Large-scale analysis of structural brain asymmetries during neurodevelopment: Associations with age and sex in 4265 children and adolescents.

Only a small number of studies have assessed structural differences between the two hemispheres during childhood and adolescence. However, the existing findings lack consistency or are restricted to a particular brain region, a specific brain feature, or a relatively narrow age range. Here, we investigated associations between brain asymmetry and age as well as sex in one of the largest pediatric samples to date (n = 4265), aged 1-18 years, scanned at 69 sites participating in the ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) consortium. Our study revealed that significant brain asymmetries already exist in childhood, but their magnitude and direction depend on the brain region examined and the morphometric measurement used (cortical volume or thickness, regional surface area, or subcortical volume). With respect to effects of age, some asymmetries became weaker over time while others became stronger; sometimes they even reversed direction. With respect to sex differences, the total number of regions exhibiting significant asymmetries was larger in females than in males, while the total number of measurements indicating significant asymmetries was larger in males (as we obtained more than one measurement per cortical region). The magnitude of the significant asymmetries was also greater in males. However, effect sizes for both age effects and sex differences were small. Taken together, these findings suggest that cerebral asymmetries are an inherent organizational pattern of the brain that manifests early in life. Overall, brain asymmetry appears to be relatively stable throughout childhood and adolescence, with some differential effects in males and females.

White matter microstructure predicts longitudinal social cognitive outcomes after paediatric traumatic brain injury: a diffusion tensor imaging study.

BACKGROUND: Deficits in social cognition may be among the most profound and disabling sequelae of paediatric traumatic brain injury (TBI); however, the neuroanatomical correlates of longitudinal outcomes in this domain remain unexplored. This study aimed to characterize social cognitive outcomes longitudinally after paediatric TBI, and to evaluate the use of sub-acute diffusion tensor imaging (DTI) to predict these outcomes. METHODS: The sample included 52 children with mild complex-severe TBI who were assessed on cognitive theory of mind (ToM), pragmatic language and affective ToM at 6- and 24-months post-injury. For comparison, 43 typically developing controls (TDCs) of similar age and sex were recruited. DTI data were acquired sub-acutely (mean = 5.5 weeks post-injury) in a subset of 65 children (TBI = 35; TDC = 30) to evaluate longitudinal prospective relationships between white matter microstructure assessed using Tract-Based Spatial Statistics and social cognitive outcomes. RESULTS: Whole brain voxel-wise analysis revealed significantly higher mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) in the sub-acute TBI group compared with TDC, with differences observed predominantly in the splenium of the corpus callosum (sCC), sagittal stratum (SS), dorsal cingulum (DC), uncinate fasciculus (UF) and middle and superior cerebellar peduncles (MCP & SCP, respectively). Relative to TDCs, children with TBI showed poorer cognitive ToM, affective ToM and pragmatic language at 6-months post-insult, and those deficits were related to abnormal diffusivity of the sCC, SS, DC, UF, MCP and SCP. Moreover, children with TBI showed poorer affective ToM and pragmatic language at 24-months post-injury, and those outcomes were predicted by sub-acute alterations in diffusivity of the DC and MCP. CONCLUSIONS: Abnormal microstructure within frontal-temporal, limbic and cerebro-cerebellar white matter may be a risk factor for long-term social difficulties observed in children with TBI. DTI may have potential to unlock early prognostic markers of long-term social outcomes.

Right parietal dysfunction in children with attention deficit hyperactivity disorder, combined type: a functional MRI study.

Attention deficit hyperactivity disorder, combined type (ADHD-CT) is associated with spatial working memory deficits. These deficits are known to be subserved by dysfunction of neural circuits involving right prefrontal, striatal and parietal brain regions. This study determines whether decreased right prefrontal, striatal and parietal activation with a mental rotation task shown in adolescents with ADHD-CT is also evident in children with ADHD-CT. A cross-sectional study of 12 pre-pubertal, right-handed, 8-12-year-old boys with ADHD-CT and 12 pre-pubertal, right-handed, performance IQ-matched, 8-12-year-old healthy boys, recruited from local primary schools, was completed. Participants underwent functional magnetic resonance imaging while performing a mental rotation task that requires spatial working memory. The two groups did not differ in their accuracy or response times for the mental rotation task. The ADHD-CT group showed significantly less activation in right parieto-occipital areas (cuneus and precuneus, BA 19), the right inferior parietal lobe (BA 40) and the right caudate nucleus. Our findings with a child cohort confirm previous reports of right striatal-parietal dysfunction in adolescents with ADHD-CT. This dysfunction suggests a widespread maturational deficit that may be developmental stage independent.

Occupational radiation exposure and mortality: second analysis of the National Registry for Radiation Workers.

The National Registry for Radiation Workers (NRRW) is the largest epidemiological study of UK radiation workers. Following the first analysis published in 1992, a second analysis has been conducted using an enlarged cohort of 124,743 workers, updated dosimetry and personal data for some workers, and a longer follow-up. Overall levels of mortality were found to be less than those expected from national rates; the standardised mortality ratio for all causes was 82, increasing to 89 after adjusting for social class. This 'healthy worker effect' was particularly strong for lung cancer and for some smoking-related non-malignant diseases. Analysis of potential radiation effects involved testing for any trend in mortality risk with external dose, after adjusting for likely confounding factors. For leukaemia, excluding chronic lymphatic leukaemia (CLL), the central estimate of excess relative risk (ERR) per Sv was similar to that estimated for the Japanese atomic bomb survivors at low doses (without the incorporation of a dose-rate correction factor); the corresponding 90% confidence limits for this trend were tighter than in the first analysis, ranging from just under four times the risk estimated at low doses from the Japanese atomic bomb survivors to about zero. For the grouping of all malignancies other than leukaemia, the central estimate of the trend in risk with dose was closer to zero than in the first analysis; also, the 90% confidence limits were tighter than before and included zero. Since results for lung cancer and non-malignant smoking-related diseases suggested the possibility of confounding by smoking, an examination was made, as in the first analysis, of all malignancies other than leukaemia and lung cancer. In this instance the central estimate of the ERR per Sv was similar to that from the A-bomb data (without the incorporation of a dose-rate correction factor), with a 90% confidence interval ranging from about four times the A-bomb value to less than zero. For multiple myeloma there was an indication of an increasing trend in risk with external dose (p = 0.06), although the evidence for this trend disappeared after omitting workers monitored for exposure to internal emitters. The second NRRW analysis provides stronger inferences than the first on occupational radiation exposure and cancer mortality; the 90% confidence intervals for the risk per unit dose are tighter than before, and now exclude values which are greater than four times those seen among the Japanese A-bomb survivors, although they are also generally consistent with an observation of no raised risk. Furthermore, there is evidence, of borderline statistical significance, of an increasing risk for leukaemia excluding CLL, and, as with solid cancers, the data are consistent with the A-bomb findings.