Heritability of subcortical volumetric traits in mesial temporal lobe epilepsy.

OBJECTIVES: We aimed to 1) determine if subcortical volume deficits are common to mesial temporal lobe epilepsy (MTLE) patients and their unaffected siblings 2) assess the suitability of subcortical volumetric traits as endophenotypes for MTLE. METHODS: MRI-based volume measurements of the hippocampus, amygdala, thalamus, caudate, putamen and pallidium were generated using an automated brain reconstruction method (FreeSurfer) for 101 unrelated 'sporadic' MTLE patients [70 with hippocampal sclerosis (MTLE+HS), 31 with MRI-negative TLE], 83 unaffected full siblings of patients and 86 healthy control subjects. Changes in the volume of subcortical structures in patients and their unaffected siblings were determined by comparison with healthy controls. Narrow sense heritability was estimated ipsilateral and contralateral to the side of seizure activity. RESULTS: MTLE+HS patients displayed significant volume deficits across the hippocampus, amygdala and thalamus ipsilaterally. In addition, volume loss was detected in the putamen bilaterally. These volume deficits were not present in the unaffected siblings of MTLE+HS patients. Ipsilaterally, the heritability estimates were dramatically reduced for the volume of the hippocampus, thalamus and putamen but remained in the expected range for the amygdala. MRI-negative TLE patients and their unaffected siblings showed no significant volume changes across the same structures and heritability estimates were comparable with calculations from a healthy population. CONCLUSIONS: The findings indicate that volume deficits for many subcortical structures in 'sporadic' MTLE+HS are not heritable and likely related to acquired factors. Therefore, they do not represent suitable endophenotypes for MTLE+HS. The findings also support the view that, at a neuroanatomical level, MTLE+HS and MRI-negative TLE represent two distinct forms of MTLE

Structural neuroimaging correlates of allelic variation of the BDNF val66met polymorphism.

BACKGROUND: The brain-derived neurotrophic factor (BDNF) val66met polymorphism is associated with altered activity dependent secretion of BDNF and a variable influence on brain morphology and cognition. Although a met-dose effect is generally assumed, to date the paucity of met-homozygotes have limited our understanding of the role of the met-allele on brain structure. METHODS: To investigate this phenomenon, we recruited sixty normal healthy subjects, twenty in each genotypic group (val/val, val/met and met/met). Global and local morphology were assessed using voxel based morphometry and surface reconstruction methods. White matter organisation was also investigated using tract-based spatial statistics and constrained spherical deconvolution tractography. RESULTS: Morphological analysis revealed an "inverted-U" shaped profile of cortical changes, with val/met heterozygotes most different relative to the two homozygous groups. These results were evident at a global and local level as well as in tractography analysis of white matter fibre bundles. CONCLUSION: In contrast to our expectations, we found no evidence of a linear met-dose effect on brain structure, rather our results support the view that the heterozygotic BDNF val66met genotype is associated with cortical morphology that is more distinct from the BDNF val66met homozygotes. These results may prove significant in furthering our understanding of the role of the BDNF met-allele in disorders such as Alzheimer's disease and depression

Widespread extrahippocampal NAA/(Cr+Cho) abnormalities in TLE with and without mesial temporal sclerosis

MR spectroscopy has demonstrated extrahippocampal NAA/(Cr+Cho) reductions in medial temporal lobe epilepsy with (TLE-MTS) and without (TLE-no) mesial temporal sclerosis. Because of the limited brain coverage of those previous studies, it was, however, not possible to assess differences in the distribution and extent of these abnormalities between TLE-MTS and TLE-no. This study used a 3D whole brain echoplanar spectroscopic imaging (EPSI) sequence to address the following questions: (1) Do TLE-MTS and TLE-no differ regarding severity and distribution of extrahippocampal NAA/(Cr+Cho) reductions? (2) Do extrahippocampal NAA/(Cr+Cho) reductions provide additional information for focus lateralization? Forty-three subjects (12 TLE-MTS, 13 TLE-no, 18 controls) were studied with 3D EPSI. Statistical parametric mapping (SPM2) was used to identify regions of significantly decreased NAA/(Cr+Cho) in TLE groups and in individual patients. TLE-MTS and TLE-no had widespread extrahippocampal NAA/(Cr+Cho) reductions. NAA/(Cr+Cho) reductions had a bilateral fronto-temporal distribution in TLE-MTS and a more diffuse, less well defined distribution in TLE-no. Extrahippocampal NAA/(Cr+Cho) decreases in the single subject analysis showed a large inter-individual variability and did not provide additional focus lateralizing information. Extrahippocampal NAA/(Cr+Cho) reductions in TLE-MTS and TLE-no are neither focal nor homogeneous. This reduces their value for focus lateralization and suggests a heterogeneous etiology of extrahippocampal spectroscopic metabolic abnormalities in TLE

Social anxiety in pre-adolescent children: what do we know about maintenance?

The cognitive theory of social anxiety disorder (SAD) is one of the most widely accepted accounts of the maintenance of the disorder in adults, yet it remains unknown if, or to what extent, the same cognitive and behavioral maintenance mechanisms that occur in adult SAD also apply to SAD among pre-adolescent children. In contrast to the adult literature, current models of SAD in children mostly account for etiology and maintenance processes are given limited attention. Consequently, their clinical utility for the treatment of SAD in children may be limited. This narrative review, first, critically examines the different theoretical conceptualizations of the maintenance of social anxiety in the child and adult literature and illustrates how these have resulted in different treatment approaches and clinical understanding. Second, it reviews the available evidence relating to hypotheses about the maintenance of SAD in children as derived from adult cognitive and etiological models. Third, it highlights the need to attend directly to child specific maintenance mechanisms in SAD, to draw on cognitive theory, and to account for the influence of childhood-specific contextual (e.g. family and school-based interactions) and developmental factors on children's social experiences

State of the climate in 2018

In 2018, the dominant greenhouse gases released into Earth’s atmosphere—carbon dioxide, methane, and nitrous oxide—continued their increase. The annual global average carbon dioxide concentration at Earth’s surface was 407.4 ± 0.1 ppm, the highest in the modern instrumental record and in ice core records dating back 800 000 years. Combined, greenhouse gases and several halogenated gases contribute just over 3 W m−2 to radiative forcing and represent a nearly 43% increase since 1990. Carbon dioxide is responsible for about 65% of this radiative forcing. With a weak La Niña in early 2018 transitioning to a weak El Niño by the year’s end, the global surface (land and ocean) temperature was the fourth highest on record, with only 2015 through 2017 being warmer. Several European countries reported record high annual temperatures. There were also more high, and fewer low, temperature extremes than in nearly all of the 68-year extremes record. Madagascar recorded a record daily temperature of 40.5°C in Morondava in March, while South Korea set its record high of 41.0°C in August in Hongcheon. Nawabshah, Pakistan, recorded its highest temperature of 50.2°C, which may be a new daily world record for April. Globally, the annual lower troposphere temperature was third to seventh highest, depending on the dataset analyzed. The lower stratospheric temperature was approximately fifth lowest. The 2018 Arctic land surface temperature was 1.2°C above the 1981–2010 average, tying for third highest in the 118-year record, following 2016 and 2017. June’s Arctic snow cover extent was almost half of what it was 35 years ago. Across Greenland, however, regional summer temperatures were generally below or near average. Additionally, a satellite survey of 47 glaciers in Greenland indicated a net increase in area for the first time since records began in 1999. Increasing permafrost temperatures were reported at most observation sites in the Arctic, with the overall increase of 0.1°–0.2°C between 2017 and 2018 being comparable to the highest rate of warming ever observed in the region. On 17 March, Arctic sea ice extent marked the second smallest annual maximum in the 38-year record, larger than only 2017. The minimum extent in 2018 was reached on 19 September and again on 23 September, tying 2008 and 2010 for the sixth lowest extent on record. The 23 September date tied 1997 as the latest sea ice minimum date on record. First-year ice now dominates the ice cover, comprising 77% of the March 2018 ice pack compared to 55% during the 1980s. Because thinner, younger ice is more vulnerable to melting out in summer, this shift in sea ice age has contributed to the decreasing trend in minimum ice extent. Regionally, Bering Sea ice extent was at record lows for almost the entire 2017/18 ice season. For the Antarctic continent as a whole, 2018 was warmer than average. On the highest points of the Antarctic Plateau, the automatic weather station Relay (74°S) broke or tied six monthly temperature records throughout the year, with August breaking its record by nearly 8°C. However, cool conditions in the western Bellingshausen Sea and Amundsen Sea sector contributed to a low melt season overall for 2017/18. High SSTs contributed to low summer sea ice extent in the Ross and Weddell Seas in 2018, underpinning the second lowest Antarctic summer minimum sea ice extent on record. Despite conducive conditions for its formation, the ozone hole at its maximum extent in September was near the 2000–18 mean, likely due to an ongoing slow decline in stratospheric chlorine monoxide concentration. Across the oceans, globally averaged SST decreased slightly since the record El Niño year of 2016 but was still far above the climatological mean. On average, SST is increasing at a rate of 0.10° ± 0.01°C decade−1 since 1950. The warming appeared largest in the tropical Indian Ocean and smallest in the North Pacific. The deeper ocean continues to warm year after year. For the seventh consecutive year, global annual mean sea level became the highest in the 26-year record, rising to 81 mm above the 1993 average. As anticipated in a warming climate, the hydrological cycle over the ocean is accelerating: dry regions are becoming drier and wet regions rainier. Closer to the equator, 95 named tropical storms were observed during 2018, well above the 1981–2010 average of 82. Eleven tropical cyclones reached Saffir–Simpson scale Category 5 intensity. North Atlantic Major Hurricane Michael’s landfall intensity of 140 kt was the fourth strongest for any continental U.S. hurricane landfall in the 168-year record. Michael caused more than 30 fatalities and $25 billion (U.S. dollars) in damages. In the western North Pacific, Super Typhoon Mangkhut led to 160 fatalities and$6 billion (U.S. dollars) in damages across the Philippines, Hong Kong, Macau, mainland China, Guam, and the Northern Mariana Islands. Tropical Storm Son-Tinh was responsible for 170 fatalities in Vietnam and Laos. Nearly all the islands of Micronesia experienced at least moderate impacts from various tropical cyclones. Across land, many areas around the globe received copious precipitation, notable at different time scales. Rodrigues and Réunion Island near southern Africa each reported their third wettest year on record. In Hawaii, 1262 mm precipitation at Waipā Gardens (Kauai) on 14–15 April set a new U.S. record for 24-h precipitation. In Brazil, the city of Belo Horizonte received nearly 75 mm of rain in just 20 minutes, nearly half its monthly average. Globally, fire activity during 2018 was the lowest since the start of the record in 1997, with a combined burned area of about 500 million hectares. This reinforced the long-term downward trend in fire emissions driven by changes in land use in frequently burning savannas. However, wildfires burned 3.5 million hectares across the United States, well above the 2000–10 average of 2.7 million hectares. Combined, U.S. wildfire damages for the 2017 and 2018 wildfire seasons exceeded $40 billion (U.S. dollars)

Evaluating learning technologies: frameworks and case studies

Evaluation frameworks have been developed for studying learning technology. In this paper, we review their application to a number of evaluation projects, reflect on recent developments in the area of evaluation and illustrate how these frameworks have been applied by reflecting on the methods employed in three contrasting case studies. Each case study is an evaluation of an innovative use of information technology. The first case study describes the evaluation activities related to the technology-enhanced components of an introductory physics course for distance learners, 'Physical World', focusing on the evaluation of multimedia tutorials. The second case study discusses an evaluation project focusing on the impact of networked technologies on learning at school level, the 'ImpaCT2' evaluation, and describes the methods used in tracking use of technology both at school and at home. The third case study involves the evaluation of a history website on a full time higher education course, 'The History of the USA'

Structural brain network analysis in families multiply affected with bipolar I disorder

Disrupted structural connectivity is associated with psychiatric illnesses including bipolar disorder (BP). Here we use structural brain network analysis to investigate connectivity abnormalities in multiply affected BP type I families, to assess the utility of dysconnectivity as a biomarker and its endophenotypic potential. Magnetic resonance diffusion images for 19 BP type I patients in remission, 21 of their first degree unaffected relatives, and 18 unrelated healthy controls underwent tractography. With the automated anatomical labelling atlas being used to define nodes, a connectivity matrix was generated for each subject. Network metrics were extracted with the Brain Connectivity Toolbox and then analysed for group differences, accounting for potential confounding effects of age, gender and familial association. Whole brain analysis revealed no differences between groups. Analysis of specific mainly frontal regions, previously implicated as potentially endophenotypic by functional magnetic resonance imaging analysis of the same cohort, revealed a significant effect of group in the right medial superior frontal gyrus and left middle frontal gyrus driven by reduced organisation in patients compared with controls. The organisation of whole brain networks of those affected with BP I does not differ from their unaffected relatives or healthy controls. In discreet frontal regions, however, anatomical connectivity is disrupted in patients but not in their unaffected relatives. (C) 2015 Elsevier Ireland Ltd. All rights reserved

Grey and white matter abnormalities in temporal lobe epilepsy with and without mesial temporal sclerosis

Temporal lobe epilepsy with (TLE-mts) and without (TLE-no) mesial temporal sclerosis display different patterns of cortical neuronal loss, suggesting that the distribution of white matter damage may also differ between the sub-groups. The purpose of this study was to examine patterns of white matter damage in TLE-mts and TLE-no and to determine if identified changes are related to neuronal loss at the presumed seizure focus. The 4 T diffusion tensor imaging (DTI) and T1-weighted data were acquired for 22 TLE-mts, 21 TLE-no and 31 healthy controls. Tract-based spatial statistics (TBSS) was used to compare fractional anisotropy (FA) maps and voxel-based morphometry (VBM) was used to identify grey matter (GM) volume atrophy. Correlation analysis was conducted between the FA maps and neuronal loss at the presumed seizure focus. In TLE-mts, reduced FA was identified in the genu, body and splenium of the corpus callosum, bilateral corona radiata, cingulum, external capsule, ipsilateral internal capsule and uncinate fasciculus. In TLE-no, FA decreases were identified in the genu, the body of the corpus callosum and ipsilateral anterior corona radiata. The FA positively correlated with ipsilateral hippocampal volume. Widespread extra-focal GM atrophy was associated with both sub-groups. Despite widespread and extensive GM atrophy displaying different anatomical patterns in both sub-groups, TLE-mts demonstrated more extensive FA abnormalities than TLE-no. The microstructural organization in the corpus callosum was related to hippocampal volume in both patients and healthy subjects demonstrating the association of these distal regions