Neuronal oscillations and cross-frequency interactions in the rat hippocampus relate in important ways to memory processes and serve as a model for studying oscillatory activity in cognition more broadly. We report here that hippocampal synchrony (CA3-CA1 coherence) increased markedly in the low gamma range as rats were exploring novel objects, particularly those for which the rat subsequently showed good memory. The gamma synchrony varied across phases of the theta rhythm such that coherence was highest at the falling slope and trough of the theta wave. Further, the shape of the theta wave was more asymmetric and elongated at the falling slope during exploration of objects for which the rat subsequently showed good memory as compared with objects for which the rat subsequently showed poor memory. The results showed a strong association between event-related gamma synchrony in rat hippocampus and memory encoding for novel objects. In addition, a novel potential mechanism of cross-frequency interactions was observed whereby dynamic alterations in the shape of theta wave related to memory in correspondence with the strength of gamma synchrony. These findings add to our understanding of how theta and gamma oscillations interact in the hippocampus in the service of memory.
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Shakira F Suglia;
Shakia T Hardy;
Alison L Cammack;
Ye Ji Kim;
Bradley D Pearce;
Amit J Shah;
Samaah Sullivan;
Matthew Wittbrodt;
J. Douglas Bremner;
Laura Vaccarino
Objective Experiences of child maltreatment are associated with cardiovascular risk and disease in adulthood; however, the mechanisms underlying these associations are poorly understood. Methods We examined associations between retrospectively self-reported exposure to child maltreatment (Early Trauma Inventory Self-Report Short Form) and inflammatory responses to mental stress among adults (mean age = 50 years) who recently had a myocardial infarction (n = 227). Inflammation was assessed as blood interleukin-6 (IL-6), matrix metalloproteinase-9 (MMP-9), and monocyte chemoattractant protein-1 concentrations, measured before and after a standardized public speaking stress task. We used mixed linear regression models adjusting for cardiovascular disease severity, medication usage, and psychosocial, demographic, and life-style factors. Results In women, increases in IL-6 levels and MMP-9 levels with stress were smaller in those exposed to sexual abuse, relative to those unexposed (IL-6 geometric mean increases = 1.6 [95% confidence interval {CI} = 1.4-1.9] pg/ml versus 2.1 [95% CI = 1.8-2.4] pg/ml; MMP-9 geometric mean increases = 1.0 [95% CI = 0.9-1.2] ng/ml versus 1.2 [95% CI = 1.1-1.4] ng/ml). No differences were noted for emotional or physical abuse. By contrast in men, individuals exposed to sexual abuse had larger IL-6 responses than those not exposed to abuse. Conclusions These findings suggest sex differences in stress response among survivors of a myocardial infarction exposed to abuse early in life. They also underscore the importance of examining sex as an effect modifier of relationships between exposure to early life adversity and inflammatory responses to mental stressors in midlife.
This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Recent evidence suggests that grammatical aspect can bias how individuals perceive criminal intentionality during discourse comprehension. Given that criminal intentionality is a common criterion for legal definitions (e.g., first-degree murder), the present study explored whether grammatical aspect may also impact legal judgments. In a series of four experiments participants were provided with a legal definition and a description of a crime in which the grammatical aspect of provocation and murder events were manipulated. Participants were asked to make a decision (first- vs. second-degree murder) and then indicate factors that impacted their decision. Findings suggest that legal judgments can be affected by grammatical aspect but the most robust effects were limited to temporal dynamics (i.e., imperfective aspect results in more murder actions than perfective aspect), which may in turn influence other representational systems (i.e., number of murder actions positively predicts perceived intentionality). In addition, findings demonstrate that the influence of grammatical aspect on situation model construction and evaluation is dependent upon the larger linguistic and semantic context. Together, the results suggest grammatical aspect has indirect influences on legal judgments to the extent that variability in aspect changes the features of the situation model that align with criteria for making legal judgments.
Epigenetics processes may play a vital role in the biological embedding of early environmental adversity and the development of psychopathology. Accumulating evidence suggests that maltreatment is linked to methylation of the glucocorticoid receptor gene, nuclear receptor subfamily 3, group C, member 1 (NR3C1), which is a key regulator of the hypothalamus-pituitary-adrenal axis. However, prior work has been exclusively cross-sectional, greatly constraining our understanding of stress-related epigenetic processes over time. In the current study, we examined the effect of maltreatment and other adversity on change in NR3C1 methylation among at-risk preschoolers to begin to characterize within-child epigenetic changes during this sensitive developmental period. Participants were 260 preschoolers (3-5 years old, 53.8% female), including 51.5% with moderate to severe maltreatment in the past 6 months. Child protection records, semistructured interviews, and parent reports were used to assess child stress exposure. Methylation of exons 1D and 1F of NR3C1 via saliva DNA were measured at two time points approximately 6 months apart. Results indicate that maltreated children evidence higher baseline levels of NR3C1 methylation, significant decreases in methylation over time, and then at follow-up, lower levels of methylation, relative to nonmaltreated preschoolers. Findings from the current study highlight the complex nature of stress-related epigenetic processes during early development.
Fragile X syndrome (FXS) is the leading inherited cause of intellectual disability. It is primarily caused by the expansion of a CGG trinucleodide repeat located in the 5′ untranslated region of the X-linked FMR1 gene. Individuals with FXS present with variable intellectual quotients (IQs) ranging from the average to the severe intellectual disability level. A range of neurocognitive strengths and challenges are observed in individuals with FXS. This article provides an overview of our current understanding related to cognition and FXS. Cognitive functioning levels, profiles, and IQ trajectories are discussed. Limitations of existing neuropsychological measures are described.
The worldwide epidemic of metabolic syndromes and the recognized burden of mental health disorders have driven increased research into the relationship between the two. A maladaptive stress response is implicated in both mental health disorders and metabolic disorders, implicating the hypothalamic-pituitary-adrenal (HPA) axis as a key mediator of this relationship. This review explores how an altered energetic state, such as hyper- or hypoglycemia, as may be manifested in obesity or diabetes, affects the stress response and the HPA axis in particular. We propose that changes in energetic state or energetic demands can result in “energetic stress” that can, if prolonged, lead to a dysfunctional stress response. In this review, we summarize the role of the hypothalamus in modulating energy homeostasis and then briefly discuss the relationship between metabolism and stress-induced activation of the HPA axis. Next, we examine seven mechanisms whereby energetic stress interacts with neuroendocrine stress response systems, including by glucocorticoid signaling both within and beyond the HPA axis; by nutrient-induced changes in glucocorticoid signaling; by impacting the sympathetic nervous system; through changes in other neuroendocrine factors; by inducing inflammatory changes; and by altering the gut-brain axis. Recognizing these effects of energetic stress can drive novel therapies and prevention strategies for mental health disorders, including dietary intervention, probiotics, and even fecal transplant.
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Jacquelyn Y Taylor;
Yunfeng Huang;
Wei Zhao;
Michelle L Wright;
Zeyuan Wang;
Qin Hui;
Stephanie Potts-Thompson;
Veronica Barcelona;
Laura Prescott;
Yutong Yao;
Cindy Crusto;
Sharon LR Kardia;
Jennifer A Smith;
Yan Sun
Objective: Obesity is a significant public health concern across the globe. Research investigating epigenetic mechanisms related to obesity and obesity-associated conditions has identified differences that may contribute to cellular dysregulation that accelerates the development of disease. However, few studies include Black women, who experience the highest incidence of obesity and early onset of cardiometabolic disorders. Methods: The association of BMI with epigenome-wide DNA methylation (DNAm) was examined using the 850K Illumina EPIC BeadChip in two Black populations (Intergenerational Impact of Genetic and Psychological Factors on Blood Pressure [InterGEN], n = 239; and The Genetic Epidemiology Network of Arteriopathy [GENOA] study, n = 961) using linear mixed-effects regression models adjusted for batch effects, cell type heterogeneity, population stratification, and confounding factors. Results: Cross-sectional analysis of the InterGEN discovery cohort identified 28 DNAm sites significantly associated with BMI, 24 of which had not been previously reported. Of these, 17 were replicated using the GENOA study. In addition, a meta-analysis, including both the InterGEN and GENOA cohorts, identified 658 DNAm sites associated with BMI with false discovery rate < 0.05. In a meta-analysis of Black women, we identified 628 DNAm sites significantly associated with BMI. Using a more stringent significance threshold of Bonferroni-corrected p value 0.05, 65 and 61 DNAm sites associated with BMI were identified from the combined sex and female-only meta-analyses, respectively. Conclusions: This study suggests that BMI is associated with differences in DNAm among women that can be identified with DNA extracted from salivary (discovery) and peripheral blood (replication) samples among Black populations across two cohorts.
Adolescent brain development is characterized by neuronal remodeling in the prefrontal cortex; relationships with behavior are largely undefined. Integrins are cell adhesion factors that link the extracellular matrix with intracellular actin cytoskeleton. We find that β1-integrin presence in the prelimbic prefrontal cortex (PL) during adolescence, but not adulthood, is necessary for mice to select actions based on reward likelihood and value. As such, adult mice that lacked β1-integrin during adolescence failed to modify response strategies when rewards lost value or failed to be delivered. This pattern suggests that β1-integrin-mediated neuronal development is necessary for PL function in adulthood. We next visualized adolescent PL neurons, including those receiving input from the basolateral amygdala (BLA) – thought to signal salience – and projecting to the dorsomedial striatum (DMS) – the striatal output by which the PL controls goal-seeking behavior. Firstly, we found that these projection-defined neurons had a distinct morphology relative to general layer V PL neurons. Secondly, β1-integrin loss triggered the overexpression of stubby-type dendritic spines at the expense of mature spines, including on projection-defined neurons. This phenotype was not observed when β1-integrins were silenced before or after adolescence. Altogether, our experiments localize β1-integrin-mediated cell adhesion within a developing di-synaptic circuit coordinating adaptive action
Child Development published by Wiley Periodicals, Inc. on behalf of Society for Research in Child Development. Nutrition plays an important role in the development of a child, particularly in low- and middle-income countries where malnutrition is often widespread. The relation between diet, hemoglobin, nutritional status, motor development, stimulation and mental development was examined in a cross-sectional sample of 1,079 children 12–18 months of age living in rural Bihar, India. Path analysis revealed associations between (a) length-for-age z-scores and motor development, standardized β (β) =.285, p <.001, and (b) motor and all mental development outcomes (language: β =.422; personal-social: β =.490; memory: β =.139; and executive function: β =.072, all p <.001). Additionally, stimulation was significantly associated with language scores and hemoglobin concentration with memory. These findings inform interventions aimed at improving child development in Northern India.
This study examined how teachers and paraprofessionals in 126 kindergarten-second grade general and special education classrooms talked with their 194 students with autism, and further, how individual student characteristics in language, autism symptoms, and social abilities influenced this talk. Using systematic observational methods and factor analysis, we identified a unidimensional model of teacher language for general and special education classrooms yet observed differences between the settings, with more language observed in special education classrooms—much of which included directives and close-ended questions. Students’ receptive vocabulary explained a significant amount of variance in teacher language beyond its shared covariance with social impairment and problem behavior in general education classrooms but was non-significant within special education classrooms. Research implications are discussed.