Atypical spatiotemporal signatures of working memory brain processes in autism

Working memory (WM) impairments may contribute to the profound behavioural manifestations in children with autism spectrum disorder (ASD). However, previous behavioural results are discrepant as are the few functional magnetic resonance imaging (fMRI) results collected in adults and adolescents with ASD. Here we investigate the precise temporal dynamics of WM-related brain activity using magnetoencephalography (MEG) in 20 children with ASD and matched controls during an n-back WM task across different load levels (1-back vs 2-back). Although behavioural results were similar between ASD and typically developing (TD) children, the between-group comparison performed on functional brain activity showed atypical WM-related brain processes in children with ASD compared with TD children. These atypical responses were observed in the ASD group from 200 to 600 ms post stimulus in both the low- (1-back) and high- (2-back) memory load conditions. During the 1-back condition, children with ASD showed reduced WM-related activations in the right hippocampus and the cingulate gyrus compared with TD children who showed more activation in the left dorso-lateral prefrontal cortex and the insulae. In the 2-back condition, children with ASD showed less activity in the left insula and midcingulate gyrus and more activity in the left precuneus than TD children. In addition, reduced activity in the anterior cingulate cortex was correlated with symptom severity in children with ASD. Thus, this MEG study identified the precise timing and sources of atypical WM-related activity in frontal, temporal and parietal regions in children with ASD. The potential impacts of such atypicalities on social deficits of autism are discussed.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Frontoparietal Network Connectivity During an N-Back Task in Adults With Autism Spectrum Disorder

Background: Short-term and working memory (STM and WM) deficits have been demonstrated in individuals with autism spectrum disorder (ASD) and may emerge through atypical functional activity and connectivity of the frontoparietal network, which exerts top-down control necessary for successful STM and WM processes. Little is known regarding the spectral properties of the frontoparietal network during STM or WM processes in ASD, although certain neural frequencies have been linked to specific neural mechanisms. Methods: We analysed magnetoencephalographic data from 39 control adults (26 males; 27.15 ± 5.91 years old) and 40 adults with ASD (26 males; 27.17 ± 6.27 years old) during a 1-back condition (STM) of an n-back task, and from a subset of this sample during a 2-back condition (WM). We performed seed-based connectivity analyses using regions of the frontoparietal network. Interregional synchrony in theta, alpha, and beta bands was assessed with the phase difference derivative and compared between groups during periods of maintenance and recognition. Results: During maintenance of newly presented vs. repeated stimuli, the two groups did not differ significantly in theta, alpha, or beta phase synchrony for either condition. Adults with ASD showed alpha-band synchrony in a network containing the right dorsolateral prefrontal cortex, bilateral inferior parietal lobules (IPL), and precuneus in both 1- and 2-back tasks, whereas controls demonstrated alpha-band synchrony in a sparser set of regions, including the left insula and IPL, in only the 1-back task. During recognition of repeated vs. newly presented stimuli, adults with ASD exhibited decreased theta-band connectivity compared to controls in a network with hubs in the right inferior frontal gyrus and left IPL in the 1-back condition. Whilst there were no group differences in connectivity in the 2-back condition, adults with ASD showed no frontoparietal network recruitment during recognition, whilst controls activated networks in the theta and beta bands. Conclusions: Our findings suggest that since adults with ASD performed well on the n-back task, their appropriate, but effortful recruitment of alpha-band mechanisms in the frontoparietal network to maintain items in STM and WM may compensate for atypical modulation of this network in the theta band to recognise previously presented items in STM.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

The temporal and spatial brain dynamics of automatic emotion regulation in children

Mechanisms for automatic emotion regulation (AER) are essential during childhood as they offset the impact of unwanted or negative emotional responses without drawing on limited attentional resources. Despite the importance of AER in improving the efficiency and flexibility of self-regulation, few research studies have investigated the underlying neurophysiological mechanisms. To fill this gap, we used magnetoencephalography (MEG) to investigate AER-related brain processes in 25 children (∼10 years old) who performed a go/no–go task that included an incidental exposure to faces containing socio-emotional cues. Whole brain results revealed that the inhibition of angry faces (compared with happy faces) was associated with a stronger recruitment of several brain regions from 100 to 425 ms. These activations involved the right angular and occipital gyri from 100 to175 ms, the right orbito-frontal gyrus (OFG) from 250 to 325 ms (pcorr < 0.05), and finally, the left anterior temporal lobe (ATL) from 325 to 425 ms. Our results suggest a specific involvement of these regions in the automatic regulation of negative emotional stimuli in children. In the future, this knowledge may help understand developmental conditions where inhibition impairments are exacerbated by an emotional context.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Inhibition in the face of emotion: Characterization of the spatial-temporal dynamics that facilitate automatic emotion regulation

Emotion regulation mediates socio-cognitive functions and is essential for interactions with others. The capacity to automatically inhibit responses to emotional stimuli is an important aspect of emotion regulation; the underlying neural mechanisms of this ability have been rarely investigated. Forty adults completed a Go/No-go task during magnetoencephalographic (MEG) recordings, where they responded rapidly to either a blue or purple frame which contained angry or happy faces. Subjects responded to the target color in an inhibition (75% Go trials) and a vigilance condition (25% Go trials). As expected, inhibition processes showed early, sustained activation (200–450 ms) in the right inferior frontal gyrus (IFG). Emotion-related inhibition processes showed greater activity with angry faces bilaterally in the orbital-frontal gyri (OFG) starting at 225 ms and temporal poles from 250 ms, with right hemisphere dominance. The presence of happy faces elicited earlier activity in the right OFG. This study demonstrates that the timing of inhibition processes varies with the emotional context and that there is much greater activation in the presence of angry faces. It underscores the importance of the right IFG for inhibition processes, but the OFG in automatic emotion regulation.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Alpha keeps it together: Alpha oscillatory synchrony underlies working memory maintenance in young children

Working Memory (WM) supports a wide range of cognitive functions, and is positively associated with academic achievement. Although fMRI studies have revealed WM networks in adults, little is known about how these networks develop to support successful WM performance in children. Using magnetoencephalography, we examined the networks underlying the maintenance of visual information in 6-year-old children. We observed an increase in mean whole-brain connectivity that was specific to the alpha frequency band during the retention interval associated with correct compared to incorrect responses. Additionally, our network analysis revealed elevated alpha synchronization during WM maintenance in a distributed network of frontal, parietal and temporal regions. Central hubs in the network were lateralized to the left hemisphere with dominant fronto-temporal connections, including the dorsolateral prefrontal cortex, middle temporal and superior temporal gyri, as well as other canonical language areas. Local changes in power were also analysed for seeds of interest, including the left inferior parietal lobe, which revealed an increase in alpha power after stimulus onset that was sustained throughout the retention period of WM. Our results therefore implicate sustained fronto-temporal alpha synchrony during the retention interval with subsequent successful WM responses in children, which may be aided by subvocal rehearsal strategies.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: A multi-ethnic meta-analysis of 45,891 individuals

Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.5×10−8- 1.2 ×10−43). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p<3×10−4). We next developed a multi-SNP genotypic risk score to test the association of adiponectin decreasing risk alleles on metabolic traits and diseases using consortia-level meta-analytic data. This risk score was associated with increased risk of T2D (p = 4.3×10−3, n = 22,044), increased triglycerides (p = 2.6×10−14, n = 93,440), increased waist-to-hip ratio (p = 1.8×10−5, n = 77,167), increased glucose two hours post oral glucose tolerance testing (p = 4.4×10−3, n = 15,234), increased fasting insulin (p = 0.015, n = 48,238), but with lower in HDL- cholesterol concentrations (p = 4.5×10−13, n = 96,748) and decreased BMI (p = 1.4×10−4, n = 121,335). These findings identify novel genetic determinants of adiponectin levels, which, taken together, influence risk of T2D and markers of insulin resistance

Search for intermediate mass black hole binaries in the first observing run of Advanced LIGO

International audienceDuring their first observational run, the two Advanced LIGO detectors attained an unprecedented sensitivity, resulting in the first direct detections of gravitational-wave signals produced by stellar-mass binary black hole systems. This paper reports on an all-sky search for gravitational waves (GWs) from merging intermediate mass black hole binaries (IMBHBs). The combined results from two independent search techniques were used in this study: the first employs a matched-filter algorithm that uses a bank of filters covering the GW signal parameter space, while the second is a generic search for GW transients (bursts). No GWs from IMBHBs were detected; therefore, we constrain the rate of several classes of IMBHB mergers. The most stringent limit is obtained for black holes of individual mass 100  M⊙, with spins aligned with the binary orbital angular momentum. For such systems, the merger rate is constrained to be less than 0.93  Gpc−3 yr−1 in comoving units at the 90% confidence level, an improvement of nearly 2 orders of magnitude over previous upper limits

First low-frequency Einstein@Home all-sky search for continuous gravitational waves in Advanced LIGO data

International audienceWe report results of a deep all-sky search for periodic gravitational waves from isolated neutron stars in data from the first Advanced LIGO observing run. This search investigates the low frequency range of Advanced LIGO data, between 20 and 100 Hz, much of which was not explored in initial LIGO. The search was made possible by the computing power provided by the volunteers of the Einstein@Home project. We find no significant signal candidate and set the most stringent upper limits to date on the amplitude of gravitational wave signals from the target population, corresponding to a sensitivity depth of 48.7  [1/Hz]. At the frequency of best strain sensitivity, near 100 Hz, we set 90% confidence upper limits of 1.8×10-25. At the low end of our frequency range, 20 Hz, we achieve upper limits of 3.9×10-24. At 55 Hz we can exclude sources with ellipticities greater than 10-5 within 100 pc of Earth with fiducial value of the principal moment of inertia of 1038  kg m2

First narrow-band search for continuous gravitational waves from known pulsars in advanced detector data

International audienceSpinning neutron stars asymmetric with respect to their rotation axis are potential sources of continuous gravitational waves for ground-based interferometric detectors. In the case of known pulsars a fully coherent search, based on matched filtering, which uses the position and rotational parameters obtained from electromagnetic observations, can be carried out. Matched filtering maximizes the signal-to-noise (SNR) ratio, but a large sensitivity loss is expected in case of even a very small mismatch between the assumed and the true signal parameters. For this reason, narrow-band analysis methods have been developed, allowing a fully coherent search for gravitational waves from known pulsars over a fraction of a hertz and several spin-down values. In this paper we describe a narrow-band search of 11 pulsars using data from Advanced LIGO’s first observing run. Although we have found several initial outliers, further studies show no significant evidence for the presence of a gravitational wave signal. Finally, we have placed upper limits on the signal strain amplitude lower than the spin-down limit for 5 of the 11 targets over the bands searched; in the case of J1813-1749 the spin-down limit has been beaten for the first time. For an additional 3 targets, the median upper limit across the search bands is below the spin-down limit. This is the most sensitive narrow-band search for continuous gravitational waves carried out so far