Hearing loss and intellectual outcome in children treated for embryonal brain tumors: Implications for young children treated with radiation sparing approaches.

PURPOSE: We investigate the impact of severe sensorineural hearing loss (SNHL) and for the first time evaluate the effect of unilateral versus bilateral SNHL on intellectual outcome in a cohort of children with embryonal brain tumors treated with and without radiation. METHODS: Data were from 94 childhood survivors of posterior fossa (PF) embryonal brain tumors who were treated with either: (1) chemotherapy alone (n = 16, 7.11 [3.41] years, 11M/5F), (2) standard-dose craniospinal irradiation (CSI) and/or large boost volumes (n = 44, 13.05 [3.26] years, 29M/15F), or (3) reduced-dose CSI with a boost restricted to the tumor bed (n = 34, 11.07 [3.80] years, 19M/15F). We compared intellectual outcome between children who: (1) did and did not develop SNHL and (2) developed unilateral versus bilateral SNHL. A Chang grade of ≥2b that required the use of a hearing aid was considered severe SNHL. Comparisons were made overall and within each treatment group separately. RESULTS: Patients who developed SNHL had lower full scale IQ (p = 0.007), verbal comprehension (p = 0.003), and working memory (p = 0.02) than patients without SNHL. No differences were observed between patients who had unilateral versus bilateral SNHL (all p > 0.05). Patients treated with chemotherapy alone who developed SNHL had lower mean working memory (p = 0.03) than patients who did not develop SNHL. Among patients treated with CSI, no IQ indices differed between those with and without SNHL (all p > 0.05). CONCLUSIONS: Children treated for embryonal brain tumors who develop severe SNHL have lower intellectual outcome than patients with preserved hearing: this association is especially profound in young children treated with radiation sparing approaches. We also demonstrate that intellectual outcome is similarly impaired in patients who develop unilateral versus bilateral SNHL. These findings suggest that early intervention to preserve hearing is critical.

Caffeine intake and cognitive functions in children.

RATIONALE: There is a growing concern over excessive caffeine use and development of caffeine use disorder in children. OBJECTIVES: This study aimed to identify the association between caffeine intake and cognitive functioning in children. METHODS: This study included 11,718 youths aged 9-10 years with cognitive and caffeine intake information that were extracted from the Adolescent Brain Cognitive Development (ABCD) study. The ABCD study is a longitudinal cohort study started in 2017 that aims to understand the relationships between substance use and neurocognition in youths living in the USA. Cognitive measures were obtained through the 7 core cognitive instruments from the NIH toolbox (vocabulary comprehension, reading decoding, inhibitory control, working memory, cognitive flexibility, processing speed, and episodic memory). Associations between caffeine intake and the seven cognitive functions were examined using multiple regression models. RESULTS: Our study revealed that caffeine intake negatively correlated with all the seven cognitive measures. After adjustment for age, gender, sleep, and socioeconomic status (SES), caffeine intake was still found to be negatively associated with most of the cognitive functions, such as vocabulary comprehension, working memory, cognitive flexibility, processing speed, and episodic memory, except reading decoding, and inhibitory control. CONCLUSIONS: As beverages with caffeine are consumed frequently, controlling their intake may reduce a risk for nonoptimal cognitive development in children.

Attitudes Toward Cognitive Enhancement: The Role of Metaphor and Context.

The widespread use of stimulants among healthy individuals to improve cognition has received growing attention; however, public attitudes toward this practice are not well understood. We determined the effect of framing metaphors and context of use on public opinion toward cognitive enhancement. We recruited 3,727 participants from the United States to complete three surveys using Amazon's Mechanical Turk between April and July 2017. Participants read vignettes describing an individual using cognitive enhancement, varying framing metaphors (fuel versus steroid), and context of use (athletes versus students versus employees). The main outcome measure was the difference in respondent-assigned level of acceptability of the use of cognitive enhancement by others and by themselves between the contrasting vignettes. Participants were more likely to support the use of cognitive enhancement by others than by themselves and more when the use of enhancement by others was framed with a fuel metaphor than with a steroid metaphor. Metaphoric framing did not affect participants' attitudes toward their own use. Participants supported the use of enhancement by employees more than by students or athletes. These results are discussed in relation to existing ethical and policy literature.

Intellectual functioning in clinically confirmed fetal valproate syndrome.

BACKGROUND: An increased risk of impaired intelligence (IQ) has been documented in valproate-exposed children, but investigations have not previously focused on those with a clinical diagnosis of Fetal Valproate Syndrome (FVS). METHODS: This cross sectional observational study recruited individuals with a diagnosis of FVS and completed standardized assessments of intellectual abilities making comparisons to a normative comparison group. Both mean difference (MD) and prevalence of scores below the lower average range were analyzed. RESULTS: The mean full-scale IQ in 31 individuals with FVS (mean age 14.97; range 6-27 years) was 19 points lower (19.55, 95% CI -24.94 to 14.15), and IQ scores <70 were present in 26%. The mean differences for verbal comprehension (21.07, 95% CI -25.84 to -16.29), working memory (19.77, 95% CI -25.00 to -14.55) and processing speed (16.87, 95% CI -22.24 to -11.50) performances were poorer than expected with the mean differences over one standard deviation from the comparison group. Sixty one percent of cases demonstrated disproportionately lower verbal comprehension ability. There were no significant group differences for IQ in high vs. moderate dose valproate or mono vs. polytherapy. There were no differences in IQ between those with and those without a major congenital malformation. The requirement for educational intervention was high at 74%. CONCLUSION: Intellectual difficulties are a central feature of FVS and are more severe in their presentation in individuals with a diagnosis of valproate embryopathy. Individuals with FVS who present with the characteristic facial presentation should be considered at high risk of cognitive difficulties regardless of the dose of valproate exposure or the presence of a major congenital malformation.

Attention-Deficit/Hyperactivity Disorder-Related Deficits and Psychostimulant Medication Effects on Comprehension of Audiovisually Presented Educational Material in Children.

Objective: We aimed to (1) examine differences in observed visual attention and motor activity, as well as comprehension of a science video between children with and without attention-deficit/hyperactivity disorder (ADHD) and (2) explore if psychostimulant medication improves ADHD behaviors and comprehension of a science video in children with ADHD. Method: Children aged 7-11 with (n = 91) and without (n = 45) ADHD watched a science video and then completed a comprehension test. Then, children with ADHD began a 4-week within-subject, randomized, double-blind crossover trial of methylphenidate (MPH). At post-testing, children were randomized to receive placebo or their optimal dosage, watched another science film, and completed a comprehension test. Results: Children with ADHD exhibited higher rates of motor activity during, and worse comprehension of material discussed within, the science video. Mediation models revealed that increased motor activity suppressed between-group differences in comprehension. MPH improved comprehension and visual attention, but not motor activity during the science video. Conclusion: Children with ADHD may benefit from MPH to improve comprehension of and sustained attention during audiovisually presented learning material.

Oxytocin Modulates Semantic Integration in Speech Comprehension.

Listeners interpret utterances by integrating information from multiple sources including word level semantics and world knowledge. When the semantics of an expression is inconsistent with their knowledge about the world, the listener may have to search through the conceptual space for alternative possible world scenarios that can make the expression more acceptable. Such cognitive exploration requires considerable computational resources and might depend on motivational factors. This study explores whether and how oxytocin, a neuropeptide known to influence social motivation by reducing social anxiety and enhancing affiliative tendencies, can modulate the integration of world knowledge and sentence meanings. The study used a between-participant double-blind randomized placebo-controlled design. Semantic integration, indexed with magnetoencephalography through the N400m marker, was quantified while 45 healthy male participants listened to sentences that were either congruent or incongruent with facts of the world, after receiving intranasally delivered oxytocin or placebo. Compared with congruent sentences, world knowledge incongruent sentences elicited a stronger N400m signal from the left inferior frontal and anterior temporal regions and medial pFC (the N400m effect) in the placebo group. Oxytocin administration significantly attenuated the N400m effect at both sensor and cortical source levels throughout the experiment, in a state-like manner. Additional electrophysiological markers suggest that the absence of the N400m effect in the oxytocin group is unlikely due to the lack of early sensory or semantic processing or a general downregulation of attention. These findings suggest that oxytocin drives listeners to resolve challenges of semantic integration, possibly by promoting the cognitive exploration of alternative possible world scenarios.

[Organophosphate pesticides and neuropsychological and motor effects in the Maule Region, Chile]. / Plaguicidas organofosforados y efecto neuropsicológico y motor en la Región del Maule, Chile.

OBJECTIVE: To evaluate organophosphate pesticide exposure and neuropsychological and motor performance in agricultural and non-agricultural workers in the Maule Region in Chile. METHOD: Analytic cross-sectional study in 93 exposed farm workers and 84 unexposed non-agricultural workers. A battery of four neuropsychological tests was administered together with a neuro-motor physical examination. RESULTS: On the Weschler adult intelligence scale (WAIS-IV), exposed agricultural workers exhibited poorer performance than non-agricultural workers in verbal comprehension (ß=-3.2; p=0.034) and processing speed (ß=-4.4; p=0.036) and in the full scale (ß=-4; p=0.016), as well as in discrimination sensitivity (ß=1, p=0,009), adjusted by years of schooling and/or age. CONCLUSIONS: We suggest the development of policies and regulations for the control, sale and use of organophosphate pesticides and intervention strategies on safety measures aimed at the exposed population.

Positive effects of short course androgen therapy on the neurodevelopmental outcome in boys with 47,XXY syndrome at 36 and 72 months of age.

The effects of early androgen treatment on neurodevelopmental performance in pre-pubertal boys with 47,XXY have not been well investigated. The influence of hormones on brain development in humans suggests that a positive effect on neurodevelopmental outcome in young boys with XXY may be plausible with hormone replacement therapy. The aim of the study was to investigate retrospectively if an early course of androgen treatment (three injections of testosterone enanthate, 25 mg, each) had an impact on specific domains of neurodevelopmental function in boys with 47,XXY at 36 and 72 months of age. One hundred one boys with a karyotype of 47,XXY had neurodevelopmental assessments. The retrospective chart review resulted in one group (n = 34) who had received androgen treatment during infancy and the second group was untreated (N = 67). Statistical analysis was completed to determine if there was a positive effect from treatment observed at 36 and at 72 months on multiple domains of development. There were significant differences in multiple cognitive domains in the group who received androgen treatment, including multiple measures of language, intellectual, and neuromotor skills. Improved function was observed in neurodevelopmental outcome in boys with 47,XXY at 36 and 72 months who had been treated with a short course of androgen treatment in infancy. Continued research is underway to expand our understanding of the relationship of androgen, brain function, and neurobehavioral and neurodevelopmental outcome in boys with 47,XXY.

Decoding of emotional components in complex communicative situations (irony) and its relation to empathic abilities in male chronic alcoholics: an issue for treatment.

BACKGROUND: Previous research has shown that deficits in the domain of emotions strongly characterize alcoholism. Patients diagnosed with alcoholism show impairments in emotional mimic recognition, as well as in the domain of emotional prosody. These data suggest that male alcoholics might suffer from a generalized emotional impairment associated with dysfunctions in empathy. Taken altogether, those deficits might influence alcoholics' relational domain and their performance in complex communicative situations such as ironic interactions. The present study investigates the ability of chronic male alcoholics to recognize the emotional component of ironic contexts and its relation to the comprehension of ironic meaning as a function of their empathic abilities. METHODS: Forty-four male subjects participated in a story comprehension task. They were asked to read stories with either an ironic or a nonironic ending. Participants were asked to fill in a questionnaire about communicative intentions and the emotional states of the stories' characters. Moreover, the correct comprehension of the ironic meaning was assessed through a self-reported questionnaire and related to the empathy quotient (EQ) which was measured in a preexperimental phase. RESULTS: Alcoholic subjects showed a lower EQ in comparison to healthy subjects and recognized significant fewer ironic endings. Social skills results were particularly impaired. The correlation between EQ and ironic endings recognition was significant. Moreover, alcoholics showed a tendency to attribute positive emotions to both ironic and nonironic contexts, showing an opposite pattern in comparison with control subjects who tended to associate negative emotions to ironic contexts. CONCLUSIONS: The present study indicates that emotional recognition deficits that have been previously observed in chronic alcoholics extend to complex interactive contexts. This deficit is associated with a more general impairment of empathy, especially in its social skill component. Clinical implications of the present results are discussed.

Two concepts of therapeutic optimism.

Researchers and ethicists have long been concerned about the expectations for direct medical benefit expressed by participants in early phase clinical trials. Early work on the issue considered the possibility that participants misunderstand the purpose of clinical research or that they are misinformed about the prospects for medical benefit from these trials. Recently, however, attention has turned to the possibility that research participants are simply expressing optimism or hope about their participation in these trials. The ethical significance of this therapeutic optimism remains unclear. This paper argues that there are two distinct phenomena that can be associated with the term 'therapeutic optimism'-one is ethically benign and the other is potentially worrisome. Distinguishing these two phenomena is crucial for understanding the nature and ethical significance of therapeutic optimism. The failure to draw a distinction between these phenomena also helps to explain why different writers on the topic often speak past one another.

Arsenic and manganese exposure and children's intellectual function.

Recently, epidemiologic studies of developmental neurotoxicology have been challenged to increase focus on co-exposure to multiple toxicants. Earlier reports, including our own work in Bangladesh, have demonstrated independent associations between neurobehavioral function and exposure to both arsenic (As) and manganese (Mn) in school-aged children. Our earlier studies, however, were not designed to examine possible interactive effects of exposure to both As and Mn. To allow investigation of possible synergistic impact of simultaneous exposures, we recruited a new sample of 299 8-11 year old children, stratified by design on As (above and below 10 µg/L) and Mn (above and below 500 µg/L) concentrations of household wells. When adjusted only for each other, both As and Mn in whole blood (BAs; BMn) were significantly negatively related to most WISC-IV subscale scores. With further adjustment for socio-demographic features and ferritin, BMn remained significantly associated with reduced Perceptual Reasoning and Working Memory scores; associations for BAs, and for other subscales, were expectably negative, significantly for Verbal Comprehension. Urinary As (per gram creatinine) was significantly negatively associated with Verbal Comprehension scores, even with adjustment for BMn and other contributors. Mn by As interactions were not significant in adjusted or unadjusted models (all p's>0.25). Findings are consistent with other reports documenting adverse impact of both As and Mn exposure on child developmental outcomes, although associations appear muted at these relatively low exposure levels.

The Australian brain and cognition and antiepileptic drugs study: IQ in school-aged children exposed to sodium valproate and polytherapy.

Prenatal exposure to sodium valproate (VPA) and polytherapy has been linked with increased risk of birth defects and cognitive impairment in young children. We evaluated the cognitive impact of prenatal exposure to VPA and polytherapy in school-aged children. Fifty-seven children exposed to VPA (n = 23), polytherapy with VPA (n = 15), or polytherapy without VPA (n = 19) were assessed using the Wechsler Intelligence Scale for Children--Fourth Edition. Information on maternal epilepsy, pregnancy, and medical history was obtained prospectively through the Australian Pregnancy Register for Women with Epilepsy and Allied Disorders. All groups had elevated frequencies of Extremely Low (<70) or Borderline (70-79) Full-Scale IQ (15.8-40.0%). Verbal Comprehension and Working Memory scores in all groups fell significantly below the standardized test mean, while Perceptual Reasoning and Processing Speed scores were relatively intact. Multivariate analysis of covariance analysis revealed significant main effects of VPA on Verbal Comprehension and Working Memory, and of polytherapy on Verbal Comprehension and Processing Speed. Our results suggest that VPA has a dose-dependent negative impact on verbal intellectual abilities, and may also affect working memory. The possibility that inclusion of VPA in many polytherapy regimens may underlie reduced mean scores of polytherapy-exposed children is discussed.

Everyday and prospective memory deficits in ecstasy/polydrug users.

The impact of ecstasy/polydrug use on real-world memory (i.e. everyday memory, cognitive failures and prospective memory [PM]) was investigated in a sample of 42 ecstasy/polydrug users and 31 non-ecstasy users. Laboratory-based PM tasks were administered along with self-reported measures of PM to test whether any ecstasy/polydrug-related impairment on the different aspects of PM was present. Self-reported measures of everyday memory and cognitive failures were also administered. Ecstasy/polydrug associated deficits were observed on both laboratory and self-reported measures of PM and everyday memory. The present study extends previous research by demonstrating that deficits in PM are real and cannot be simply attributed to self-misperceptions. The deficits observed reflect some general capacity underpinning both time- and event-based PM contexts and are not task specific. Among this group of ecstasy/polydrug users recreational use of cocaine was also prominently associated with PM deficits. Further research might explore the differential effects of individual illicit drugs on real-world memory.

Awareness of deficits during intracarotid anesthetic procedures in epilepsy: Comparisons of motor, naming, and comprehension awareness under amobarbital versus under etomidate.

Awareness of deficits is often impaired following disruption of the right hemisphere. Intracarotid anesthetic procedures (IAPs) represent a unique method by which we can assess functioning of each hemisphere in isolation. We used this technique to explore deficits of awareness of specific functions-motor ability, naming, and comprehension-in patients with temporal lobe epilepsy. Some patients were injected with amobarbital, whereas others were injected with etomidate. We found that injection into the right hemisphere, or epileptogenic focus in the right hemisphere following injection in the left, resulted in the lowest levels of motor awareness. We also found a higher level of awareness for expressive language deficits and less awareness for receptive language deficits. Comparison of etomidate and amobarbital suggested more awareness following injection of etomidate. We discuss how these findings contribute to our understanding of the right hemisphere's special role in awareness, and how research in other disorders and in comparative neurology has shaped our conceptualization of the neuroanatomy of insight.

Out for a smoke: the impact of cigarette craving on zoning out during reading.

Cigarette craving has powerful effects on cognitive functioning, which may promote smoking behavior and relapse. One area of cognition that has had little impact on craving research is human consciousness. Developments in consciousness research using a mindless-reading paradigm permit examination of the effects of craving on both the occurrence and the awareness of mental lapses. Forty-four smokers, who were either nicotine deprived (crave condition) or nondeprived (low-crave condition), performed a mindless-reading task. This task assesses both self-caught and probe-caught mind-wandering episodes to distinguish between lapses that are within and outside of awareness. Compared with the low cravers, those in the cigarette-crave condition were significantly more likely to acknowledge that their mind was wandering when they were probed. When we adjusted for this more-than-threefold increase in zoning out, craving also lowered the probability of catching oneself. Results suggest that craving simultaneously increases mental lapses while reducing the metacognitive capacity to notice them.

The influence of idiomatic salience during the comprehension of ambiguous idioms by patients with schizophrenia.

This study investigates whether figurative comprehension in schizophrenia is influenced by the salience of idiomatic meaning, and whether it is affected by clinical and demographic factors and IQ. Twenty-seven schizophrenic patients and 25 healthy participants performed a semantic relatedness judgement task which required the comprehension of idioms with two plausible meanings (literal and figurative). The study also used literal expressions. The figurative meaning of the idioms was less salient (ILS), more salient (IFS), or equally salient (IES) compared to the literal meaning. The results showed "a salience effect" (i.e., all participants understood the salient meanings better than the less salient meanings). There was also a "figurativeness effect" (i.e., healthy individuals understood the figurative meaning of IES better than the literal meaning but not schizophrenic patients). In patients, their thought disorder influenced the figurative comprehension of IFS. The verbal IQ influenced the figurative comprehension of ILS. The thought disorder, the verbal IQ, and the educational level influenced the figurative comprehension of IES. The patients' clinically evaluated concretism was associated with a reduced figurative comprehension of IFS and IES evaluated at a cognitive level. The results are discussed in relation to cognitive mechanisms which underscore figurative comprehension in schizophrenia.

[Graphomotor functions in children with attention deficit hyperactivity disorder (ADHD)]. / Funkcje grafomotoryczne u dzieci z zespolem nadpobudliwosci psychoruchowej (ADHD).

The present article is a review of studies concerning graphomotor functions (handwriting) in children with attention deficit hyperactivity disorder (ADHD) and the stimulant-induced (methylphenidate) alterations of both qualitative and quantitative aspects of handwriting. This review indicates an interaction between attentional functions and handwriting in ADHD children treated with methylphenidate. The comparison of writing movements of children on and off methylphenidate revealed that medication resulted in improved handwriting. However, kinematic analysis showed a deterioration in handwriting fluency on methylphenidate. A number of studies have demonstrated that children with ADHD display deficits regarding attentional functions. Treatment with methylphenidate has been shown to induce improvements of various attentional functions. Children with ADHD may use their increased attentional capacities to focus on skills (e.g. handwriting) that are independent of conscious control or may even be disturbed by attention.

Dopaminergic neuromodulation of semantic processing: a 4-T FMRI study with levodopa.

There is emerging evidence that alterations in dopaminergic transmission can influence semantic processing, yet the neural mechanisms involved are unknown. The influence of levodopa (L-DOPA) on semantic priming was investigated in healthy individuals (n = 20) using event-related functional magnetic resonance imaging with a randomized, double-blind crossover design. Critical prime-target pairs consisted of a lexical ambiguity prime and 1) a target related to the dominant meaning of the prime (e.g., bank-money), 2) a target related to the subordinate meaning (e.g., fence-sword), or 3) an unrelated target (e.g., ball-desk). Behavioral data showed that both dominant and subordinate meanings were primed on placebo. In contrast, there was preserved priming of dominant meanings and no significant priming of subordinate meanings on L-DOPA, the latter associated with decreased anterior cingulate and dorsal prefrontal cortex activity. Dominant meaning activation on L-DOPA was associated with increased activity in the left rolandic operculum and left middle temporal gyrus. These findings suggest that L-DOPA enhances frequency-based semantic focus via prefrontal and temporal modulation of automatic semantic priming and through engagement of anterior cingulate mechanisms supporting attentional/controlled priming.

Assessing the effect of docosahexaenoic acid on cognitive functions in healthy, preschool children: a randomized, placebo-controlled, double-blind study.

The utility of multicenter cognitive test methodology and resultant outcomes of supplementation with docosahexaenoic acid in healthy 4-year-old children was evaluated in a randomized, placebo-controlled, double-blind study. Subjects received 400-mg/d docosahexaenoic acid (n = 85) or matching placebo (n = 90) in capsules for 4 months. Cognitive tests included the Leiter-R Test of Sustained Attention, Peabody Picture Vocabulary Test, Day-Night Stroop Test, and Conners' Kiddie Continuous Performance Test. The relationship of docosahexaenoic acid levels in capillary whole blood from a subsample (n = 93) with scores on cognitive tests was evaluated. For each test, results indicated that changes from baseline to end of treatment were not statistically significantly different between the docosahexaenoic acid group and the placebo group. Regression analysis, however, yielded a statistically significant positive (P = .018) association between the blood level of docosahexaenoic acid and higher scores on the Peabody Picture Vocabulary Test, a test of listening comprehension and vocabulary acquisition.

Estrogen and comprehension of metaphoric speech in women suffering from schizophrenia: results of a double-blind, placebo-controlled trial.

OBJECTIVE: The effects of estrogen on comprehension of metaphoric speech, word fluency, and verbal ability were investigated in women suffering from schizophrenia. The issue of estrogen-dependent neuropsychological performance could be highly relevant because women with schizophrenia frequently suffer from hypoestrogenism. METHOD: A placebo-controlled, double-blind, crossover study using 17beta-estradiol for replacement therapy and as an adjunct to a naturalistic maintenance antipsychotic treatment was carried out over a period of 8 months. Nineteen women (mean age = 38.0 years, SD = 9.9 years) with schizophrenia were included in the study. Comprehension of metaphoric speech was measured by a lexical decision paradigm, word fluency, and verbal ability by a paper-and-pencil test. RESULTS: Significant improvement was seen for the activation of metaphoric meaning during estrogen treatment (P = .013); in contrast, no difference was found for the activation of concrete meaning under this condition. Verbal ability and word fluency did not improve under estrogen replacement therapy either. CONCLUSIONS: This is the very first study based on estrogen intervention instead of the physiological hormone changes to examine the estrogen effects on neuropsychological performance in women with schizophrenia. In addition, it is the first time that the effect of estrogen on metaphoric speech comprehension was investigated in this context. While in a previous study estrogen therapy as adjunct to a naturalistic maintenance treatment with antipsychotics did not show an effect on psychopathology measured by a rating scale, a significant effect of estrogen on the comprehension of metaphoric speech and/or concretism, a main feature of schizophrenic thought and language disturbance, was found in the present study. Because the improvement of formal thought disorders and language disturbances is crucial for social integration of patients with schizophrenia, the results may have implications for the treatment of these individuals.