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BackgroundIntraindividual variability (IIV) during cognitive task performance is a key behavioral index of attention and a consistent marker of attention-deficit/hyperactivity disorder. In adults, lower IIV has been associated with anticorrelation between the default mode network (DMN) and dorsal attention network (DAN)-thought to underlie effective allocation of attention. However, whether these behavioral and neural markers of attention are 1) associated with each other and 2) can predict future attention-related deficits has not been examined in a developmental, population-based cohort.MethodsWe examined relationships at the baseline visit between IIV on 3 cognitive tasks, DMN-DAN anticorrelation, and parent-reported attention problems using data from the Adolescent Brain Cognitive Development (ABCD) Study (N = 11,878 participants, ages 9 to 10 years, female = 47.8%). We also investigated whether behavioral and neural markers of attention at baseline predicted attention problems 1, 2, and 3 years later.ResultsAt baseline, greater DMN-DAN anticorrelation was associated with lower IIV across all 3 cognitive tasks (B = 0.22 to 0.25). Older age at baseline was associated with stronger DMN-DAN anticorrelation and lower IIV (B = -0.005 to -0.0004). Weaker DMN-DAN anticorrelation and IIV were cross-sectionally associated with attention problems (B = 1.41 to 7.63). Longitudinally, lower IIV at baseline was associated with less severe attention problems 1 to 3 years later, after accounting for baseline attention problems (B = 0.288 to 0.77).ConclusionsThe results suggest that IIV in early adolescence is associated with worsening attention problems in a representative cohort of U.S. youth. Attention deficits in early adolescence may be important for understanding and predicting future cognitive and clinical outcomes.

Background: Family dementia caregivers often suffer from an immense toll of grief while caring for their loved ones. We sought to identify the clinical relationship between grief, depression and mindfulness and identify neural predictors of symptomatology and improvement. Methods: Twenty three family dementia caregivers were assessed at baseline for grief, mindfulness and depression, of which 17 underwent functional magnetic resonance imaging (fMRI). During fMRI, caregivers were shown faces of either their dementia-stricken relative or that of a stranger, paired with grief-related or neutral words. In nine subjects, post fMRI scans were also obtained after 4 weeks of either guided imagery or relaxation. Robust regression was used to predict changes in symptoms with longitudinal brain activation (BA) changes as the dependent variable. Results: Grief and depression symptoms were correlated (r = 0.50, p = 0.01), and both were negatively correlated with mindfulness (r = -0.70, p = 0.0002; r = -0.52, p = 0.01). Relative to viewing strangers, caregivers showed pictures of their loved ones (picture factor) exhibited increased activation in the dorsal anterior cingulate gyrus and precuneus. Improvement in grief but not mindfulness or depression was predicted by increased relative BA in the precuneus and anterior cingulate (different subregions from baseline). Viewing grief-related vs. neutral words elicited activity in the medial prefrontal cortex and precuneus. Conclusions: Caregiver grief, depression and mindfulness are interrelated but have at least partially nonoverlapping neural mechanisms. Picture and word stimuli related to caregiver grief evoked brain activity in regions previously identified with bereavement grief. These activation foci might be useful as biomarkers of treatment response.

Background and Aims Current understanding of histone post-translational modifications [histone modifications] across immune cell types in patients with inflammatory bowel disease [IBD] during remission and flare is limited. The present study aimed to quantify histone modifications at a single-cell resolution in IBD patients during remission and flare and how they differ compared to healthy controls. Methods We performed a case-control study of 94 subjects [83 IBD patients and 11 healthy controls]. IBD patients had either ulcerative colitis [ n  = 38] or Crohn's disease [ n  = 45] in clinical remission or flare. We used epigenetic profiling by time-of-flight [EpiTOF] to investigate changes in histone modifications within peripheral blood mononuclear cells from IBD patients. Results We discovered substantial heterogeneity in histone modifications across multiple immune cell types in IBD patients. They had a higher proportion of less differentiated CD34+ haematopoietic progenitors, and a subset of CD56bright natural killer [NK] cells and γδ T cells characterized by distinct histone modifications associated with gene transcription. The subset of CD56bright NK cells had increases in several histone acetylations. An epigenetically defined subset of NK cells was associated with higher levels of C-reactive protein in peripheral blood. CD34+ monocytes from IBD patients had significantly decreased cleaved H3T22, suggesting they were epigenetically primed for macrophage differentiation. Conclusion We describe the first systems-level quantification of histone modifications across immune cells from IBD patients at a single-cell resolution, revealing the increased epigenetic heterogeneity that is not possible with traditional ChIP-seq profiling. Our data open new directions in investigating the association between histone modifications and IBD pathology using other epigenomic tools. [ABSTRACT FROM AUTHOR]

Background: Family caregivers of dementia patients experience high levels of interpersonal stress that often results in elevated anxiety, and depression, and negative impacts on interpersonal relationships. Changes in behaviors and the structure of relationships with the care recipient and others in the social milieu challenge the caregivers' ability to mentalize or understand the links between mental states and behaviors. This study investigates the experiences and perceived benefits of family dementia caregivers who underwent Mentalizing Imagery Therapy (MIT), a treatment aiming to improve balanced self-other mentalizing and reduce psychological symptoms. Method: Purposeful sampling was used to select 11 family dementia caregivers who underwent a 4-week pilot trial of MIT. Semistructured interviews were completed postintervention to identify subjective benefits, putative psychological mediators, and perceived active components. Results: Caregivers reported improvements in well-being, mood, anxiety, and sleep, and a majority stated MIT helped with forming and maintaining healthier relationships. Some participants noted benefits extending to how they reacted to their social environment and perceived themselves more objectively from others' perspectives. Specific elements of MIT, including self-compassion, self-care, and the ability to reflect on emotionally arousing challenges, might have mediated these improvements. Conclusion: Family dementia caregivers perceived the salutary benefits of MIT on multiple domains of well-being. The self-reports suggest MIT holds promise for improving well-being, reducing nonmentalizing patterns of thought, and facilitating improvements in balanced mentalization within the caregivers' relationships. [ABSTRACT FROM AUTHOR]

Importance: Rates of prenatal cannabis exposure (PCE) are rising with increasingly permissive legislation regarding cannabis use, which may be a risk factor for psychosis. Disrupted reward-related neural circuitry may underlie this relationship., Objective: To elucidate neural mechanisms involved in the association between PCE and youth-onset psychotic-like experiences by probing correlates of reward anticipation, a neurobehavioral marker of endocannabinoid-mediated dopaminergic function., Design Setting and Participants: This longitudinal, prospective study analyzed task-related functional neuroimaging data from baseline (n=11,368), 2-year follow-up (n=7,928), and 4-year follow-up (n=2,982) of the ongoing Adolescent Brain and Cognitive Development (ABCD) Study, which recruited children aged 9 to 10 years old at baseline from 22 sites across the United States., Results: PCE (n=652 exposed youth) is longitudinally associated with psychotic-like experiences. Blunted neural response to reward anticipation is associated with psychotic-like experiences, with stronger effects observed in PCE youth (all |β| > 0.5; false discovery rate [FDR]-corrected P < .05). This hypoactivation at baseline predicts psychosis symptomatology in middle adolescence (4-year follow-up visit; β=-.004; FDR-corrected P < .05). Dampened behavioral reward sensitivity is associated with psychotic-like experiences across baseline, 2-year follow-up visit, and 4-year follow-up visit (|β| = .21; FDR-corrected P < .001). Psychotic-like experiences are positively associated with trait-level measures of reward motivation and impulsivity, with stronger effects for PCE youth (all |β| > 0.1; all FDR-corrected P < .05)., Conclusions and Relevance: Blunted activation in reward-related brain regions may serve as a biomarker for disrupted reward processing and increased psychosis risk during development. PCE may affect childhood behaviors and traits related to altered reward sensitivity., Competing Interests: The authors have nothing to disclose.