Compared with children and adults, teens and young adults often exhibit greater impulsivity and corresponding increases in emergency room visits, accidents from drug or alcohol use, and increased ...mortality risk. However, it remains poorly understood how increased impulsivity during adolescence may be explained in terms of brain and cognitive development. We focused on impatience, a central component of impulsiveness. We relate impatient behavior on a decision-making task to changes in connectivity within the brainâs frontostriatal circuitry. Our results suggest that relative future orientation, not sensitivity to immediate rewards, determines adolescent impatience. These findings may help to design interventions to prevent the detrimental effects of adolescent impulsiveness and serve as a template for understanding neurodevelopmental disorders.
Adolescence is a developmental period associated with an increase in impulsivity. Impulsivity is a multidimensional construct, and in this study we focus on one of the underlying components: impatience. Impatience can result from ( i ) disregard of future outcomes and/or ( ii ) oversensitivity to immediate rewards, but it is not known which of these evaluative processes underlie developmental changes. To distinguish between these two causes, we investigated developmental changes in the structural and functional connectivity of different frontostriatal tracts. We report that adolescents were more impatient on an intertemporal choice task and reported less future orientation, but not more present hedonism, than young adults. Developmental increases in structural connectivity strength in the right dorsolateral prefrontal tract were related to increased negative functional coupling with the striatum and an age-related decrease in discount rates. Our results suggest that mainly increased control, and the integration of future-oriented thought, drives the reduction in impatience across adolescence.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Large individual differences exist in the ability to delay gratification for the sake of satisfying longer-term goals. These individual differences are commonly assayed by studying intertemporal ...preferences, as revealed by choices between immediate and delayed rewards. In the brain, reward-based and goal-oriented decisions are believed to rely on the striatum and its interactions with other cortical and subcortical networks. However, it remains unknown which specific cortical-striatal tracts are involved in intertemporal decision making. We use connectivity analyses in both structural and functional MRI to further our understanding of the relationship between distinct corticostriatal networks and intertemporal preferences in humans. Our results revealed distinct striatal pathways that are differentially related to delay discounting. Structural and functional connectivity between striatum and lateral prefrontal cortex was associated with increased patience, whereas connectivity between subcortical areas and striatum was associated with increased impulsivity. These findings provide novel insights into how the anatomy and functioning of striatal circuits mediate individual differences in intertemporal choice.
Abstract Heightened distractibility in participants with ADHD as indexed by increased reaction time (RT) variability has been hypothesized to be due to a failure to sufficiently suppress activation ...in the default attention network during cognitively demanding situations. The present study utilized fMRI to examine the relationship between intra-individual variability (IIV) in task RT and suppression of BOLD response in regions of the default network, using a working memory paradigm and two levels of control tasks. IIV was calculated separately for thirteen healthy control and twelve children with ADHD, Combined Type. Children with ADHD displayed significantly more RT variability than controls. Neural measures showed that although both groups displayed a pattern of increasing deactivation of the medial prefrontal cortex (PFC) with increasing task difficulty, the ADHD group was significantly less deactive than controls. Correlations between IIV and brain activation suggested that greater variability was associated with a failure to deactivate ventromedial PFC with increasing task difficulty. T -tests on brain activation between participants with ADHD with low versus high IIV implicated a similar region so that high variability was associated with greater activity in this region. These data provide support for the theory that increased distractibility in at least some participants with ADHD may be due to an inability to sufficiently suppress activity in the default attention network in response to increasing task difficulty.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPUK
Scavenger receptor A (SR-A), also known as the macrophage scavenger receptor and cluster of differentiation 204 (CD204), plays roles in lipid metabolism, atherogenesis, and a number of metabolic ...processes. However, recent evidence points to important roles for SR-A in inflammation, innate immunity, host defense, sepsis, and ischemic injury. Herein, we review the role of SR-A in inflammation, innate immunity, host defense, sepsis, cardiac and cerebral ischemic injury, Alzheimer's disease, virus recognition and uptake, bone metabolism, and pulmonary injury. Interestingly, SR-A is reported to be host protective in some disease states, but there is also compelling evidence that SR-A plays a role in the pathophysiology of other diseases. These observations of both harmful and beneficial effects of SR-A are discussed here in the framework of inflammation, innate immunity, and endoplasmic reticulum stress.
•Included 627 children between the ages of 2–5 from CHARGE, a case-control study.•Measured 44 environmental compounds and metabolites in urine.•Estimated risks of autism spectrum disorder (ASD) and ...developmental delay (DD).•Conducted a weighted quantile sum regression analysis and single chemical analyses.•Higher concentrations increased odds of ASD and DD compared to typical.
To determine if higher exposures measured in early childhood to environmental phenols, phthalates, pesticides, and/or trace elements, are associated with increased odds of having a diagnosis of Autism Spectrum Disorder (ASD), Developmental Delay (DD), or Other Early Concerns (OEC) compared to typically developing children (TD).
This study included 627 children between the ages of 2–5 who participated in the Childhood Autism Risks from Genetics and Environment (CHARGE) study. Urine samples were collected at the same study visit where diagnostic assessments to confirm diagnosis indicated during the recruitment process were performed. Adjusted multinomial regression models of each chemical with diagnosis as the outcome were conducted. Additionally, two methods were used to analyze mixtures: repeated holdout multinomial weighted quantile sum (WQS) regression for each chemical class; and a total urinary mixture effect was assessed with repeated holdout random subset WQS.
Many urinary chemicals were associated with increased odds of ASD, DD or OEC compared to TD; however, most did not remain significant after false discovery rate adjustment. Repeated holdout WQS indices provided evidence for associations of both a phenol/paraben mixture effect and a trace element mixture effect on DD independently. In analyses adjusted for confounders and other exposures, results suggested an association of a pesticide mixture effect with increased risk for ASD. Results also suggested associations of a total urinary mixture with greater odds of both ASD and DD separately.
Higher concentrations of urinary biomarkers were associated with ASD, DD, and OEC compared to TD, with consistency of the results comparing single chemical analyses and mixture analyses. Given that the biospecimens used for chemical analysis were generally collected many months after diagnoses were made, the direction of any causal association is unknown. Hence findings may reflect higher exposures among children with non-typical development than TD children due to differences in behaviors, metabolism, or toxicokinetics.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPUK, ZAGLJ, ZRSKP
Abstract
Background
The ability to perform objective pain assessment is very important in paediatric patients. The goal of this study was to investigate the relationship between the analgesia ...nociception index (ANI), which is based on the heart rate variability, and objective measurements of pain intensity in young or cognitively impaired children, after surgical or imaging procedures (control group) under general anaesthesia.
Methods
On arrival in the recovery room and subsequently at 5-10 min intervals, the level of pain was rated using the FLACC pain scale (0-10). The ANI values (0-100; 0 indicating the worst pain) were recorded simultaneously. The area under the receiver operating characteristic curve (AUC) and grey zone approach were used to evaluate the performance of the ANI to detect patients with FLACC >4. Instantaneous ANI values were compared with ANI values averaged over 256 s periods of time.
Results
All children in the surgical group (n=32) developed moderate-to-severe pain (FLACC >4). Children in the control group (n=30) exhibited minimal pain. Instantaneous ANI values were lower in children of the surgical group than in the control group 52 (sd16) vs 69 (16), P<0.001. The AUC for the 256 s ANI recording period 0.94 (95% confidence interval 0.85-0.99) was significantly higher than for instantaneous ANI (P<0.05). When measured for a period of 256 s, an ANI cut-off value of 56 (grey zone 58-60) was most predictive of a FLACC ≥4.
Conclusions
The ANI may provide an objective measurement of acute postoperative pain, which is correlated with that measured on a FLACC scale in young or cognitively impaired children.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPUK, ZAGLJ, ZRSKP
Working memory impairments are frequent in Attention Deficit/Hyperactivity Disorder (ADHD) and create problems along numerous functional dimensions. The present study utilized the Visual Serial ...Addition Task (VSAT) and functional magnetic resonance imaging (fMRI) to explore working memory processes in thirteen typically developing (TD) control and thirteen children with ADHD, Combined type. Analysis of Variance (ANOVA) was used to examine both main effects and interactions. Working memory-specific activity was found in TD children in the bilateral prefrontal cortex. In contrast the within-group map in ADHD did not reveal any working-memory specific regions. Main effects of condition suggested that the right middle frontal gyrus (BA6) and the right precuneus were engaged by both groups during working memory processing. Group differences were driven by significantly greater, non-working memory-specific, activation in the ADHD relative to TD group in the bilateral insula extending into basal ganglia and the medial prefrontal cortex. A region of interest analysis revealed a region in left middle frontal gyrus that was more active during working memory in TD controls. Thus, only the TD group appeared to display working memory-modulated brain activation. In conclusion, children with ADHD demonstrated reduced working memory task specific brain activation in comparison to their peers. These data suggest inefficiency in functional recruitment by individuals with ADHD represented by a poor match between task demands and appropriate levels of brain activity.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A growing body of literature investigated childhood exposure to environmental chemicals in association with attention-deficit/hyperactivity disorder (ADHD) symptoms, but limited studies considered ...urinary mixtures of multiple chemical classes. This study examined associations of concurrent exposure to non-persistent chemicals with ADHD symptoms in children diagnosed with autism spectrum disorder (ASD), developmental delay (DD), and typical development (TD).
A total of 549 children aged 2-5 years from the Childhood Autism Risks from Genetics and Environment (CHARGE) case-control study were administered the Aberrant Behavior Checklist (ABC). This study focused on the ADHD/noncompliance subscale and its two subdomains (hyperactivity/impulsivity, inattention). Sixty-two chemicals from four classes (phenols/parabens, phthalates, organophosphate pesticides, trace elements) were quantified in child urine samples, and 43 chemicals detected in > 70% samples were used to investigate their associations with ADHD symptoms. Negative binomial regression was used for single-chemical analysis, and weighted quantile sum regression with repeated holdout validation was applied for mixture analysis for each chemical class and all chemicals. The mixture analyses were further stratified by diagnostic group.
A phthalate metabolite mixture was associated with higher ADHD/noncompliance scores (median count ratio CR = 1.10; 2.5th, 97.5th percentile: 1.00, 1.21), especially hyperactivity/impulsivity (median CR = 1.09; 2.5th, 97.5th percentile: 1.00, 1.25). The possible contributors to these mixture effects were di-2-ethylhexyl phthalate (DEHP) metabolites and mono-2-heptyl phthalate (MHPP). These associations were likely driven by children with ASD as these were observed among children with ASD, but not among TD or those with DD. Additionally, among children with ASD, a mixture of all chemicals was associated with ADHD/noncompliance and hyperactivity/impulsivity, and possible contributors were 3,4-dihydroxy benzoic acid, DEHP metabolites, MHPP, mono-n-butyl phthalate, and cadmium.
Early childhood exposure to a phthalate mixture was associated with ADHD symptoms, particularly among children with ASD. While the diverse diagnostic profiles limited generalizability, our findings suggest a potential link between phthalate exposure and the comorbidity of ASD and ADHD.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
While effective general practitioner (GP)–patient communication is required for the provision of good palliative care, barriers and facilitators for this communication are largely unknown. We aimed ...to identify barriers and facilitators for GP–patient communication in palliative care. In a systematic review seven computerized databases were searched to find empirical studies on GP–patient communication in palliative care. Fifteen qualitative studies and seven quantitative questionnaire studies were included. The main perceived barriers were GPs’ lack of availability, and patients’ and GPs’ ambivalence to discuss ‘bad prognosis’. Main perceived facilitators were GPs being available, initiating discussion about several end-of-life issues and anticipating various scenarios. Lack of availability and failure to discuss former mistakes appear to be blind spots of GPs. GPs should be more forthcoming to initiate discussions with palliative care patients about prognosis and end-of-life issues. Empirical studies are needed to investigate the effectiveness of the perceived barriers and facilitators.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
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