Maternal prepregnancy body mass index and offspring white matter microstructure: results from three birth cohorts

Prepregnancy maternal obesity is a global health problem and has been associated with offspring metabolic and mental ill-health. However, there is a knowledge gap in understanding potential neurobiological factors related to these associations. This study explored the relation between maternal prepregnancy body mass index (BMI) and offspring brain white matter microstructure at the age of 6, 10, and 26 years in three independent cohorts. Maternal BMI was associated with higher FA and lower MD in multiple brain tracts in offspring aged 10 and 26 years, but not at 6 years of age. Future studies should examine whether our observations can be replicated and explore the potential causal nature of the findings.This work was supported by the European Union’s Horizon 2020 research and innovation program [grant agreement no. 633595 DynaHEALTH] and no. 733206 LifeCycle], the Netherlands Organization for Health Research and Development [ZONMW Vici project 016.VICI.170.200]. The PREOBE cohort was funded by Spanish Ministry of Innovation and Science. Junta de Andalucía: Excellence Projects (P06-CTS-02341) and Spanish Ministry of Economy and Competitiveness (BFU2012-40254-C03-01). The first phase of the Generation R Study is made possible by financial support from the Erasmus Medical Centre, the Erasmus University, and the Netherlands Organization for Health Research and Development (ZonMW, grant ZonMW Geestkracht 10.000.1003). The Northern Finland Birth Cohort 1986 is funded by University of Oulu, University Hospital of Oulu, Academy of Finland (EGEA), Sigrid Juselius Foundation, European Commission (EURO-BLCS, Framework 5 award QLG1-CT-2000-01643), NIH/NIMH (5R01MH63706:02

Extra-Visual Functional and Structural Connection Abnormalities in Leber's Hereditary Optic Neuropathy

We assessed abnormalities within the principal brain resting state networks (RSNs) in patients with Leber's hereditary optic neuropathy (LHON) to define whether functional abnormalities in this disease are limited to the visual system or, conversely, tend to be more diffuse. We also defined the structural substrates of fMRI changes using a connectivity-based analysis of diffusion tensor (DT) MRI data. Neuro-ophthalmologic assessment, DT MRI and RS fMRI data were acquired from 13 LHON patients and 13 healthy controls. RS fMRI data were analyzed using independent component analysis and SPM5. A DT MRI connectivity-based parcellation analysis was performed using the primary visual and auditory cortices, bilaterally, as seed regions. Compared to controls, LHON patients had a significant increase of RS fluctuations in the primary visual and auditory cortices, bilaterally. They also showed decreased RS fluctuations in the right lateral occipital cortex and right temporal occipital fusiform cortex. Abnormalities of RS fluctuations were correlated significantly with retinal damage and disease duration. The DT MRI connectivity-based parcellation identified a higher number of clusters in the right auditory cortex in LHON vs. controls. Differences of cluster-centroid profiles were found between the two groups for all the four seeds analyzed. For three of these areas, a correspondence was found between abnormalities of functional and structural connectivities. These results suggest that functional and structural abnormalities extend beyond the visual network in LHON patients. Such abnormalities also involve the auditory network, thus corroborating the notion of a cross-modal plasticity between these sensory modalities in patients with severe visual deficits

Computational Models of Classical Conditioning guest editors’ introduction

In the present special issue, the performance of current computational models of classical conditioning was evaluated under three requirements: (1) Models were to be tested against a list of previously agreed-upon phenomena; (2) the parameters were fixed across simulations; and (3) the simulations used to test the models had to be made available. These requirements resulted in three major products: (a) a list of fundamental classical-conditioning results for which there is a consensus about their reliability; (b) the necessary information to evaluate each of the models on the basis of its ordinal successes in accounting for the experimental data; and (c) a repository of computational models ready to generate simulations. We believe that the contents of this issue represent the 2012 state of the art in computational modeling of classical conditioning and provide a way to find promising avenues for future model development

The role of the myosin ATPase activity in adaptive thermogenesis by skeletal muscle

Resting skeletal muscle is a major contributor to adaptive thermogenesis, i.e., the thermogenesis that changes in response to exposure to cold or to overfeeding. The identification of the “furnace” that is responsible for increased heat generation in resting muscle has been the subject of a number of investigations. A new state of myosin, the super relaxed state (SRX), with a very slow ATP turnover rate has recently been observed in skeletal muscle (Stewart et al. in Proc Natl Acad Sci USA 107:430–435, 2010). Inhibition of the myosin ATPase activity in the SRX was suggested to be caused by binding of the myosin head to the core of the thick filament in a structural motif identified earlier by electron microscopy. To be compatible with the basal metabolic rate observed in vivo for resting muscle, most myosin heads would have to be in the SRX. Modulation of the population of this state, relative to the normal relaxed state, was proposed to be a major contributor to adaptive thermogenesis in resting muscle. Transfer of only 20% of myosin heads from the SRX into the normal relaxed state would cause muscle thermogenesis to double. Phosphorylation of the myosin regulatory light chain was shown to transfer myosin heads from the SRX into the relaxed state, which would increase thermogenesis. In particular, thermogenesis by myosin has been proposed to play a role in the dissipation of calories during overfeeding. Up-regulation of muscle thermogenesis by pharmaceuticals that target the SRX would provide new approaches to the treatment of obesity or high blood sugar levels

White Matter Microstructure Predicts Autistic Traits in Attention-Deficit/Hyperactivity Disorder

Traits of autism spectrum disorder (ASD) in children with attention-deficit/hyperactivity disorder (ADHD) have previously been found to index clinical severity. This study examined the association of ASD traits with diffusion parameters in adolescent males with ADHD (n = 17), and also compared WM microstructure relative to controls (n = 17). Significant associations (p < 0.05, corrected) were found between fractional anisotropy/radial diffusivity and ASD trait severity (positive and negative correlations respectively), mostly in the right posterior limb of the internal capsule/corticospinal tract, right cerebellar peduncle and the midbrain. No case–control differences were found for the diffusion parameters investigated. This is the first report of a WM microstructural signature of autistic traits in ADHD. Thus, even in the absence of full disorder, ASD traits may index a distinctive underlying neurobiology in ADHD