Improved frontoparietal white matter integrity in overweight children is associated with attendance at an after-school exercise program.

Aerobic fitness is associated with white matter integrity (WMI) in adults as measured by diffusion tensor imaging (DTI). This study examined the effect of an 8-month exercise intervention on WMI in children. Participants were 18 sedentary, overweight (BMI≥85th percentile) 8- to 11-year-old children (94% Black), randomly assigned to either an aerobic exercise (n=10) or sedentary attention control group (n=8). Each group was offered an instructor-led after-school program every school day for approximately 8 months. Before and after the program, all subjects participated in DTI scans. Tractography was conducted to isolate the superior longitudinal fasciculus and investigate whether the exercise intervention affected WMI in this region. There was no group by time interaction for WMI in the superior longitudinal fasciculus. There was a group by time by attendance interaction, however, such that higher attendance at the exercise intervention, but not the control intervention, was associated with increased WMI. Heart rate and the total dose of exercise correlated with WMI changes in the exercise group. In the overall sample, increased WMI was associated with improved scores on a measure of attention and improved teacher ratings of executive function. This study indicates that participating in an exercise intervention improves WMI in children as compared to a sedentary after-school program.

Microstructural differences in visual white matter tracts in people with aniridia.

Aniridia is a panocular disorder characterized chiefly by iris hypoplasia. Most cases result from mutations of the PAX6 gene, which is important in both eye and brain development. In addition to ocular alterations, differences in global brain volume and functional connectivity have been reported in humans with aniridia. Understanding neural alterations in aniridia may require examination of possible differences in white matter structure, as few studies have assessed white matter in this population. The current study utilized diffusion-weighted imaging to assess white matter structure in 11 people with aniridia and 11 healthy comparison participants, matched for sex and age. A map of the local connectome was calculated to compare quantitative anisotropy (QA), an index of white matter tract density, in all white matter voxels, revealing subcomponents of white matter tracts with differing QA between people with aniridia and healthy comparisons. The analysis indicated that QA was lower for people with aniridia in portions of bilateral optic tract [t(20)=-4.23, P=0.001, d=-1.80], bilateral optic radiation [t(20)=-4.06, P=0.001, d=-1.73], forceps major [t(20)=-3.65, P=0.002, d=-1.55], bilateral superior longitudinal fasciculus [left: t(20)=-3.15, P=0.005, d=-1.34; right, t(20)=-4.28, P<0.001, d=-1.83], and right posterior corona radiata [t(20)=-3.19, P=0.006, d=-1.36]. These differences demonstrate that white matter structure is altered in people with aniridia in both visual tracts and associated posterior visual pathways.

A Multi-omic Association Study of Trimethylamine N-Oxide.

Trimethylamine N-oxide (TMAO) is a circulating metabolite that has been implicated in the development of atherosclerosis and cardiovascular disease (CVD). In this paper, we identify blood markers, metabolites, proteins, gut microbiota patterns, and diets that are significantly associated with levels of plasma TMAO. We find that kidney markers are strongly associated with TMAO and identify CVD-related proteins that are positively correlated with TMAO. We show that metabolites derived by the gut microbiota are strongly correlated with TMAO and that the magnitude of this correlation varies with kidney function. Moreover, we identify diet-associated patterns in the microbiome that are correlated with TMAO. These findings suggest that both the process of TMAO accumulation and the mechanism by which TMAO promotes atherosclerosis are a complex interplay between diet and the microbiome on one hand and other system-level factors such as circulating proteins, metabolites, and kidney function.

Differentiating SCT and inattentive symptoms in ADHD using fMRI measures of cognitive control.

Attention Deficit/Hyperactivity Disorder (ADHD) is associated with different impairment profiles in the symptom domains of hyperactivity/impulsivity and/or inattention. An additional symptom domain of sluggish cognitive tempo (SCT) has also been proposed. Although there is a degree of correlation between the SCT symptom domain and inattention, it has been proposed as a distinct disorder independent of ADHD. The objective of this study was to examine the neural substrates of cue-related preparatory processes associated with SCT symptoms versus inattentive symptoms in a group of adolescents with ADHD. We also compared cue-related effects in the entire ADHD group compared with a group of typically developing (TD) peers. A modified cued flanker paradigm and fMRI examined brain activity associated with attention preparation and motor response preparation. Between group contrasts between the ADHD and TD group revealed significant hypoactivity in the ADHD group during general attention preparation in the supplementary motor area (SMA) and in the right superior parietal lobe (SPL) during response preparation. In the ADHD group, greater numbers of SCT symptoms were associated with hypoactivity in the left SPL to cues in general whereas greater numbers of inattentive symptoms were associated with greater activity in the SMA to cues that provided no information and less activity in the thalamus during response preparation. Hypoactivity in the SPL with increasing SCT symptoms may be associated with impaired reorienting or shifting of attention. Altered activity in the SMA and thalamus with increasing inattention may be associated with a general problem with response preparation, which may also reflect inefficient processing of the response preparation cue. Our results support a degree of differentiation between SCT and inattentive symptom profiles within adolescents with ADHD.

Individual differences in working memory moderate the relationship between prosaccade latency and antisaccade error rate.

Cognitive control is required for flexible responses in changing environments and can be assessed by measuring antisaccade error rate. Considerable variance in antisaccade error rate is observed in healthy participants, which motivated the current study to explore the cognitive factors affecting antisaccade performance. Relationships exist between prosaccade latency and antisaccade error rate, with faster prosaccade latencies linked to more antisaccade errors. Individual differences in working memory also impact saccadic performance. The current study tested the relationships among prosaccade latency, antisaccade error rate, and working memory in 153 healthy participants. Correlation and multiple regression analyses demonstrated that prosaccade latency predicted antisaccade error rate, and working memory moderated this relationship. These results may help elucidate individual differences in cognitive control among healthy individuals.

Antisaccade-related brain activation in children with attention-deficit/hyperactivity disorder--A pilot study.

While antisaccade paradigms invoke circuitry associated with cognitive control and attention-deficit/hyperactivity disorder (ADHD), there is a dearth of functional magnetic resonance imaging (fMRI) investigations using antisaccade tasks among children with ADHD. Neural correlates associated with antisaccade performance were examined with fMRI in 11 children with ADHD (10 medicated) matched to 11 typically developing children. Significantly greater brain activation in regions in right dorsolateral prefrontal cortex and caudate nucleus was observed in children with ADHD relative to the control group. This pattern separated the children into their respective groups in a taxonomic manner. Sensitivity analyses probing comorbidity and medication-specific effects showed that results were consistent; however, the caudate nucleus difference was only detectable in the full sample, or in subsets with a more relaxed cluster threshold. Antisaccade performance did not significantly differ between the groups, perhaps as a result of greater brain activation or medication effects in the ADHD group. Thus, antisaccade paradigms may have sensitivity and specificity for the investigation of cognitive control deficits and associated neural correlates in ADHD, and may contribute towards the development of new treatment approaches for children with the disorder.

Increased functional connectivity in intrinsic neural networks in individuals with aniridia.

Mutations affecting the PAX6 gene result in aniridia, a condition characterized by the lack of an iris and other panocular defects. Among humans with aniridia, structural abnormalities also have been reported within the brain. The current study examined the functional implications of these deficits through "resting state" or task-free functional magnetic resonance imaging (fMRI) in 12 individuals with aniridia and 12 healthy age- and gender-matched controls. Using independent components analysis (ICA) and dual regression, individual patterns of functional connectivity associated with three intrinsic connectivity networks (ICNs; executive control, primary visual, and default mode) were compared across groups. In all three analyses, the aniridia group exhibited regions of greater connectivity correlated with the network, while the controls did not show any such regions. These differences suggest that individuals with aniridia recruit additional neural regions to supplement function in critical intrinsic networks, possibly due to inherent structural or sensory abnormalities related to the disorder.

The relationship between uncinate fasciculus white matter integrity and verbal memory proficiency in children.

During childhood, verbal learning and memory are important for academic performance. Recent functional MRI studies have reported on the functional correlates of verbal memory proficiency, but few have reported the underlying structural correlates. The present study sought to test the relationship between fronto-temporal white matter integrity and verbal memory proficiency in children. Diffusion weighted images were collected from 17 Black children (age 8-11 years) who also completed the California Verbal Learning Test. To index white matter integrity, fractional anisotropy values were calculated for bilateral uncinate fasciculus. The results revealed that low anisotropy values corresponded to poor verbal memory, whereas high anisotropy values corresponded to significantly better verbal memory scores. These findings suggest that a greater degree of myelination and cohesiveness of axonal fibers in uncinate fasciculus underlie better verbal memory proficiency in children.

An 8-month exercise intervention alters frontotemporal white matter integrity in overweight children.

In childhood, excess adiposity and low fitness are linked to poor academic performance, lower cognitive function, and differences in brain structure. Identifying ways to mitigate obesity-related alterations is of current clinical importance. This study examined the effects of an 8-month exercise intervention on the uncinate fasciculus, a white matter fiber tract connecting frontal and temporal lobes. Participants consisted of 18 unfit, overweight 8- to 11-year-old children (94% Black) who were randomly assigned to either an aerobic exercise (n = 10) or a sedentary control group (n = 8). Before and after the intervention, all subjects participated in a diffusion tensor MRI scan. Tractography was conducted to isolate the uncinate fasciculus. The exercise group showed improved white matter integrity as compared to the control group. These findings are consistent with an emerging literature suggesting beneficial effects of exercise on white matter integrity.

An 8-month randomized controlled exercise trial alters brain activation during cognitive tasks in overweight children.

OBJECTIVE: Children who are less fit reportedly have lower performance on tests of cognitive control and differences in brain function. This study examined the effect of an exercise intervention on brain function during two cognitive control tasks in overweight children. DESIGN AND METHODS: Participants included 43 unfit, overweight (BMI ≥ 85th percentile) children 8- to 11-years old (91% Black), who were randomly divided into either an aerobic exercise (n = 24) or attention control group (n = 19). Each group was offered a separate instructor-led after-school program every school day for 8 months. Before and after the program, all children performed two cognitive control tasks during functional magnetic resonance imaging (fMRI): antisaccade and flanker. RESULTS: Compared to the control group, the exercise group decreased activation in several regions supporting antisaccade performance, including precentral gyrus and posterior parietal cortex, and increased activation in several regions supporting flanker performance, including anterior cingulate and superior frontal gyrus. CONCLUSIONS: Exercise may differentially impact these two task conditions, or the paradigms in which cognitive control tasks were presented may be sensitive to distinct types of brain activation that show different effects of exercise. In sum, exercise appears to alter efficiency or flexible modulation of neural circuitry supporting cognitive control in overweight children.

Neural correlates of behavioral variation in healthy adults' antisaccade performance.

Cognitive control is required for correct antisaccade performance. High antisaccade error rates characterize certain psychiatric disorders, but can be highly variable, even among healthy groups. Antisaccade data were acquired from a large sample of healthy undergraduates, and error rate was quantified. Participants who reliably made few errors (good, n = 13) or many errors (poor, n = 13) were recruited back to perform antisaccades during fMRI acquisition. A data-derived model was used to compare signal between good and poor performers during blocks of antisaccade trials. Behaviorally derived regressors were used to compare signal between good and poor performers during correct and error trials. Results show differential activation in middle frontal gyrus and inferior parietal lobule between good and poor performers, suggesting that failure to recruit these top-down control regions corresponds to poor antisaccade performance in healthy young adults.