Nur77 induced by HIF-1α mediates vascular remodeling in hypoxic pulmonary hypertension.

Nur77 is a member of the NR4A subfamily of orphan nuclear receptors that is expressed and has a function within the immune system. This study aimed to investigate the role of Nur77 in hypoxic pulmonary hypertension. SPF male SD rats were exposed in hypobaric chamber simulating 5000 m high altitude for 0, 3, 7, 14, 21 or 28 days. Rat pulmonary artery smooth muscle cells (RPASMCs) were cultured under normoxic conditions (5% CO2-95% ambient air) or hypoxic conditions (5% O2 for 6 h, 12 h, 24 h, 48 h). Hypoxic rats developed pulmonary arterial remodeling and right ventricular hypertrophy with significantly increased pulmonary arterial pressure. The levels of Nur77, HIF-1α and PNCA were upregulated in pulmonary arterial smooth muscle from hypoxic rats. Silencing of either Nur77 or HIF-1α attenuated hypoxia-induced proliferation. Silencing of HIF-1α down-regulated Nur77 protein level, but Nur77 silence did not reduce HIF-1α. Nur77 was not con-immunoprecipitated with HIF-1α. This study demonstrated that Nur77 acted as a downstream regulator of HIF-1α under hypoxia, and plays a critical role in the hypoxia-induced pulmonary vascular remodeling, which is regulated by HIF-1α. Nur77 maybe a novel target of HPH therapy.

The golden key to open mystery boxes of SMARCA4-deficient undifferentiated thoracic tumor: focusing immunotherapy, tumor microenvironment and epigenetic regulation.

SMARCA4-deficient undifferentiated thoracic tumor is extremely invasive. This tumor with poor prognosis is easily confused with SMARCA4-deficent non-small cell lung cancer or sarcoma. Standard and efficient treatment has not been established. In this review, we summarized the etiology, pathogenesis and diagnosis, reviewed current and proposed innovative strategies for treatment and improving prognosis. Immunotherapy, targeting tumor microenvironment and epigenetic regulator have improved the prognosis of cancer patients. We summarized clinicopathological features and immunotherapy strategies and analyzed the progression-free survival (PFS) and overall survival (OS) of patients with SMARCA4-UT who received immune checkpoint inhibitors (ICIs). In addition, we proposed the feasibility of epigenetic regulation in the treatment of SMARCA4-UT. To our knowledge, this is the first review that aims to explore innovative strategies for targeting tumor microenvironment and epigenetic regulation and identify potential benefit population for immunotherapy to improve the prognosis.

Imaging the neural substrate of trigeminal neuralgia pain using deep learning.

Trigeminal neuralgia (TN) is a severe and disabling facial pain condition and is characterized by intermittent, severe, electric shock-like pain in one (or more) trigeminal subdivisions. This pain can be triggered by an innocuous stimulus or can be spontaneous. Presently available therapies for TN include both surgical and pharmacological management; however, the lack of a known etiology for TN contributes to the unpredictable response to treatment and the variability in long-term clinical outcomes. Given this, a range of peripheral and central mechanisms underlying TN pain remain to be understood. We acquired functional magnetic resonance imaging (fMRI) data from TN patients who (1) rested comfortably in the scanner during a resting state session and (2) rated their pain levels in real time using a calibrated tracking ball-controlled scale in a pain tracking session. Following data acquisition, the data was analyzed using the conventional correlation analysis and two artificial intelligence (AI)-inspired deep learning methods: convolutional neural network (CNN) and graph convolutional neural network (GCNN). Each of the three methods yielded a set of brain regions related to the generation and perception of pain in TN. There were 6 regions that were identified by all three methods, including the superior temporal cortex, the insula, the fusiform, the precentral gyrus, the superior frontal gyrus, and the supramarginal gyrus. Additionally, 17 regions, including dorsal anterior cingulate cortex (dACC) and the thalamus, were identified by at least two of the three methods. Collectively, these 23 regions are taken to represent signature centers of TN pain and provide target areas for future studies seeking to understand the central mechanisms of TN.

Symptom Burden among Older COVID-19 Survivors Two Years after Hospital Discharge.

To study the long-term symptom burden among older COVID-19 survivors 2 years after hospital discharge and identify associated risk factors. The current cohort study included COVID-19 survivors aged 60 years and above, who were discharged between February 12 and April 10, 2020, from two designated hospitals in Wuhan, China. All patients were contacted via telephone and completed a standardized questionnaire assessing self-reported symptoms, the Checklist Individual Strength (CIS)-fatigue subscale, and two subscales of the Hospital Anxiety and Depression Scale (HADS). Of the 1,212 patients surveyed, the median (IQR) age was 68.0 (64.0-72.0), and 586 (48.3%) were male. At the two-year follow-up, 259 patients (21.4%) still reported at least one symptom. The most frequently self-reported symptoms were fatigue, anxiety, and dyspnea. Fatigue or myalgia, which was the most common symptom cluster (11.8%; 143/1212), often co-occurred with anxiety and chest symptoms. A total of 89 patients (7.7%) had CIS-fatigue scores ≥ 27, with older age (odds ratio [OR], 1.08; 95% CI: 1.05-1.11, P < 0.001) and oxygen therapy (OR, 2.19; 95% CI: 1.06-4.50, P= 0.03) being risk factors. A total of 43 patients (3.8%) had HADS-Anxiety scores ≥ 8, and 130 patients (11.5%) had HADS-Depression scores ≥ 8. For the 59 patients (5.2%) who had HADS total scores ≥ 16, older age, serious illness during hospitalization and coexisting cerebrovascular diseases were risk factors. Cooccurring fatigue, anxiety, and chest symptoms, as well as depression, were mainly responsible for long-term symptom burden among older COVID-19 survivors 2 years after discharge.

Depth-dependent effects of tree species identity on soil microbial community characteristics and multifunctionality.

Soil microbes play key roles that support forest ecosystem functioning, while their community characteristics are strongly determined by tree species identity. However, the majority studies primarily focus on soil microorganisms in the topsoil, resulting in limited understanding of the linkages between tree species identity and the microbial communities that inhabit deep soils. Here we investigated the diversity, structure, function, and co-occurrence networks of soil bacterial and fungal communities, as well as related soil physicochemical properties, to a depth of two meters in dryland forests dominated by either Pinus tabuliformis, a native coniferous species, Robinia pseudoacacia, an exotic broadleaf and nitrogen-fixing species, or both. Tree species identity had stronger effects on soil multifunctionality and microbial community structure in the deep layers (80-200 cm) than in the top layers (0-60 cm). In addition, fungal communities were more responsive to tree species identity, whereas bacteria were more sensitive to soil depth. Tree species identity strongly influenced microbial network stability and complexity, with higher quantities in R. pseudoacacia than the other plantations, by affecting microbial composition and their associations. The increased in microbial network complexity and the relative abundance of keystone taxa enhance the soil multifunctionality of microbial productivity, sugar and chitin degradation, and nutrient availability and cycling. Meanwhile, the relative abundance of keystone taxa was more representative of soil multifunctionality than microbial diversity. Our study highlights that tree species identity significantly influences soil microbial community characteristics and multifunctionality, especially in deep soils, which will help us understand soil nutrients processed in plantation forest ecosystem and provide a reference for tree species selection in ecological restoration.

Aftereffects of frontoparietal theta tACS on verbal working memory: Behavioral and neurophysiological analysis.

Verbal working memory is supported by a left-lateralized frontoparietal theta oscillatory (4-8 Hz) network. We tested whether stimulating the left frontoparietal network at theta frequency during verbal working memory can produce observable after-stimulation effects in behavior and neurophysiology. Weak theta-band alternating electric currents were delivered via two 4 × 1 HD electrode arrays centered at F3 and P3. Three stimulation configurations, including in-phase, anti-phase, or sham, were tested on three different days in a cross-over (within-subject) design. On each test day, the subject underwent three experimental sessions: pre-, during- and post-stimulation sessions. In all sessions, the subject performed a Sternberg verbal working memory task with three levels of memory load (load 2, 4 and 6), imposing three levels of cognitive demand. Analyzing behavioral and EEG data from the post-stimulation session, we report two main observations. First, in-phase stimulation improved task performance in subjects with higher working memory capacity (WMC) under higher memory load (load 6). Second, in-phase stimulation enhanced frontoparietal theta synchrony during working memory retention in subjects with higher WMC under higher memory loads (load 4 and load 6), and the enhanced frontoparietal theta synchronization is mainly driven by enhanced frontal→parietal theta Granger causality. These observations suggest that (1) in-phase theta transcranial alternating current stimulation (tACS) during verbal working memory can result in observable behavioral and neurophysiological consequences post stimulation, (2) the short-term plasticity effects are state- and individual-dependent, and (3) enhanced executive control underlies improved behavioral performance.

Decoding the temporal dynamics of affective scene processing.

Natural images containing affective scenes are used extensively to investigate the neural mechanisms of visual emotion processing. Functional fMRI studies have shown that these images activate a large-scale distributed brain network that encompasses areas in visual, temporal, and frontal cortices. The underlying spatial and temporal dynamics, however, remain to be better characterized. We recorded simultaneous EEG-fMRI data while participants passively viewed affective images from the International Affective Picture System (IAPS). Applying multivariate pattern analysis to decode EEG data, and representational similarity analysis to fuse EEG data with simultaneously recorded fMRI data, we found that: (1) ∼80 ms after picture onset, perceptual processing of complex visual scenes began in early visual cortex, proceeding to ventral visual cortex at ∼100 ms, (2) between ∼200 and ∼300 ms (pleasant pictures: ∼200 ms; unpleasant pictures: ∼260 ms), affect-specific neural representations began to form, supported mainly by areas in occipital and temporal cortices, and (3) affect-specific neural representations were stable, lasting up to ∼2 s, and exhibited temporally generalizable activity patterns. These results suggest that affective scene representations in the brain are formed temporally in a valence-dependent manner and may be sustained by recurrent neural interactions among distributed brain areas.

Variations in Plant Water Use Efficiency Response to Manipulated Precipitation in a Temperate Grassland.

Water use efficiency (WUE) plays important role in understanding the interaction between carbon and water cycles in the plant-soil-atmosphere system. However, little is known regarding the impact of altered precipitation on plant WUE in arid and semi-arid regions. The study examined the effects of altered precipitation [i.e., ambient precipitation (100% of natural precipitation), decreased precipitation (DP, -50%) and increased precipitation (IP, +50%)] on the WUE of grass species (Stipa grandis and Stipa bungeana) and forb species (Artemisia gmelinii) in a temperate grassland. The results found that WUE was significantly affected by growth stages, precipitation and plant species. DP increased the WUE of S. grandis and S. bungeana generally, but IP decreased WUE especially in A. gmelinii. And the grasses had the higher WUE than forbs. For different growth stages, the WUE in the initial growth stage was lower than that in the middle and late growth stages. Soil temperature, available nutrients (i.e., NO3 -, NH4 +, and AP) and microorganisms under the altered precipitations were the main factors affecting plant WUE. These findings highlighted that the grasses have higher WUE than forbs, which can be given priority to vegetation restoration in arid and semi-arid areas.

Clinical characteristics, risk factors, and cardiac manifestations of cancer patients with COVID-19.

Coronavirus disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been associated with cardiovascular features, which may be deteriorated in patients with cancer. However, cardiac outcomes of cancer patients with COVID-19 have not been closely examined. We retrospectively assessed 1,244 patients with COVID-19 from February 1 to August 31, 2020 (140 cancer and 1,104 noncancer patients). Demographic and clinical data were obtained and compared between cancer and noncancer groups. Including the cardiac biomarkers, we also analyzed laboratory findings between these two groups. Risk factors for in-hospital mortality were identified by multivariable Cox regression models. For cancer group, 56% were in severe and critical status with more diabetes and immune deficiency, whereas the proportion was 10% for noncancer group. Patients with cancer had increased levels of leukocyte, neutrophil count, and blood urea nitrogen (BUN) (all P < 0.01), whereas lymphocyte count was significantly lower (P < 0.001). The most common solid tumor types were gastrointestinal cancer (26%), lung cancer (21%), and breast and reproductive cancer (both 19%). There is a rising for cardiac biomarkers, including pro-B-type natriuretic peptide (Pro-BNP), sensitive troponin I (cTnI), myoglobin (MYO), creatine kinase-MB (CK-MB), as well as D-Dimer in COVID-19 cancer population, especially in deceased subjects with cancer. The 30-day in-hospital mortality in cancer group was dramatically raised than that in noncancer group (12.9% vs. 4.0%, P < 0.01). In multivariable Cox regression models, fever, disease severity status, and underlying diseases were risk factors for mortality. COVID-19 patients with cancer relate to deteriorating conditions and poor cardiac outcomes accompanied by a high in-hospital mortality, which warrants more aggressive treatment.NEW & NOTEWORTHY Our study indicates that the 30-day mortality is higher in COVID-19 patients with cancer; more COVID-19 patients with cancer are in severe and critical status; age, respiratory rate, neutrophil count, AST, BUN, MYO, Pro-BNP, disease severity status, underlying diseases, and fever are risk factors for in-hospital mortality among COVID-19 cancer cases; COVID-19 patients with cancer display severely impaired myocardium, damaged heart function, and imbalanced homeostasis of coagulation; what is more, those with both cancer and CVD have more significantly increased Pro-BNP and D-Dimer level.

MicroRNA-146a inhibits autophagy to maintain the intracellular survival of Burkholderia pseudomallei by targeting LIPA.

Burkholderia pseudomallei is the etiological agent of melioidosis, which is an emerging infectious disease endemic to many tropical regions. Autophagy is an intrinsic cellular process that degrades cytoplasmic components and plays an important role in protecting the host against pathogens. Like many intracellular pathogens, B. pseudomallei can evade the autophagy-dependent cellular clearance. However, the underlying mechanism remains unclear. In this study, we applied a combination of multiple assays to monitor autophagy processes and found that B. pseudomallei induced an incomplete autophagic flux and eliminate autophagy clearance in macrophages by blocking autophagosome-lysosome fusion. Based on a high-throughput microarray screening, we found that LIPA (lysosomal acid LIPAse A) was downregulated during B. pseudomallei infection. MiR-146a was then identified to be specifically upregulated upon infection with B. pseudomallei and further regulated LIPA expression by interacting with 3'UTR of LIPA. Furthermore, overexpression of miR-146a contributed to the defect of autophagic flux caused by B. pseudomallei and was beneficial for the survival of B. pseudomallei in macrophages. Therefore, our findings suggest that miR-146a inhibits autophagy via posttranscriptional suppression of LIPA expression to maintain B. pseudomallei survival in macrophages.

Decoding Neural Representations of Affective Scenes in Retinotopic Visual Cortex.

The perception of opportunities and threats in complex visual scenes represents one of the main functions of the human visual system. The underlying neurophysiology is often studied by having observers view pictures varying in affective content. It has been shown that viewing emotionally engaging, compared with neutral, pictures (1) heightens blood flow in limbic, frontoparietal, and anterior visual structures and (2) enhances the late positive event-related potential (LPP). The role of retinotopic visual cortex in this process has, however, been contentious, with competing theories predicting the presence versus absence of emotion-specific signals in retinotopic visual areas. Recording simultaneous electroencephalography-functional magnetic resonance imaging while observers viewed pleasant, unpleasant, and neutral affective pictures, and applying multivariate pattern analysis, we found that (1) unpleasant versus neutral and pleasant versus neutral decoding accuracy were well above chance level in retinotopic visual areas, (2) decoding accuracy in ventral visual cortex (VVC), but not in early or dorsal visual cortex, was correlated with LPP, and (3) effective connectivity from amygdala to VVC predicted unpleasant versus neutral decoding accuracy, whereas effective connectivity from ventral frontal cortex to VVC predicted pleasant versus neutral decoding accuracy. These results suggest that affective scenes evoke valence-specific neural representations in retinotopic visual cortex and that these representations are influenced by reentry signals from anterior brain regions.

An association between resting state EEG parameters and the severity of topiramate-related cognitive impairment.

INTRODUCTION: Many commonly prescribed drugs cause cognitive deficits. We investigated whether parameters of the resting-state electroencephalogram (rsEEG) are related to the severity of cognitive impairments associated with administration of the antiseizure drug topiramate (TPM) and the benzodiazepine lorazepam (LZP). METHODS: We conducted a double-blind, randomized, placebo-controlled crossover study. After a baseline visit, subjects completed three sessions at which they received either a single dose of TPM, LZP, or placebo. Four-hours after drug administration and at baseline, subjects completed a working memory (WM) task after their rsEEG was recorded. After quantifying drug-related behavioral (WM accuracy (ACC)/reaction time (RT)) and electrophysiological (alpha, theta, beta (1,2), gamma power) change for each subject, we constructed drug-specific mixed effects models of change for each WM and EEG measure. Regression models were constructed to characterize the relationship between baseline rsEEG measures and drug-related performance changes. RESULTS: Linear mixed effects models showed theta power increases in response to TPM administration. The results of the regression models revealed a number of robust relationships between baseline rsEEG parameters and TPM-related, but not LZP-related, WM impairment. CONCLUSIONS: We showed for the first time that parameters of the rsEEG are associated with the severity of TPM-related WM deficits; this suggests that rsEEG measures may have novel clinical applications in the future.

Thymosin Alpha 1 Reduces the Mortality of Severe Coronavirus Disease 2019 by Restoration of Lymphocytopenia and Reversion of Exhausted T Cells.

BACKGROUND: Thymosin alpha 1 (Tα1) had been used in the treatment of viral infections as an immune response modifier for many years. However, clinical benefits and the mechanism of Tα1 treatment for COVID-19 patients are still unclear. METHODS: We retrospectively reviewed the clinical outcomes of 76 severe COVID-19 cases admitted to 2 hospitals in Wuhan, China, from December 2019 to March 2020. The thymus output in peripheral blood mononuclear cells from COVID-19 patients was measured by T-cell receptor excision circles (TRECs). The levels of T-cell exhaustion markers programmed death-1 (PD-1) and T-cell immunoglobulin and mucin domain protein 3 (Tim-3) on CD8+ T cells were detected by flow cytometry. RESULTS: Compared with the untreated group, Tα1 treatment significantly reduced the mortality of severe COVID-19 patients (11.11% vs 30.00%, P = .044). Tα1 enhanced blood T-cell numbers in COVID-19 patients with severe lymphocytopenia. Under such conditions, Tα1 also successfully restored CD8+ and CD4+ T-cell numbers in elderly patients. Meanwhile, Tα1 reduced PD-1 and Tim-3 expression on CD8+ T cells from severe COVID-19 patients compared with untreated cases. It is of note that restoration of lymphocytopenia and acute exhaustion of T cells were roughly parallel to the rise of TRECs. CONCLUSIONS: Tα1 treatment significantly reduced mortality of severe COVID-19 patients. COVID-19 patients with counts of CD8+ T cells or CD4+ T cells in circulation less than 400/µL or 650/µL, respectively, gained more benefits from Tα1. Tα1 reversed T-cell exhaustion and recovered immune reconstitution through promoting thymus output during severe acute respiratory syndrome-coronavirus 2 infection.

A preliminary study on serological assay for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 238 admitted hospital patients.

In this study, we aimed to evaluate the diagnostic value of serological assay for SARS-CoV-2. A newly-developed ELISA assay for IgM and IgG antibodies against N protein of SARS-CoV-2 was used to screen the serums of 238 admitted hospital patients between February 6 and February 14, 2020 with confirmed or suspected SARS-CoV-2. SARS-CoV-2 RNA was detected on pharyngeal swab specimens using real time RT-PCR. 194 (81.5%) of the serums were detected to be antibody (IgM and/or IgG) positive, significantly higher than the positive rate of viral RNA (64.3%). There was no difference in the positive rate of antibodies between the confirmed patients (83.0%, 127/153) and the suspected patients (78.8%, 67/85), whose nucleic acid tests were negative. The antibody positive rates were very low in the first five days after initial onset of symptoms, and then rapidly increased as the disease progressed. After 10 days, the antibody positive rates jumped from below 50% to over 80%. However, the positive rates of viral RNA maintained above 60% in the first 11 days after initial onset of symptoms, and then rapidly decreased. Overall, the suspected patients were most likely infected by SARS-CoV-2. Before the 11th day after initial onset of symptoms, nucleic acid test is key for confirmation of viral infection. The combination of serological assay can greatly improve the diagnostic efficacy. After the 11th day post-disease onset, the diagnosis for viral infection should be majorly dependent on serological assay.

Traits mediate drought effects on wood carbon fluxes.

CO2 fluxes from wood decomposition represent an important source of carbon from forest ecosystems to the atmosphere, which are determined by both wood traits and climate influencing the metabolic rates of decomposers. Previous studies have quantified the effects of moisture and temperature on wood decomposition, but these effects were not separated from the potential influence of wood traits. Indeed, it is not well understood how traits and climate interact to influence wood CO2 fluxes. Here, we examined the responses of CO2 fluxes from dead wood with different traits (angiosperm and gymnosperm) to 0%, 35%, and 70% rainfall reduction across seasonal temperature gradients. Our results showed that drought significantly decreased wood CO2 fluxes, but its effects varied with both taxonomical group and drought intensity. Drought-induced reduction in wood CO2 fluxes was larger in angiosperms than gymnosperms for the 35% rainfall reduction treatment, but there was no significant difference between these groups for the 70% reduction treatment. This is because wood nitrogen density and carbon quality were significantly higher in angiosperms than gymnosperms, yielding a higher moisture sensitivity of wood decomposition. These findings were demonstrated by a significant positive interaction effect between wood nitrogen and moisture on CO2 fluxes in a structural equation model. Additionally, we ascertained that a constant temperature sensitivity of CO2 fluxes was independent of wood traits and consistent with previous estimates for extracellular enzyme kinetics. Our results highlight the key role of wood traits in regulating drought responses of wood carbon fluxes. Given that both climate and forest management might extensively modify taxonomic compositions in the future, it is critical for carbon cycle models to account for such interactions between wood traits and climate in driving dynamics of wood decomposition.

Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding.

BACKGROUND: In late December, 2019, patients presenting with viral pneumonia due to an unidentified microbial agent were reported in Wuhan, China. A novel coronavirus was subsequently identified as the causative pathogen, provisionally named 2019 novel coronavirus (2019-nCoV). As of Jan 26, 2020, more than 2000 cases of 2019-nCoV infection have been confirmed, most of which involved people living in or visiting Wuhan, and human-to-human transmission has been confirmed. METHODS: We did next-generation sequencing of samples from bronchoalveolar lavage fluid and cultured isolates from nine inpatients, eight of whom had visited the Huanan seafood market in Wuhan. Complete and partial 2019-nCoV genome sequences were obtained from these individuals. Viral contigs were connected using Sanger sequencing to obtain the full-length genomes, with the terminal regions determined by rapid amplification of cDNA ends. Phylogenetic analysis of these 2019-nCoV genomes and those of other coronaviruses was used to determine the evolutionary history of the virus and help infer its likely origin. Homology modelling was done to explore the likely receptor-binding properties of the virus. FINDINGS: The ten genome sequences of 2019-nCoV obtained from the nine patients were extremely similar, exhibiting more than 99·98% sequence identity. Notably, 2019-nCoV was closely related (with 88% identity) to two bat-derived severe acute respiratory syndrome (SARS)-like coronaviruses, bat-SL-CoVZC45 and bat-SL-CoVZXC21, collected in 2018 in Zhoushan, eastern China, but were more distant from SARS-CoV (about 79%) and MERS-CoV (about 50%). Phylogenetic analysis revealed that 2019-nCoV fell within the subgenus Sarbecovirus of the genus Betacoronavirus, with a relatively long branch length to its closest relatives bat-SL-CoVZC45 and bat-SL-CoVZXC21, and was genetically distinct from SARS-CoV. Notably, homology modelling revealed that 2019-nCoV had a similar receptor-binding domain structure to that of SARS-CoV, despite amino acid variation at some key residues. INTERPRETATION: 2019-nCoV is sufficiently divergent from SARS-CoV to be considered a new human-infecting betacoronavirus. Although our phylogenetic analysis suggests that bats might be the original host of this virus, an animal sold at the seafood market in Wuhan might represent an intermediate host facilitating the emergence of the virus in humans. Importantly, structural analysis suggests that 2019-nCoV might be able to bind to the angiotensin-converting enzyme 2 receptor in humans. The future evolution, adaptation, and spread of this virus warrant urgent investigation. FUNDING: National Key Research and Development Program of China, National Major Project for Control and Prevention of Infectious Disease in China, Chinese Academy of Sciences, Shandong First Medical University.

Working Memory Capacity Is Negatively Associated with Memory Load Modulation of Alpha Oscillations in Retention of Verbal Working Memory.

Working memory capacity (WMC) measures the amount of information that can be maintained online in the face of distraction. Past work has shown that the efficiency with which the frontostriatal circuit filters out task-irrelevant distracting information is positively correlated with WMC. Recent work has demonstrated a role of posterior alpha oscillations (8-13 Hz) in providing a sensory gating mechanism. We investigated the relationship between memory load modulation of alpha power and WMC in two verbal working memory experiments. In both experiments, we found that posterior alpha power increased with memory load during memory, in agreement with previous reports. Across individuals, the degree of alpha power modulation by memory load was negatively associated with WMC, namely, the higher the WMC, the less alpha power was modulated by memory load. After the administration of topiramate, a drug known to affect alpha oscillations and have a negative impact on working memory function, the negative correlation between memory load modulation of alpha power and WMC was no longer statistically significant but still somewhat detectable. These results suggest that (1) individuals with low WMC demonstrate stronger alpha power modulation by memory load, reflecting possibly an increased reliance on sensory gating to suppress task-irrelevant information in these individuals, in contrast to their high WMC counterparts who rely more on frontal areas to perform this function and (2) this negative association between memory load modulation of alpha oscillations and WMC is vulnerable to drug-related cognitive disruption.

Author Correction: Dissociable functional activities of cortical theta and beta oscillations in the lateral prefrontal cortex during intertemporal choice.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Neural mechanisms of internal distraction suppression in visual attention.

When performing a demanding cognitive task, internal distraction in the form of task-irrelevant thoughts and mind wandering can shift our attention away from the task, negatively affecting task performance. Behaviorally, individuals with higher executive function indexed by higher working memory capacity (WMC) exhibit less mind wandering during cognitive tasks, but the underlying neural mechanisms are unknown. To address this problem, we recorded functional magnetic resonance imaging (fMRI) data from subjects performing a cued visual attention task, and assessed their WMC in a separate experiment. Applying machine learning and time-series analysis techniques, we showed that (1) higher WMC individuals experienced lower internal distraction through stronger suppression of posterior cingulate cortex (PCC) activity, (2) higher WMC individuals had better neural representations of attended information as evidenced by higher multivoxel decoding accuracy of cue-related activities in the dorsal attention network (DAN), (3) the positive relationship between WMC and DAN decoding accuracy was mediated by suppression of PCC activity, (4) the dorsal anterior cingulate (dACC) was a source of top-down signals that regulate PCC activity as evidenced by the negative association between Granger-causal influence dACC→PCC and PCC activity levels, and (5) higher WMC individuals exhibiting stronger dACC→PCC Granger-causal influence. These results shed light on the neural mechanisms underlying the executive suppression of internal distraction in tasks requiring externally oriented attention and provide an explanation of the individual differences in such suppression.