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The retrograde geostationary earth orbit (retro-GEO) is an Earth’s orbit. It has almost the same orbital altitude with that of a GEO, but an inclination of 180°. A retro-GEO monitor-satellite gives the GEO-assets vicinity space-debris warnings per 12 h. For various reasons, the westward launch direction is not compatible or economical. Thereby the transfer from a low earth orbit (LEO) to the retro-GEO via once lunar swing-by is a priority. The monitor-satellite departures from LEO and inserts into the retro-GEO both using only one tangential maneuver, in this paper, its transfer’s property is investigated. The existence of this transfer is verified firstly in the planar circular restricted three-body problem (CR3BP) model based on the Poincaré-section methodology. Then, the two-impulse values and the perilune altitudes are computed with different transfer durations in the planar CR3BP. Their dispersions are compared with different Sun azimuths in the planar bi-circular restricted four-body problem (BR4BP) model. Besides, the transfer’s inclination changeable capacity via lunar swing-by and the Sun-perturbed inclination changeable capacity are investigated. The results show that the two-impulse fuel-optimal transfer has the duration of 1.76 TU (i.e., 7.65 days) with the minimum values of 4.251 km s−1 in planar CR3BP, this value has a range of 4.249–4.252 km s−1 due to different Sun azimuths in planar BR4BP. Its perilune altitude changes from 552.6 to 621.9 km. In the spatial CR3BP, if the transfer duration is more than or equal to 4.00 TU (i.e., 17.59 days), the lunar gravity assisted transfer could insert the retro-GEO with any inclination. In the spatial BR4BP, the Sun’s perturbation does not affect this conclusion in most cases.

Multimodal neuroimaging grants a powerful window into the structure and function of the human brain at multiple scales. Recent methodological and conceptual advances have enabled investigations of the interplay between large-scale spatial trends (also referred to as gradients) in brain microstructure and connectivity, offering an integrative framework to study multiscale brain organization. Here, we share a multimodal MRI dataset for Microstructure-Informed Connectomics (MICA-MICs) acquired in 50 healthy adults (23 women; 29.54 ± 5.62 years) who underwent high-resolution T1-weighted MRI, myelin-sensitive quantitative T1 relaxometry, diffusion-weighted MRI, and resting-state functional MRI at 3 Tesla. In addition to raw anonymized MRI data, this release includes brain-wide connectomes derived from (i) resting-state functional imaging, (ii) diffusion tractography, (iii) microstructure covariance analysis, and (iv) geodesic cortical distance, gathered across multiple parcellation scales. Alongside, we share large-scale gradients estimated from each modality and parcellation scale. Our dataset will facilitate future research examining the coupling between brain microstructure, connectivity, and function. MICA-MICs is available on the Canadian Open Neuroscience Platform data portal (https://portal.conp.ca) and the Open Science Framework (https://osf.io/j532r/).

Nature Communications 13(1), 2341 (2022). doi:10.1038/s41467-022-29886-1, Brain structure scaffolds intrinsic function, supporting cognition and ultimately behavioral flexibility. However, it remains unclear how a static, genetically controlled architecture supports flexible cognition and behavior. Here, we synthesize genetic, phylogenetic and cognitive analyses to understand how the macroscale organization of structure-function coupling across the cortex can inform its role in cognition. In humans, structure-function coupling was highest in regions of unimodal cortex and lowest in transmodal cortex, a pattern that was mirrored by a reduced alignment with heritable connectivity profiles. Structure-function uncoupling in macaques had a similar spatial distribution, but we observed an increased coupling between structure and function in association cortices relative to humans. Meta-analysis suggested regions with the least genetic control (low heritable correspondence and different across primates) are linked to social-cognition and autobiographical memory. Our findings suggest that genetic and evolutionary uncoupling of structure and function in different transmodal systems may support the emergence of complex forms of cognition., Published by Nature Publishing Group UK, [London]

Identification of predictive neuroimaging markers of pain intensity changes is a crucial issue to better understand macroscopic neural mechanisms of pain. Although a single connection between the medial prefrontal cortex and nucleus accumbens has been suggested as a powerful marker, how the complex interactions on a large-scale brain network can serve as the markers is underexplored. Here, we aimed to identify a set of functional connections predictive of longitudinal changes in pain intensity using large-scale brain networks. We re-analyzed previously published resting-state functional magnetic resonance imaging data of 49 subacute back pain (SBP) patients. We built a network-level model that predicts changes in pain intensity over one year by combining independent component analysis and a penalized regression framework. Connections involving top-down pain modulation, multisensory integration, and mesocorticolimbic circuits were identified as predictive markers for pain intensity changes. Pearson’s correlations between actual and predicted pain scores were r = 0.33–0.72, and group classification results between SBP patients with persisting pain and recovering patients, in terms of area under the curve (AUC), were 0.89/0.75/0.75 for visits four/three/two, thus outperforming the previous work (AUC 0.83/0.73/0.67). This study identified functional connections important for longitudinal changes in pain intensity in SBP patients, providing provisional markers to predict future pain using large-scale brain networks.

Supplemental material, sj-pdf-1-jcb-10.1177_0271678X221103006 for Cerebrovascular reactivity and deep white matter hyperintensities in migraine: A prospective CO2 targeting study by Mi Ji Lee, Bo-yong Park, Soohyun Cho, Seonwoo Kim, Hyunjin Park, Sung Tae Kim and Chin-Sang Chung in Journal of Cerebral Blood Flow & Metabolism

Adolescence is a critical time for the continued maturation of brain networks. Here, we assessed structural connectome development in a large longitudinal sample ranging from childhood to young adulthood. By projecting high-dimensional connectomes into compact manifold spaces, we identified a marked expansion of structural connectomes, with strongest effects in transmodal regions during adolescence. Findings reflected increased within-module connectivity together with increased segregation, indicating increasing differentiation of higher-order association networks from the rest of the brain. Projection of subcortico-cortical connectivity patterns into these manifolds showed parallel alterations in pathways centered on the caudate and thalamus. Connectome findings were contextualized via spatial transcriptome association analysis, highlighting genes enriched in cortex, thalamus, and striatum. Statistical learning of cortical and subcortical manifold features at baseline and their maturational change predicted measures of intelligence at follow-up. Our findings demonstrate that connectome manifold learning can bridge the conceptual and empirical gaps between macroscale network reconfigurations, microscale processes, and cognitive outcomes in adolescent development.

It is increasingly recognized that multiple psychiatric conditions are underpinned by shared neural pathways, affecting similar brain systems. Here, we assessed i) shared dimensions of alterations in cortical morphology across six major psychiatric conditions (autism spectrum disorder, attention deficit/hyperactivity disorder, major depression, obsessive-compulsive disorder, bipolar disorder, schizophrenia) and ii) carried out a multiscale neural contextualization, by cross-referencing shared anomalies against cortical myeloarchitecture and cytoarchitecture, as well as connectome and neurotransmitter organization. Pooling disease-related effects on MRI-based cortical thickness measures across six ENIGMA working groups, including a total of 28,546 participants (12,876 patients and 15,670 controls), we computed a shared disease dimension on cortical morphology using principal component analysis that described a sensory-fugal pattern with paralimbic regions showing the most consistent abnormalities across conditions. The shared disease dimension was closely related to cortical gradients of microstructure and intrinsic connectivity, as well as neurotransmitter systems, specifically serotonin and dopamine. Our findings embed the shared effects of major psychiatric conditions on brain structure in multiple scales of brain organization and may provide novel insights into neural mechanisms into transdiagnostic vulnerability.

Background Mesenchymal stem cells (MSCs) capable of differentiating into other cell types and having immunomodulatory effects are affected by a variety of intrinsic and/or extrinsic signaling factors, including growth factors, cytokines, extracellular matrix, and hormones. Melatonin made by the pineal gland is a hormone that regulates sleep cycles. Recent studies show that melatonin improves the therapeutic effects of stem cells. Here, we aimed to investigate whether melatonin enhances biological activities of human adipose-derived MSCs (AdMSCs). Methods AdMSCs were obtained from normal healthy donors after obtaining written informed consent. Cell proliferation assay was performed by using EZ-cytox based on WST. To evaluate the stemness of AdMSCs, CFU and β-galactosidase assay were performed. To investigate the effects of melatonin on suppression of T cells proliferation, human peripheral blood mononuclear cells were co-cultured with AdMSC. 10 μM of melatonin and 5 μM of luzindole were treated, and 10 μg/ml phytohaemagglutinin was applied for activation of T cells. Results Melatonin promoted cell proliferation by inducing Sox2 gene and preventing replicative senescence. In addition, melatonin has anti-adipogenesis effects on MSCs. In PCR analysis, C/EPB gene, a key transcription factor of adipogenesis, was decreased by melatonin, resulting in reduced adipogenic differentiation in vitro assay. We also examined immunomodulatory effects using co-culture system of human peripheral blood mononuclear cells and MSCs. Activated T cells exposed to melatonin were strongly inhibited compared to the control. We have confirmed the favourable effects of melatonin on MSCs by using luzindole, a selective melatonin receptor antagonist. Conclusion The proliferation-accelerating, anti-inflammatory effects of melatonin suggest that melatonin-mediated MSCs will be used for effective cellular therapy (This work was supported by National Research Foundation of Korea (NRF) grant funded by the Korea government (No. NRF-2018R1D1A1B07050071)).

Migraine headache is an episodic phenomenon, and patients with episodic migraine have ictal (headache), peri-ictal (premonitory, aura, and postdrome), and interictal (asymptomatic) phases. We aimed to find the functional characteristics of the migraine brain regardless of headache phase using dynamic functional connectivity analysis. We prospectively recruited 50 patients with migraine and 50 age- and sex-matched controls. All subjects underwent a resting-state functional magnetic resonance imaging. Significant networks were defined in a data-driven fashion from the interictal (48 hours apart from headache phases) patients and matched controls (interictal data set) and tested to ictal or peri-ictal patients and controls (ictal/peri-ictal data set). Both static and dynamic analyses were used for the between-group comparison. A false discovery rate correction was performed. As a result, the static analysis did not reveal a network which was significant in both interictal and ictal/peri-ictal data sets. Dynamic analysis revealed significant between-group differences in 7 brain networks in the interictal data set, among which a frontoparietal network (controlspatients, P = 0.0467), 2 brainstem networks (patientscontrols, P = 0.0467 and0.001), and a cerebellar network (controlspatients, P = 0.0408 and0.001 in 2 states) remained significant in the ictal/peri-ictal data set. Using these networks, migraine was classified with a sensitivity of 0.70 and specificity of 0.76 in the ictal/peri-ictal data set. In conclusion, the dynamic connectivity analysis revealed more functional networks related to migraine than the conventional static analysis, suggesting a substantial temporal fluctuation in functional characteristics. Our data also revealed migraine-related networks which show significant difference regardless of headache phases between patients and controls.

AIMS We conducted a 4-week randomized, sham-controlled, single-blind, parallel-group trial to examine the effect of repetitive transcranial magnetic stimulation (rTMS) delivered to the left dorsolateral prefrontal cortex (DLPFC) on functional brain connectivity and body weight in adults with obesity. MATERIALS AND METHODS Of the 45 volunteers with obesity, aged between 18 and 70 years (body mass index [BMI] ≥25 kg/m2 according to the obesity criterion for an Asian population), 36 participants (54.1 ± 11.0 years, BMI 30.2 ± 3.5 kg/m2 , 77.8% female) completed the 4 weeks of follow-up, undergoing two resting state fMRI scans (20 in the real stimulation group and 16 in the sham stimulation group). A total of eight sessions of high-frequency rTMS targeting the left DLPFC were provided over a period of 4 weeks (5-second trains with 25-second inter-train intervals, 10 Hz, 110% motor threshold; 2000 pulses over 20 minutes). RESULTS Participants in the real stimulation group showed significantly greater weight loss from baseline following the eight session of rTMS (-2.53 ± 2.41 kg vs 0.38 ± 1.13 kg, P

Objective To investigate the whole-brain resting-state functional connectivity in patients with chronic migraine (CM) using a data-driven method. Methods We prospectively recruited patients with either episodic migraine (EM) or CM aged 18–60 years who visited the headache clinic of the Samsung Medical Center from July 2016 to December 2017. All patients underwent 3 T MRI using an identical scanner. Patients were considered interictal if they did not have a migraine headache at the day and ± 1 days of functional MRI acquisition. Using the group-independent component analysis (ICA), connectivity analysis with a weighted and undirected network model was performed. The between-group differences in degree centrality (DC) values were assessed using 5000 permutation tests corrected with false discovery rate (FDR). Results A total of 62 patients (44 EM and 18 CM) were enrolled in this study. Among the seven functionally interpretable spatially independent components (ICs) identified, only one IC, interpreted as the pain matrix, showed a significant between-group difference in DC (CM > EM, p = 0.046). This association remained significant after adjustment for age, sex, migraine with aura (MWA), allodynia, depression, and anxiety (p = 0.038). The pain matrix was functionally correlated with the hypothalamus (p = 0.040, EM > CM) and dorsal raphe nucleus (p = 0.039, CM > EM) with different levels of strength in EM and CM. Conclusion CM patients have a stronger connectivity in the pain matrix than do EM patients. Functional alteration of the pain network might play a role in migraine chronification.

Conventional functional connectivity analysis using functional magnetic resonance imaging (fMRI) measures the correlation of temporally synchronized brain activities between brain regions. Lag structure analysis relaxes the synchronicity constraint of fMRI signals, and thus, this approach might be better at explaining functional connectivity. However, the sources of the lag structure in fMRI are primarily unknown. Here, we applied lag structure analysis to the human visual cortex to identify the possible sources of lag structure. A total of 1,250 fMRI data from two independent databases were considered. We explored the temporal lag patterns between the central and peripheral visual fields in early visual cortex and those in two visual pathways of dorsal and ventral streams. We also compared the lag patterns with effective connectivity obtained with dynamic causal modeling. We found that the lag structure in early visual cortex flows from the central to peripheral visual fields and the order of the lag structure flow was consistent with the order of signal flows in visual pathways. The effective connectivity computed by dynamic causal modeling exhibited similar patterns with the lag structure results. This study suggests that signal flows in visual streams are possible sources of the lag structure in human visual cortex.

ObjectiveTo evaluate the association between the cerebrovascular reactivity to carbon dioxide (CO2-CVR) and the deep white matter hyperintensity (WMH) burden in patients with migraine.MethodsA total of 86 nonelderly patients with episodic migraine without vascular risk factors and 35 headache-free controls underwent 3T MRI. Deep WMHs were quantified with a segmentation method developed for nonelderly migraineurs. The interictal CO2-CVR was measured with transcranial Doppler with the breath-holding method. The mean breath-holding index of the bilateral middle cerebral arteries (MCA-BHI) was square root transformed and analyzed with univariate and multivariate logistic regression models to determine its association with the highest tertiles of deep WMH burden (number and volume).ResultsA low MCA-BHI was independently associated with the highest tertile of deep WMH number in patients with migraine (adjusted odds ratio [OR] 0.02, 95% confidence interval [CI] 0.0007–0.63, p = 0.026). In controls, the MCA-BHI was not associated with deep WMH number. Interaction analysis revealed that migraine modified the effect of MCA-BHI on deep WMH number (p for interaction = 0.029). The MCA-BHI was not associated with increased deep WMH volume in both patients and controls. Age was independently associated with deep WMH volume in patients (adjusted OR 1.07, 95% CI 1.004–1.15, p = 0.037).ConclusionsIn this study, we found a migraine-specific association between a reduced CVR to apnea and increased number of deep WMHs in healthy, nonelderly patients with migraine. A dysfunctional vascular response to apnea may predispose migraineurs to an increased risk of WMHs.

Temporal lobe epilepsy (TLE), a common drug-resistant epilepsy in adults, is primarily a limbic network disorder associated with predominant unilateral hippocampal pathology. Structural MRI has provided an in vivo window into whole-brain grey matter pathology in TLE relative to controls, by either mapping (i) atypical inter-hemispheric asymmetry or (ii) regional atrophy. However, similarities and differences of both atypical asymmetry and regional atrophy measures have not been systematically investigated. Here, we addressed this gap using the multi-site ENIGMA-Epilepsy dataset comprising MRI brain morphological measures in 732 TLE patients and 1,418 healthy controls. We compared spatial distributions of grey matter asymmetry and atrophy in TLE, contextualized their topographies relative to spatial gradients in cortical microstructure and functional connectivity, and examined clinical associations using machine learning. We identified a marked divergence in the spatial distribution of atypical inter-hemispheric asymmetry and regional atrophy mapping. The former revealed a temporo-limbic disease signature while the latter showed diffuse and bilateral patterns. Our findings were robust across individual sites and patients. Cortical atrophy was significantly correlated with disease duration and age at seizure onset, while degrees of asymmetry did not show a significant relationship to these clinical variables. Our findings highlight that the mapping of atypical inter-hemispheric asymmetry and regional atrophy tap into two complementary aspects of TLE-related pathology, with the former revealing primary substrates in ipsilateral limbic circuits and the latter capturing bilateral disease effects. These findings refine our notion of the neuropathology of TLE and may inform future discovery and validation of complementary MRI biomarkers in TLE.

The pathophysiology of autism has been suggested to involve a combination of both macroscale connectome miswiring and microcircuit anomalies. Here, we combine connectome-wide manifold learning with biophysical simulation models to understand associations between global network perturbations and microcircuit dysfunctions in autism. We studied neuroimaging and phenotypic data in 47 individuals with autism and 37 typically developing controls obtained from the Autism Brain Imaging Data Exchange initiative. Our analysis establishes significant differences in structural connectome organization in individuals with autism relative to controls, with strong between-group effects in low-level somatosensory regions and moderate effects in high-level association cortices. Computational models reveal that the degree of macroscale anomalies is related to atypical increases of recurrent excitation/inhibition, as well as subcortical inputs into cortical microcircuits, especially in sensory and motor areas. Transcriptomic association analysis based on postmortem datasets identifies genes expressed in cortical and thalamic areas from childhood to young adulthood. Finally, supervised machine learning finds that the macroscale perturbations are associated with symptom severity scores on the Autism Diagnostic Observation Schedule. Together, our analyses suggest that atypical subcortico-cortical interactions are associated with both microcircuit and macroscale connectome differences in autism., Autism is increasingly recognized to impact multiple scales of neural organization. Here, the authors show alterations in individuals with autism relative to typically developing controls, with findings particularly pointing to atypically organized subcortical-cortical networks.

Autism is a common neurodevelopmental condition characterized by substantial phenotypic heterogeneity, which hinders diagnosis, research, and intervention. A leading example can be found in marked imbalances in language and perceptual skills, where deficits in one domain often co-exist with normal or even superior performance in the other domain. The current work capitalized on multiple data analytics including data-driven subtyping and dimensional approaches to quantify cognitive imbalances in multi-site datasets of individuals diagnosed with autism spectrum disorder (ASD) and neurotypical controls, and assessed structural and functional brain network substrates. Studying cognitive dimensions as well as multimodal neuroimaging signatures in 155 ASD and 151 neurotypical individuals, we observed robust evidence for a structure-function substrate of cognitive imbalances in ASD. Specifically, ASD presented with marked imbalances in cognitive profiles relative to neurotypical controls, characterized by verbal to non-verbal intelligence discrepancy. Different analytical approaches including subtyping and dimensional regression methods converged in showing that these imbalances were reflected in atypical cortical thickening and functional integration of language networks, alongside with sensory and higher cognitive networks. Phenotypic findings could be replicated in an independent sample of 325 ASD and 569 neurotypical controls. Although verbal and non-verbal intelligence are currently considered as specifiers unrelated to the categorical diagnosis of autism, our results show that intelligence disparities are accentuated in ASD and relate to a consistent structure-function substrate affecting multiple brain networks. Our findings motivate the incorporation of cognitive imbalances in future autism research, which may help to parse the phenotypic heterogeneity of autism and potentially inform intervention-oriented subtyping.

Narrative comprehension involves a constant interplay of the accumulation of incoming events and their integration into a coherent structure. This study characterizes cognitive states during narrative comprehension and the network-level reconfiguration occurring dynamically in the functional brain. We presented movie clips of temporally scrambled sequences to human participants (male and female), eliciting fluctuations in the subjective feeling of comprehension. Comprehension occurred when processing events that were highly causally related to the previous events, suggesting that comprehension entails the integration of narratives into a causally coherent structure. The functional neuroimaging results demonstrated that the integrated and efficient brain state emerged during the moments of narrative integration with the increased level of activation and across-modular connections in the default mode network. Underlying brain states were synchronized across individuals when comprehending novel narratives, with increased occurrences of the default mode network state, integrated with sensory processing network, during narrative integration. A model based on time-resolved functional brain connectivity predicted changing cognitive states related to comprehension that are general across narratives. Together, these results support adaptive reconfiguration and interaction of the functional brain networks on causal integration of the narratives.SIGNIFICANCE STATEMENTThe human brain can integrate temporally disconnected pieces of information into coherent narratives. However, the underlying cognitive and neural mechanisms of how the brain builds a narrative representation remain largely unknown. We showed that comprehension occurs as the causally related events are integrated to form a coherent situational model. Using fMRI, we revealed that the large-scale brain states and interaction between brain regions dynamically reconfigure as comprehension evolves, with the default mode network playing a central role during moments of narrative integration. Overall, the study demonstrates that narrative comprehension occurs through a dynamic process of information accumulation and causal integration, supported by the time-varying reconfiguration and brain network interaction.

Human cognition is dynamic, alternating over time between externally-focused states and more abstract, often self-generated, patterns of thought. Although cognitive neuroscience has documented how networks anchor particular modes of brain function, mechanisms that describe transitions between distinct functional states remain poorly understood. Here, we examined how time-varying changes in brain function emerge within the constraints imposed by macroscale structural network organization. Studying a large cohort of healthy adults (n = 326), we capitalized on manifold learning techniques that identify low dimensional representations of structural connectome organization and we decomposed neurophysiological activity into distinct functional states and their transition patterns using Hidden Markov Models. Structural connectome organization predicted dynamic transitions anchored in sensorimotor systems and those between sensorimotor and transmodal states. Connectome topology analyses revealed that transitions involving sensorimotor states traversed short and intermediary distances and adhered strongly to communication mechanisms of network diffusion. Conversely, transitions between transmodal states involved spatially distributed hubs and increasingly engaged long-range routing. These findings establish that the structure of the cortex is optimized to allow neural states the freedom to vary between distinct modes of processing, and so provides a key insight into the neural mechanisms that give rise to the flexibility of human cognition.Keywords: Hidden Markov Model; diffusion MRI; functional dynamics; gradients; multimodal imaging; structural connectome.

Autism spectrum disorder (ASD) is commonly understood as an alteration of brain networks, yet case-control analyses against typically-developing controls (TD) have yielded inconsistent results. Here, we devised a novel approach to profile the inter-individual variability in functional network organization and tested whether such idiosyncrasy contributes to connectivity alterations in ASD. Studying a multi-centric dataset with 157 ASD and 172 TD, we obtained robust evidence for increased idiosyncrasy in ASD relative to TD in default mode, somatomotor and attention networks, but also reduced idiosyncrasy in lateral temporal cortices. Idiosyncrasy increased with age and significantly correlated with symptom severity in ASD. Furthermore, while patterns of functional idiosyncrasy were not correlated with ASD-related cortical thickness alterations, they co-localized with the expression patterns of ASD risk genes. Notably, we could demonstrate that patterns of atypical idiosyncrasy in ASD closely overlapped with connectivity alterations that are measurable with conventional case-control designs and may, thus, be a principal driver of inconsistency in the autism connectomics literature. These findings support important interactions between inter-individual heterogeneity in autism and functional signatures. Our findings provide novel biomarkers to study atypical brain development and may consolidate prior research findings on the variable nature of connectome level anomalies in autism., Benkarim et al devise an approach to profile inter-individual variability in functional network organization and test whether such idiosyncrasy contributes to the connectivity alterations found in Autism Spectrum Disorder. Their approach provides potential biomarkers to study atypical brain development and may be used to consolidate prior research findings on the variable nature of connectome level anomalies in autism.

Autism spectrum disorder (ASD) is commonly understood as a network disorder, yet case-control analyses against typically-developing controls (TD) have yielded somewhat inconsistent patterns of results. The current work was centered on a novel approach to profile functional network idiosyncrasy, the inter-individual variability in the association between functional network organization and brain anatomy, and we tested the hypothesis that idiosyncrasy contributes to connectivity alterations in ASD. Studying functional network idiosyncrasy in a multi-centric dataset with 157 ASD and 172 TD, our approach revealed higher idiosyncrasy in ASD in the default mode, somatomotor and attention networks together with reduced idiosyncrasy in the lateral temporal lobe. Idiosyncrasy was found to increase with age in both ASD and TD, and was significantly correlated with symptom severity in the former group. Association analysis with structural and molecular brain features indicated that patterns of functional network idiosyncrasy were not correlated with ASD-related cortical thickness alterations, but closely with the spatial expression patterns of intracortical ASD risk genes. In line with our main hypothesis, we could demonstrate that idiosyncrasy indeed plays a strong role in the manifestation of connectivity alterations that are measurable with conventional case-control designs and may, thus, be a principal driver of inconsistency in the autism connectomics literature. These findings support important interactions between the heterogeneity of individuals with an autism diagnosis and group-level functional signatures, and help to consolidate prior research findings on the highly variable nature of the functional connectome in ASD. Our study promotes idiosyncrasy as a potential individualized diagnostic marker of atypical brain network development.

PIWI (P element induced wimpy testis) integrating RNAs (piRNAs) are small non-coding RNAs with the length of approximately 30 nucleotides that plays crucial roles in germ cells and adult stem cells. Recently, accumulating data have shown that piRNA and PIWI proteins are involved in tumorigenesis. However, the roles of PIWI proteins and piRNAs in pancreatic cancer are still elusive. Here, we showed that piR-017061 is significantly downregulated in pancreatic cancer patients' samples and pancreatic cancer cell lines. Furthermore, we studied the function of piR-017061 in pancreatic cancer and our data revealed that piR-017061 inhibits pancreatic cancer cell growth in vitro and in vivo. Moreover, we analyzed the genomic loci around piR-017061 and identified EFNA5 as a novel target of piR-017061. Importantly, our data further revealed a direct binding between piR-017061 and EFNA5 mRNA mediated by PIWIL1. Mechanically, piR-017061 cooperates with PIWIL1 to facilitate EFNA5 mRNA degradation and loss of piR-017061 results in accumulation of EFNA5 which facilitates pancreatic cancer development. Hence, our data provided novel insights into PIWI/piRNA-mediated gene regulation and their function in pancreatic cancer. Since PIWI proteins and piRNA predominately express in germline and cancer cells, our study provided novel therapeutic strategy for pancreatic cancer treatment.

Episodic memory is the ability to remember events from our past accurately. The process of pattern separation is hypothesized to underpin this ability and is defined as the capacity to orthogonalize memory traces, to maximize the features that make them unique. Contemporary cognitive neuroscience suggests that pattern separation entails complex interactions between the hippocampus and neocortex, where specific hippocampal subregions shape neural reinstatement in the neocortex. To test this hypothesis, the current work studied both healthy controls and patients with temporal lobe epilepsy who presented with hippocampal structural anomalies. We measured neural activity in all participants using functional MRI while they retrieved memorized items or lure items, which shared features with the target. Behaviourally, patients with temporal lobe epilepsy were less able to exclude lures than controls and showed a reduction in pattern separation. To assess the hypothesized relationship between neural patterns in the hippocampus and neocortex, we identified the topographic gradients of intrinsic connectivity along neocortical and hippocampal subfield surfaces and determined the topographic profile of the neural activity accompanying pattern separation. In healthy controls, pattern separation followed a graded topography of neural activity, both along the hippocampal long axis (and peaked in anterior segments that are more heavily engaged in transmodal processing) and along the neocortical hierarchy running from unimodal to transmodal regions (peaking in transmodal default mode regions). In patients with temporal lobe epilepsy, however, this concordance between task-based functional activations and topographic gradients was markedly reduced. Furthermore, person-specific measures of concordance between task-related activity and connectivity gradients in patients and controls were related to inter-individual differences in behavioural measures of pattern separation and episodic memory, highlighting the functional relevance of the observed topographic motifs. Our work is consistent with an emerging understanding that successful discrimination between memories with similar features entails a shift in the locus of neural activity away from sensory systems, a pattern that is mirrored along the hippocampal long axis and with respect to neocortical hierarchies. More broadly, our study establishes topographic profiling using intrinsic connectivity gradients, capturing the functional underpinnings of episodic memory processes in a manner that is sensitive to their reorganization in pathology.

Episodic memory is our ability to remember past events accurately. Pattern separation, the process of of orthogonalizing similar aspects of external information into nonoverlapping representations, is one of its mechanisms. Converging evidence suggests a pivotal role of the hippocampus, in concert with neocortical areas, in this process. The current study aimed to identify principal dimensions of functional activation associated with pattern separation in hippocampal and neocortical areas, in both healthy individuals and patients with lesions to the hippocampus. Administering a pattern separation fMRI paradigm to a group of healthy adults, we detected task-related activation in bilateral hippocampal and distributed neocortical areas. Capitalizing on manifold learning techniques applied to parallel resting-state fMRI data, we could identify that hippocampal and neocortical activity patterns were efficiently captured by their principal gradients of intrinsic functional connectivity, which follows the hippocampal long axis and sensory-fugal cortical organization. Functional activation patterns and their alignment with these principal dimensions were altered in patients. Notably, inter-individual differences in the concordance between task-related activity and intrinsic functional gradients were correlated with pattern separation performance in both patients and controls. Our work outlines a parsimonious approach to capture the functional underpinnings of episodic memory processes at the systems level, and to decode functional reorganization in clinical populations.

Adolescence is a critical time for the continued maturation of brain networks. Here, we assessed structural connectome development in a large longitudinal sample ranging from childhood to young adulthood. By projecting high-dimensional connectomes into compact manifold spaces, we identified a marked expansion of structural connectomes with the strongest effects in transmodal regions during adolescence. Findings reflected increased within-module connectivity together with increased segregation, indicating increasing differentiation of higher-order association networks from the rest of the brain. Projection of subcortico-cortical connectivity patterns into these manifolds showed parallel alterations in pathways centered on the caudate and thalamus. Connectome findings were contextualized via spatial transcriptome association analysis, highlighting genes enriched in cortex, thalamus, and striatum. Statistical learning of cortical and subcortical manifold features at baseline and their maturational change predicted measures of intelligence at follow-up. Our findings demonstrate that connectome manifold learning can bridge the conceptual and empirical gaps between macroscale network reconfigurations, microscale processes, and cognitive outcomes in adolescent development.ImpactManifold learning of longitudinal brain network data provides novel insights into adolescent structural connectome maturation, and how multiple scales of cortical and subcortical organization interact in typical neurodevelopment.

Both macroscale connectome miswiring and microcircuit anomalies have been suggested to play a role in the pathophysiology of autism. However, an overarching framework that consolidates these macro and microscale perspectives of the condition is lacking. Here, we combined connectome-wide manifold learning and biophysical simulation models to understand associations between global network perturbations and microcircuit dysfunctions in autism. Our analysis established that autism showed significant differences in structural connectome organization relative to neurotypical controls, with strong effects in low-level somatosensory regions and moderate effects in high-level association cortices. Computational models revealed that the degree of macroscale anomalies was related to atypical increases of subcortical inputs into cortical microcircuits, especially in sensory and motor areas. Transcriptomic decoding and developmental gene enrichment analyses provided biological context and pointed to genes expressed in cortical and thalamic areas during childhood and adolescence. Supervised machine learning showed the macroscale perturbations predicted socio-cognitive symptoms and repetitive behaviors. Our analyses provide convergent support that atypical subcortico-cortical interactions may contribute to both microcircuit and macroscale connectome anomalies in autism.

Autism spectrum disorder (ASD) and anxiety disorders (ANX) are common neurodevelopmental conditions with several overlapping symptoms. Notably, many children and adolescents with ASD also have an ANX diagnosis, suggesting shared pathological mechanisms. Here, we leveraged structural imaging and phenotypic data from 82 closely matched children (28 ASD, 28 ANX, 26 typically developing controls). Our neuroimaging paradigm assessed cortical thickness and studied inter-regional structural covariance networks. Both ASD and ANX presented with atypical structural network organization relative to controls. Specifically, ASD presented with increased thickness in temporal and parietal midline cortices, while ANX was associated with increased cortical thickness in the left inferior frontal and precentral gyri. Despite the overall difference in the spatial distributions these clusters, unconstrained spin permutation testing showed that statistical maps from the ANX-vs-controls and ASD-vs-controls analyses were significantly correlated. The two diagnostic groups also presented with common decreases in structural covariance patterns, collectively pointing to decreased structural coupling between lateral frontal, lateral temporal, and temporo-parietal regions. Dimensional analysis of trait anxiety and social responsiveness partially recapitulated diagnosis-based findings. Collectively, our findings provide evidence for both shared as well as distinct effects of ASD and ANX on on regional and inter-regional structural network organization.

Sustained pain is a major characteristic of clinical pain disorders, but it is difficult to assess in isolation from co-occurring cognitive and emotional features in patients. In this study, we developed a functional magnetic resonance imaging signature based on whole-brain functional connectivity that tracks experimentally induced tonic pain intensity and tested its sensitivity, specificity and generalizability to clinical pain across six studies (total n = 334). The signature displayed high sensitivity and specificity to tonic pain across three independent studies of orofacial tonic pain and aversive taste. It also predicted clinical pain severity and classified patients versus controls in two independent studies of clinical low back pain. Tonic and clinical pain showed similar network-level representations, particularly in somatomotor, frontoparietal and dorsal attention networks. These patterns were distinct from representations of experimental phasic pain. This study identified a brain biomarker for sustained pain with high potential for clinical translation. The functional magnetic resonance imaging connectivity pattern of tonic experimental orofacial pain can be used as a quantitative and unbiased biomarker of clinical pain.

Many studies have linked dysfunction in cognitive control-related brain regions with obesity and the burden of white matter hyperintensities (WMHs). This study aimed to explore how functional connectivity differences in the brain are associated with WMH burden and degree of obesity using resting-state functional magnetic resonance imaging (fMRI) in 182 participants. Functional connectivity measures were compared among four different groups: (1) low WMH burden, non-obese; (2) low WMH burden, obese; (3) high WMH burden, non-obese; and (4) high WMH burden, obese. At a large-scale network-level, no networks showed significant interaction effects, but the frontoparietal network showed a main effect of degree of obesity. At a finer node level, the orbitofrontal cortex showed interaction effects between periventricular WMH burden and degree of obesity. Higher functional connectivity was observed when the periventricular WMH burden and degree of obesity were both high. These results indicate that the functional connectivity of the orbitofrontal cortex is affected by the mutual interaction between the periventricular WMHs and degree of obesity. Our results suggest that this region links obesity with WMHs in terms of functional connectivity.

Background Kidney cancer is one of the most common cancers in the world. It is necessary to clarify its underlying mechanism and find its prognostic biomarkers. Current studies showed that SHMT2 may be participated in several kinds of cancer. Methods Our studies investigated the expression of SHMT2 in kidney cancer by Oncomine, Human Protein Atlas database and ULCAN database. Meanwhile, we found its co-expression gene by cBioPortal online tool and validated their relationship in A498 and ACHN cells by cell transfection, western blot and qRT-PCR. Besides these, we also explored their prognostic values via the Kaplan–Meier plotter database in different types of kidney cancer patients. Results SHMT2 was found to be increased in 7 kidney cancer datasets, compared to normal renal tissues. For the cancer stages, ages and races, there existed significant difference in the expression of SHMT2 among different groups by mining of the UALCAN database. High SHMT2 expression is associated with poor overall survival in patients with kidney cancer. Among all co-expressed genes, NDUFA4L2 and SHMT2 had a high co-expression efficient. SHMT2 overexpression led to the increased expression of NDUFA4L2 at both mRNA and protein levels. Like SHMT2, overexpressed NDUFA4L2 also was associated with worse overall survival in patients with kidney cancer. Conclusion Based on above results, overexpressed SHMT2 and its co-expressed gene NDUFA4L2 were all correlated with the prognosis in kidney cancer. The present study might be benefit for better understanding the clinical significance of SHMT2 and provided a potential therapeutic target for kidney cancer in future.

Eating disorder is highly associated with obesity and it is related to brain dysfunction as well. Still, the functional substrates of the brain associated with behavioral traits of eating disorder are underexplored. Existing neuroimaging studies have explored the association between eating disorder and brain function without using all the information provided by the eating disorder related questionnaire but by adopting summary factors. Here, we aimed to investigate the multivariate association between brain function and eating disorder at fine-grained question-level information. Our study is a retrospective secondary analysis that re-analyzed resting-state functional magnetic resonance imaging of 284 participants from the enhanced Nathan Kline Institute-Rockland Sample database. Leveraging sparse canonical correlation analysis, we associated the functional connectivity of all brain regions and all questions in the eating disorder questionnaires. We found that executive- and inhibitory control-related frontoparietal networks showed positive associations with questions of restraint eating, while brain regions involved in the reward system showed negative associations. Notably, inhibitory control-related brain regions showed a positive association with the degree of obesity. Findings were well replicated in the independent validation dataset (n = 34). The results of this study might contribute to a better understanding of brain function with respect to eating disorder.

Human brain can be divided into multiple brain regions based on anatomical and functional properties. Recent studies showed that resting‐state connectivity can be utilized for parcellating brain regions and identifying their distinctive roles. In this study, we aimed to parcellate the primary and secondary visual cortices (V1 and V2) into several subregions based on functional connectivity and to examine the functional characteristics of each subregion. We used resting‐state data from a research database and also acquired resting‐state data with retinotopy results from a local site. The long‐range connectivity profile and three different algorithms (i.e., K‐means, Gaussian mixture model distribution, and Ward's clustering algorithms) were adopted for the parcellation. We compared the parcellation results within V1 and V2 with the eccentric map in retinotopy. We found that the boundaries between subregions within V1 and V2 were located in the parafovea, indicating that the anterior and posterior subregions within V1 and V2 corresponded to peripheral and central visual field representations, respectively. Next, we computed correlations between each subregion within V1 and V2 and intermediate and high‐order regions in ventral and dorsal visual pathways. We found that the anterior subregions of V1 and V2 were strongly associated with regions in the dorsal stream (V3A and inferior parietal gyrus), whereas the posterior subregions of V1 and V2 were highly related to regions in the ventral stream (V4v and inferior temporal gyrus). Our findings suggest that the anterior and posterior subregions of V1 and V2, parcellated based on functional connectivity, may have distinct functional properties.

Hexafluoropropylene oxide dimer acid, also known as GenX, is a poly- and perfluoroalkyl substance (PFAS). PFASs are nonvolatile synthetic substances that can be readily disseminated into the environment during processing and use, making them easy to implement in the soil, drinking water, and air. Compared to other PFASs, GenX has a comparatively short carbon chain length and is expected to have a lower tendency to accumulate in humans; therefore, GenX has recently been used as a substitute to other PFASs. However, the mechanisms underlying GenX action and intoxication in humans remains unclear. In this study, the apoptotic capacity of GenX in human liver cells was investigated. When representative human-derived liver cells (HepG2 cells) were treated with GenX for 12 h, cell viability was reduced, and apoptosis was greatly increased. In addition, GenX increased the generation of intracellular reactive oxygen species (ROS), indicating the induction of oxidative stress in a dose-dependent manner. GenX treatment increased the expression of major apoptosis-related genes relative to the untreated control group. This research indicates that GenX causes apoptosis through ROS mediation in HepG2 cells, which may expand our knowledge of the molecular and toxicological mechanisms of GenX., Graphical abstract Image 1, Highlights • Hexafluoropropylene oxide dimer acid (GenX) can be harmful to the liver. • Through the mediation of ROS, GenX causes apoptosis in HepG2 cells. • GenX activates Bax, caspase 3/9, CHOP, and p53 via the apoptosis. • The intrinsic pathway links GenX mode of action to apoptosis-related stimuli., Poly- and perfluoroalkyl substance; Hexafluoropropylene oxide dimer acid; Oxidative stress; Apoptosis; Liver cells.

Obesity is a serious medical condition highly associated with health problems such as diabetes, hypertension, and stroke. Obesity is highly associated with negative emotional states, but the relationship between obesity and emotional states in terms of neuroimaging has not been fully explored. We obtained 196 emotion task functional magnetic resonance imaging (t-fMRI) from the Human Connectome Project database using a sampling scheme similar to a bootstrapping approach. Brain regions were specified by automated anatomical labeling atlas and the brain activity (z-statistics) of each brain region was correlated with body mass index (BMI) values. Regions with significant correlation were identified and the brain activity of the identified regions was correlated with emotion-related clinical scores. Hippocampus, amygdala, and inferior temporal gyrus consistently showed significant correlation between brain activity and BMI and only the brain activity in amygdala consistently showed significant negative correlation with fear-affect score. The brain activity in amygdala derived from t-fMRI might be good neuroimaging biomarker for explaining the relationship between obesity and a negative emotional state.

Attention deficit and hyperactivity disorder (ADHD) is a disorder characterized by behavioral symptoms including hyperactivity/impulsivity among children, adolescents, and adults. These ADHD related symptoms are influenced by the complex interaction of brain networks which were under explored. We explored age-related brain network differences between ADHD patients and typically developing (TD) subjects using resting state fMRI (rs-fMRI) for three age groups of children, adolescents, and adults. We collected rs-fMRI data from 184 individuals (27 ADHD children and 31 TD children; 32 ADHD adolescents and 32 TD adolescents; and 31 ADHD adults and 31 TD adults). The Brainnetome Atlas was used to define nodes in the network analysis. We compared three age groups of ADHD and TD subjects to identify the distinct regions that could explain age-related brain network differences based on degree centrality, a well-known measure of nodal centrality. The left middle temporal gyrus showed significant interaction effects between disease status (i.e., ADHD or TD) and age (i.e., child, adolescent, or adult) (P < 0.001). Additional regions were identified at a relaxed threshold (P < 0.05). Many of the identified regions (the left inferior frontal gyrus, the left middle temporal gyrus, and the left insular gyrus) were related to cognitive function. The results of our study suggest that aberrant development in cognitive brain regions might be associated with age-related brain network changes in ADHD patients. These findings contribute to better understand how brain function influences the symptoms of ADHD.

Background An increased risk of acute ischemic stroke is recognized among patients with cancer. However, the mechanism behind cancer‐related stroke is unclear. In this study, we determined the presence of associated venous thromboembolism and arterial thromboembolism and their clinical impact on patients with cancer‐related stroke. Methods and Results Patients with embolic stroke of undetermined source with or without cancer were evaluated for venous thromboembolism (deep vein thrombosis [ DVT ] and/or pulmonary embolism) and arterial thromboembolism by using Doppler sonography to determine the presence of lower‐extremity DVT and the microembolic signal of the symptomatic cerebral circulation, respectively. Infarct volume was determined by diffusion‐weighted magnetic resonance imaging. The multivariable linear regression and Cox proportional hazard analysis were used to investigate the effect of DVT and microembolic signal on infarct volume and 1‐year survival, respectively. Of 142 screened patients, 118 were included (37 with, 81 without cancer). Those with cancer had a higher prevalence of DVT or microembolic signal than did the noncancer group (62.2% versus 19.8%; P DVT was associated with a greater infarct volume in magnetic resonance imaging (beta, 13.14; 95% CI , 1.62–24.66; P =0.028). Presence of DVT (hazard ratio, 16.79; 95% CI, 2.05–137.75; P =0.009) and microembolic signal (hazard ratio, 8.16; 95% CI , 1.36–48.85; P =0.022) were independent predictors of poor 1‐year survival. Conclusions Patients with cancer‐associated embolic stroke of undetermined source have an elevated risk of associated venous thromboembolism and arterial thromboembolism, both of which have a significant negative impact on 1‐year survival. The results of this study may enhance our understanding of cancer‐associated stroke and improve risk stratification of patients with this disease. Clinical Trial Registration URL : https://www.clinicaltrials.gov/.Unique identifier: NCT 02212496

Purpose Medical image synthesis can simulate a target modality of interest based on existing modalities and has the potential to save scanning time while contributing to efficient data collection. This study proposed a three-dimensional (3D) deep learning architecture based on a fully convolutional network (FCN) to synthesize diffusion-tensor imaging (DTI) from resting-state functional magnetic resonance imaging (fMRI). Methods: fMRI signals derived from white matter (WM) exist and can be used for assessing WM alterations. We constructed an initial functional correlation tensor image using the correlation patterns of adjacent fMRI voxels as one input to the FCN. We considered T1-weighted images as an additional input to provide an algorithm with the structural information needed to synthesize DTI. Our architecture was trained and tested using a large-scale open database dataset (training n = 648; testing n = 293). Results The average correlation value between synthesized and actual diffusion tensors for 38 WM regions was 0.808, which significantly improves upon an existing study (r = 0.480). We also validated our approach using two open databases. Our proposed method showed a higher correlation with the actual diffusion tensor than the conventional machine-learning method for many WM regions. Conclusions Our method synthesized DTI images from fMRI images using a 3D FCN architecture. We hope to expand our method of synthesizing various other imaging modalities from a single image source.

Obesity is often associated with cardiovascular complications. Adolescent obesity is a risk factor for cardiovascular disease in adulthood; thus, intensive management is warranted in adolescence. The brain state contributes to the development of obesity in addition to metabolic conditions, and hence neuroimaging is an important tool for accurately assessing an individual’s risk of developing obesity. Here, we aimed to predict body mass index (BMI) progression in adolescents with neuroimaging features using machine learning approaches. From an open database, we adopted 76 resting-state functional magnetic resonance imaging (rs-fMRI) datasets from adolescents with longitudinal BMI scores. Functional connectivity analyses were performed on cortical surfaces and subcortical volumes. We identified baseline functional connectivity features in the prefrontal-, posterior cingulate-, sensorimotor-, and inferior parietal-cortices as significant determinants of BMI changes. A BMI prediction model based on the identified fMRI biomarkers exhibited a high accuracy (intra-class correlation = 0.98) in predicting BMI at the second visit (1~2 years later). The identified brain regions were significantly correlated with the eating disorder-, anxiety-, and depression-related scores. Based on these results, we concluded that these functional connectivity features in brain regions related to eating disorders and emotional processing could be important neuroimaging biomarkers for predicting BMI progression.

Obesity causes critical health problems including cardiovascular disease, diabetes, and stroke. Various neuroimaging methods including diffusion tensor imaging (DTI) are used to explore white matter (WM) alterations in obesity. The functional correlation tensor (FCT) is a method to simulate DTI in WM using resting-state functional magnetic resonance imaging (rs-fMRI). In this study, we enhanced the FCT with additional anatomical information from T1-weighted data in a regression framework. The goal was to 1) develop a spatially guided enhanced FCT (s-eFCT) and to 2) use it to identify imaging biomarkers for obesity. We computed fractional anisotropy (FA) and the mean diffusivity (MD) from the s-eFCT. The regional FA and MD values that can explain body mass index (BMI) well were chosen. The identified regional FA and MD values were used to predict BMI values. The correlation between real and predicted BMIs was 0.57. There was no significant correlation between real and predicted DTI using the MD. The BMI predicted using FA was used to classify participants into three obesity subgroups. The classification accuracy was 57.20%. In summary, we found potential imaging biomarkers of obesity based on the s-eFCT.

A high power 755 nm continuous-wave (CW) laser with high beam quality based on the Alexandrite crystal was demonstrated. The Alexandrite lasers single-end-pumped by 638 nm laser diodes (LDs) and 532 nm solid-state laser were studied comparatively, then the CW output power, optical-to-optical conversion efficiency, and slope efficiency pumped by 638 nm LDs were 3.9 W, 19.7%, and 23.7%, respectively, while they were 2.1 W, 10.0%, and 12.9%, at nearly the same conditions except that it was pumped by 532 nm solid-state laser. The results show that the Alexandrite laser pumped with 638 nm LDs can obtain higher CW output power and higher conversion efficiency. Moreover, a CW output power of 6.2 W at 755 nm of Alexandrite laser double-end-pumped by a 638 nm LDs was achieved with the optical-to-optical conversion efficiency and the slope efficiency of 16.3% and 24.2%, respectively. The beam quality factor M2 was better than 1.47 at the CW output power of 5.0 W, which was the highest CW output power of Alexandrite laser with the diffraction limit to the best. This high power and high beam quality 755 nm Alexandrite laser provides the fundamental frequency source for the development of CW ultraviolet lasers.

Background and Objective Patients with migraine show an increased presence of white matter hyperintensities (WMHs), especially deep WMHs. Segmentation of small, deep WMHs is a critical issue in managing migraine care. Here, we aim to develop a novel approach to segmenting deep WMHs using deep neural networks based on the U-Net. Methods 148 non-elderly subjects with migraine were recruited for this study. Our model consists of two networks: the first identifies potential deep WMH candidates, and the second reduces the false positives within the candidates. The first network for initial segmentation includes four down-sampling layers and four up-sampling layers to sort the candidates. The second network for false positive reduction uses a smaller field-of-view and depth than the first network to increase utilization of local information. Results Our proposed model segments deep WMHs with a high true positive rate of 0.88, a low false discovery rate of 0.13, and F1 score of 0.88 tested with ten-fold cross-validation. Our model was automatic and performed better than existing models based on conventional machine learning. Conclusion We developed a novel segmentation framework tailored for deep WMHs using U-Net. Our algorithm is open-access to promote future research in quantifying deep WMHs and might contribute to the effective management of WMHs in migraineurs.

Abdominal obesity is important for understanding obesity, which is a worldwide medical problem. We explored structural and functional brain differences in people with abdominal and non-abdominal obesity by using multimodal neuroimaging and up-to-date analysis methods. A total of 274 overweight people, whose body mass index exceeded 25, were enrolled in this study. Participants were divided into abdominal and non-abdominal obesity groups using a waist–hip ratio threshold of 0.9 for males and 0.85 for females. Structural and functional brain differences were assessed with diffusion tensor imaging and resting-state functional magnetic resonance imaging. Centrality measures were computed from structural fiber tractography, and static and dynamic functional connectivity matrices. Significant inter-group differences in structural and functional connectivity were found using degree centrality (DC) values. The associations between the DC values of the identified regions/networks and behaviors of eating disorder scores were explored. The highest association was achieved by combining DC values of the cerebral peduncle, anterior corona radiata, posterior corona radiata (from structural connectivity), frontoparietal network (from static connectivity), and executive control network (from dynamic connectivity) compared to the use of structural or functional connectivity only. Our results demonstrated the effectiveness of multimodal imaging data and found brain regions or networks that may be responsible for behaviors of eating disorders in people with abdominal obesity.

Depression is one of the most common and important neuropsychiatric symptoms in Parkinson’s disease and often becomes worse as Parkinson’s disease progresses. However, the underlying mechanisms of depression in Parkinson’s disease are not clear. The aim of our study was to find genetic features related to depression in Parkinson’s disease using an imaging genetics approach and to construct an analytical model for predicting the degree of depression in Parkinson’s disease. The neuroimaging and genotyping data were obtained from an openly accessible database. We computed imaging features through connectivity analysis derived from tractography of diffusion tensor imaging. The imaging features were used as intermediate phenotypes to identify genetic variants according to the imaging genetics approach. We then constructed a linear regression model using the genetic features from imaging genetics approach to describe clinical scores indicating the degree of depression. As a comparison, we constructed other models using imaging features and genetic features based on references to demonstrate the effectiveness of our imaging genetics model. The models were trained and tested in a five-fold cross-validation. The imaging genetics approach identified several brain regions and genes known to be involved in depression, with the potential to be used as meaningful biomarkers. Our proposed model using imaging genetic features predicted and explained the degree of depression in Parkinson’s disease appropriately (adjusted R2 larger than 0.6 over five training folds) and with a lower error and higher correlation than with other models over five test folds.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide. Despite progress in diagnostics and treatment of HCC, its prognosis remains poor. Emerging studies showed that long noncoding RNAs (lncRNAs) have crucial regulatory roles in cancer biology. In the current study, differentially expressed lncRNAs between HCC and paired non-tumor tissues were identified using microarrays. The effects of a specific differentially expressed lncRNA (termed ZEB1-AS1) on tumor progression were investigated in vitro and in vivo. We found that ZEB1-AS1 is frequently upregulated in HCC samples, especially in metastatic tumor tissues. DNA methylation analysis shows a tumor-specific ZEB1-AS1 promoter hypomethylation. Aberrant methylation is tightly correlated with overexpression of ZEB1-AS1 in HCC. Patients with ZEB1-AS1 hypomethylation or with high ZEB1-AS1 expression have poor recurrence-free survival. Functionally, ZEB1-AS1 promotes tumor growth and metastasis, acts as an oncogene in HCC. The ZEB1-AS1 gene is located in physical contiguity with ZEB1 and positively regulates the ZEB1 expression. ZEB1 inhibition partially abrogates ZEB1-AS1-induced epithelial to mesenchymal transition (EMT) and cancer metastasis. Our results provide novel insights into the function of lncRNA-driven hepatocarcinogenesis, highlight the important role of ZEB1-AS1 and ZEB1 in HCC progression, and indicate that ZEB1-AS1 may be served as a valuable prognostic biomarker for HCC.

Migraineurs show an increased load of white matter hyperintensities (WMHs) and more rapid deep WMH progression. Previous methods for WMH segmentation have limited efficacy to detect small deep WMHs. We developed a new fully automated detection pipeline, DEWS (DEep White matter hyperintensity Segmentation framework), for small and superficially-located deep WMHs. A total of 148 non-elderly subjects with migraine were included in this study. The pipeline consists of three components: 1) white matter (WM) extraction, 2) WMH detection, and 3) false positive reduction. In WM extraction, we adjusted the WM mask to re-assign misclassified WMHs back to WM using many sequential low-level image processing steps. In WMH detection, the potential WMH clusters were detected using an intensity based threshold and region growing approach. For false positive reduction, the detected WMH clusters were classified into final WMHs and non-WMHs using the random forest (RF) classifier. Size, texture, and multi-scale deep features were used to train the RF classifier. DEWS successfully detected small deep WMHs with a high positive predictive value (PPV) of 0.98 and true positive rate (TPR) of 0.70 in the training and test sets. Similar performance of PPV (0.96) and TPR (0.68) was attained in the validation set. DEWS showed a superior performance in comparison with other methods. Our proposed pipeline is freely available online to help the research community in quantifying deep WMHs in non-elderly adults., Highlights • A fully automated deep white matter hyperintensity detection algorithm was developed. • An exquisite white matter mask region was constructed. • Size, texture, and multi-scale deep features were used for false positive reduction. • DEWS detected white matter hyperintensities with a high positive predictive value.

Barrett's esophagus is a diseased condition with abnormal changes of the cells in the esophagus. Intestinal metaplasia (IM) and gastric metaplasia (GM) are two sub-classes of Barrett's esophagus. As IM can progress to the esophageal cancer, the neoplasia (NPL), developing methods for classifying between IM and GM are important issues in clinical practice. We adopted a deep learning (DL) algorithm to classify three conditions of IM, GM, and NPL based on endimicroscopy images. We constructed a convolutional neural network (CNN) architecture to distinguish among three classes. A total of 262 endomicroscopy imaging data of Barrett's esophagus were obtained from the international symposium on biomedical imaging (ISBI) 2016 challenge. 155 IM, 26 GM and 55 NPL cases were used to train the architecture. We implemented image distortion to augment the sample size of the training data. We tested our proposed architecture using the 26 test images that include 17 IM, 4 GM and 5 NPL cases. The classification accuracy was 80.77%. Our results suggest that CNN architecture could be used as a good classifier for distinguishing endomicroscopy imaging data of Barrett's esophagus.

Uncontrollable eating behavior is highly associated with dysfunction in neurocognitive systems. We aimed to quantitatively link brain networks and eating behaviors based on dynamic functional connectivity analysis, which reflects temporal dynamics of brain networks. We used 62 resting-state functional magnetic resonance imaging data sets representing 31 healthy weight (HW) and 31 non-HW participants based on body mass index (BMI). Brain networks were defined using a data-driven group-independent component analysis and a dynamic connectivity analysis with a sliding window technique was applied. The network centrality parameters of the dynamic brain networks were extracted from each brain network and they were correlated to eating behavior and BMI scores. The network parameters of the executive control network showed a strong correlation with eating behavior and BMI scores only when a dynamic (p0.05), not static (p0.05), connectivity analysis was adopted. We demonstrated that dynamic connectivity analysis was more effective at linking brain networks and eating behaviors than static approach. We also confirmed that the executive control network was highly associated with eating behaviors.