Test-retest reliability and longitudinal analysis of automated hippocampal subregion volumes in healthy ageing and Alzheimer's disease populations

The hippocampal formation is a complex brain structure that is important in cognitive processes such as memory, mood, reward processing and other executive functions. Histological and neuroimaging studies have implicated the hippocampal region in neuropsychiatric disorders as well as in neurodegenerative diseases. This highly plastic limbic region is made up of several subregions that are believed to have different functional roles. Therefore, there is a growing interest in imaging the subregions of the hippocampal formation rather than modelling the hippocampus as a homogenous structure, driving the development of new automated analysis tools. Consequently, there is a pressing need to understand the stability of the measures derived from these new techniques. In this study, an automated hippocampal subregion segmentation pipeline, released as a developmental version of Freesurfer (v6.0), was applied to T1-weighted magnetic resonance imaging (MRI) scans of 22 healthy older participants, scanned on 3 separate occasions and a separate longitudinal dataset of 40 Alzheimer's disease (AD) patients. Test-retest reliability of hippocampal subregion volumes was assessed using the intra-class correlation coefficient (ICC), percentage volume difference and percentage volume overlap (Dice). Sensitivity of the regional estimates to longitudinal change was estimated using linear mixed effects (LME) modelling. The results show that out of the 24 hippocampal subregions, 20 had ICC scores of 0.9 or higher in both samples; these regions include the molecular layer, granule cell layer of the dentate gyrus, CA1, CA3 and the subiculum (ICC > 0.9), whilst the hippocampal fissure and fimbria had lower ICC scores (0.73-0.88). Furthermore, LME analysis of the independent AD dataset demonstrated sensitivity to group and individual differences in the rate of volume change over time in several hippocampal subregions (CA1, molecular layer, CA3, hippocampal tail, fissure and presubiculum). These results indicate that this automated segmentation method provides a robust method with which to measure hippocampal subregions, and may be useful in tracking disease progression and measuring the effects of pharmacological intervention

Quantum localization in rough billiards

We study the level spacing statistics p(s) and eigenfunction properties in a billiard with a rough boundary. Quantum effects lead to localization of classical diffusion in the angular momentum space and the Shnirelman peak in p(s) at small s. The ergodic regime with Wigner-Dyson statistics is identified as a function of roughness. Applications for the Q-spoiling in optical resonators are also discussed.Comment: revtex, 4 pages, 5 figure

Neural Circuitry of Novelty Salience Processing in Psychosis Risk: Association With Clinical Outcome

Psychosis has been proposed to develop from dysfunction in a hippocampal-striatal-midbrain circuit, leading to aberrant salience processing. Here, we used functional magnetic resonance imaging (fMRI) during novelty salience processing to investigate this model in people at clinical high risk (CHR) for psychosis according to their subsequent clinical outcomes. Seventy-six CHR participants as defined using the Comprehensive Assessment of At-Risk Mental States (CAARMS) and 31 healthy controls (HC) were studied while performing a novelty salience fMRI task that engaged an a priori hippocampal-striatal-midbrain circuit of interest. The CHR sample was then followed clinically for a mean of 59.7 months (~5 y), when clinical outcomes were assessed in terms of transition (CHR-T) or non-transition (CHR-NT) to psychosis (CAARMS criteria): during this period, 13 individuals (17%) developed a psychotic disorder (CHR-T) and 63 did not. Functional activation and effective connectivity within a hippocampal-striatal-midbrain circuit were compared between groups. In CHR individuals compared to HC, hippocampal response to novel stimuli was significantly attenuated (P = .041 family-wise error corrected). Dynamic Causal Modelling revealed that stimulus novelty modulated effective connectivity from the hippocampus to the striatum, and from the midbrain to the hippocampus, significantly more in CHR participants than in HC. Conversely, stimulus novelty modulated connectivity from the midbrain to the striatum significantly less in CHR participants than in HC, and less in CHR participants who subsequently developed psychosis than in CHR individuals who did not become psychotic. Our findings are consistent with preclinical evidence implicating hippocampal-striatal-midbrain circuit dysfunction in altered salience processing and the onset of psychosis

Emergence of Quantum Ergodicity in Rough Billiards

By analytical mapping of the eigenvalue problem in rough billiards on to a band random matrix model a new regime of Wigner ergodicity is found. There the eigenstates are extended over the whole energy surface but have a strongly peaked structure. The results of numerical simulations and implications for level statistics are also discussed.Comment: revtex, 4 pages, 4 figure

Imaging of brain structural and functional effects in people with human immunodeficiency virus

Before the introduction of antiretroviral therapy, human immunodeficiency virus (HIV) infection was often accompanied by central nervous system (CNS) opportunistic infections and HIV encephalopathy marked by profound structural and functional alterations detectable with neuroimaging. Treatment with antiretroviral therapy nearly eliminated CNS opportunistic infections, while neuropsychiatric impairment and peripheral nerve and organ damage have persisted among virally suppressed people with HIV (PWH), suggesting ongoing brain injury. Neuroimaging research must use methods sensitive for detecting subtle HIV-associated brain structural and functional abnormalities, while allowing for adjustments for potential confounders, such as age, sex, substance use, hepatitis C coinfection, cardiovascular risk, and others. Here, we review existing and emerging neuroimaging tools that demonstrated promise in detecting markers of HIV-associated brain pathology and explore strategies to study the impact of potential confounding factors on these brain measures. We emphasize neuroimaging approaches that may be used in parallel to gather complementary information, allowing efficient detection and interpretation of altered brain structure and function associated with suboptimal clinical outcomes among virally suppressed PWH. We examine the advantages of each imaging modality and systematic approaches in study design and analysis. We also consider advantages of combining experimental and statistical control techniques to improve sensitivity and specificity of biotype identification and explore the costs and benefits of aggregating data from multiple studies to achieve larger sample sizes, enabling use of emerging methods for combining and analyzing large, multifaceted data sets. Many of the topics addressed in this article were discussed at the National Institute of Mental Health meeting Biotypes of CNS Complications in People Living with HIV, held in October 2021, and are part of ongoing research initiatives to define the role of neuroimaging in emerging alternative approaches to identifying biotypes of CNS complications in PWH. An outcome of these considerations may be the development of a common neuroimaging protocol available for researchers to use in future studies examining neurological changes in the brains of PWH

Polygenic risk for circulating reproductive hormone levels and their influence on hippocampal volume and depression susceptibility

Altered reproductive hormone levels have been associated with the pathophysiology of depressive disorders and this risk may be imparted by their modulatory effect upon hippocampal structure and function. Currently it is unclear whether altered levels of reproductive hormones are causally associated with hippocampal volume reductions and the risk of depressive disorders. Here, we utilize genome-wide association study (GWAS) summary statistics from a GWAS focusing on reproductive hormones, consisting of 2913 individuals. Using this data, we generated polygenic risk scores (PRS) for estradiol, progesterone, prolactin and testosterone in the European RADIANT cohort consisting of 176 postpartum depression (PPD) cases (100% female, mean age: 41.6 years old), 2772 major depressive disorder (MDD) cases (68.6% female, mean age: 46.9 years old) and 1588 control participants (62.5% female, mean age: 42.4 years old), for which there was also a neuroimaging subset of 111 individuals (60.4% female, mean age: 50.0 years old). Only the best-fit PRS for estradiol showed a significant negative association with hippocampal volume, as well as many of its individual subfields; including the molecular layer and granule cell layer of the dentate gyrus, subiculum, CA1, CA2/3 and CA4 regions. Interestingly, several of these subfields are implicated in adult hippocampal neurogenesis. When we tested the same estradiol PRS for association with case-control status for PPD or MDD there was no significant relationship observed. Here, we provide evidence that genetic risk for higher plasma estradiol is negatively associated with hippocampal volume, but this does not translate into an increased risk of MDD or PPD. This work suggests that the relationship between reproductive hormones, the hippocampus, and depression is complex, and that there may not be a clear-cut pathway for etiology or risk moderation

A Search for Jet Handedness in Hadronic Z0Z^0 Decays

We have searched for signatures of polarization in hadronic jets from $Z^0 \to q \bar{q}$ decays using the ``jet handedness'' method. The polar angle asymmetry induced by the high SLC electron-beam polarization was used to separate quark jets from antiquark jets, expected to be left- and right-polarized, respectively. We find no evidence for jet handedness in our global sample or in a sample of light quark jets and we set upper limits at the 95% C.L. of 0.063 and 0.099 respectively on the magnitude of the analyzing power of the method proposed by Efremov {\it et al.}Comment: Revtex, 8 pages, 2 figure

ENIGMA and global neuroscience: A decade of large-scale studies of the brain in health and disease across more than 40 countries

This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of "big data" (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA's activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors

Impact of the Coronavirus Pandemic (COVID-19) Lockdown on Mental Health and Well-Being in the United Arab Emirates

United Arab Emirates (UAE) has taken unprecedented precautionary measures including complete lockdowns against COVID-19 to control its spread and ensure the well-being of individuals. This study investigated the impact of COVID-19 and societal lockdown measures on the mental health of adults in the UAE. A cross-sectional study was conducted using an English and Arabic online questionnaire between May and June 2020. The psychological impact was assessed by the Impact of Event Scale-Revised (IES-R), and the social and family support impact was evaluated using questions from the Perceived Support Scale (PSS). A total of 4,426 participants (3,325 females and 1,101 males) completed the questionnaire. The mean IES-R score was 28.0 ± 14.6, reflecting a mild stressful impact with 27.3% reporting severe psychological impact. Over 36% reported increased stress from work, home and financial matters. Also, 43–63% of the participants felt horrified, apprehensive or helpless due to COVID-19. Females, younger participants, part-timers, and college or University graduates were more likely to have a high IES-R score (p \u3c 0.05). The majority of participants reported receiving increased support from family members, paying more attention to their mental health, and spending more time to rest and relax. The results of this study demonstrate the impact of the COVID-19 pandemic on mental health among the UAE residents and highlight the need to adopt culturally appropriate interventions for the general population and vulnerable groups, such as females and younger adults