Design and Methods of the Early Age-Related Hearing Loss Investigation Randomized Controlled Trial.

OBJECTIVE: Hearing loss has been identified as a major modifiable risk factor for cognitive decline. The Early Age-Related Hearing Loss Investigation (EARHLI) study will assess the mechanisms linking early age-related hearing loss (ARHL) and cognitive impairment. STUDY DESIGN: Randomized, controlled, single-site, early phase II, superiority trial. SETTING: Tertiary academic medical center. PARTICIPANTS: One hundred fifty participants aged 55 to 75 years with early ARHL (severity defined as borderline to moderate) and amnestic mild cognitive impairment will be included. INTERVENTIONS: Participants will be randomized 1:1 to a best practice hearing intervention or a health education control. MAIN OUTCOME MEASURES: The primary study outcome is cognition measured by the Alzheimer Disease Cooperative Study-Preclinical Alzheimer Cognitive Composite. Secondary outcomes include additional measures of cognition, social engagement, and brain organization/connectivity. RESULTS: Trial enrollment will begin in early 2024. CONCLUSIONS: After its completion in 2028, the EARHLI trial should offer evidence on the effect of hearing treatment versus a health education control on cognitive performance, social engagement, and brain organization/connectivity in 55- to 75-year-old community-dwelling adults with early ARHL and amnestic mild cognitive impairment.

Neighborhood Opportunity and Vulnerability and Incident Asthma Among Children.

Background: The extent to which physical and social attributes of neighborhoods play a role in childhood asthma remains understudied. Objective: To examine associations of neighborhood-level opportunity and social vulnerability measures with childhood asthma incidence. Design, Setting, and Participants: This cohort study used data from children in 46 cohorts participating in the Environmental Influences on Child Health Outcomes (ECHO) Program between January 1, 1995, and August 31, 2022. Participant inclusion required at least 1 geocoded residential address from birth and parent or caregiver report of a physician's diagnosis of asthma. Participants were followed up to the date of asthma diagnosis, date of last visit or loss to follow-up, or age 20 years. Exposures: Census tract-level Child Opportunity Index (COI) and Social Vulnerability Index (SVI) at birth, infancy, or early childhood, grouped into very low (<20th percentile), low (20th to <40th percentile), moderate (40th to <60th percentile), high (60th to <80th percentile), or very high (≥80th percentile) COI or SVI. Main Outcomes and Measures: The main outcome was parent or caregiver report of a physician's diagnosis of childhood asthma (yes or no). Poisson regression models estimated asthma incidence rate ratios (IRRs) associated with COI and SVI scores at each life stage. Results: The study included 10 516 children (median age at follow-up, 9.1 years [IQR, 7.0-11.6 years]; 52.2% male), of whom 20.6% lived in neighborhoods with very high COI and very low SVI. The overall asthma incidence rate was 23.3 cases per 1000 child-years (median age at asthma diagnosis, 6.6 years [IQR, 4.1-9.9 years]). High and very high (vs very low) COI at birth, infancy, or early childhood were associated with lower subsequent asthma incidence independent of sociodemographic characteristics, parental asthma history, and parity. For example, compared with very low COI, the adjusted IRR for asthma was 0.87 (95% CI, 0.75-1.00) for high COI at birth and 0.83 (95% CI, 0.71-0.98) for very high COI at birth. These associations appeared to be attributable to the health and environmental and the social and economic domains of the COI. The SVI during early life was not significantly associated with asthma incidence. For example, compared with a very high SVI, the adjusted IRR for asthma was 0.88 (95% CI, 0.75-1.02) for low SVI at birth and 0.89 (95% CI, 0.76-1.03) for very low SVI at birth. Conclusions: In this cohort study, high and very high neighborhood opportunity during early life compared with very low neighborhood opportunity were associated with lower childhood asthma incidence. These findings suggest the need for future studies examining whether investing in health and environmental or social and economic resources in early life would promote health equity in pediatric asthma.

Linear Classification of Neural Manifolds with Correlated Variability.

Understanding how the statistical and geometric properties of neural activity relate to performance is a key problem in theoretical neuroscience and deep learning. Here, we calculate how correlations between object representations affect the capacity, a measure of linear separability. We show that for spherical object manifolds, introducing correlations between centroids effectively pushes the spheres closer together, while introducing correlations between the axes effectively shrinks their radii, revealing a duality between correlations and geometry with respect to the problem of classification. We then apply our results to accurately estimate the capacity of deep network data.

No Meta-analytic Evidence for Risks due to Prenatal Magnetic Resonance Imaging in Animal Models.

BACKGROUND: Magnetic resonance imaging (MRI) is a powerful, noninvasive tool for both clinical practice and research. Though the safety of MRI has been endorsed by many professional societies and government bodies, some concerns have remained about potential risk from prenatal MRI. Case-control animal studies of MRI scanning during gestation and effects on offspring are the most direct test available for potential risks. We performed a meta-analysis of extant animal studies of prenatal MRI examining reproductive and offspring outcomes. METHODS: Relevant articles were identified through PubMed search and citation searching of known articles and review papers. Eighteen relevant studies were identified with case-control designs of prenatal scanning conducted in vivo with mammalian species using MRI-relevant field strength. Standardized mean difference effect sizes were analyzed across k = 81 outcomes assessed across 649 unexposed dams, 622 exposed dams, 3024 unexposed offspring, and 3328 exposed offspring using a multilevel meta-analytic approach that clustered effect sizes within publications. RESULTS: The meta-analysis indicated no significant evidence for a deleterious effects of prenatal MRI (standardized mean difference = 0.17, 95% CI [-0.19, 0.54], t80 = 0.94, p = .35) across outcomes. Similarly, no effects were observed when separately examining the 4 most commonly assessed outcomes: birth weight, litter size, fetal viability, and physical malformations (p > .05). CONCLUSIONS: Case-control mammalian animal studies indicate no significant known risks of prenatal MRI to reproductive outcomes or offspring development. This finding is largely mirrored in human research, though the lack of randomized case-control designs limits direct comparison. The current findings provide additional support to the prevailing consensus that prenatal MRI poses no known risk to offspring.

Associations of Neighborhood Opportunity and Social Vulnerability With Trajectories of Childhood Body Mass Index and Obesity Among US Children.

Importance: Physical and social neighborhood attributes may have implications for children's growth and development patterns. The extent to which these attributes are associated with body mass index (BMI) trajectories and obesity risk from childhood to adolescence remains understudied. Objective: To examine associations of neighborhood-level measures of opportunity and social vulnerability with trajectories of BMI and obesity risk from birth to adolescence. Design, Setting, and Participants: This cohort study used data from 54 cohorts (20 677 children) participating in the Environmental Influences on Child Health Outcomes (ECHO) program from January 1, 1995, to January 1, 2022. Participant inclusion required at least 1 geocoded residential address and anthropometric measure (taken at the same time or after the address date) from birth through adolescence. Data were analyzed from February 1 to June 30, 2022. Exposures: Census tract-level Child Opportunity Index (COI) and Social Vulnerability Index (SVI) linked to geocoded residential addresses at birth and in infancy (age range, 0.5-1.5 years), early childhood (age range, 2.0-4.8 years), and mid-childhood (age range, 5.0-9.8 years). Main Outcomes and Measures: BMI (calculated as weight in kilograms divided by length [if aged <2 years] or height in meters squared) and obesity (age- and sex-specific BMI ≥95th percentile). Based on nationwide distributions of the COI and SVI, Census tract rankings were grouped into 5 categories: very low (<20th percentile), low (20th percentile to <40th percentile), moderate (40th percentile to <60th percentile), high (60th percentile to <80th percentile), or very high (≥80th percentile) opportunity (COI) or vulnerability (SVI). Results: Among 20 677 children, 10 747 (52.0%) were male; 12 463 of 20 105 (62.0%) were White, and 16 036 of 20 333 (78.9%) were non-Hispanic. (Some data for race and ethnicity were missing.) Overall, 29.9% of children in the ECHO program resided in areas with the most advantageous characteristics. For example, at birth, 26.7% of children lived in areas with very high COI, and 25.3% lived in areas with very low SVI; in mid-childhood, 30.6% lived in areas with very high COI and 28.4% lived in areas with very low SVI. Linear mixed-effects models revealed that at every life stage, children who resided in areas with higher COI (vs very low COI) had lower mean BMI trajectories and lower risk of obesity from childhood to adolescence, independent of family sociodemographic and prenatal characteristics. For example, among children with obesity at age 10 years, the risk ratio was 0.21 (95% CI, 0.12-0.34) for very high COI at birth, 0.31 (95% CI, 0.20-0.51) for high COI at birth, 0.46 (95% CI, 0.28-0.74) for moderate COI at birth, and 0.53 (95% CI, 0.32-0.86) for low COI at birth. Similar patterns of findings were observed for children who resided in areas with lower SVI (vs very high SVI). For example, among children with obesity at age 10 years, the risk ratio was 0.17 (95% CI, 0.10-0.30) for very low SVI at birth, 0.20 (95% CI, 0.11-0.35) for low SVI at birth, 0.42 (95% CI, 0.24-0.75) for moderate SVI at birth, and 0.43 (95% CI, 0.24-0.76) for high SVI at birth. For both indices, effect estimates for mean BMI difference and obesity risk were larger at an older age of outcome measurement. In addition, exposure to COI or SVI at birth was associated with the most substantial difference in subsequent mean BMI and risk of obesity compared with exposure at later life stages. Conclusions and Relevance: In this cohort study, residing in higher-opportunity and lower-vulnerability neighborhoods in early life, especially at birth, was associated with a lower mean BMI trajectory and a lower risk of obesity from childhood to adolescence. Future research should clarify whether initiatives or policies that alter specific components of neighborhood environment would be beneficial in preventing excess weight in children.

The relationship between recent PTSD secondary to sexual assault, hippocampal volume and resting state functional connectivity in adolescent girls.

Objective: Improved understanding of the time course of neural changes associated with adolescent PTSD would elucidate the development of the disorder and could inform approaches to treatment. We compared hippocampal volumes and resting state functional connectivity (RSFC) in adolescent girls with post-traumatic stress disorder (PTSD) secondary to sexual assault, within six months of onset and age- and gender-matched, non-trauma exposed healthy controls (HCs) in São Paulo, Brazil. We also examined the relationship between pre- and post-treatment PTSD symptoms and RSFC. Method: We collected brain structure, RSFC, and PTSD symptoms in 30 adolescents with PTSD (mean age: 15.7 ± 1.04 years) and 21 HCs (mean age: 16.2 ± 1.21 years) at baseline. We collected repeated measures in 21 participants with PTSD following treatment; 9 participants dropped out. Hippocampal volume and RSFC from hippocampal and default mode network (DMN) seeds were compared between participants with PTSD and HCs. We examined associations between within-subject changes in RSFC and PTSD symptoms following treatment. Results: No hippocampal volumetric differences between groups were found. Compared to HCs, adolescents with recent PTSD had reduced RSFC between hippocampus and the lateral parietal node of the DMN, encompassing the angular gyrus, peak coordinates: -38, -54, 16; 116 voxels; peak F 1,47 = 31.76; FDR corrected p = 0.038. Improvements in PTSD symptoms were associated with increased RSFC between hippocampus and part of the lateral parietal node of the DMN, peak coordinates: -38, -84, 38; 316 voxels; peak F 1,47 = 40.28; FDR corrected p < 0.001. Conclusion: Adolescents with recent PTSD had reduced hippocampal-DMN RSFC, while no group differences in hippocampal volume were found, suggesting that hippocampal function, but not structure, is altered early in the course of PSTD. Following treatment, hippocampal-DMN RSFC increased with symptom improvement and may indicate an important neural mechanism related to successful PTSD treatment.

Do Trajectories of Sensation Seeking Vary by Sex and Child Maltreatment Subtypes?

Child maltreatment and elevated sensation seeking are associated with a wide range of negative outcomes. Longitudinal data from a study of Puerto Ricans living in two sociocultural contexts were used to determine whether child maltreatment subtypes, sex, or sociocultural context relate to trajectories of sensation seeking. Participants were 2,489 individuals from the Boricua Youth Study (48.5% girls) living in New York and in Puerto Rico (PR; 5-15 years old at Wave 1). Subtypes of child maltreatment were measured using child report on the Parent-Child Conflict Tactics Scale and the Sexual Victimization Scale at Wave 1. The association between child maltreatment subtypes, sex, sociocultural context, and previously established sensation-seeking trajectories across three waves of data collection was probed using multinomial logistic regression. Girls, but not boys, who experienced neglect (adjusted odds ratio; AOR; 95% confidence interval [95% CI] = 5.33 [1.35, 21.03]), or physical abuse (AOR [95% CI] = 3.66 [1.07, 12.54]), were more likely to have an elevated sensation-seeking trajectory than a normative trajectory. For boys, none of the maltreatment subtypes were linked to the elevated sensation-seeking class. Girls exposed to verbal abuse (AOR [95% CI] = 0.33 [0.15, 0.75]) and boys exposed to physical abuse (AOR [95% CI] = 0.39 [0.16, 0.97]) were less likely to belong to the low sensation-seeking class. No significant interactions between sociocultural context (i.e., PR vs. New York) and maltreatment subtype on the development of sensation seeking were found. This research suggests sensation-seeking levels vary by experiences of childhood maltreatment, and that sex moderates the relationship between child maltreatment experiences and sensation seeking, with an association between some maltreatment subtypes and elevated sensation-seeking trajectories found in girls, but not boys. These results underline the importance of considering sex when examining how child maltreatment relates to outcomes.

The relationship between persistent organic pollutants and Attention Deficit Hyperactivity Disorder phenotypes: Evidence from task-based neural activity in an observational study of a community sample of Canadian mother-child dyads.

BACKGROUND: Prenatal exposure to persistent organic pollutants (POPs), widespread in North America, is associated with increased Attention Deficit/Hyperactivity Disorder (ADHD) symptoms and may be a modifiable risk for ADHD phenotypes. However, the effects of moderate exposure to POPs on task-based inhibitory control performance, related brain function, and ADHD-related symptoms remain unknown, limiting our ability to develop interventions targeting the neural impact of common levels of exposure. OBJECTIVES: The goal of this study was to examine the association between prenatal POP exposure and inhibitory control performance, neural correlates of inhibitory control and ADHD-related symptoms. METHODS: Prospective data was gathered in an observational study of Canadian mother-child dyads, with moderate exposure to POPs, including polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs), as part of the GESTation and the Environment (GESTE) cohort in Sherbrooke, Quebec, Canada. The sample included 87 eligible children, 46 with maternal plasma samples, functional magnetic resonance imaging (fMRI) data of Simon task performance at 9-11 years, and parental report of clinical symptoms via the Behavioral Assessment System for Children 3 (BASC-3). Simon task performance was probed via drift diffusion modeling, and parameter estimates were related to POP exposure. Simon task-based fMRI data was modeled to examine the difference in incongruent vs congruent trials in regions of interest (ROIs) identified by meta analysis. RESULTS: Of the 46 participants with complete data, 29 were male, and mean age was 10.42 ± 0.55 years. Increased POP exposure was associated with reduced accuracy (e.g. PCB molar sum rate ratio = 0.95; 95% CI [0.90, 0.99]), drift rate (e.g. for PCB molar sum ß = -0.42; 95% CI [-0.77, -0.07]), and task-related brain activity (e.g. in inferior frontal cortex for PCB molar sum ß = -0.35; 95% CI [-0.69, -0.02]), and increased ADHD symptoms (e.g. hyperactivity PCB molar sum ß = 2.35; 95%CI [0.17, 4.53]), supporting the possibility that prenatal exposure to POPs is a modifiable risk for ADHD phenotypes. DISCUSSION: We showed that exposure to POPs is related to task-based changes in neural activity in brain regions important for inhibitory control, suggesting a biological mechanism underlying previously documented associations between POPs and neurobehavioral deficits found in ADHD phenotypes.

Effects of a Brief Mindfulness-Based Attentional Intervention on Threat-Related Perceptual Decision-Making.

OBJECTIVES: Threat-related cues and contexts facilitate perceptual decision-making, yet it is unclear whether this threat-driven tuning of perceptual decision-making is modifiable by top-down attentional control. Since state and dispositional mindfulness are linked to improved attentional control, we examined whether these factors assist the use of prior knowledge to detect threatening stimuli. METHODS: Participants were randomly assigned to a brief mindfulness-based intervention (N=32) or a physics lecture audio recording (N=31) and then asked to perform a task in which they used threatening and neutral cues to discriminate between threatening and neutral faces. RESULTS: Results showed that threatening cues led to faster and more sensitive perceptual decision-making, specifically for threatening faces. Furthermore, higher levels of dispositional mindfulness were associated with improved ability to use cues to discriminate between threatening and neutral stimuli in the group that underwent a brief mindfulness induction but not in the control group. CONCLUSIONS: Our findings highlight how top-down attention-related dispositions and strategies can influence our ability to detect threats in our environment.

The role of imagery in threat-related perceptual decision making.

Visual perception is heavily influenced by "top-down" factors, including goals, expectations, and prior knowledge about the environmental context. Recent research has demonstrated the beneficial role threat-related cues play in perceptual decision making; however, the psychological processes contributing to this differential effect remain unclear. Since visual imagery helps to create perceptual representations or "templates" based on prior knowledge (e.g., cues), the present study examines the role vividness of visual imagery plays in enhanced perceptual decision making following threatening cues. In a perceptual decision-making task, participants used threat-related and neutral cues to detect perceptually degraded fearful and neutral faces presented at predetermined perceptual thresholds. Participants' vividness of imagery was measured by the Vividness of Visual Imagery Questionnaire-2 (VVIQ-2). Our results replicated prior work demonstrating that threat cues improve accuracy, perceptual sensitivity, and speed of perceptual decision making compared to neutral cues. Furthermore, better performance following threat and neutral cues was associated with higher VVIQ-2 scores. Importantly, more precise and rapid perceptual decision making following threatening cues was associated with greater VVIQ-2 scores, even after controlling for performance related to neutral cues. This association may be because greater imagery ability allows one to conjure more vivid threat-related templates, which facilitate subsequent perception. While the detection of threatening stimuli is well studied in the literature, our findings elucidate how threatening cues occurring prior to the stimulus aid in subsequent perception. Overall, these findings highlight the necessity of considering top-down threat-related factors in visual perceptual decision making. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Editorial: Neural Correlates of Sluggish Cognitive Tempo: Biological Evidence of a Distinct Clinical Entity?

Attention-deficit/hyperactivity disorder (ADHD) is a heterogeneous disorder encompassing a wide array of clinical presentations, levels of impairment, etiologies, and neurobiological correlates. Despite this well-known heterogeneity, most research into the pathophysiology of ADHD has relied on comparisons between typically developing youth and those with the disorder (or perhaps further stratifying by DSM-defined ADHD subtypes). Although informative, this approach assumes a level of pathophysiologic homogeneity that belies the large and growing body of literature underscoring diverse neurobiological and neuropsychological profiles subsumed under the umbrella of this complex syndrome.1 For example, deficits in executive functions are characteristic of ADHD, yet meta-analysis suggests that these deficits are neither necessary nor sufficient to define all cases2 and that substantial overlaps in levels of executive functioning exist between children with ADHD and their typically developing peers.1 Likewise, neuroimaging research points to distinct neural circuits underlying different clinical presentations of ADHD, suggesting that, within the diagnosis of ADHD, the neural circuits that are most salient to the disorder can differ from one child to the next.3 Refining our understanding of ADHD subtypes not only on the basis of symptoms, but also by incorporating neurobiology, physiology, and neurocognitive profiles, could help propel the field toward greater specificity in diagnosis and treatment.

Here Comes Trouble: Prestimulus Brain Activity Predicts Enhanced Perception of Threat.

Research on the perceptual prioritization of threatening stimuli has focused primarily on the physical characteristics and evolutionary salience of these stimuli. However, perceptual decision-making is strongly influenced by prestimulus factors such as goals, expectations, and prior knowledge. Using both event-related potentials and functional magnetic resonance imaging, we test the hypothesis that prior threat-related information and related increases in prestimulus brain activity play a key role in subsequent threat-related perceptual decision-making. After viewing threatening and neutral cues, participants detected perceptually degraded threatening and neutral faces presented at individually predetermined perceptual thresholds in a perceptual decision-making task. Compared with neutral cues, threat cues resulted in (1) improved perceptual sensitivity and faster detection of target stimuli; (2) increased late positive potential (LPP) and superior temporal sulcus (STS) activity, both of which are measures of emotional face processing; and (3) increased amygdala activity for subsequently presented threatening versus and neutral faces. Importantly, threat cue-related LPP and STS activity predicted subsequent improvement in the speed and precision of perceptual decisions specifically for threatening faces. Present findings establish the importance of top-down factors and prestimulus neural processing in understanding how the perceptual system prioritizes threatening information.

Top-down and bottom-up factors in threat-related perception and attention in anxiety.

Anxiety is characterized by the anticipation of aversive future events. The importance of prestimulus anticipatory factors, such as goals and expectations, is well-established in both visual perception and attention. Nevertheless, the prioritized perception of threatening stimuli in anxiety has been attributed to the automatic processing of these stimuli and the role of prestimulus factors has been neglected. The present review will focus on the role of top-down processes that occur before stimulus onset in the perceptual and attentional prioritization of threatening stimuli in anxiety. We will review both the cognitive and neuroscience literature, showing how top-down factors, and interactions between top-down and bottom-up factors may contribute to biased perception of threatening stimuli in normal function and anxiety. The shift in focus from stimulus-driven to endogenous factors and interactions between top-down and bottom-up factors in the prioritization of threat-related stimuli represents an important conceptual advance. In addition, it may yield important clues into the development and maintenance of anxiety, as well as inform novel treatments for anxiety.

It's all in the anticipation: How perception of threat is enhanced in anxiety.

The importance of top-down factors such as goals and expectations is well-established in both visual perception and anxiety. However, researchers have attributed the perceptual prioritization of threatening stimuli in anxiety to bottom-up, automatic processing of these stimuli while neglecting the role of prestimulus, top-down factors. Furthermore, different kinds of anxiety (dispositional versus induced) impact cognitive functions differently, suggesting that top-down factors may have distinct effects on threat perception. In the present study, we examined whether prestimulus representations of threatening stimuli facilitate perception differently, depending on induced and trait anxiety. Two groups of participants completed a cued discrimination task using threatening or neutral cues to identify subsequently presented fearful and neutral faces, degraded to each participant's perceptual threshold. In Group 1, threat of shock induced anxiety (n = 22; 12 men), whereas in Group 2, no anxiety was induced (n = 29; 7 men). The impact of induced anxiety on perception interacted with trait anxiety. Following fear cues, higher trait anxiety was associated with improved perceptual sensitivity and faster reaction time under threat of shock, and worse perceptual sensitivity and slower reaction time in absence of shock. The present findings represent an important advance in the literature because they elucidate the role of previously ignored top-down factors in threat perception for individuals with varying levels of anxiety and highlight the distinct impact that different types of anxiety have on the perception of threatening stimuli. Furthermore, these findings underline the importance of including top-down factors in future conceptualizations of perceptual bias toward threat in anxiety.

Developing the yearning in situations of loss scale: convergent and discriminant validity for bereavement, romantic breakup, and homesickness.

Yearning is common in situations involving loss, and a hallmark of complicated grief. To study yearning empirically, the present study develops the Yearning in Situations of Loss scale (YSL), which measures yearning bereavement, romantic breakup, or homesickness. In Study 1, we identified shared characteristics across situations of loss, tested an initial version and removed items with the lowest item-scale reliability. In Study 2, the 21-item YSL was compared to scales of anxiety, depression, and loneliness, and existing scales, relevant to each loss situation. The YSL showed discriminant and convergent validity that applies to bereavement, romantic breakup, and homesickness.

Emotional distractors can enhance attention.

The deleterious effects of emotional distractors on attention have been well demonstrated. However, it is unclear whether emotional distractors inevitably disrupt task-relevant attention. In the research reported here, the impact of the valence and arousal of distracting emotional stimuli and individual differences in anxiety on task-relevant processing were examined using multilevel modeling. Consistent with prior literature, results showed that high-arousal negative distractors, compared with positive and neutral distractors, were associated with poorer task-relevant attention. However, low-arousal negative distractors were associated with better task-relevant performance than were positive and neutral distractors. Furthermore, these effects were accentuated by individual differences in worry. These findings challenge assumptions that distraction and worry must be minimized for augmented attentional performance. Overall, these results emphasize the importance of taking into account emotional dimensions of arousal and valence as well as individual differences in anxiety when examining attention in the presence of emotional distractors.