It is challenging for clinicians to tailor treatment to patients, due to the lack of prognosis information on the neurological pathogenesis that underlies HZ. In the current study, we aimed at characterizing the brain structural pattern of HZ before treatment with medication that could help predict medication responses. High-resolution structural magnetic resonance imaging (MRI) scans of 14 right-handed HZ patients (aged 61.0 ± 7.0, 8 males) with poor response and 15 (aged 62.6 ± 8.3, 5 males) age- (p = 0.58), gender-matched (p = 0.20) patients responding well, were acquired and analyzed. Multivoxel pattern analysis (MVPA) with a searchlight algorithm and support vector machine (SVM), was applied to identify the spatial pattern of the gray matter (GM) volume, with high predicting accuracy. The predictive regions, with an accuracy higher than 79%, were located within the cerebellum, posterior insular cortex (pIC), middle and orbital frontal lobes (mFC and OFC), anterior and middle cingulum (ACC and MCC), precuneus (PCu) and cuneus. Among these regions, mFC, pIC and MCC displayed significant increases of GM volumes in patients with poor response, compared to those with a good response. The combination of sMRI and MVPA might be a useful tool to explore the neuroanatomical imaging biomarkers of HZ-related pain associated with medication responses.

Short communication: Diffusion tensor anisotropy in the cingulate in borderline and schizotypal personality disorder

Despite considerable phenomentological differences between borderline personality disorder (BPD) and schizotypal personality disorder (SPD), research increasingly provides evidence that some BPD symptoms overlap with SPD symptoms (e.g., disturbed cognitions). We examined the cingulate, a brain region implicated in the pathophysiology of both disorders, to determine similarities/differences between the groups, and similarities/differences from healthy controls (HC's). 3T structural and diffusion tensor magnetic resonance imaging scans were acquired in BPD (n = 27), SPD (n = 32), HC's (n = 34). Results revealed that BPD patients exhibited significantly lower FA in posterior cingulate white matter compared to HC's (p = 0.04), but SPD patients did not.

The amygdala in adolescents with attention-deficit/hyperactivity disorder: Structural and functional correlates of delay aversion

Objectives Recent magnetic resonance imaging (MRI) studies implicate structural alterations of amygdala, a brain region responsible for processing and experiencing negative emotions, in adolescents with attention-deficit/hyperactivity disorder (ADHD). Here we examined ADHD-related structural correlates of amygdala functional activity elicited during a functional MRI task designed to test behavioural and brain responses to the imposition of delay – an event known to both elicit amygdala hyperactivation and aversity in ADHD. Methods Structural MRI scans from 28 right-handed male adolescents with combined type ADHD and 32 age-matched controls were analysed. Regional grey matter volumes of ADHD and control participants (P[FWE] < 0.05) were correlated with delay aversion self-ratings and neural activity in response to delay-related cues on the Escape Delay Incentive fMRI task. Results ADHD was associated with significantly reduced volumes in bilateral amygdala, parahippocampal and temporal gyrus (P[FWE] < 0.05), greater basolateral amygdala activation to delay-related cues (P[FWE] < 0.05) and higher delay aversion self-ratings. Amygdala volume reductions were significantly correlated with, and statistically mediated the pathway from ADHD to, delay-cue-related amygdala hyperactivity (P < 0.01) and self-reported delay aversion (P < 0.01). Conclusions We provide the first evidence of the functional significance of reduced amygdala volumes in adolescents with ADHD by highlighting its relation to delay-induced brain activity that is linked to delay aversion.

ASSOCIATIONS BETWEEN CYTOKINES AND CORTICAL THICKNESS IN PATIENTS WITH LATE-LIFE DEPRESSION

Introduction Late-life depression (LLD), defined as depression that occurs after the age of 60 years, is associated with a poor quality of life, cognitive impairment, and increased morbidity and mortality. Immune factors are now recognized as involved in the pathophysiology of depression. We aimed to evaluate the relationship between plasma cytokine levels and cortical thickness in patients with LLD. Methods Blood samples and structural magnetic resonance imaging scans (Siemens 3T Prisma) were acquired in 29 older adults (≥60 years old) with major depression (62% female; mean age, 70.7 (7.3) years; mean MADRS 15.9 (3.2)). Associations between plasma cytokine levels (log-transformed) and cortical thickness were evaluated in a multivariate analysis using partial least squares. Cytokines with detectable levels in at least 27 of the 29 subjects (exotaxin, IFN-a2, GRO, MDC, IL-12(p70), sCD40L, IL-8, IP-10, MCP-1, MIP-1b, TNF-a, and VEGF) were included in the analysis. Results The first latent variable was significant (accounting for 32% of the cross-block covariance, p=.036) and reflected negative correlations between exotaxin, IL-8, IP-10, MIP-1b, and TNF-a levels and cortical thickness in numerous brain regions, including cingulate, insular, temporal, orbitofrontal, and prefrontal cortices (Figure 1). Conclusions Patients with LLD who have high plasma levels of exotoxin, IL-8, IP-10, MIP-1b, and TNF-a have less cortical thickness in brain regions previously implicated in depression than patients with LLD who have lower levels of these chemokines and pro-inflammatory cytokines. The affected brain regions have functions in self-referential processes, emotional regulation, social cognition, and attentional switching. Thus, the observed reductions in cortical thickness may contribute to the emotional, cognitive, and behavioral disturbances in LLD. Recently, chemokines have been implicated in many neurobiological processes and are considered to play a role in linking peripheral and central inflammation. The present results further support the importance of chemokines and proinflammatory cytokines in depressive pathophysiology. This research was funded by Sponsored by NIMH R01 MH097892, NCCIH AT009198, MH086481; Alzheimer's Research & Prevention Foundation, Allergan, PCORI; Advisory Board: Alzheimer's Research & Prevention Foundation; Royalties for books from Oxford University Press and Hopkins University Press.

Alterations in Cortical Thickness and Subcortical Volume are Associated With Neurological Symptoms and Neck Pain in Patients With Cervical Spondylosis.

Advanced cervical spondylosis (CS) can cause structural damage to the spinal cord resulting in long-term neurological impairment including neck pain and motor weakness. We hypothesized long-term structural reorganization within the brain in patients with CS. To explore the associations between cortical thickness, subcortical volumes, neurological symptoms, and pain severity in CS patients with or without myelopathy and healthy controls (HCs). High-resolution T1-weighted structural magnetic resonance imaging (MRI) scans from 26 CS patients and 45 HCs were acquired. Cortical thickness and subcortical volumes were computed and compared to the modified Japanese Orthopedic Association (mJOA) and the Neck Disability Index (NDI) scores. Cortical thinning within the superior frontal gyrus, anterior cingulate, precuneus, and reduction in putamen volume were associated with worsening neurological and pain symptoms. Among the strongest associations were cortical thickness within the left precuneus (R2 = 0.34) and left and right putamen (R2 = 0.43, 0.47, respectively) vs mJOA, and the left precuneus (R2 = 0.55), insula (R2 = 0.57), and right putamen (R2 = 0.54) vs NDI (P≤.0001 for all). Cortical thickness along Brodmann areas 3a, 4a, and 4p were also moderately associated with mJOA. Preliminary evidence also suggests that patients with CS may undergo cortical atrophy at a faster rate than HCs. Patients with CS appear to exhibit cortical thinning and atrophy with worsening neurological and pain symptoms in specific brain regions associated with sensorimotor and pain processing.

Marijuana use and major depressive disorder are additively associated with reduced verbal learning and altered cortical thickness.

Marijuana (MJ) use and major depressive disorder (MDD) have both been associated with deficits in verbal learning and memory as well as structural brain abnormalities. It is not known if MJ use by those with MDD confers additional impairment. The goal of this study was to examine unique and combined effects of MDD and MJ use on verbal memory and brain structure. Young adults (n=141) aged 18-25 years with MJ use and no lifetime MDD (MJ, n=46), MDD and no MJ use (MDD, n=23), MJ use and lifetime MDD (MDD+MJ, n=24), and healthy controls without MDD or MJ use (CON, n=48) were enrolled. Participants completed the California Verbal Learning Test, Second Edition (CVLT-II), a measure of verbal learning and memory. A sub-sample of 82 participants also underwent a structural magnetic resonance imaging (MRI) scan. Group differences in CVLT-II performance, cortical thickness, and hippocampal volume were assessed. We found an additive effect of MDD and MJ on memory recall. Only MDD, but not MJ, was associated with poorer initial learning, fewer words recalled, more intrusion errors, and lower percent retention. There was also an additive effect of MDD and MJ use on reduced cortical thickness in the middle temporal gyrus. Findings indicate that MJ use and MDD have additive adverse associations with verbal recall and cortical thickness in the middle temporal gyrus, suggesting that MJ use among those with MDD may be contraindicated. Prospective studies are warranted to determine whether this association may be causal.

Effect of stress gene-by-environment interactions on hippocampal volumes and cortisol secretion in adolescent girls.

Adolescence is a time of increased susceptibility to environmental stress and mood disorders, and girls are particularly at risk. Genes interacting with the environment (G × E) are implicated in hypothalamic-pituitary-adrenal axis dysregulation, hippocampal volume changes and risk or resilience to mood disorders. In this study, we assessed the effects of stress system G × E interactions on hippocampal volumes and cortisol secretion in adolescent girls. We recruited 229 girls aged 12-18 years, and scans were obtained from 202 girls. Of these, 76 had been exposed to higher emotional trauma (abuse or neglect). Hippocampal volumes were measured using Freesurfer and high-resolution structural magnetic resonance imaging scans. Saliva samples were collected for measurement of cortisol levels and genotyping of stress system genes: FKBP5, NR3C1 (both N = 194) and NR3C2 ( N = 193). Among girls with the 'G' allelic variant of the NR3C1 gene, those who had been exposed to higher emotional trauma had significantly smaller left hippocampal volumes ( N = 44; mean = 4069.58 mm3, standard deviation = 376.99) than girls who had been exposed to minimal emotional trauma with the same allelic variant ( N = 69; mean = 4222.34 mm3, standard deviation = 366.74). In healthy adolescents, interactions between emotional trauma and the 'protective' NR3C1 'GG' variant seem to induce reductions in left hippocampal volumes. These G × E interactions suggest that vulnerability to mood disorders is perhaps driven by reduced 'protection' that may be specific to emotional trauma. This novel but preliminary evidence has implications for targeted prevention of mood disorders and prospective multimodal neuroimaging and longitudinal studies are now needed to investigate this possibility.

Involvement in Sports, Hippocampal Volume, and Depressive Symptoms in Children

BackgroundRecent studies have found that higher levels of exercise are associated with fewer symptoms of depression among young people. In addition, research suggests that exercise may modify hippocampal volume, a brain region that has been found to show reduced volume in depression. However, it is not clear whether this relationship emerges as early as preadolescence. MethodsWe examined data from a nationwide sample of 4191 children 9 to 11 years of age from the Adolescent Brain and Cognitive Development Study. The parents of the children completed the Child Behavior Checklist, providing data about the child’s depressive symptoms, and the Sports and Activities Questionnaire, which provided data about the child’s participation in 23 sports. Children also took part in a structural magnetic resonance imaging scan, providing us with measures of bilateral hippocampal volume. ResultsSports involvement interacted with sex to predict depressive symptoms, with a negative relationship found in boys only (t = −5.257, β = −.115, p < .001). Sports involvement was positively correlated with hippocampal volume in both boys and girls (t = 2.810, β = .035, p = .007). Hippocampal volume also interacted with sex to predict depressive symptoms, with a negative relationship in boys (t = −2.562, β = −.070, p = .010), and served as a partial mediator for the relationship between involvement in sports and depressive symptoms in boys. ConclusionsThese findings help illuminate a potential neural mechanism for the impact of exercise on the developing brain, and the differential effects in boys versus girls mirror findings in the animal literature. More research is needed to understand the causal relationships between these constructs.

Parenting × Brain Development interactions as predictors of adolescent depressive symptoms and well-being: Differential susceptibility or diathesis-stress?

It is unclear how individual differences in parenting and brain development interact to influence adolescent mental health outcomes. This study examined interactions between structural brain development and observed maternal parenting behavior in the prediction of adolescent depressive symptoms and psychological well-being. Whether findings supported diathesis-stress or differential susceptibility frameworks was tested. Participants completed observed interactions with their mothers during early adolescence (age 13), and the frequency of positive and aggressive maternal behavior were coded. Adolescents also completed structural magnetic resonance imaging scans at three time points: mean ages 13, 17, and 19. Regression models analyzed interactions between maternal behavior and longitudinal brain development in the prediction of late adolescent (age 19) outcomes. Indices designed to distinguish between diathesis-stress and differential susceptibility effects were employed. Results supported differential susceptibility: less thinning of frontal regions was associated with higher well-being in the context of low levels of aggressive maternal behavior, and lower well-being in the context of high levels of aggressive maternal behavior. Findings suggest that reduced frontal cortical thinning during adolescence may underlie increased sensitivity to maternal aggressive behavior for better and worse and highlight the importance of investigating biological vulnerability versus susceptibility.

The effects of childhood trauma on adolescent hippocampal subfields.

Mood disorders are more common among girls and typically emerge during adolescence. The precise reasons for this are unknown, but among the many mechanisms implicated are stress-induced hippocampal structural changes during this developmental stage. The hippocampus is a complex structure comprised of subfields that develop differentially and respond variably to stress and childhood adversity, both of which are risk factors for mood disorders. To better understand vulnerability to mood disorders, we investigated a cohort of adolescent girls and determined volumetric changes in their hippocampal subfields to elucidate the potential effects of childhood trauma. Of the 229 participants, 201 girls (aged 12-17 years) fulfilled our analysis inclusion criteria. Of these, 76 had been exposed to higher emotional trauma (emotional abuse or neglect). The girls underwent high-resolution structural magnetic resonance imaging scans, and hippocampal subfield volumes were measured using FreeSurfer. We compared hippocampal subfield volumes in those exposed to higher emotional trauma and those exposed to minimal emotional trauma, at three time-points of adolescent development: early (12-13 years), mid (14-15 years) and late (16-17 years). Mid-adolescent girls exposed to higher emotional trauma had significantly smaller left CA3 volumes than minimal emotional trauma girls ( p = 0.028). Within the minimal emotional trauma group, mid-adolescents had significantly larger left CA3 volumes than early ( p = 0.034) and late ( p = 0.036) adolescents. Within the higher emotional trauma group, early adolescents had significantly larger left CA3 volumes than late adolescents ( p = 0.036). In our exploratory study, we observed higher emotional trauma-induced volume changes in the left CA3 hippocampal subfield, which varied depending on age, and may ultimately produce deficits in behavioural, cognitive and emotional processes. We propose that these changes (1) may provide a mechanism through which vulnerability to mood disorders may be increased in adolescent girls, and (2) may signal the best times to implement targeted prevention interventions.

Subclinical eating disorder traits are correlated with cortical thickness in regions associated with food reward and perception.

Behavioral traits associated with various forms of psychopathology are conceptualized as dimensional, varying from those present in a frank disorder to subclinical expression. Demonstrating links between these behavioral traits and neurobiological indicators, such as brain structure, provides one form of validation for this view. However, unlike behavioral dimensions associated with other forms of psychopathology (e.g., autism spectrum disorder, attention deficit hyperactivity disorder, antisocial disorders), eating disorder traits have not been investigated in this manner in spite of the potential that such an approach has to elucidate etiological mechanisms. Therefore, we examined for the first time neural endophenotypes of Anorexia Nervosa and Bulimia via dimensional traits (measured using the Eating Disorders Inventory-3) in a large subclinical sample of young adults (n = 456 and n = 247, respectively; ages = 18-22years) who each provided a structural magnetic resonance imaging scan. Cortical thickness was quantified at 81,924 vertices across the cortical surface. We found: 1) increasing eating disorder traits correlated with thinner cortex in the insula and orbitofrontal cortex, among other regions, and 2) using these regions as seeds, increasing eating disorder trait scores negatively modulated structural covariance between these seed regions and other cortical regions linked to regulatory and sensorimotor functions (e.g., frontal and temporal cortices). These findings parallel those found in the clinical literature (i.e., thinner cortex in these food-related regions in individuals with eating disorders) and therefore provide evidence supporting the dimensional view of behavioral traits associated with eating disorders. Extending this approach to genetic and neuroimaging genetics studies holds promise to inform etiology.

Mapping abnormal subcortical neurodevelopment in a cohort of Thai children with HIV.

Alterations in subcortical brain structures have been reported in adults with HIV and, to a lesser extent, pediatric cohorts. The extent of longitudinal structural abnormalities in children with perinatal HIV infection (PaHIV) remains unclear. We modeled subcortical morphometry from whole brain structural magnetic resonance imaging (1.5 T) scans of 43 Thai children with PaHIV (baseline age = 11.09±2.36 years) and 50 HIV− children (11.26±2.80 years) using volumetric and surface-based shape analyses. The PaHIV sample were randomized to initiate combination antiretroviral treatment (cART) when CD4 counts were 15–24% (immediate: n = 22) or when CD4 < 15% (deferred: n = 21). Follow-up scans were acquired approximately 52 weeks after baseline. Volumetric and shape descriptors capturing local thickness and surface area dilation were defined for the bilateral accumbens, amygdala, putamen, pallidum, thalamus, caudate, and hippocampus. Regression models adjusting for clinical and demographic variables examined between and within group differences in morphometry associated with HIV. We assessed whether baseline CD4 count and cART status or timing associated with brain maturation within the PaHIV group. All models were adjusted for multiple comparisons using the false discovery rate. A pallidal subregion was significantly thinner in children with PaHIV. Regional thickness, surface area, and volume of the pallidum was associated with CD4 count in children with PaHIV. Longitudinal morphometry was not associated with HIV or cART status or timing, however, the trajectory of the left pallidum volume was positively associated with baseline CD4 count. Our findings corroborate reports in adult cohorts demonstrating a high predilection for HIV-mediated abnormalities in the basal ganglia, but suggest the effect of stable PaHIV infection on morphological aspects of brain development may be subtle.