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BackgroundDigital cognitive assessments, particularly those that can be done at home, present as low-burden biomarkers for participants and patients alike, but their effectiveness in the diagnosis of Alzheimer's disease (AD) or predicting its trajectory is still unclear. Here, we assessed what utility or added value these digital cognitive assessments provide for identifying those at high risk of cognitive decline.MethodsWe analyzed >500 Alzheimer's Disease Neuroimaging Initiative participants who underwent a brief digital cognitive assessment and amyloid beta (Aβ)/tau positron emission tomography scans, examining their ability to distinguish cognitive status and predict cognitive decline.ResultsPerformance on the digital cognitive assessment was superior to both cortical Aβ and entorhinal tau in detecting mild cognitive impairment and future cognitive decline, with mnemonic discrimination deficits emerging as the most critical measure for predicting decline and future tau accumulation.DiscussionDigital assessments are effective at identifying at-risk individuals, supporting their utility as low-burden tools for early AD detection and monitoring.HighlightsPerformance on digital cognitive assessments predicts progression to mild cognitive impairment at a higher proficiency compared to amyloid beta and tau. Deficits in mnemonic discrimination are indicative of future cognitive decline. Impaired mnemonic discrimination predicts future entorhinal and inferior temporal tau.

The fundamental organization of the human brain is established before birth, with rapid growth continuing over the first postnatal years. Children exposed before or after birth to various biological (e.g., substance exposure) or psychosocial hazards (e.g., maltreatment) are at elevated likelihood of deviating from a typical developmental trajectory, which in turn can be associated with psychological, behavioral, and physical health sequelae. In the HEALthy Brain and Child Development (HBCD) Study, a multi-site prospective longitudinal cohort study, brain, physical, biological, cognitive, behavioral, social, and emotional development is being examined starting in pregnancy and planned through age 10 (data are sampled at varying degrees of granularity depending on age, with more dense sampling earlier in life). HBCD aims to determine the short- and long-term impacts of a variety of both harmful and protective factors, including prenatal substance use, on developmental trajectories through early childhood. Organized as a nationwide consortium across 27 sites, the HBCD Study will collect multimodal data that will be made publicly available on a yearly basis, through a data use application and approval process. Here we provide an overview of the HBCD Study design, sampling, protocol development, and data management. Data collected through HBCD will be fundamental to informing future prenatal and early childhood interventions and policies to promote wellbeing and resilience in all children.

PurposeTraumatic brain injury (TBI) and potentially traumatic events (PTEs) contribute to increased substance use, mental health issues, and cognitive impairments. However, there's not enough research on how TBI and PTEs combined impact mental heath, substance use, and neurocognition.MethodsThis study leverages a subset of The National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA) multi-site dataset with 551 adolescents to assess the combined and distinctive impacts of TBI, PTEs, and TBI+PTEs (prior to age 18) on substance use, mental health, and neurocognitive outcomes at age 18.ResultsTBI, PTEs, and TBI+PTEs predicted greater lifetime substance use and past-year alcohol and cannabis use. PTEs predicted greater internalizing symptoms, while TBI+PTEs predicted greater externalizing symptoms. Varying effects on neurocognitive outcomes included PTEs influencing attention accuracy and TBI+PTEs predicting faster speed in emotion tasks. PTEs predicted greater accuracy in abstraction-related tasks. Associations with working memory were not detected.ConclusionThis exploratory study contributes to the growing literature on the complex interplay between TBI, PTEs, and adolescent mental health, substance use, and neurocognition. The developmental implications of trauma via TBIs and/or PTEs during adolescence are considerable and worthy of further investigation.

Early adolescent drinking onset is linked to myriad negative consequences. Using the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA) baseline to year 8 data, this study (1) leveraged best subsets selection and Cox Proportional Hazards regressions to identify the most robust predictors of adolescent first and regular drinking onset, and (2) examined the clinical utility of drinking onset in forecasting later binge drinking and withdrawal effects. Baseline predictors included youth psychodevelopmental characteristics, cognition, brain structure, family, peer, and neighborhood domains. Participants (N=538) were alcohol-naïve at baseline. The strongest predictors of first and regular drinking onset were positive alcohol expectancies (Hazard Ratios [HRs]=1.67-1.87), easy home alcohol access (HRs=1.62-1.67), more parental solicitation (e.g., inquiring about activities; HRs=1.72-1.76), and less parental control and knowledge (HRs=.72-.73). Robust linear regressions showed earlier first and regular drinking onset predicted earlier transition into binge and regular binge drinking (βs=0.57-0.95). Zero-inflated Poisson regressions revealed that delayed first and regular drinking increased the likelihood (Incidence Rate Ratios [IRR]=1.62 and IRR=1.29, respectively) of never experiencing withdrawal. Findings identified behavioral and environmental factors predicting temporal paths to youthful drinking, dissociated first from regular drinking initiation, and revealed adverse sequelae of younger drinking initiation, supporting efforts to delay drinking onset.

Although stress is often related to substance use, it remains unclear whether substance use is related to individual differences in how adolescents respond to stress. Therefore the present study examined associations between substance use and daily emotional reactivity to stress within a year across adolescence. Adolescents (N = 330; Mage = 16.40, SD = 0.74 at study entry; n = 186 female; n = 138 Latine; n = 101 European American; n = 72 Asian American; n = 19 identifying as another ethnicity including African American and Middle Eastern) completed a longitudinal study, including three assessments between the 10th grade and 3-years post-high school. At each assessment, participants reported frequency of alcohol and cannabis use and the number of substances they had ever used. They also completed 15 daily checklists, in which they reported the number of daily arguments and their daily emotion. Multilevel models suggested that more frequent alcohol and cannabis use were related to attenuated positive emotional reactivity to daily stress (i.e., smaller declines in positive emotion on days when they experienced more arguments) for both male and female adolescents. Associations for negative emotional reactivity to stress varied by sex; more frequent alcohol use and use of more substances in one's lifetime were related to greater anxious emotional reactivity to stress among female adolescents, whereas more frequent alcohol and cannabis use and higher lifetime substance use were related to attenuated depressive emotional reactivity to stress among male adolescents. Taken together, substance use was related to emotional reactivity to daily stress within the same year during adolescence, although associations differed by valence and adolescent sex.

The COVID-19 pandemic has uniquely impacted people living with HIV (PLWH) worldwide. The negative impacts on PLWH's mental health from fear of COVID-19 are labeled as "a double stress." The association between fear of COVID-19 and HIV (internalized) stigma has been found among PLWH. Studies that explore the relationships between fear of COVID-19 and physical health outcomes are few, especially among PLWH. In this study, we explored the relationship between fear of COVID-19 and physical health among PLWH and the mediated effects of HIV stigma, social support, and substance use. A cross-sectional online survey of PLWH (n = 201) from November 2021 to May 2022 was carried out in Shanghai, China. The data on socio-demographics, fear of COVID-19, physical health, HIV-related perceived stigma, social support, and substance use were gathered and analyzed by structure equation modeling (SEM). In SEM analysis, fear of COVID-19 showed a significant and indirect effect on physical health (β=-0.085) which was primarily mediated by HIV stigma. In SEM analysis, the final model had a good fit. Fear of COVID-19 showed a significant effect on HIV stigma (β = 0.223) with the majority being direct effects (β = 0.262) and a small indirect effect via substance use (β=-0.039). Furthermore, HIV stigma showed a significant effect on physical health (β=-0.382), the majority of which was direct (β=-0.340), and a small indirect effect via social support (β=-0.042). This is one of the first studies to explore how fear of contracting COVID-19 can affect PLWH's coping behaviors (e.g., using substances and obtaining social support) used to combat HIV stigma as well as to achieve better physical health in China.

To determine how neuronal circuits encode and drive behavior, it is often necessary to measure and manipulate different aspects of neurochemical signaling in awake animals. Optogenetics and calcium sensors have paved the way for these types of studies, allowing for the perturbation and readout of spiking activity within genetically defined cell types. However, these methods lack the ability to further disentangle the roles of individual neuromodulator and neuropeptides on circuits and behavior. We review recent advances in chemical biology tools that enable precise spatiotemporal monitoring and control over individual neuroeffectors and their receptors in vivo. We also highlight discoveries enabled by such tools, revealing how these molecules signal across different timescales to drive learning, orchestrate behavioral changes, and modulate circuit activity.

ObjectivesLatinos are about twice as likely to develop cognitive impairment. Culturally, filial support and familismo are expected within Latino families. Yet approximately twenty percent of Latinos live alone in the United States. The purpose of this study is to explore the concerns and priorities of older Latinos living alone with cognitive impairment, using a precarity framework.MethodWe conducted 22 in-home interviews with older Latinos living alone with cognitive impairment, and we supplemented the interviews with interviews with members of the older adults' social circle and providers. Themes influencing the precarity of Latino older adults living alone were organized through the major areas of the precarity lens; 1) Limited awareness of cognitive impairment; 2) Self-management of cognitive impairment; and 3) Lacking tailored services for cognitive impairment.ResultsLatino culture permeated and intersected across the lived experiences of participants living alone with cognitive impairment. Precarity was prevalent in all participants' lives and was exacerbated by familismo combined with cognitive impairment.ConclusionFindings showed precarity in the experiences the participants shared. Participant narratives reveal how the Latino culture intersects with the experience of precarity while living alone with cognitive impairment, especially in reference to the role that family plays through the expectation of familismo. However, given the difficult demands of employment and raising their own families, familismo can become more like a goal than a practice. Further research is needed to better understand how to bridge the gap between the needs of these older Latino adults living alone with cognitive impairment, their families, and formal services.

BackgroundReward and threat processes work together to support adaptive learning during development. Adolescence is associated with increasing approach behavior (e.g., novelty-seeking, risk-taking) but often also coincides with emerging internalizing symptoms, which are characterized by heightened avoidance behavior. Peaking engagement of the nucleus accumbens (NAcc) during adolescence, often studied in reward paradigms, may also relate to threat mechanisms of adolescent psychopathology.Methods47 typically developing adolescents (9.9-22.9 years) completed an aversive learning task during functional magnetic resonance imaging, wherein visual cues were paired with an aversive sound or no sound. Task blocks involved an escapable aversively reinforced stimulus (CS+r), the same stimulus without reinforcement (CS+nr), or a stimulus that was never reinforced (CS-). Parent-reported internalizing symptoms were measured using Revised Child Anxiety and Depression Scales.ResultsFunctional connectivity between the NAcc and amygdala differentiated the stimuli, such that connectivity increased for the CS+r (p = .023) but not for the CS+nr and CS-. Adolescents with greater internalizing symptoms demonstrated greater positive functional connectivity for the CS- (p = .041).ConclusionsAdolescents show heightened NAcc-amygdala functional connectivity during escape from threat. Higher anxiety and depression symptoms are associated with elevated NAcc-amygdala connectivity during safety, which may reflect poor safety versus threat discrimination.

BACKGROUND: Unpredictable childhood experiences are an understudied form of early life adversity that impacts neurodevelopment in a sex-specific manner. The neurobiological processes by which exposure to early-life unpredictability impacts development and vulnerability to psychopathology remain poorly understood. The present study investigates the sex-specific consequences of early-life unpredictability on the limbic network, focusing on the hippocampus and the amygdala. METHODS: Participants included 150 youth (54% female). Early life unpredictability was assessed using the Questionnaire of Unpredictability in Childhood (QUIC). Participants engaged in a task-fMRI scan between the ages of 8 and 17 (223 total observations) measuring BOLD responses to novel and familiar scenes. RESULTS: Exposure to early-life unpredictability associated with BOLD contrast (novel vs. familiar) in a sex-specific manner. For males, but not females, higher QUIC scores were associated with lower BOLD activation in response to novel vs. familiar stimuli in the hippocampal head and amygdala. Secondary psychophysiological interaction (PPI) analyses revealed complementary sex-specific associations between QUIC and condition-specific functional connectivity between the right and left amygdala, as well as between the right amygdala and hippocampus bilaterally. CONCLUSION: Exposure to unpredictability in early life has persistent implications for the functional operations of limbic circuits. Importantly, consistent with emerging experimental animal and human studies, the consequences of early life unpredictability differ for males and females. Further, impacts of early-life unpredictability were independent of other risk factors including lower household income and negative life events, indicating distinct consequences of early-life unpredictability over and above more commonly studied types of early life adversity.

Several models of visual search consider visual attention as part of a perceptual inference process, in which top-down priors disambiguate bottom-up sensory information. Many of these models have focused on gaze behavior, but there are relatively fewer models of covert spatial attention, in which attention is directed to a peripheral location in visual space without a shift in gaze direction. Here, we propose a biologically plausible model of covert attention during visual search that helps to bridge the gap between Bayesian modeling and neurophysiological modeling by using (1) top-down priors over target features that are acquired through Hebbian learning, and (2) spatial resampling of modeled cortical receptive fields to enhance local spatial resolution of image representations for downstream target classification. By training a simple generative model using a Hebbian update rule, top-down priors for target features naturally emerge without the need for hand-tuned or predetermined priors. Furthermore, the implementation of covert spatial attention in our model is based on a known neurobiological mechanism, providing a plausible process through which Bayesian priors could locally enhance the spatial resolution of image representations. We validate this model during simulated visual search for handwritten digits among nondigit distractors, demonstrating that top-down priors improve accuracy for estimation of target location and classification, relative to bottom-up signals alone. Our results support previous reports in the literature that demonstrated beneficial effects of top-down priors on visual search performance, while extending this literature to incorporate known neural mechanisms of covert spatial attention.

To achieve cardiovascular health (CVH) equity in the United States, an understanding of the social and structural factors that contribute to differences and disparities in health is necessary. The Asian American population is the fastest-growing racial group in the United States but remains persistently underrepresented in health research. There is heterogeneity in how individual Asian American ethnic groups experience CVH and cardiovascular disease outcomes, with certain ethnic groups experiencing a higher burden of adverse social conditions, disproportionately high burden of suboptimal CVH, or excess adverse cardiovascular disease outcomes. In this scientific statement, upstream structural and social determinants that influence CVH in the Asian American population are highlighted, with particular emphasis on the role of social determinants of health across disaggregated Asian American ethnic groups. Key social determinants that operate in Asian American communities include socioeconomic position, immigration and nativity, social and physical environments, food and nutrition access, and health system-level factors. The role of underlying structural factors such as health, social, and economic policies and structural racism is also discussed in the context of CVH in Asian Americans. To improve individual-, community-, and population-level CVH and to reduce CVH disparities in Asian American ethnic subgroups, multilevel interventions that address adverse structural and social determinants are critical to achieve CVH equity for the Asian American population. Critical research gaps for the Asian American population are given, along with recommendations for strategic approaches to investigate social determinants of health and intervene to reduce health disparities in these communities.

Challenging goals can induce harder work but also greater stress, in turn potentially undermining goal achievement. We sought to examine how mental effort and subjective experiences thereof interact as a function of the challenge level and the size of the incentives at stake. Participants performed a task that rewarded individual units of effort investment (correctly performed Stroop trials) but only if they met a threshold number of correct trials within a fixed time interval (challenge level). We varied this challenge level (Study 1, n = 40) and the rewards at stake (Study 2, n = 79) and measured variability in task performance and self-reported affect across task intervals. Greater challenge and higher rewards facilitated greater effort investment but also induced greater stress, whereas higher rewards (and lower challenge) simultaneously induced greater positive affect. Within intervals, we observed an initial speed up then slowdown in performance, which could reflect dynamic reconfiguration of control. Collectively, these findings further our understanding of the influence of task demands and incentives on mental effort exertion and well-being.

During breeding when testosterone concentrations are high, male songbirds that are open-ended vocal learners like canaries (Serinus canaria) tend to produce a stable, stereotyped song that facilitates mate attraction or territory defense. Outside breeding contexts, song becomes more variable. The neuroendocrine mechanisms controlling this vocal variability across seasons are not entirely clear. We tested whether androgen signaling within the lateral magnocellular nucleus of the anterior nidopallium (LMAN), a cortical-like brain region of the vocal control system known as a vocal variability generator, plays a role in seasonal vocal variability. We first characterized song in birds housed alone on a short day (SD) photoperiod, which simulates non-breeding conditions. Then, cannulae filled with the androgen receptor (AR) blocker flutamide or left empty as control were implanted bilaterally in LMAN. Birds were then transferred to long days (LD) to simulate the breeding season and song was analyzed again. Blocking AR in LMAN increased acoustic variability of song and the acoustic variability of syllables. However, blocking AR in LMAN did not impact the variability of syllable usage nor their sequencing in LD birds, song features that are controlled by androgen signaling in a somatosensory brain region of the vocal control system called HVC. These findings highlight the multifactorial, non-redundant actions of steroid hormones in controlling complex social behaviors such as birdsong. They also support the hypothesis that LMAN is a key brain area for the effects of testosterone on song plasticity both seasonally in adults and during the song crystallization process at sexual maturity.

Peripheral sensorimotor stimming activity, such as rocking and fidgeting, is widely considered irrelevant to and even distracting from learning. In this critical-pedagogy conceptual paper, we argue that stimming is an intrinsic part of adaptive functioning, interaction, and cognitive dynamics. We submit that when cultural resources build from students’ own sensorimotor dynamics, rather than subjugating them to hegemonic corporeal norms, learners’ intrinsic sensorimotor behaviors may be embraced and empowered as mental activity. This call for transformative inclusive pedagogy is of particular importance for neurodivergent children whose sensorimotor engagements have historically been ostracized as disruptive. Following a conceptual analysis of stimming that builds on a range of neuro-cognitive empirical studies drawing on post-cognitivist embodied cognition theory, we imagine inclusive educational futures that disrupt sedentary instructional design to elevate minoritized learners’ sensorimotor activity. As proof of concept, we present an example inclusive embodied activity, balance board math, a pedagogical tool designed to elicit stimming as thinking. We propose a set of design heuristics for realizing stimming’s pedagogical potential.

IntroductionSchool-based social support for Black students may mediate or modify the association between school segregation and late-life cognition.MethodsStudy of Healthy Aging in African Americans participants (n = 574) reported segregated school attendance and school-based social support. Associations of segregated schooling with domain-specific cognitive outcomes and effect modification or mediation by school-based social support were evaluated with linear mixed models.ResultsSegregated school attendance was associated with increased likelihood of school-based social support. Segregated (vs. desegregated in 6th grade) school attendance was associated with lower executive function (β = -0.18 [-0.34, -0.02]) and semantic memory z-scores (β = -0.31 [-0.48, -0.13]). Social support did not mediate these associations. Estimates for segregated school attendance were attenuated among those who felt supported, although there was limited evidence of statistically significant effect modification.DiscussionEarly-childhood school segregation was associated with poorer cognitive function. Sources of resilience within racialized educational experiences should be further evaluated to bridge inequities.HighlightsSchool segregation is a form of structural racism that affected the educational experiences of Black youth with potentially lasting consequences for healthy brain aging. Black students who attended a segregated school experienced greater school-based social support, which may highlight a potential source of resilience and resistance against the effects of racism-related stressors on cognitive function. The estimated adverse association between attending a segregated school on cognition was larger for students without an adult at school who cared about them versus those with an adult at school who cared about them, but estimates were imprecise.

Everyone agrees that feelings and actions are intertwined, but cannot agree how. According to dominant models, actions are directed by estimates of value and these values shape or are shaped by affect. I propose instead that affect is the only form of value that drives actions. Our mind constantly represents potential future states and how they would make us feel. These states collectively form a gradient reflecting feelings we could experience depending on actions we take. Motivated behavior reflects the process of traversing this affective gradient, towards desirable states and away from undesirable ones. This affective gradient hypothesis solves the puzzle of where values and goals come from, and offers a parsimonious account of apparent conflicts between emotion and cognition.

Although maternal stress during pregnancy and even before conception shapes offspring risk for mental health problems, relatively little is known about the mechanisms through which these associations operate. In theory, preconception and prenatal stress may affect offspring mental health by influencing child responses to postnatal caregiving. To address this knowledge gap, this study had two aims. First, we examined associations between preconception and prenatal stress with child temperament profiles at age four using multilevel assessment of maternal perceived stress and stress physiology. Second, we tested child temperament profiles as moderators of associations between observed parenting behaviors during a parent-child free-play interaction when children were 4 years old and child behavior problems 1 year later. Latent profile analyses yielded four distinct child temperament profiles: inhibited, exuberant, regulated low reactive, and regulated high reactive. Consistent with hypotheses, preconception, and prenatal stress each independently predicted the likelihood of children having temperament profiles characterized by higher negative emotionality and lower regulation. Specifically, preconception perceived stress and prenatal cortisol predicted likelihood of children having an exuberant temperament, whereas prenatal perceived stress predicted likelihood of children having an inhibited temperament. Contrary to hypotheses, temperament profiles did not moderate predictions of child behavior problems from observed parenting behaviors; however, responsive parenting behaviors inversely predicted child behavior problems independently of child temperament. These findings add to growing evidence regarding effects of preconception factors on child outcomes and underscore a central role for responsive parenting behaviors in predicting more favorable child mental health independent of child temperament. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Sexual and gender minority (SGM) communities are underrepresented in biomedical studies, highlighting the importance of developing biospecimen collection protocols aimed at engaging SGM participants. We aimed to learn more about SGM participants’ experiences with a remote (i.e., not performed at a central location) biospecimen collection study pioneered by The PRIDE Study, a cohort study of SGM adults residing in the United States and its territories. Feedback was collected from 112 SGM participants following blood donation for a parent study investigating the relationship between minority stress, substance use, and epigenetic markers of substance use and minority stress. We used an inductive and collaborative approach to qualitative analysis and identified major themes and areas for protocol improvement. Major themes among participant feedback were as follows: (1) communication with the research team, (2) convenience of donation, (3) interactions with clinical laboratory staff, and (4) anonymity and privacy. Most participants indicated that they experienced little to no problems during the donation process and expressed approval for the clarity and transparency of the informed consent process, ease of communication with the research team, and measures taken to protect participant confidentiality during their appointment. The most common challenges encountered by participants related to the inconvenience of handling and transporting study materials to the clinical laboratory site and the clinical laboratory staff’s unfamiliarity with the study protocol. Some participants indicated a preference for more elements of the study protocol (e.g., transporting collection materials) to be left to the responsibility of the research team. Future studies should carefully consider the delegation of responsibility between participants and the research team to balance both study reach and participant accessibility. Alternative formats, such as at-home collection or collaboration with community health workers, may further enhance participant satisfaction and convenience.

The value associated with reward is sensitive to external factors, such as the time between the choice and reward delivery as classically manipulated in temporal discounting tasks. Subjective preference for two reward options is dependent on objective variables of reward magnitude and reward delay. Single neuron correlates of reward value have been observed in regions, including ventral striatum, orbital, and medial prefrontal cortex. Brain imaging studies show cortico-striatal-limbic network activity related to subjective preferences. To explore how oscillatory dynamics represent reward processing across brain regions, we measured local field potentials of rats performing a temporal discounting task. Our goal was to use a data-driven approach to identify an electrophysiological marker that correlates with reward preference. We found that reward-locked oscillations at beta frequencies signaled the magnitude of reward and decayed with longer temporal delays. Electrodes in orbitofrontal/medial prefrontal cortex, anterior insula, ventral striatum, and amygdala individually increased power and were functionally connected at beta frequencies during reward outcome. Beta power during reward outcome correlated with subjective value as defined by a computational model fit to the discounting behavior. These data suggest that cortico-striatal beta oscillations are a reward signal correlated, which may represent subjective value and hold potential to serve as a biomarker and potential therapeutic target.

Humans are immensely curious and motivated to reduce uncertainty, but little is known about the neural mechanisms that generate curiosity. Curiosity is inversely associated with confidence, suggesting that it is triggered by states of low confidence (subjective uncertainty), but the neural mechanisms of this link, have been little investigated. Inspired by studies of sensory uncertainty, we hypothesized that visual areas provide multivariate representations of uncertainty, which are read out by higher-order structures to generate signals of confidence and, ultimately, curiosity. We scanned participants (17 female, 15 male) using fMRI while they performed a new task in which they rated their confidence in identifying distorted images of animals and objects and their curiosity to see the clear image. We measured the activity evoked by each image in the occipitotemporal cortex (OTC) and devised a new metric of "OTC Certainty" indicating the strength of evidence this activity conveys about the animal versus object categories. We show that, perceptual curiosity peaked at low confidence and OTC Certainty negatively correlated with curiosity, establishing a link between curiosity and a multivariate representation of sensory uncertainty. Moreover, univariate (average) activity in two frontal areas-vmPFC and ACC-correlated positively with confidence and negatively with curiosity, and the vmPFC mediated the relationship between OTC Certainty and curiosity. The results reveal novel mechanisms through which uncertainty about an event generates curiosity about that event.

Delay discounting refers to the behavioral tendency to devalue rewards as a function of their delay in receipt. Heightened delay discounting has been associated with substance use disorders and multiple co-occurring psychopathologies. Human and animal genetic studies have established that delay discounting is heritable, but only a few associated genes have been identified. We aimed to identify novel genetic loci associated with delay discounting through a genome-wide association study (GWAS) using Heterogeneous Stock (HS) rats, a genetically diverse outbred population derived from eight inbred founder strains. We assessed delay discounting in 650 male and female HS rats using an adjusting amount procedure in which rats chose between smaller immediate sucrose rewards or a larger reward at various delays. Preference switch points were calculated and both exponential and hyperbolic functions were fitted to these indifference points. Area under the curve (AUC) and the discounting parameter k of both functions were used as delay discounting measures. GWAS for AUC, exponential k, and one indifference point identified significant loci on chromosomes 20 and 14. The gene Slc35f1, which encodes a member of the solute carrier family, was the sole gene within the chromosome 20 locus. That locus also contained an eQTL for Slc35f1, suggesting that heritable differences in the expression might be responsible for the association with behavior. Adgrl3, which encodes a latrophilin subfamily G-protein coupled receptor, was the sole gene within the chromosome 14 locus. These findings implicate novel genes in delay discounting and highlight the need for further exploration.

IntroductionAlthough frontotemporal dementia (FTD) with right anterior temporal lobe (RATL) predominance has been recognized, a uniform description of the syndrome is still missing. This multicenter study aims to establish a cohesive clinical phenotype.MethodsRetrospective clinical data from 18 centers across 12 countries yielded 360 FTD patients with predominant RATL atrophy through initial neuroimaging assessments.ResultsCommon symptoms included mental rigidity/preoccupations (78%), disinhibition/socially inappropriate behavior (74%), naming/word-finding difficulties (70%), memory deficits (67%), apathy (65%), loss of empathy (65%), and face-recognition deficits (60%). Real-life examples unveiled impairments regarding landmarks, smells, sounds, tastes, and bodily sensations (74%). Cognitive test scores indicated deficits in emotion, people, social interactions, and visual semantics however, lacked objective assessments for mental rigidity and preoccupations.DiscussionThis study cumulates the largest RATL cohort unveiling unique RATL symptoms subdued in prior diagnostic guidelines. Our novel approach, combining real-life examples with cognitive tests, offers clinicians a comprehensive toolkit for managing these patients.HighlightsThis project is the first international collaboration and largest reported cohort. Further efforts are warranted for precise nomenclature reflecting neural mechanisms. Our results will serve as a clinical guideline for early and accurate diagnoses.

Traumatic brain injury (TBI) survivors face debilitating long-term psychosocial consequences, including social isolation and depression. TBI modifies neurovascular physiology and behavior but the chronic physiological implications of altered brain perfusion on social interactions are unknown. Adult C57/BL6 male mice received a moderate cortical TBI, and social behaviors were assessed at baseline, 3-, 7-, 14-, 30-, and 60-days post injury (dpi). Magnetic resonance imaging (MRI, 9.4T) using dynamic susceptibility contrast perfusion weighted MRI were acquired. At 60dpi mice underwent histological angioarchitectural mapping. Analysis utilized standardized protocols followed by cross-correlation metrics. Social behavior deficits at 60dpi emerged as reduced interactions with a familiar cage-mate (partner) that mirrored significant reductions in cerebral blood flow (CBF) at 60dpi. CBF perturbations were dynamic temporally and across brain regions including regions known to regulate social behavior such as hippocampus, hypothalamus, and rhinal cortex. Social isolation in TBI-mice emerged with a significant decline in preference to spend time with a cage mate. Cortical vascular density was also reduced corroborating the decline in brain perfusion and social interactions. Thus, the late emergence of social interaction deficits mirrored the reduced vascular density and CBF in regions known to be involved in social behaviors. Vascular morphology and function improved prior to the late decrements in social function and our correlations strongly implicate a linkage between vascular density, cerebral perfusion, and social interactions. Our study provides a clinically relevant timeline of alterations in social deficits alongside functional vascular recovery that can guide future therapeutics.

Anxiety disorders are common and highly distressing mental health conditions. Exposure therapy is a gold-standard treatment for anxiety disorders. Mechanisms of Pavlovian fear learning, and particularly fear extinction, are central to exposure therapy. A growing body of evidence suggests an important role of reward processes during Pavlovian fear extinction. Nonetheless, predominant models of exposure therapy do not currently incorporate reward processes. Herein, we present a theoretical model of reward processes in relation to Pavlovian mechanisms of exposure therapy, including a focus on dopaminergic prediction error signaling, coinciding positive emotional experiences (i.e., relief), and unexpected positive outcomes. We then highlight avenues for further research and discuss potential strategies to leverage reward processes to maximize exposure therapy response, such as pre-exposure interventions to increase reward sensitivity or post-exposure rehearsal (e.g., savoring, imaginal recounting strategies) to enhance retrieval and retention of learned associations.

ObjectivesIncreasingly diverse caregiver populations have prompted studies examining culture and caregiver outcomes. Still, little is known about the influence of sociocultural factors and how they interact with caregiving context variables to influence psychological health. We explored the role of caregiving and acculturation factors on psychological distress among a diverse sample of adults.DesignSecondary data analysis of the California Health Interview Survey (CHIS).ParticipantsThe 2009 CHIS surveyed 47,613 adults representative of the population of California. This study included Latino and Asian American Pacific Islander (AAPI) caregivers and non-caregivers (n = 13,161).MeasurementsMultivariate weighted regression analyses examined caregiver status and acculturation variables (generational status, language of interview, and English language proficiency) and their associations with psychological distress (Kessler-6 scale). Covariates included caregiving context (e.g., support and neighborhood factors) and demographic variables.ResultsFirst generation caregivers had more distress than first-generation non-caregivers (β=0.92, 95% CI: (0.18, 1.65)); the difference in distress between caregivers and non-caregivers was smaller in the third than first generation (β=-1.21, 95% CI: (-2.24, -0.17)). Among those who did not interview in English (β=1.17, 95% CI: (0.13, 2.22)) and with low English proficiency (β=2.60, 95% CI: (1.21, 3.98)), caregivers reported more distress than non-caregivers.ConclusionsNon-caregivers exhibited the "healthy immigrant effect," where less acculturated individuals reported less distress. In contrast, caregivers who were less acculturated reported more distress.

IntroductionRecent technology has enabled researchers to collect ecological momentary assessments (EMA) to examine within-person correlates of suicidal thoughts. Prior studies examined generalized temporal dynamics of emotions and suicidal thinking over brief periods, but it is not yet known how variable these processes are across people.MethodWe use data EMA data delivered over two weeks with youth/young adults (N = 60) who reported past year self-injurious thoughts/behaviors. We used group iterative multiple model estimation (GIMME) to model group- and person-specific associations of negative emotions (i.e., fear, sadness, shame, guilt, and anger) and suicidal thoughts.Results29 participants (48.33%) reported at least one instance of a suicidal thought and were included in GIMME models. In group level models, we consistently observed autoregressive effects for suicidal thoughts (e.g., earlier thoughts predicting later thoughts), although the magnitude and direction of this link varied from person-to-person. Among emotions, sadness was most frequently associated with contemporaneous suicidal thoughts, but this was evident for less than half of the sample, while other emotional correlates of suicidal thoughts broadly differed across people. No emotion variable was linked to future suicidal thoughts in >14% of the sample, CONCLUSIONS: Emotion-based correlates of suicidal thoughts are heterogeneous across people. Better understanding of the individual-level pathways maintaining suicidal thoughts/behaviors may lead to more effective, personalized interventions.

Abstract: Large Language Models (LLMs) have been criticized for failing to connect linguistic meaning to the world—for failing to solve the “symbol grounding problem.” Multimodal Large Language Models (MLLMs) offer a potential solution to this challenge by combining linguistic representations and processing with other modalities. However, much is still unknown about exactly how and to what degree MLLMs integrate their distinct modalities—and whether the way they do so mirrors the mechanisms believed to underpin grounding in humans. In humans, it has been hypothesized that linguistic meaning is grounded through “embodied simulation,” the activation of sensorimotor and affective representations reflecting described experiences. Across four pre-registered studies, we adapt experimental techniques originally developed to investigate embodied simulation in human comprehenders to ask whether MLLMs are sensitive to sensorimotor features that are implied but not explicit in descriptions of an event. In Experiment 1, we find sensitivity to some features (color and shape) but not others (size, orientation, and volume). In Experiment 2, we identify likely bottlenecks to explain an MLLM’s lack of sensitivity. In Experiment 3, we find that despite sensitivity to implicit sensorimotor features, MLLMs cannot fully account for human behavior on the same task. Finally, in Experiment 4, we compare the psychometric predictive power of different MLLM architectures and find that ViLT, a single-stream architecture, is more predictive of human responses to one sensorimotor feature (shape) than CLIP, a dual-encoder architecture—despite being trained on orders of magnitude less data. These results reveal strengths and limitations in the ability of current MLLMs to integrate language with other modalities, and also shed light on the likely mechanisms underlying human language comprehension.

Psychosocial experiences affect brain health and aging trajectories, but the molecular pathways underlying these associations remain unclear. Normal brain function relies on energy transformation by mitochondria oxidative phosphorylation (OxPhos). Two main lines of evidence position mitochondria both as targets and drivers of psychosocial experiences. On the one hand, chronic stress exposure and mood states may alter multiple aspects of mitochondrial biology; on the other hand, functional variations in mitochondrial OxPhos capacity may alter social behavior, stress reactivity, and mood. But are psychosocial exposures and subjective experiences linked to mitochondrial biology in the human brain? By combining longitudinal antemortem assessments of psychosocial factors with postmortem brain (dorsolateral prefrontal cortex) proteomics in older adults, we find that higher well-being is linked to greater abundance of the mitochondrial OxPhos machinery, whereas higher negative mood is linked to lower OxPhos protein content. Combined, positive and negative psychosocial factors explained 18 to 25% of the variance in the abundance of OxPhos complex I, the primary biochemical entry point that energizes brain mitochondria. Moreover, interrogating mitochondrial psychobiological associations in specific neuronal and nonneuronal brain cells with single-nucleus RNA sequencing (RNA-seq) revealed strong cell-type-specific associations for positive psychosocial experiences and mitochondria in glia but opposite associations in neurons. As a result, these "mind-mitochondria" associations were masked in bulk RNA-seq, highlighting the likely underestimation of true psychobiological effect sizes in bulk brain tissues. Thus, self-reported psychosocial experiences are linked to human brain mitochondrial phenotypes.

Neuropsychiatric complications such as neurocognitive impairment and depression are common in people with HIV despite viral suppression on antiretroviral therapy, but these conditions are heterogeneous in their clinical presentations and associated disability. Identifying novel biopsychosocial phenotypes that account for neurocognitive performance and depressive and functional symptoms will better reflect the complexities encountered in clinical practice and may have pathological and therapeutic implications. We classified 1580 people with HIV based on 17 features, including 7 cognitive domains, 4 subscales of the Beck depression inventory-II, 5 components of the patient's assessment of own functioning inventory, and dependence in instrumental and basic activities of daily living. A two-stage clustering procedure consisting of dimension reduction with self-organizing maps and Mahalanobis distance-based k-means clustering algorithms was applied to cross-sectional data. Baseline demographic and clinical characteristics were compared between the phenotypes, and their prediction on the biopsychosocial phenotypes was evaluated using multinomial logistic regression. Four distinct phenotypes were identified. Participants in Phenotype 1 overall did well in all domains. Phenotype 2 had mild-to-moderate depressive symptoms and the most substance use disorders. Phenotype 3 had mild-to-moderate cognitive impairment, moderate depressive symptoms, and the worst daily functioning; they also had the highest proportion of females and non-HIV conditions that could affect cognition. Phenotype 4 had mild-to-moderate cognitive impairment but with relatively good mood, and daily functioning. Multivariable analysis showed that demographic characteristics, medical conditions, lifetime cocaine use disorder, triglycerides, and non-antiretroviral therapy medications were important variables associated with biopsychosocial phenotype. We found complex, multidimensional biopsychosocial profiles in people with HIV that were associated with different risk patterns. Future longitudinal work should determine the stability of these phenotypes, assess factors that influence transitions from one phenotype to another, and characterize their biological associations.

Elucidating the mechanisms by which late-life neurodegeneration causes cognitive decline requires understanding why some individuals are more resilient than others to the effects of brain change on cognition (cognitive reserve). Currently, there is no way of measuring cognitive reserve that is valid (e.g. capable of moderating brain-cognition associations), widely accessible (e.g. does not require neuroimaging and large sample sizes), and able to provide insight into resilience-promoting mechanisms. To address these limitations, this study sought to determine whether a machine learning approach to combining standard clinical variables could (i) predict a residual-based cognitive reserve criterion standard and (ii) prospectively moderate brain-cognition associations. In a training sample combining data from the University of California (UC) Davis and the Alzheimer's Disease Neuroimaging Initiative-2 (ADNI-2) cohort (N = 1665), we operationalized cognitive reserve using an MRI-based residual approach. An eXtreme Gradient Boosting machine learning algorithm was trained to predict this residual reserve index (RRI) using three models: Minimal (basic clinical data, such as age, education, anthropometrics, and blood pressure), Extended (Minimal model plus cognitive screening, word reading, and depression measures), and Full [Extended model plus Clinical Dementia Rating (CDR) and Everyday Cognition (ECog) scale]. External validation was performed in an independent sample of ADNI 1/3/GO participants (N = 1640), which examined whether the effects of brain change on cognitive change were moderated by the machine learning models' cognitive reserve estimates. The three machine learning models differed in their accuracy and validity. The Minimal model did not correlate strongly with the criterion standard (r = 0.23) and did not moderate the effects of brain change on cognitive change. In contrast, the Extended and Full models were modestly correlated with the criterion standard (r = 0.49 and 0.54, respectively) and prospectively moderated longitudinal brain-cognition associations, outperforming other cognitive reserve proxies (education, word reading). The primary difference between the Minimal model-which did not perform well as a measure of cognitive reserve-and the Extended and Full models-which demonstrated good accuracy and validity-is the lack of cognitive performance and informant-report data in the Minimal model. This suggests that basic clinical variables like anthropometrics, vital signs, and demographics are not sufficient for estimating cognitive reserve. Rather, the most accurate and valid estimates of cognitive reserve were obtained when cognitive performance data-ideally augmented by informant-reported functioning-was used. These results indicate that a dynamic and accessible proxy for cognitive reserve can be generated for individuals without neuroimaging data and gives some insight into factors that may promote resilience.

Recent work has identified a critical role for the hippocampus in reward-sensitive behaviors, including motivated memory, reinforcement learning, and decision-making. Animal histology and human functional neuroimaging have shown that brain regions involved in reward processing and motivation are more interconnected with the ventral/anterior hippocampus. However, direct evidence examining gradients of structural connectivity between reward regions and the hippocampus in humans is lacking. The present study used diffusion MRI (dMRI) and probabilistic tractography to quantify the structural connectivity of the hippocampus with key reward processing regions in vivo. Using a large sample of subjects (N = 628) from the human connectome dMRI data release, we found that connectivity profiles with the hippocampus varied widely between different regions of the reward circuit. While the dopaminergic midbrain (ventral tegmental area) showed stronger connectivity with the anterior versus posterior hippocampus, the ventromedial prefrontal cortex showed stronger connectivity with the posterior hippocampus. The limbic (ventral) striatum demonstrated a more homogeneous connectivity profile along the hippocampal long axis. This is the first study to generate a probabilistic atlas of the hippocampal structural connectivity with reward-related networks, which is essential to investigating how these circuits contribute to normative adaptive behavior and maladaptive behaviors in psychiatric illness. These findings describe nuanced structural connectivity that sets the foundation to better understand how the hippocampus influences reward-guided behavior in humans.

Abstract: In recent years, the study of codeswitching has made great strides by leveraging a multidisciplinary approach that integrates insights from experimental psycholinguistics, corpus linguistics, cognitive psychology, neurolinguistics, and other allied fields. We provide an overview of 2 main strands of this research, focusing on the control process model of codeswitching (e.g., Green, 2018), the variable equivalence hypothesis (e.g., Torres Cacoullos, 2020), and the ways in which these accounts of codeswitching behavior intersect and complement one another. We argue that the common insight of these 2 distinct approaches is their focus on conventionalized linguistic norms at the level of the speech community. The second portion of the article sheds light on how various aspects of codeswitching experience give rise to adaptive change through bilingual phenotyping, highlighting the centrality of our mentor Judy Kroll's contributions to this research. Finally, we present a social network analysis of Judy's research publications and argue that the high degree of interconnectivity in Judy's research network, combined with the many positive community norms that she has been instrumental in establishing, have greatly benefited both the individual members of the network and the research enterprise itself.

Introduction. Several frameworks exist to measure vulnerability to extreme heat events using a health equity approach, but little evidence validates these measures and their applications. We investigated the degree to which social vulnerability measures and their constituent elements correlate with excess emergency room visits as an outcome measure. Methods. The relationship between six commonly used social vulnerability indicators and measured excess emergency room visit rates (processed by including heat-related illnesses and all-internal causes diagnosis, with considerations for age and heat days) was tested through geospatial analytics and statistical regressions, for both California and Los Angeles County. Results. The vulnerability indicators and the outcome measure were significantly positively associated at the census tract-level but weaker (∼0.2 rs) at the scale of California and stronger (∼0.6 rs) at the scale of Los Angeles County. Hazard-specific vulnerability indicators showed stronger relationships with outcome measures regardless of scale. A Poisson regression model showed a significant inter-county variation, indicating the importance of localized assessments for equitable environmental policies. Conclusion. The findings identify communities that are overburdened by heat and pollution and highlight the need for use of both social vulnerability and indicators of adverse outcomes from excessive heat. Patterns are found across all measures that suggest that populations facing accessibility barriers may be less likely to visit emergency rooms. This suggestion needs to be tested in other environmental settings to draw broader conclusions but has direct implications for environmental scientists and mitigation planners who use these methods.

BackgroundPavlovian fear paradigms involve learning to associate cues with threat or safety. Aberrances in Pavlovian fear learning correlate with psychopathology, especially anxiety disorders. This study evaluated symptom dimensions of anxiety and depression in relation to Pavlovian fear acquisition and generalization.Methods256 participants (70.31 % female) completed a Pavlovian fear acquisition and generalization paradigm at ages 18-19 and 21-22 years. Analyses focused on indices of learning (self-reported US expectancy, skin conductance). Multilevel models tested associations with orthogonal symptom dimensions (Anhedonia-Apprehension, Fears, General Distress) at each timepoint.ResultsAll dimensions were associated with weaker acquisition of US expectancies at each timepoint. Fears was associated with overgeneralization only at age 21-22. General Distress was associated with overgeneralization only at age 18-19. Anhedonia-Apprehension was associated with overgeneralization at ages 18-19 and 21-22.ConclusionsAnhedonia-Apprehension disrupts Pavlovian fear acquisition and increases overgeneralization of fear. These effects may emerge during adolescence and remain into young adulthood. General Distress and Fears also contribute to overgeneralization of fear, but these effects may vary as prefrontal mechanisms of fear inhibition continue to develop during late adolescence. Targeting specific symptom dimensions, particularly Anhedonia-Apprehension, may decrease fear generalization and augment interventions built on Pavlovian principles, such as exposure therapy.

The Hispanic/Latino population is one of the largest and most diverse ethnoracial groups in the United States at high risk for dementia. We examined cognitive constructs and associations with subsequent hippocampal volume (HV) and white matter hyperintensity volume (WMHV). Participants were from the Hispanic Community Health Study/Study of Latinos-Magnetic Resonance Imaging Study (n = 2029). We examined confirmatory factor analysis and longitudinal invariance using neurocognitive scores at Visits 1 (2008-2011) and 2 (2014-2018) and path analyses. We obtained a longitudinally invariant two-factor episodic memory (EM) and working memory (WM) construct. Lower EM profile at both visits was associated with greater WMHV and smaller HV at Visit 2. Lower WM profile at both visits was associated with larger WMHV and smaller HV at Visit 2. Neurocognitive profiles were associated with subsequent neurodegeneration in a sample of Hispanics/Latinos. Identifying neurocognitive risk profiles may lead to early detection and intervention, and significantly impact the course of neurodegeneration.HighlightsCognitive profiles predict brain integrity up to 10 years later.We observed two-factor latent memory constructs and longitudinal invariance.These findings were observed in a Hispanic/Latino cohort.

IntroductionThere is a dearth of research on cognitive aging and dementia in Asian Americans, particularly in Vietnamese Americans, the fourth largest Asian subgroup in the United States.MethodsThe Vietnamese Insights into Cognitive Aging Program (VIP) investigates early life adversity and war-related trauma and their associations with cognitive health in a community-based sample of older Vietnamese Americans in Northern California (i.e., Sacramento and Santa Clara counties). Baseline measurements include a comprehensive neuropsychological battery, including measures of global cognition along with executive function, semantic memory, and episodic memory. Data also include measures of functioning, early life adversity and trauma exposure, and psychosocial and traditional cardiovascular disease risk factors. Cognitive assessments will be repeated twice over the course of the data collection period, approximately 12- and 24- months post-baseline. Blood samples collected during Wave 2 will be assayed for biochemical risk factors.ResultsBaseline assessments were conducted from January 2022 to November 2023, with N = 548 Vietnamese Americans; mean age ± SD was 73 ± 5.31 years and 55% of participants were women. There were significant differences in social factors by site, with Santa Clara participants having higher education (some college or higher: Sacramento, ≈25%; Santa Clara: ≈48%) and marginally higher incomes compared to Sacramento participants. A higher percentage of Santa Clara participants reported speaking English well or very well (24%) compared to Sacramento participants (13%), although the majority of the entire sample (81%) reported speaking some to no English (response options: not at all; some/a little bit; well/very well).DiscussionThis longitudinal study providea a unique opportunity to more fully delineate psychosocial factors that contribute to dementia disparities in diverse and under-engaged populations. Future work will examine cognition, the prevalence of mild cognitive impairment and dementia, and other health outcomes, while controlling for site differences in all analyses.HighlightsVietnamese Insights into Cognitive Aging Program (VIP) is a new study.VIP has detailed early life and health data on 548 older Vietnamese Americans.History of war and trauma may contribute to Alzheimer's disease and related dementias (ADRD)-related burden.VIP may provide insight into ADRD burden in other understudied groups.

Chronic stress is well known to erode cognitive functions. Yet, our understanding of how repeated stress exposure impacts one of the fundamental bases of cognition: sensory processing, remains limited. The posterior parietal cortex (PPC) is a high order visual region, known for its role in visually guided decision making, multimodal integration, attention, and working memory. Here, we used functional measures to determine how repeated exposure to multiple concurrent stressors (RMS) affects sensory processing in the PPC in adult male mice. A longitudinal experimental design, repeatedly surveying the same population of neurons using in vivo two-photon imaging, revealed that RMS disrupts the balanced turnover of visually responsive cells in layer 2/3 of the PPC. Across the population, RMS-induced changes in visual responsiveness followed a bimodal distribution suggesting idiosyncratic stress effects. In cells that maintained their responsiveness across recording sessions, we found that stress reduced visual response magnitudes and feature selectivity. While we did not observe stress-induced elimination of excitatory synapses, noise correlation statistics indicated that RMS altered visual input to the neuronal population. The impact of RMS was restricted to visually evoked responses and was not evident in neuronal activity associated with locomotion onset. Together, our results indicate that despite no apparent synaptic reorganization, stress exposure in adulthood can disrupt sensory processing in the PPC, with the effects showing remarkable individual variation.

ObjectiveHispanic/Latino individuals in the U.S. have the highest prevalence of undiagnosed and untreated diabetes and are at increased risk for cognitive impairment. In this study, we examine glycemic control in relation to cognitive aging and impairment in a large prospective cohort of middle-aged and older Hispanic/Latino individuals of diverse heritages.Research design and methodsStudy of Latinos-Investigation of Neurocognitive Aging (SOL-INCA) is a Hispanic Community Health Study/Study of Latinos (HCHS/SOL) ancillary study. HCHS/SOL is a multisite (Bronx, NY; Chicago, IL; Miami, FL; and San Diego, CA), probability sampled prospective cohort study. SOL-INCA enrolled 6,377 diverse Hispanic/Latino individuals aged 50 years and older (2016-2018). The primary outcomes were cognitive function, 7-year cognitive decline, and mild cognitive impairment (MCI). The primary glycemia exposure variables were measured from fasting blood samples collected at HCHS/SOL visit 1 (2008-2011).ResultsVisit 1 mean age was 56.5 years ± 8.2 SD, and the average glycosylated hemoglobin A1C (HbA1c) was 6.12% (43.5 ± 14.6 mmol/mol). After covariate adjustment, higher HbA1c was associated with accelerated 7-year global (b = -0.045; 95% CI -0.070; -0.021; in z score units) and executive cognitive decline and a higher prevalence of MCI (odds ratio 1.20; 95% CI 1.11; 1.29).ConclusionsElevated HbA1c levels were associated with 7-year executive cognitive decline and increased MCI risk among diverse middle-aged and older Hispanic/Latino individuals. Our findings indicate that poor glycemic control in midlife may pose significant risks for cognitive decline and MCI later in life among Hispanic/Latino individuals of diverse heritages.

Background and aimsThe precise roles of screen media activity (SMA) and sleep problems in relation to child/adolescent psychopathology remain ambiguous. We investigated temporal relationships among sleep problems, SMA, and psychopathology and potential involvement of thalamus-prefrontal-cortex (PFC)-brainstem structural covariation.MethodsThis study utilized data from the Adolescent Brain Cognitive Development study (n = 4,641 ages 9-12) at baseline, Year1, and Year2 follow-up. Cross-Lagged Panel Models (CLPMs) investigated reciprocal predictive relationships between sleep duration/problems, SMA, and psychopathology symptoms. A potential mediating role of baseline Thalamus-PFC-brainstem covariation on SMA-externalizing relationships was examined.ResultsParticipants were divided into discovery (n = 2,359, 1,054 girls) and replication (n = 2,282, 997 girls) sets. CLPMs showed 1) bidirectional associations between sleep duration and SMA in late childhood, with higher frequency SMA predicting shorter sleep duration (β = -0.10 [95%CI: -0.16, -0.03], p = 0.004) and vice versa (β = -0.11 [95%CI: -0.18, -0.05], p < 0.001); 2) externalizing symptoms at age 10-11 predicting sleep problems (β = 0.11 [95%CI: 0.04, 0.19], p = 0.002), SMA (β = 0.07 [95%CI: 0.01, 0.13], p = 0.014), and internalizing symptoms (β = 0.09 [95%CI: 0.05, 0.13], p < 0.001) at age 11-12; and 3) externalizing behavior at age 10-11 partially mediating the relationship between baseline thalamus-PFC-brainstem covariation and SMA at age 11-12 (indirect effect = 0.032 [95%CI: 0.003, 0.067], p-value = 0.030). Findings were replicable.ConclusionWe found bi-directional SMA-sleep-duration associations in late childhood. Externalizing symptoms preceded future SMA and sleep disturbances and partially mediated relationships between structural brain covariation and SMA. The findings emphasize the need for understanding individual differences and developing and implementing integrated strategies addressing both sleep concerns and screen time to mitigate potential impacts on psychopathology.

Reward cues are often ambiguous; what is good in one context is not necessarily good in another context. To solve this ambiguity, animals form hierarchical associations in which the context acts as a gatekeeper in the retrieval of the appropriate cue-evoked memory, ensuring context-appropriate behavior. These hierarchical associative structures also influence future learning by promoting the formation of new context-dependent associations (leading to the inference of context-dependency for new associations). The orbitofrontal cortex (OFC) and the dorsal hippocampus (DH) are both proposed to encode a “cognitive map” that includes the representation of hierarchical, context-dependent, associations. However the causal role of the OFC and DH in the different functional properties of hierarchical associations remains controversial. Here we used chemogenetic inactivations, in rats, to examine the role of OFC and DH in 1) the contextual regulation of performance, and 2) the contextual learning bias conferred by hierarchical associations. We show that OFC is required for both manifestations of hierarchical associations. In contrast, DH contribution appears limited to the contextual learning bias. This study provides novel insight into the different functional properties of context-dependent hierarchical associations, and establishes the OFC as a critical orchestrator of these different contextual effects.

Abstract: The twenty-first century has seen the proliferation of new sexual identity subcultures rooted in creative role-play dynamics, expanding our cultural and scientific understanding of diversity in sexuality and intimacy. In an international sample of 568 people who identified with the kink subculture of pup play, we analyzed responses to open-ended questions about the discovery of pup play and communities, definitions of pup play, and motivations for engagement. Four themes were identified: (1) social technologies as central to discovery of the subculture; (2) constructionist accounts of pup identity development emerging from relationships and exposure to other kink communities; (3) individual psychological benefits of subculture participation, including stress relief, relaxation, and pleasure; and (4) social psychological benefits in identity and community building. We situate these findings in relation to the expansion of diversity in sexual identity and intimacy in the twenty-first century, facilitated by the heightened visibility and opportunities for social and intimate creativity which have accompanied the growth of social media and exposure to new sexual stories.

Neuroimaging is a popular method to map brain structural and functional patterns to complex human traits. Recently published observations cast doubt upon these prospects, particularly for prediction of cognitive traits from structural and resting state functional magnetic resonance imaging (MRI). We leverage baseline data from thousands of children in the Adolescent Brain Cognitive DevelopmentSM Study to inform the replication sample size required with univariate and multivariate methods across different imaging modalities to detect reproducible brain-behavior associations. We demonstrate that by applying multivariate methods to high-dimensional brain imaging data, we can capture lower dimensional patterns of structural and functional brain architecture that correlate robustly with cognitive phenotypes and are reproducible with only 41 individuals in the replication sample for working memory-related functional MRI, and ~ 100 subjects for structural and resting state MRI. Even with 100 random re-samplings of 100 subjects in discovery, prediction can be adequately powered with 66 subjects in replication for multivariate prediction of cognition with working memory task functional MRI. These results point to an important role for neuroimaging in translational neurodevelopmental research and showcase how findings in large samples can inform reproducible brain-behavior associations in small sample sizes that are at the heart of many research programs and grants.

ImportanceDespite the changing legal status of cannabis and the potential impact on health, few health systems routinely screen for cannabis use, and data on the epidemiology of cannabis use, and especially medical cannabis use among primary care patients, are limited.ObjectiveTo describe the prevalence of, factors associated with, and reasons for past-3 month cannabis use reported by primary care patients.Design, setting, and participantsThis cross-sectional study used electronic health record data from patients aged 18 years and older who had an annual wellness visit between January 2021 and May 2023 from a primary care clinic within a university-based health system in Los Angeles, California.ExposuresFactors of interest included age, race and ethnicity, sex, employment status, and neighborhood Area Deprivation Index (ADI).Main outcomes and measuresCannabis use was assessed using the Alcohol Substance Involvement Screening Test (ASSIST). Patients were also asked about reasons for use, symptoms for which they used cannabis, and mode of use.ResultsAmong the 175 734 patients screened, the median (range) age was 47 (18-102) years; 101 657 (58.0%) were female; 25 278 (15.7%) were Asian, 21 971 (13.7%) were Hispanic, and 51 063 (31.7%) were White. Cannabis use was reported by 29 898 (17.0%), with 10 360 (34.7%) having ASSIST scores indicative of moderate to high risk for cannabis use disorder (CUD). Prevalence of cannabis use was higher among male patients than female patients (14 939 [20.0%] vs 14 916 [14.7%]) and younger patients (18-29 years, 7592 [31.0%]; ≥60 years, 4200 [8.5%]), and lower among those who lived in the most disadvantaged neighborhoods (ADI decile 9-10, 189 [13.8%]; ADI decile 1-2, 12 431 [17.4%]). The most common modes of use included edibles (18 201 [61.6%]), smoking (15 256 [51.7%]), and vaporizing (8555 [29.0%]). While 4375 patients who reported using cannabis (15.6%) did so for medical reasons only, 21 986 patients (75.7%) reported using cannabis to manage symptoms including pain (9196 [31.7%]), stress (14 542 [50.2%]), and sleep (16 221 [56.0%]). The median (IQR) number of symptoms managed was 2 (1-4), which was higher among patients who were at moderate to high risk for CUD (4 [2-6] symptoms).Conclusions and relevanceIn this study, cannabis use and risk of CUD were common, and more than three-quarters of patients who reported any cannabis use reported doing so to manage a health-related symptom. These findings suggest that integration of information regarding cannabis use for symptom management could help provide a crucial point-of-care opportunity for clinicians to understand their patients' risk for CUD.

The language network, comprised of brain regions in the left frontal and temporal cortex, responds robustly and reliably during language comprehension but shows little or no response during many nonlinguistic cognitive tasks (e.g., Fedorenko & Blank, 2020). However, one domain whose relationship with language remains debated is semantics-our conceptual knowledge of the world. Given that the language network responds strongly to meaningful linguistic stimuli, could some of this response be driven by the presence of rich conceptual representations encoded in linguistic inputs? In this study, we used a naturalistic cognition paradigm to test whether the cognitive and neural resources that are responsible for language processing are also recruited for processing semantically rich nonverbal stimuli. To do so, we measured BOLD responses to a set of ∼5-minute-long video and audio clips that consisted of meaningful event sequences but did not contain any linguistic content. We then used the intersubject correlation (ISC) approach (Hasson et al., 2004) to examine the extent to which the language network "tracks" these stimuli, that is, exhibits stimulus-related variation. Across all the regions of the language network, meaningful nonverbal stimuli elicited reliable ISCs. These ISCs were higher than the ISCs elicited by semantically impoverished nonverbal stimuli (e.g., a music clip), but substantially lower than the ISCs elicited by linguistic stimuli. Our results complement earlier findings from controlled experiments (e.g., Ivanova et al., 2021) in providing further evidence that the language network shows some sensitivity to semantic content in nonverbal stimuli.

This primer describes research on the development of motor behavior. We focus on infancy when basic action systems are acquired-posture, locomotion, manual actions, and facial actions-and we adopt a developmental systems perspective to understand the causes and consequences of developmental change. Experience facilitates improvements in motor behavior and infants accumulate immense amounts of varied everyday experience with all the basic action systems. At every point in development, perception guides behavior by providing feedback about the results of just prior movements and information about what to do next. Across development, new motor behaviors provide new inputs for perception. Thus, motor development opens up new opportunities for acquiring knowledge and acting on the world, instigating cascades of developmental changes in perceptual, cognitive, and social domains. This article is categorized under: Cognitive Biology > Cognitive Development Psychology > Motor Skill and Performance Neuroscience > Development.

Menopause is associated with declines in cognitive control. However, there is individual variability in the slope of this decline. Recent work suggests that indices of cognitive control are mediated by communicative demands of the language environment. However, little is known about how the impact of bilingual experience generalizes across the lifespan, particularly in females who exhibit steeper cognitive decline due to increasing age and menopausal transition. Thus, we investigated whether diversity of language use in distinct communicative contexts modulated the effects of aging and menopause on cognitive control in an adult lifespan sample of healthy females. We performed robust linear regressions on a sample of 120 females (age range 20-65 years) to characterize age- (n = 120) and menopause-related (n = 59) declines in cognitive control (as assessed by the Wisconsin Card Sorting Test) and to determine whether they are modulated by different facets of bilingual language experience, including the diversity of language use (i.e., language entropy) in home and workplace environments. Workplace but not home language diversity modulated age- and menopause-related declines in cognitive control, suggesting that females may compensate for decline by virtue of adapting to the externally imposed demands of the language environment. These findings have implications for identifying which aspects of bilingual experience may contribute to cognitive reserve in healthy aging. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

BackgroundEarly-life exposure to phthalates alters behaviors in animals. However, epidemiological evidence on childhood phthalate exposure and attention-deficit/hyperactivity disorder (ADHD) behaviors is limited.MethodsThis study included 243 children from the ReCHARGE (Revisiting Childhood Autism Risks from Genetics and Environment) study, who were previously classified as having autism spectrum disorder (ASD), developmental delay, other early concerns, and typical development in the CHARGE case-control study. Twenty phthalate metabolites were measured in spot urine samples collected from children aged 2-5 years. Parents reported on children's ADHD symptoms at ages 8-18 years using Conners-3 Parent Rating Scale. Covariate-adjusted negative binomial generalized linear models were used to investigate associations between individual phthalate metabolite concentrations and raw scores. Weighted quantile sum (WQS) regression with repeated holdout validation was used to examine mixture effects of phthalate metabolites on behavioral scores. Effect modification by child sex was evaluated.ResultsAmong 12 phthalate metabolites detected in >75% of the samples, higher mono-2-heptyl phthalate (MHPP) was associated with higher scores on Inattentive (β per doubling = 0.05, 95% confidence interval [CI]: 0.02, 0.08) and Hyperactive/Impulsive scales (β = 0.04, 95% CI: 0.00, 0.07), especially among children with ASD. Higher mono-carboxy isooctyl phthalate (MCiOP) was associated with higher Hyperactivity/Impulsivity scores (β = 0.07, 95% CI: -0.01, 0.15), especially among typically developing children. The associations of the molar sum of high molecular weight (HMW) phthalate metabolites and a phthalate metabolite mixture with Hyperactivity/Impulsivity scores were modified by sex, showing more pronounced adverse associations among females.ConclusionExposure to phthalates during early childhood may impact ADHD behaviors in middle childhood and adolescence, particularly among females. Although our findings may not be broadly generalizable due to the diverse diagnostic profiles within our study population, our robust findings on sex-specific associations warrant further investigations.

While the majority of studies have concluded that sleep deprivation causes detrimental effects on various cognitive processes, some studies reported conflicting results. We examined the effects of a 108-h total sleep deprivation (TSD) on working memory in the northern fur seal, an animal with unusual sleep phenomenology and long-range annual migrations. The performance of fur seals was evaluated in a two-choice visual delayed matching to sample (DMTS) task, which is commonly used to evaluate working memory. In baseline conditions, the performance of fur seals in a DMTS task based on the percentage of errors was somewhat comparable with that in nonhuman primates at similar delays. We have determined that a 108-h TSD did not affect fur seals' performance in a visual DMTS task as measured by overall percentage of errors and response latencies. On the contrary, all fur seals improved task performance over the study, including the baseline, TSD and recovery conditions. In addition, TSD did not change the direction and strength of the pattern of behavioral lateralization in fur seals. We conclude that a 108-h TSD did not interfere with working memory in a DMTS test in northern fur seals.

BackgroundExaggerated responses to sensory stimuli, a hallmark of Fragile X syndrome (FXS), contribute to anxiety and learning challenges. Sensory hypersensitivity is recapitulated in the Fmr1 knockout (KO) mouse model of FXS. Recent studies in Fmr1 KO mice have demonstrated differences in activity of cortical interneurons and a delayed switch in the polarity of GABA signaling during development. Previously, we reported that blocking the chloride transporter NKCC1 with the diuretic bumetanide, could rescue synaptic circuit phenotypes in primary somatosensory cortex (S1) of Fmr1 KO mice. However, it remains unknown whether bumetanide can rescue earlier circuit phenotypes or sensory hypersensitivity in Fmr1 KO mice.MethodsWe used acute and chronic systemic administration of bumetanide in Fmr1 KO mice and performed in vivo 2-photon calcium imaging to record neuronal activity, while tracking mouse behavior with high-resolution videos.ResultsWe demonstrate that layer (L) 2/3 pyramidal neurons in S1 of Fmr1 KO mice show a higher frequency of synchronous events at postnatal day (P) 6 compared to wild-type controls. This was reversed by acute administration of bumetanide. Furthermore, chronic bumetanide treatment (P5-P14) restored S1 circuit differences in Fmr1 KO mice, including reduced neuronal adaptation to repetitive whisker stimulation, and ameliorated tactile defensiveness. Bumetanide treatment also rectified the reduced feedforward inhibition of L2/3 neurons in S1 and boosted the circuit participation of parvalbumin interneurons.ConclusionsThis further supports the notion that synaptic, circuit, and sensory behavioral phenotypes in Fmr1 KO can be mitigated by inhibitors of NKCC1, such as the FDA-approved diuretic bumetanide.