The genetic architecture of the human hypothalamus and its involvement in neuropsychiatric behaviours and disorders.

Despite its crucial role in the regulation of vital metabolic and neurological functions, the genetic architecture of the hypothalamus remains unknown. Here we conducted multivariate genome-wide association studies (GWAS) using hypothalamic imaging data from 32,956 individuals to uncover the genetic underpinnings of the hypothalamus and its involvement in neuropsychiatric traits. There were 23 significant loci associated with the whole hypothalamus and its subunits, with functional enrichment for genes involved in intracellular trafficking systems and metabolic processes of steroid-related compounds. The hypothalamus exhibited substantial genetic associations with limbic system structures and neuropsychiatric traits including chronotype, risky behaviour, cognition, satiety and sympathetic-parasympathetic activity. The strongest signal in the primary GWAS, the ADAMTS8 locus, was replicated in three independent datasets (N = 1,685-4,321) and was strengthened after meta-analysis. Exome-wide association analyses added evidence to the association for ADAMTS8, and Mendelian randomization showed lower ADAMTS8 expression with larger hypothalamic volumes. The current study advances our understanding of complex structure-function relationships of the hypothalamus and provides insights into the molecular mechanisms that underlie hypothalamic formation.

Circulating polyunsaturated fatty acids, fish oil supplementation, and risk of incident dementia: a prospective cohort study of 440,750 participants.

Cohort studies report inconsistent associations between omega-3 polyunsaturated fatty acids (n-3 PUFA) or fish oil and dementia risk. Furthermore, evidence relating omega-6 polyunsaturated fatty acids (n-6 PUFA) with dementia is scarce. Here, we included 440,750 dementia-free participants from UK Biobank to comprehensively investigate the associations between plasma levels of different types of PUFA, fish oil supplementation, and dementia risk. During a median follow-up of 9.25 years, 7768 incident dementia events occurred. Higher plasma levels of five PUFA measures showed consistent associations with lower dementia risk (hazard ratios [95% confidence intervals] for per standard deviation increment of plasma concentrations 0.85 [0.81-0.89] for total PUFAs; 0.90 [0.86-0.95] for omega-3 PUFAs; 0.92 [0.87-0.96] for docosahexaenoic acid (DHA); 0.86 [0.82-0.90] for omega-6 PUFAs; 0.86 [0.82-0.90] for linoleic acid (LA); all p < 0.001). Compared with non-users, fish oil supplement users had a 7% decreased risk of developing all-cause dementia (0.93 [0.89-0.97], p = 0.002), and the relationship was partially mediated by plasma n-3 PUFA levels (omega-3 PUFAs: proportion of mediation = 57.99%; DHA: proportion of mediation = 56.95%). Furthermore, we observed significant associations of plasma n-3 PUFA levels and fish oil supplementation with peripheral immune markers that were related to dementia risk, as well as the positive associations of plasma PUFA levels with brain gray matter volumes and white matter microstructural integrity, suggesting they may affect dementia risk by affecting peripheral immunity and brain structure. Taken together, higher plasma PUFA levels and fish oil supplementation were associated with lower risk of incident dementia. This study may support the value of interventions to target PUFAs (specifically n-3 PUFAs) to prevent dementia.

Developing Ecological Thresholds for Nitrogen and Phosphorus in the Haihe River Basin in China.

Many aquatic ecosystems are eutrophicated due to human inputs of nitrogen and phosphorus. Therefore, it is now considered important to establish nutrient criteria to prevent eutrophication. In this study, the water quality and biological data for 26 stations in the lower reaches of the Haihe River Basin were collected. The total nitrogen (TN) and total phosphorus (TP) ecological thresholds were derived from the threshold indicator taxa analysis (TITAN) and frequency distribution approach. The results showed that the TN threshold was 1.8 mg/L based on the TITAN and the TP threshold was 0.039 mg/L based on the frequency distribution approach. The TITAN also identified 29 indicator species of TN and 28 indicator species of TP. Based on these criteria, we found 73% sites with TN concentrations higher than the 1.8 mg/L. As for TP, 58% sites exceeded 0.039 mg/L. This study showed that most of the downstream areas of the Haihe River are subject to relatively serious disturbances. This finding could provide implications for identifying the water quality traits of and generating protection strategies for the Haihe River in Tianjin.

Effects of Environmental Concentrations of Total Phosphorus on the Plankton Community Structure and Function in a Microcosm Study.

The excessive nutrients in freshwater have been proven to promote eutrophication and harmful algae blooms, which have become great threats to water quality and human health. To elucidate the responses of the plankton community structure and function to total phosphorus (TP) at environmental concentrations in the freshwater ecosystem, a microcosm study was implemented. The results showed that plankton communities were significantly affected by the TP concentration ≥ 0.1 mg/L treatments. In terms of community structure, TP promoted the growth of Cyanophyta. This effect was transmitted to the zooplankton community, resulting in the promotion of Cladocera growth from day 42. The community diversities of phytoplankton and zooplankton had been continuously inhibited by TP. The principal response curve (PRC) analysis results demonstrated that the species composition of phytoplankton and zooplankton community in TP enrichment treatments significantly (p ≤ 0.05) deviated from the control. For community function, TP resulted in the decline in phytoplankton photosynthesis. The chlorophyll fluorescence parameters were significantly inhibited when TP concentration reached 0.4 mg/L. In TP ≥ 0.1 mg/L treatments, the reductions in total phytoplankton abundances led to a continuous decrease in pH. This study can directly prove that the plankton community changes significantly when TP concentrations are greater than 0.1 mg/L and can help managers to establish specific nutrient management strategies for surface water.

Common abnormal connectivity in first-episode and chronic schizophrenia in pre- and post-central regions: Implications for neuromodulation targeting.

Schizophrenia is a neurodevelopmental disorder manifesting differing impairments at early onset and chronic disease stages. Brain imaging research suggests a core pathological region in patients with first-episode schizophrenia is Broca's area. With disease progression, alterations in thalamic connectivity becomes more prevalent. Understanding the common circuitry underlying pathology in these two groups might highlight a critical common network and novel targets for treatment. In this study, 937 subject samples were collected including patients with first-episode schizophrenia and those with chronic schizophrenia. We used hypothesis-based voxel-level functional connectivity analyses to calculate functional connectivity using the left Broca's area and thalamus as regions of interest in those with first-episode and chronic schizophrenia, respectively. We show for the first time that in both patients with first-episode and chronic schizophrenia the greatest functional connectivity disruption ended in the pre- and postcentral regions. At the early-onset stage, the core brain region is abnormally connected to pre- and postcentral areas responsible for mouth movement, while in the chronic stage, it expanded to a wider range of sensorimotor areas. Our findings suggest that expanding the focus on the low-order sensory-motor systems beyond high-order cognitive impairments in schizophrenia may show potential for neuromodulation treatment, given the relative accessibility of these cortical regions and their functional and structural connections to the core region at different stages of illness.

Increased brain volume from higher cereal and lower coffee intake: shared genetic determinants and impacts on cognition and metabolism.

It is unclear how different diets may affect human brain development and if genetic and environmental factors play a part. We investigated diet effects in the UK Biobank data from 18,879 healthy adults and discovered anticorrelated brain-wide gray matter volume (GMV)-association patterns between coffee and cereal intake, coincidence with their anticorrelated genetic constructs. The Mendelian randomization approach further indicated a causal effect of higher coffee intake on reduced total GMV, which is likely through regulating the expression of genes responsible for synaptic development in the brain. The identified genetic factors may further affect people's lifestyle habits and body/blood fat levels through the mediation of cereal/coffee intake, and the brain-wide expression pattern of gene CPLX3, a dedicated marker of subplate neurons that regulate cortical development and plasticity, may underlie the shared GMV-association patterns among the coffee/cereal intake and cognitive functions. All the main findings were successfully replicated. Our findings thus revealed that high-cereal and low-coffee diets shared similar brain and genetic constructs, leading to long-term beneficial associations regarding cognitive, body mass index (BMI), and other metabolic measures. This study has important implications for public health, especially during the pandemic, given the poorer outcomes of COVID-19 patients with greater BMIs.

Riverine flux of dissolved phosphorus to the coastal sea may be overestimated, especially in estuaries of gated rivers: Implications of phosphorus adsorption/desorption on suspended sediments.

The flux of terrestrial dissolved inorganic phosphorous (DIP, i.e. PO43-) via rivers into coastal seas is usually calculated by simply multiplying its concentration with the corresponding water flow at the river mouth. Subsequent adsorption/desorption of DIP onto suspended sediment and the influence of salinity in the estuary are often overlooked. A series of DIP adsorption/desorption experiments under different salinities (0, 5, 15, 30) and suspended sediment concentrations (1-40 g L-1) were conducted in order to assess the potential influence of these factors on the overall DIP loading to the coastal zone. The effect of different sea-salt ions on DIP adsorption/desorption was also assessed by comparing different experimental solutions (NaCl solution, artificial seawater and real seawater). In estuaries, the adsorption of DIP to suspended sediments was greater than desorption, and the net adsorption increased with increasing concentration of suspended sediments and salinity. This enhanced DIP adsorption onto suspended sediment reduces the riverine discharge of DIP to coastal ecosystems. Disregarding this process, especially for the gated estuaries with high sediment resuspension, potentially leads to an overestimation of the terrestrial DIP input to the coastal region.

An extended Human Connectome Project multimodal parcellation atlas of the human cortex and subcortical areas.

A modified and extended version, HCPex, is provided of the surface-based Human Connectome Project-MultiModal Parcellation atlas of human cortical areas (HCP-MMP v1.0, Glasser et al. 2016). The original atlas with 360 cortical areas has been modified in HCPex for ease of use with volumetric neuroimaging software, such as SPM, FSL, and MRIcroGL. HCPex is also an extended version of the original atlas in which 66 subcortical areas (33 in each hemisphere) have been added, including the amygdala, thalamus, putamen, caudate nucleus, nucleus accumbens, globus pallidus, mammillary bodies, septal nuclei and nucleus basalis. HCPex makes available the excellent parcellation of cortical areas in HCP-MMP v1.0 to users of volumetric software, such as SPM and FSL, as well as adding some subcortical regions, and providing labelled coronal views of the human brain.

Mindfulness practice for protecting mental health during the COVID-19 pandemic.

Emerging evidence shows that the coronavirus disease 2019 (COVID-19) pandemic is negatively affecting mental health around the globe. Interventions to alleviate the psychological impact of the pandemic are urgently needed. Whether mindfulness practice may protect against the harmful emotional effects of a pandemic crisis remains hitherto unknown. We investigated the influence of mindfulness training on mental health during the COVID-19 outbreak in China. We hypothesized that mindfulness practitioners might manifest less pandemic-related distress, depression, anxiety, and stress than non-practitioners and that more frequent practice would be associated with an improvement in mental health during the pandemic. Therefore, we assessed pandemic-related distress and symptoms of depression, anxiety, and stress, as well as the frequency of meditation practice at the peak of new infections (Feb 4-5; N = 673) and three weeks later (Feb 29-30; N = 521) in mindfulness practitioners via online questionnaires. Self-reported symptoms were also collected from non-practitioners at peak time only (N = 1550). We found lower scores of pandemic-related distress in mindfulness practitioners compared to non-practitioners. In general, older participants showed fewer symptoms of depression and anxiety. In younger practitioners, pandemic-related distress decreased from peak to follow-up. Importantly, increased mindfulness training during the preceding two weeks was associated with lower scores of depression and anxiety at both assessments. Likewise, practice frequency predicted individual improvement in scores of depression, anxiety, and stress at follow-up. Our results indicate that mindfulness meditation might be a viable low-cost intervention to mitigate the psychological impact of the COVID-19 crisis and future pandemics.

Chlorophyll a predictability and relative importance of factors governing lake phytoplankton at different timescales.

Assessing the key drivers of eutrophication in lakes and reservoirs has long been a challenge, and many studies have developed empirical models for predicting the relative importance of these drivers. However, the relative roles of various parameters might differ not only spatially (between regions or localities) but also at a temporal scale. In this study, the relative roles of total phosphorus, total nitrogen, ammonia, wind speed and water temperature were selected as potential drivers of phytoplankton biomass by using chlorophyll a as a proxy for biomass. A generalized additive model (GAM) and a random forest model (RF) were developed to assess the predictability of chlorophyll a and the relative importance of various predictors driving algal blooms at different timescales in a freshwater lake. The results showed that the daily datasets yielded better predictability than the monthly datasets. In addition, at a daily scale, water temperature was a more important predictor of chlorophyll a than nutrients, and the importance of phosphorus was comparable to that of nitrogen. In contrast, at a monthly scale, nutrients are more important predictors than water temperature and phosphorus is a better predictor than nitrogen. This study indicates that the drivers of phytoplankton fluctuations vary at different timescales and that timescale has an influence on the relative roles of nitrogen and phosphorus limitation in lakes, which suggests that the temporal scale should be considered when explaining phytoplankton fluctuations. Moreover, this study provides a reference for the monitoring of phytoplankton fluctuations and for understanding the mechanisms underlying phytoplankton fluctuations at different timescales.

"Brain Connectivity Deviates by Sex and Hemisphere in the First Episode of Schizophrenia"-A Route to the Genetic Basis of Language and Psychosis?

Schizophrenia is genetic in origin and associated with a fecundity disadvantage. The deficits in schizophrenia have been attributed to variation related to the human capacity for language or brain laterality. How sex influences the relative connectivity of the 2 hemispheres is a route to understanding these 2 functions. Using resting-state functional magnetic resonance imaging (fMRI) we searched for sex- and hemisphere-specific changes in whole-brain functional-connectivity in multi-site datasets (altogether 672 subjects including 286 patients, all right-handed) in the first-episode schizophrenia (illness duration ≤ 1 year, mostly drug naive) and in chronic stages of schizophrenia (illness duration > 1 year), respectively. We used meta-analyses to integrate data from different sources concerning individuals at the same illness stage. We found first-episode male patients are predominantly left-lateralized in aberrant connectivity with a focus on Broca's area. Female patients show a lesser degree of lateralization than males, but to the right particularly in orbital frontal cortex. In the chronic stage, the focus of aberrant connectivity shifted from anterior to posterior structures with prominent involvement of the thalamus and pre- and post-central gyri bilaterally and in both sexes. While the "deviant connectivity" is right-sided in both the first-episode and the chronic stages in females, in males there is a shift between stages from the left to the right hemisphere. We hypothesized that the pathophysiology of schizophrenia may lie in the interaction between sex and lateralization, ie, in genetic mechanisms located on the X and Y chromosomes, intrinsic to the evolution of language.

A Bayesian modeling approach for phosphorus load apportionment in a reservoir with high water transfer disturbance.

Phosphorus loading from external and internal sources poses a potential risk to eutrophication of lakes or reservoirs. However, the relative contribution of external and internal sources to eutrophication is still unclear especially for reservoirs with water transfer disturbance. The objective of this paper is to estimate the phosphorus loading from external (water transfer and diffusing emission) and internal sources (sediment release) in Yuqiao Reservoir (YQR) and compare their relative contribution of external and internal sources. In this study, we estimated the phosphorus loading considering both external (water transfer and diffusing source emission) and internal (release from sediment) sources of YQR. The phosphorus loading from water transfer was estimated by total phosphorus (TP) concentration × monthly flow of inflow. The phosphorus loading from nonpoint source emission was estimated using a generalized watershed loading function (GWLF). The phosphorus loading from internal sources was estimated with a Bayesian phosphorus budget model. Our result showed that water transfer TP load is the biggest (45.2%) source of TP load in YQR and internal TP load (20.5%) accounts for a comparable proportion of TP load as nonpoint source (34.3%) in YQR and dominates the total loading in some months. Analysis of seasonal total phosphorus load apportionment indicated that water transfer TP load takes the largest proportion in winter (60.8%), spring (60.2%), and autumn (47.8%). Nonpoint source TP load takes the largest proportion in summer (60.1%), and internal TP load is the second source of YQR in summer (22.4%). Our study indicates that water transfer may be the major driver of eutrophication for some reservoir systems, and sediment release may prevent recovery of many eutrophic lakes and reservoirs. Our analysis suggests that TP pollution control strategies in YQR should be preferentially focused on the improvement of water quality in the upstream reservoir, and nonpoint source TP load reductions should be focused on summer. Compared with conventional nutrient apportionment model applications, this paper provides a new approach to estimate external and internal TP loads simultaneously. Graphical abstract ᅟ.

Distinguishable brain networks relate disease susceptibility to symptom expression in schizophrenia.

Disease association studies have characterized altered resting-state functional connectivities describing schizophrenia, but failed to model symptom expression well. We developed a model that could account for symptom severity and meanwhile relate this to disease-related functional pathology. We correlated BOLD signal across brain regions and tested separately for associations with disease (disease edges) and with symptom severity (symptom edges) in a prediction-based scheme. We then integrated them in an "edge bi-color" graph, and adopted mediation analysis to test for causality between the disease and symptom networks and symptom scores. For first-episode schizophrenics (FES, 161 drug-naïve patients and 150 controls), the disease network (with inferior frontal gyrus being the hub) and the symptom-network (posterior occipital-parietal cortex being the hub) were found to overlap in the temporal lobe. For chronic schizophrenis (CS, 69 medicated patients and 62 controls), disease network was dominated by thalamocortical connectivities, and overlapped with symptom network in the middle frontal gyrus. We found that symptom network mediates the relationship between disease network and symptom scores in FEP, but was unable to define a relationship between them for the smaller CS population. Our results suggest that the disease network distinguishing core functional pathology in resting-state brain may be responsible for symptom expression in FES through a wider brain network associated with core symptoms. We hypothesize that top-down control from heteromodal prefrontal cortex to posterior transmodal cortex contributes to positive symptoms of schizophrenia. Our work also suggests differences in mechanisms of symptom expression between FES and CS, highlighting a need to distinguish between these groups.

Long-term changes in nutrients, chlorophyll a and their relationships in a semi-enclosed eutrophic ecosystem, Bohai Bay, China.

As the representative semi-enclosed bay of China, Bohai Bay has experienced severe eutrophication in recent decades. Monitoring data from 1995 to 2013 were analysed by generalized additive models (GAMs) to explore the temporal variations in nutrients concentrations, nutrient ratios, chlorophyll a (Chl a) concentrations and the responses of Chl a to the changes in nutrients in the spring and summer. The results showed that dissolved inorganic nitrogen (DIN) decreased from 1995 to 2000 but increased after 2000 in both the spring and summer, and soluble reactive phosphorus (SRP) decreased while the molar nitrogen/phosphorus (N/P) ratios (DIN to SRP) increased over the last two decades. Generally, P-limited phytoplankton growth was observed in the spring and summer and DIN was identified as the main pollutant constituent in Bohai Bay. Furthermore, negative correlations were found between DIN and Chl a in summer in Bohai Bay.

A Bayesian approach of high impaired river reaches identification and total nitrogen load estimation in a sparsely monitored basin.

In this study, a modeling framework based on the theory of SPAtially Referenced Regression On Watershed attributes (SPARROW) model was developed to identify impaired river reaches with respect to total nitrogen (TN) and estimate the TN sources in the Xin'anjiang River basin, which had limited monitoring sites. A Bayesian approach was applied to estimate the mean values and uncertainties of parameters, including land use export coefficients and in-stream attention rates. Based on the parameters, the midranges (25-75 %) of annual TN concentrations were assessed by the model and 4.5 % of river reaches in the basin were found to be with higher impaired probabilities (namely [TN] > 1.5 mg/l) than other reaches. The amount and yields of TN discharged from diffuse sources were estimated for each county in the basin. The results suggested that Tunxi City had the highest TN yields from farm land and population, while the highest TN yields in Huangshan City were from tea plantations. The outcomes of this study will guide the implementation of practical management measures to reduce TN loads.

Brain-Wide Analysis of Functional Connectivity in First-Episode and Chronic Stages of Schizophrenia.

Published reports of functional abnormalities in schizophrenia remain divergent due to lack of staging point-of-view and whole-brain analysis. To identify key functional-connectivity differences of first-episode (FE) and chronic patients from controls using resting-state functional MRI, and determine changes that are specifically associated with disease onset, a clinical staging model is adopted. We analyze functional-connectivity differences in prodromal, FE (mostly drug naïve), and chronic patients from their matched controls from 6 independent datasets involving a total of 789 participants (343 patients). Brain-wide functional-connectivity analysis was performed in different datasets and the results from the datasets of the same stage were then integrated by meta-analysis, with Bonferroni correction for multiple comparisons. Prodromal patients differed from controls in their pattern of functional-connectivity involving the inferior frontal gyri (Broca's area). In FE patients, 90% of the functional-connectivity changes involved the frontal lobes, mostly the inferior frontal gyrus including Broca's area, and these changes were correlated with delusions/blunted affect. For chronic patients, functional-connectivity differences extended to wider areas of the brain, including reduced thalamo-frontal connectivity, and increased thalamo-temporal and thalamo-sensorimoter connectivity that were correlated with the positive, negative, and general symptoms, respectively. Thalamic changes became prominent at the chronic stage. These results provide evidence for distinct patterns of functional-dysconnectivity across FE and chronic stages of schizophrenia. Importantly, abnormalities in the frontal language networks appear early, at the time of disease onset. The identification of stage-specific pathological processes may help to understand the disease course of schizophrenia and identify neurobiological markers crucial for early diagnosis.

Using real-time fMRI to influence effective connectivity in the developing emotion regulation network.

For most people, adolescence is synonymous with emotional turmoil and it has been shown that early difficulties with emotion regulation can lead to persistent problems for some people. This suggests that intervention during development might reduce long-term negative consequences for those individuals. Recent research has highlighted the suitability of real-time fMRI-based neurofeedback (NF) in training emotion regulation (ER) networks in adults. However, its usefulness in directly influencing plasticity in the maturing ER networks remains unclear. Here, we used NF to teach a group of 17 7-16 year-olds to up-regulate the bilateral insula, a key ER region. We found that all participants learned to increase activation during the up-regulation trials in comparison to the down-regulation trials. Importantly, a subsequent Granger causality analysis of Granger information flow within the wider ER network found that during up-regulation trials, bottom-up driven Granger information flow increased from the amygdala to the bilateral insula and from the left insula to the mid-cingulate cortex, supplementary motor area and the inferior parietal lobe. This was reversed during the down-regulation trials, where we observed an increase in top-down driven Granger information flow to the bilateral insula from mid-cingulate cortex, pre-central gyrus and inferior parietal lobule. This suggests that: 1) NF training had a differential effect on up-regulation vs down-regulation network connections, and that 2) our training was not only superficially concentrated on surface effects but also relevant with regards to the underlying neurocognitive bases. Together these findings highlight the feasibility of using NF in children and adolescents and its possible use for shaping key social cognitive networks during development.

Frequency-dependent amplitude alterations of resting-state spontaneous fluctuations in idiopathic generalized epilepsy.

PURPOSE: Amplitude of low-frequency fluctuation (ALFF) of blood-oxygenation level-dependent (BOLD) has proven a promising way to detect disease-related local brain activity. However, routine approach employs an arbitrary frequency band of 0.01-0.08 Hz, which lacks frequency specificity and blinds to the information contained in other frequency bands. This study investigated the amplitude of fluctuations in full BOLD frequency bands, and addressed how amplitudes of fluctuations change in each specific frequency range in idiopathic generalized epilepsy (IGE). METHODS: Thirty-four IGE patients with generalized tonic-clonic seizure and the same number of age- and sex-matched healthy controls were included. Functional MRI data were acquired using a 2s repetition time. Routine amplitude of low-frequency fluctuation analysis was first performed. The regions showing group difference were set as Region-of-interest for analysis of amplitudes of full-frequency. The amplitudes of BOLD fluctuations were consecutively performed at each frequency bin of 0.002 Hz, and specific frequency amplitude analyses were performed in five different frequency ranges (0-0.01 Hz, 0.01-0.027 Hz, 0.027-0.073 Hz, 0.073-0.198 Hz, and 0.198-0.25 Hz). KEY FINDINGS: The thalamus and prefrontal cortex showed significant group differences in routine amplitude analysis. For amplitude of full-frequency analysis, a reverse pattern was found in the dynamic changes between the thalamus and prefrontal cortex in IGE. Moreover, the prefrontal cortex showed amplitude difference in the 0.01-0.027 Hz band, while the thalamus showed amplitude difference in the 0.027-0.073 Hz band. Both these two regions showed amplitude differences in 0.198-0.25 Hz band. SIGNIFICANCE: We demonstrated the characteristic alterations of amplitude of BOLD fluctuations in IGE in frequency domain. The amplitude analysis of full frequency may potentially help to select specific frequency range for detecting epilepsy-related brain activity, and provide insights into the pathophysiological mechanism of IGE.