Biology subjects

Ding, M.

Publications and source records attributed to Ding, M..

At least 73 records · Page 4Linked to original sources

bioRxiv2022

Pathogen Clearance-based Correlates of Immunoprotection Reveal Insightful Features of Vaccine Immunity

Vaccination has significantly reduced the incidence of invasive infections caused by several bacterial pathogens, including Streptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitidis. However, no vaccines are available for many other invasive pathogens. A major hurdle in vaccine development is the lack of functional markers to quantify vaccine immunity in eliminating pathogens in the process of infection. Based on our recent discovery of the liver as the major organ of vaccine-induced clearance of blood-borne virulent bacteria, we here describe a new vaccine evaluation system that quantitatively characterize important properties of effective vaccines in shuffling virulent bacteria from the blood circulation to the liver resident macrophage Kupffer cells (KCs) and sinusoidal endothelial cells (LSECs) in animal models. This system consists of three related correlates or assays: pathogen clearance from the bloodstream, pathogen trapping in the liver, and pathogen capture by KCs/LSECs. The readouts of these correlates were consistently associated with the serotype-specific immunoprotection levels of the 13-valent pneumococcal polysaccharide conjugate vaccine (PCV13) against lethal infections of S. pneumoniae, a major invasive pathogen of community-acquired infections in humans. Furthermore, the reliability and sensitivity of these correlates in reflecting vaccine efficacy were verified with whole cell vaccines of Klebsiella pneumoniae and Escherichia coli, two major pathogens in hospital-acquired invasive infections. This system may be used as cost effective readouts to evaluate the immunoprotective potential of vaccine candidates in the preclinical phase by filling the current technical gap in vaccine evaluation between the conventional in vitro approaches (e.g., antibody production and pathogen neutralization/opsonophagocytosis) and survival of immunized animals.

immunology↗

bioRxiv2022

Potent Bacterial Vaccines Require FcγRIIB-mediated Pathogen Capture by Liver Sinusoidal Endothelium

Certain vaccines are more effective than others against microbial infections, but the molecular mechanisms separating the two types of vaccines are largely undefined. Here, by comparing two vaccines of Streptococcus pneumoniae with identical antigens but different efficacies (pneumococcal conjugate vaccine - PCV13 and pneumococcal polysaccharide vaccine - PPV23), we reveal that superior vaccine protection against blood-borne bacteria is primarily achieved by activating pathogen capture of the sinusoidal endothelial cells (ECs) in the liver. Consistent with its superior protection in humans, PCV13 confers a more potent protection than PPV23 against pneumococcal infection in mice. In vivo real-time imaging and genetic mutagenesis revealed that PCV13 activates both liver ECs and resident macrophages Kupffer cells (KCs) to capture IgG-coated bacteria via IgG Fc gamma receptor (Fc{gamma}R). In particular, the Fc{gamma}RIIB-mediated capture by ECs is responsible for PCV13-induced superior protection. In contrast, PPV23 only activates KCs (but not ECs) to achieve a less effective pathogen capture and protection through complement receptor-mediated recognition of IgM- and C3-coated bacteria. These liver-based vaccine protection mechanisms are also found with the vaccines of Neisseria meningitidis and Klebsiella pneumoniae, another two important invasive human pathogens. Our findings have uncovered a novel EC- and Fc{gamma}RIIB-mediated mechanism in the liver for more efficacious vaccine protection. These findings can serve as in vivo functional readouts to evaluate vaccine efficacy and guide the future vaccine development. One Sentence SummaryVaccine efficacy is defined by Fc{gamma}RIIB-mediated capture of antibody-coated bacteria via liver sinusoidal endothelial cells.

immunology↗

bioRxiv2022

Regulation of mRNA transcripts, protein isoforms, glycosylation and spatial localization of ACE2 and other SARS-CoV-2-associated molecules in human airway epithelium upon viral infection and type 2 inflammation

SARS-CoV-2 infection continues to pose a significant life threat, especially in patients with comorbidities. It remains unknown, if asthma or allergen- and virus-induced airway inflammation are risk factors or can constitute some forms of protection against COVID-19. ACE2 and other SARS-CoV-2-related host proteins are limiting factors of an infection, expression of which is regulated in a more complex way than previously anticipated. Hence, we studied the expression of ACE2 mRNA and protein isoforms, together with its glycosylation and spatial localization in house dust mite (HDM)-, interleukin-13 (IL-13)- and human rhinovirus (RV)-induced inflammation in the primary human bronchial airway epithelium of healthy subjects and patients with asthma. IL-13 decreased the expression of long ACE2 mRNA and glycosylation of full-length ACE2 protein via alteration of the N-linked glycosylation process, limiting its availability on the apical side of ciliated cells. RV infection increased short ACE2 mRNA, but it did not influence its protein expression. HDM exposure did not affect ACE2 mRNA or protein. IL-13 and RV significantly regulated mRNA, but not protein expression of TMPRSS2 and NRP1. Regulation of ACE2 and other host proteins was similar in healthy and asthmatic epithelium, underlining the lack of intrinsic differences, but rather the dependence on the inflammatory milieu in the airways.

immunology↗

bioRxiv2022

Long non coding RNA L13Rik promotes high glucose-induced mesangial cell injury by regulating miR-2861/CDKN1B axis

Diabetic nephropathy (DN) is a frequent and severe microvascular complication of diabetes. Glomerular mesangial cell (MC) injury occurs at the initial phase of DN and acts as a critical role in the pathogenesis of DN. Given the importance of long non-coding RNA (lncRNA) in regulating MC hyperplasia and extracellular matrix (ECM) accumulation, it is essential to identify functional lncRNAs during MC injury. Here a novel lncRNA, C920021L13Rik (L13Rik for short), was identified to up-regulated in DN progression. The expression of L13Rik in DN patients and diabetic rats was assessed using quantitative real-time PCR (qRT-PCR), and the function of L13Rik on regulating HG-induced MC injury was assessed using cell counting kit-8 (CCK-8) and western blot assay to analyze MC viability and ECM accumulation. We found that L13Rik level was significantly increased while miR-2861 level was significantly decreased in peripheral blood of DN patients, renal tissues of diabetic rats, and HG-treated MCs. Functionally, both L13Rik depletion and miR-2861 overexpression effectively reduced HG-induced MC survival, ECM accumulation, and cell hypertrophy. Mechanistically, L13Rik functioned as a competing endogenous RNA (ceRNA) to sponge miR-2861, resulting in the de-repression of its target cyclin-dependent kinase inhibitor 1B (CDKN1B), a gene known to accelerate MC injury. Collectively, the current results demonstrate that up-regulated L13Rik is correlated with DN, and may be a hopeful therapeutic target for DN.

cancer biology↗

bioRxiv2022

Contrasting effects of reduced phosphatidylcholine synthesis in absence of seipin: embryonic lethality goes down while lipid droplets get even larger

Seipin plays a vital role in lipid droplet homeostasis and its deficiency causes congenital generalized lipodystrophy type II in humans. It is not known whether the physiological defects are all caused by cellular lipid droplet defects. Loss-of-function mutation of seip-1, the C. elegans seipin ortholog, causes embryonic lethality and lipid droplet abnormality. We uncover nhr-114 and spin-4 as two suppressors of seip-1 embryonic lethality. Mechanistically, nhr-114 and spin-4 act in the "B12-one-carbon cycle-phosphatidylcholine (PC)" axis and reducing PC synthesis suppresses the embryonic lethality of seip-1 mutants. Conversely, PC deficiency enhances the lipid droplet abnormality of seip-1 mutants. The suppression of seip-1 embryonic lethality by PC reduction requires polyunsaturated fatty acid (PUFA). Therefore, seipin and phosphatidylcholine exhibit opposite actions in embryogenesis, while they function similarly in lipid droplet homeostasis. Our results demonstrate that seipin-mediated embryogenesis is independent of lipid droplet homeostasis. HighlightsO_LIseip-1 suppressors act in the "B12-one-carbon cycle-PC" pathway. C_LIO_LIReducing PC synthesis suppresses the embryonic lethality of seip-1 mutants. C_LIO_LISuppression of the embryonic lethality by PC reduction requires PUFA. C_LIO_LIReduced PC synthesis enhances the large lipid droplet of seip-1 mutants. C_LI

developmental biology↗

bioRxiv2022

Top-down control of the left visual field bias in cued visual spatial attention

A left visual field (LVF) bias in perceptual judgements, response speed and discrimination accuracy are well documented in humans. However, LVF bias can be modulated by perceptual and task demands. For example, cuing spatial attention can reduce or eliminate the LVF bias, suggesting that attentional control can compensate for the LVF bias. We investigated this possibility directly by recording pupillometry together with fMRI in a cued visual spatial attention task. Prior to the onset of a task-relevant target stimulus, we observed that the pupil was significantly more dilated following attend-right than attend-left cues even though task performance did not differ. This difference in pupil dilation was inversely related to the corresponding difference in later target-evoked pupil dilation and in the reaction times to those targets, suggesting that an increased attentional effort was triggered by the attend-right cues, and this offset the LVF bias, equating behavioral performance. The differences in pupil dilation to the right versus left hemifield were correlated with corresponding fMRI differences primarily in the right hemisphere, supporting the idea that the increased attentional effort for rightward attention is mediated by activity in right hemisphere networks, which illuminates how attentional control mediates attentional biases in vision.

neuroscience↗

bioRxiv2022

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 among these network structures, however, remain to be 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) ~100 ms after picture onset, perceptual processing of complex visual scenes began in early visual cortex, proceeding to ventral visual cortex at ~160 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, lasting up to ~2 s, were stable and exhibited temporally generalizable activity patterns. These results suggest that affective scene representations in the brain are formed in a valence-dependent manner and are sustained by recurrent neural interactions among distributed brain areas.

neuroscience↗

bioRxiv2021

The cyclin Cln1 controls polyploid titan cell formation following a stress-induced G2 arrest in Cryptococcus

The pathogenic yeast Cryptococcus neoformans produces polyploid titan cells in response to the host lung environment that are critical for host adaptation and subsequent disease. We analyzed the in vivo and in vitro cell cycles to identify key aspects of the C. neoformans cell cycle that are important for the formation of titan cells. We identified unbudded 2C cells, referred to as a G2 arrest, produced both in vivo and in vitro in response to various stresses. Deletion of the non-essential cyclin Cln1 resulted in over-production of titan cells in vivo, and transient morphology defects upon release from stationary phase in vivo. Using a copper-repressible promoter PCTR4-CLN1 strain and a two-step in vitro titan cell formation assay, our in vitro studies revealed Cln1 functions after the G2 arrest. These studies highlight unique cell cycle alterations in C. neoformans that ultimately promote genomic diversity and virulence in this important fungal pathogen. ImportanceDysregulation of the cell cycle underlies many human genetic diseases and cancers. Yet numerous organisms, including microbes, also manipulate the cell cycle to generate both morphologic and genetic diversity as a natural mechanism to enhance their chances for survival. The eukaryotic pathogen Cryptococcus neoformans generates morphologically distinct polyploid titan cells critical for host adaptation and subsequent disease. We analyzed the C. neoformans in vivo and in vitro cell cycles to identify changes required to generate the polyploid titan cells. C. neoformans paused cell cycle progression in response to various environmental stresses after DNA replication and before morphological changes associated with cell division, referred to as a G2 arrest. Release from this G2 arrest was coordinated by the cyclin Cln1. Reduced CLN1 expression after the G2 arrest was associated with polyploid titan cell production. These results demonstrate a mechanism to generate genomic diversity in eukaryotic cells through manipulation of the cell cycle that has broad disease implications.

microbiology↗

bioRxiv2021

Effects of Frontoparietal Theta tACS on Verbal Working Memory: Behavioral and Neurophysiological Analysis

Left-lateralized frontoparietal theta oscillations are thought to play an important role in verbal working memory. We causally tested this idea by stimulating the frontoparietal theta network at individual theta frequencies (4 to 8 Hz) during verbal working memory and observing the subsequent behavioral and neurophysiological effects. Weak electric currents were delivered via two 4x1 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 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, EEG, and pupillometry data from the post-stimulation sessions, we report three results. First, in-phase stimulation improved task performance only in subjects with higher working memory capacity (WMC) and under higher memory load (load 6). Second, in-phase stimulation enhanced frontoparietal theta synchrony during working memory retention only 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. Third, the pupil diameter was not different irrespective of whether the preceding stimulation was in-phase, anti-phase, or sham. These findings suggest that theta tACS effects on verbal working memory were load- and subject-dependent, rooted in tACS-induced changes in frontoparietal network interactions, and not driven by changes in arousal levels.

neuroscience↗

bioRxiv2021

ERp44 is Required for Endocardial Cushion Development by Regulating VEGFA Secretion in Myocardium

Rationale: Endocardial cushions are precursors of the valvoseptal complex that separates the four heart chambers and control blood flow through the heart. Abnormalities in endocardial cushion development lead to atrioventricular septal defects (AVSDs), which affect 1 in 2,100 live births. Several genes have been implicated in the development of endocardial cushions. Specifically, endoplasmic reticulum-resident protein 44 (ERp44) has been found to play a role in the early secretory pathway, but its function in heart development has not been well studied. Objective: The goal of this study was to investigate the role of ERp44 in heart development in mice. Approach and Results: Using conventional and tissue-specific knockout mouse models, we demonstrated that ERp44 plays a specific role in heart development. ERp44 knockout (KO) mice were smaller in size, and most mice died during early postnatal life. KO hearts exhibited the typical phenotypes of congenital heart diseases, such as abnormal heart shapes as well as severe septal and valvular defects. Similar phenotypes were found in cTnt-cre+/-; Erp44fl/fl mice, which indicated that myocardial ERp44 principally controls endocardial cushion formation. Further studies demonstrated that the deletion of ERp44 significantly decreased the proliferation of cushion cells and impaired the endocardial-mesenchymal transition (EndMT), which was followed by endocardial cushion dysplasia. Finally, we found that ERp44 directly bound to VEGFA and controlled its release. Conclusions: ERp44 contributes to the development of the endocardial cushion by affecting the EndMT of cushion cells by regulating VEGFA release in myocardial cells.

developmental biology↗

bioRxiv2021

Transcranial stimulation of alpha oscillations upregulates the default mode network

The default mode network (DMN) is the most prominent intrinsic connectivity network, serving as a key architecture of the brains functional organization. Conversely, dysregulated DMN is characteristic of major neuropsychiatric disorders. However, the field still lacks mechanistic insights into the regulation of the DMN and effective interventions for DMN dysregulation. The current study approached this problem by manipulating neural synchrony, particularly, alpha (8-12 Hz) oscillations, a dominant intrinsic oscillatory activity that has been increasingly associated with the DMN in both function and physiology. Using high-definition (HD) alpha-frequency transcranial alternating current stimulation (-tACS) to stimulate the cortical source of alpha oscillations, in combination with simultaneous EEG-fMRI, we demonstrated that -tACS (vs. sham control) not only augmented EEG alpha oscillations but also strengthened fMRI and (source-level) alpha connectivity within the core of the DMN. Importantly, increase in alpha oscillations mediated the DMN connectivity enhancement. These findings thus identify a mechanistic link between alpha oscillations and DMN functioning. That transcranial alpha modulation can upregulate the DMN further highlights an effective non-invasive intervention to normalize DMN functioning in various disorders. Significance StatementIn the brains functional organization, the default mode network (DMN) represents a key architecture, whose dysregulation is involved in a host of major neuropsychiatric disorders. However, insights into the regulation of the DMN remain scarce. Through neural synchrony, the alpha-frequency oscillation represents another key underpinning of the brains organization and is thought to share an inherent interdependence with the DMN. Here, we demonstrated that transcranial alternating current stimulation of alpha oscillations (-tACS) not only augmented alpha activity but also strengthened connectivity of the DMN, with the former serving as a mediator of the latter. These findings reveal that alpha oscillations can support DMN functioning. In addition, they identify an effective non-invasive approach to regulate the DMN via -tACS.

neuroscience↗

bioRxiv2021

Aerodynamics and motor control of ultrasonic vocalizations for social communication in mice and rats

Rodent ultrasonic vocalizations (USVs) are crucial to their social communication and a widely used translational tool for linking gene mutations to behavior. To maximize the causal interpretation of experimental treatments, we need to understand how neural control affects USV production. However, both the aerodynamics of USV production and its neural control remain poorly understood. Here we test three intralaryngeal whistle mechanisms - the wall and alar edge impingement, and shallow cavity tone - by combining in vitro larynx physiology and individual-based 3D airway reconstructions with fluid dynamics simulations. Our results show that in the mouse and rat larynx USVs are produced by a glottal jet impinging on the thyroid inner wall. Furthermore, we implemented an empirically based motor control model that predicts motor gesture trajectories of USV call types. Our work provides a quantitative neuromechanical framework to evaluate the contributions of brain and body in shaping USVs, and a first step in linking descending motor control to USV production.

neuroscience↗

bioRxiv2020

Chemoproteomics Maps Glycolytic Targetome in Cancer Cells

Hyperactivated glycolysis, favoring uncontrolled growth and metastasis by producing essential metabolic intermediates engaging bioenergetics and biosynthesis, is a metabolic hallmark of most cancer cells. Although sporadic information has revealed glycolytic metabolites also possess non-metabolic function as signaling molecules, it remains largely elusive how these metabolites interact with and functionally regulate their binding targets. Here we introduce a Target Responsive Accessibility Profiling (TRAP) approach that measures ligand binding-induced steric hindrance in protein targets via global profiling accessibility changes in reactive lysines, and mapped 913 target candidates and 2,487 interactions for 10 major glycolytic metabolites in cancer cells via TRAP. The elucidated targetome uncovers diverse regulatory modalities of glycolytic metabolites involving the direct perturbation of carbohydrate metabolism enzymes, intervention of transcriptional control, modulation of proteome-level acetylation and protein complex assemblies. The advantages gained from glycolysis by cancer cells are expanded by discovering lactate as a ligand for an orphan transcriptional regulator TRIM 28 that promotes p53 degradation, and by identifying pyruvate acting against a cell apoptosis inducer trichostatin A via attenuating protein acetylation. Lastly, the inhibition of glycolytic key enzymes led to identify an intrinsically active glycolytic intermediate glyceraldehyde 3-phosphate that elicits its cytotoxicity by engaging with ENO1 and MTHFD1. Collectively, the glycolytic targetome depicted by TRAP constitutes a fertile resource for understanding how glycolysis finely tunes metabolism and signaling in support of cancer cells, and fostering the exploitation of glycolytic targetome as promising nodes for anti-cancer therapeutics development.

cancer biology↗

bioRxiv2020

Role of Inferior Frontal Junction (IFJ) in the Control of Feature vs Spatial Attention

Feature-based attention refers to preferential selection and processing of items and objects based on their non-spatial attributes such as color or shape. While it is intuitively an easier form of attention to relate to in our day to day lives, the neural mechanisms of feature-based attention are not well understood. Studies have long implicated the dorsal attention network as a key control system for voluntary spatial, feature and object-based attention. Recent studies have expanded on this model by focusing on the inferior frontal junction (IFJ), a region in the pre-frontal cortex to be the source of feature attention control, but not spatial attention control. However, the extent to which IFJ contributes to spatial attention remains a topic of debate. We investigated the role of IFJ in the control of feature versus spatial attention in a cued visual spatial (attend left or right) and feature attention (attend red or green) task using fMRI. Analyzing single-trial cue-evoked fMRI responses using univariate GLM and multi-voxel pattern analysis (MVPA), we observed the following. First, the univariate BOLD activation responses yielded no significant differences between feature and spatial cues. Second, MVPA analysis showed above chance level decoding in classifying feature attention (attend-red vs. attend-green) in both the left and right IFJ, whereas during spatial attention (attend-left vs. attend-right) decoding was at chance. Third, while the cue-evoked decoding accuracy was significant for both left and right IFJ during feature attention, target stimulus-evoked neural responses were not different. Importantly, only the connectivity patterns from the right IFJ was predictive of target-evoked activity in visual cortex (V4); this was true for both left and right V4. Finally, the strength of this connectivity between right IFJ and V4 (bilaterally) was found to be predictive of behavioral performance. These results support a model where the right IFJ plays a crucial role in top down control of feature but not spatial attention.

neuroscience↗

bioRxiv2020

Single-cell Characterization of Acute Myeloid Leukemia and its Microenvironment Following PD-1 Blockade Based Therapy

Acute myeloid leukemia (AML) and effector cells of immune checkpoint blockade (ICB) therapy co-reside in a complex bone marrow (BM) milieu. The interplay of tumor intrinsic and microenvironment (TME) mechanisms that influences the response to ICB-based therapies in AML have not been elucidated. Here we report our analyses of single cell RNA profiling of more than 127,000 BM cells from healthy donors and relapsed/refractory (R/R) AML patients at pre/post treatment with azacitidine/nivolumab, paired with single cell T cell receptor (TCR) repertoire profiles, to uncover factors impacting response and resistance. Loss of chromosome 7/7q conferred an immunosuppressive TME and was associated with resistance to ICB-based therapy in R/R AML. Our trajectory analysis revealed a continuum of CD8+ T cell phenotypes, characterized by differential expression of granzyme B (GZMB) and GZMK. GZMK expression defined a BM residing memory CD8+ T cell subset with stem-like properties likely an intermediary between naive and cytotoxic lymphocytes. Responses to ICB-based therapy were primarily driven by novel and expanded T cell clonotypes. Our findings support an adaptable T cell plasticity in response to PD-1 blockade in AML. Disentangling AML cells from their complex, immune-rich microenvironment revealed characteristics that shaped resistance to ICB-based therapy and could inform strategies to target AML vulnerabilities. SignificanceDetermining the cellular and molecular underpinnings of response and resistance to PD-1 blockade based therapy in AML can guide immune-based therapeutic strategies. Our results reveal AML intrinsic characteristics (chromosome 7/7q status and oxidative stressors) and tumor microenvironment to modulate responses to checkpoint blockers. CD8 cells exist in the bone marrow in a continuum with GZMK expression defining a memory, stem-like T cell population that could play a role in response to therapy.

cancer biology↗

bioRxiv2020

Intracellular accumulation and secretion of hydrophobin-enriched vesicles aid the rapid sporulation of molds

Fungi can rapidly produce large amounts of spores suitable for aerial dispersal. The hydrophobicity of spores is provided by the unique amphiphilic and superior surface-active proteins - hydrophobins (HFBs) - that self-assemble at hydrophobic/hydrophilic interfaces and thus change surface properties. Using the HFB-enriched mold Trichoderma and the HFB-free yeast Pichia pastoris, we revealed a distinctive HFB secretory pathway that includes an intracellular accumulation of HFBs in lipid bodies (LBs) that can internalize in vacuoles. The resulting vacuolar multicisternal structures (VMS) are stabilized by HFB layers that line up on their surfaces. These HFB-enriched VMSs can move to the periplasm for secretion or become fused in large tonoplast-like organelles. The latter contributes to the maintenance of turgor pressure required for the erection of sporogenic structures and rapid HFB secretion by squeezing out periplasmic VMSs through the cell wall. Thus, HFBs are essential accessory proteins for the development of aerial hyphae and colony architecture.

microbiology↗

bioRxiv2020

Decoding Multivoxel Representations of Affective Scenes in Retinotopic Visual Cortex

The perception of opportunities and threats in complex scenes represents one of the main functions of the human visual system. In the laboratory, its neurophysiological basis is often studied by having observers view pictures varying in affective content. This body of work has consistently shown that viewing emotionally engaging, compared to neutral, pictures (1) heightens blood flow in limbic structures and frontoparietal cortex, as well as in anterior ventral and dorsal visual cortex, and (2) prompts an increase in the late positive event-related potential (LPP), a scalp-recorded and time-sensitive index of engagement within the network of aforementioned neural structures. The role of retinotopic visual cortex in this process has, however, been contentious, with competing theoretical notions predicting the presence versus absence of emotion-specific signals in retinotopic visual areas. The present study used multimodal neuroimaging and machine learning to address this question by examining the large-scale neural representations of affective pictures. Recording EEG and fMRI simultaneously while observers viewed pleasant, unpleasant, and neutral affective pictures, and applying multivariate pattern analysis to single-trial BOLD activities in retinotopic visual cortex, we identified three robust findings: First, unpleasant-versus-neutral decoding accuracy, as well as pleasant-versus-neutral decoding accuracy, were well above chance level in all retinotopic visual areas, including primary visual cortex. Second, the decoding accuracy in ventral visual cortex, but not in early visual cortex or dorsal visual cortex, was significantly correlated with LPP amplitude. Third, effective connectivity from amygdala to ventral visual cortex predicted unpleasant-versus-neutral decoding accuracy, and effective connectivity from ventral frontal cortex to ventral visual cortex predicted pleasant-versus-neutral decoding accuracy. These results suggest that affective pictures evoked valence-specific multivoxel neural representations in retinotopic visual cortex and that these multivoxel representations were influenced by reentry signals from limbic and frontal brain regions.

neuroscience↗

bioRxiv2020

Conflict Processing in Schizophrenia: Dissociable Neural Mechanisms Revealed by the N2 and Frontal Midline Theta

Deficits in executive control have long been regarded as one of the hallmark cognitive characteristics in people with schizophrenia (SZ), and current neurocognitive models of SZ generally regard the dysfunctional anterior cingulate cortex (ACC) as the possible neural mechanism. This however, contrasts with recent studies showing that conflict processing, a key component of executive functions that relies on ACC, remains relatively intact in SZ. The current study aimed to investigate this issue through two well-known electrophysiological signatures of conflict processing that have been suggested to origin from ACC, i.e., the N2 component of event-related potentials (ERPs) and frontal midline theta (FM{theta}) oscillations. We recorded 64-channel scalp electroencephalography from 29 SZ (17 women; mean age: 30.4 years) and 31 healthy control subjects (HC; 17 women; mean age: 29.1 years) performing a modified flanker task. Behavioral data revealed no significant differences in flanker conflict effects (lower accuracy and longer reaction time in incongruent trials than in congruent trials) between HC and SZ. Trial-averaged ERP and spectral analysis suggested that both N2 and FM{theta} were significantly impaired in SZ relative to HC. Furthermore, by sorting incongruent trials according to their reaction times within individual subjects, we found that the trial-by-trial modulation of N2 (larger amplitude and longer latency in slower trials) which was observed and localized in ACC in HC was totally absent in SZ. By contrast, the trial-by-trial modulation of FM{theta} (larger power in slower trials) was observed and localized in ACC in both groups, despite a relatively smaller magnitude in SZ. Notably, such trial-by-trial FM{theta} modulation was only present in incongruent trials that demanded conflict processing. Taken together, our results not only support the idea that FM{theta}, not N2, serves as the neural substrate of conflict processing in SZ, but also provide novel insights into the functional roles of ACC during executive control, enriching the current neurocognitive models of SZ.

neuroscience↗