Biology subjects

Di, X.

Publications and source records attributed to Di, X..

At least 37 records · Page 2Linked to original sources

bioRxiv2023

The Significance and Limited Influence of Cerebrovascular Reactivity on Age and Sex Effects in Task- and Resting-State Brain Activity

Functional MRI (fMRI) measures the blood-oxygen-level dependent (BOLD) signals, which provide an indirect measure of neural activity mediated by neurovascular responses. Cerebrovascular reactivity affects both task-induced and resting-state BOLD activity and may confound inter-individual effects observed in BOLD-based measures, such as those related to aging and biological sex. To investigate this, we examined a large open-access fMRI dataset containing a breath-holding task, checkerboard task, and resting-state scans. We used the breath-holding task to measure cerebrovascular reactivity, used the checkerboard task to obtain task-based activations, and from the resting-state data, we quantified the resting-state amplitude of low-frequency fluctuations (ALFF), and resting-state regional homogeneity (ReHo). We hypothesized that cerebrovascular reactivity would be correlated with BOLD measures and that accounting for these correlations would result in better estimates of age and sex effects. Our analysis showed that cerebrovascular reactivity was correlated with checkerboard task activations in the visual cortex and with ALFF and ReHo in widespread fronto-parietal regions, as well as regions with large vessels. We also found significant age and sex effects in cerebrovascular reactivity, some of which overlapped with those observed in ALFF and ReHo scores. Finally, we demonstrated that correcting for the effects of cerebrovascular reactivity had very limited influence on the estimates of age and sex. Our results highlight the limitations of accounting for cerebrovascular reactivity with the current breath-holding task.

neuroscience↗

bioRxiv2023

Boosting pro-vitamin A content and bioaccessibility in leaves by combining engineered biosynthesis and storage pathways with high-light treatments

The relevance of plants as food is expected to grow for a more sustainable diet. In this new context, improving the nutritional quality of plant-derived foods is a must. Biofortification of green leafy vegetables with pro-vitamin A carotenoids such as {beta}-carotene has remained challenging to date. Here we combined two strategies to achieve this goal. One of them (that we call strategy C) involves producing {beta}-carotene in extraplastidial locations of leaf cells to avoid the negative impacts on photosynthesis derived from changing the balance of carotenoids and chlorophylls in chloroplasts. The second approach (that we refer to as strategy P) involves the conversion of chloroplasts into non-photosynthetic, carotenoid-overaccumulating chromoplasts in some leaves, leaving other non-engineered leaves to sustain normal plant growth. Combination of these two strategies resulted in a 5- fold increase in the amount of {beta}-carotene in Nicotiana benthamiana leaves. Following several attempts to further improve {beta}-carotene leaf contents by metabolic engineering, hormone treatments and genetic screenings, it was found that promoting the proliferation of plastoglobules with high-light treatments not only improved {beta}-carotene accumulation but it also resulted in a much higher bioaccessibility. Combination of strategies C and P together with a high-light treatment increased the levels of accessible {beta}-carotene 30-fold compared to controls. We further demonstrate that stimulating plastoglobule proliferation with strategy P but also with high-light alone can also stimulate and hence improve {beta}-carotene contents and bioaccessibility in edible lettuce (Lactuca sativa) leaves, unveiling the power of non-GMO approaches for leaf biofortification.

plant biology↗

bioRxiv2023

Individual differences in time-varying and stationary brain connectivity during movie watching from childhood to early adulthood: Effects of age, sex, and behavioral associations

Spatially remote brain regions exhibit dynamic functional interactions across various task conditions. While time-varying functional connectivity during movie watching shows sensitivity to movie content, stationary functional connectivity remains relatively stable across videos. These findings suggest that dynamic and stationary functional interactions may represent different aspects of brain function. However, the relationship between individual differences in time-varying and stationary connectivity and behavioral phenotypes remains elusive. To address this gap, we analyzed an open-access functional MRI dataset comprising participants aged 5 to 22 years, who watched two cartoon movie clips. We calculated regional brain activity, time-varying connectivity, and stationary connectivity, examining associations with age, sex, and behavioral assessments. Model comparison revealed that time-varying connectivity was more sensitive to age and sex effects compared with stationary connectivity. The preferred age models exhibited quadratic log age or quadratic age effects, indicative of inverted-U shaped developmental patterns. In addition, females showed higher consistency in regional brain activity and time-varying connectivity than males. However, in terms of behavioral predictions, only stationary connectivity demonstrated the ability to predict full-scale intelligence quotient. These findings suggest that individual differences in time-varying and stationary connectivity may capture distinct aspects of behavioral phenotypes.

neuroscience↗

bioRxiv2023

Neurovascular reactivity increases across development in the visual and frontal pole networks as revealed by a breath-holding task: a longitudinal fMRI study

Functional magnetic resonance imaging (fMRI) has been widely used to understand the neurodevelopmental changes that occur in cognition and behavior across childhood. The blood-oxygen-level-dependent (BOLD) signal obtained from fMRI is understood to be comprised of both neuronal and vascular information. However, it is unclear whether the vascular response is altered across age in studies investigating development in children. Since the breath-hold task is commonly used to understand cerebrovascular reactivity in fMRI studies, it can be used to account for developmental differences in vascular response. This study examines how the cerebrovascular response changes over age in a longitudinal childrens breath-hold dataset from the Nathan Kline Institute (NKI) Rockland Sample (ages 6 to 18 years old at enrollment). A general linear model (GLM) approach was applied to derive cerebrovascular reactivity from breath-hold data. To model both the longitudinal and cross-sectional effects of age on breath-hold response, we used mixed effects modeling with the following terms: linear, quadratic, logarithmic, and quadratic-logarithmic, to find the best-fitting model. We observed increased breath-hold BOLD signal in multiple networks across age, in which linear and logarithmic mixed effects models provided the best fit with the lowest Akaike Information Criterion (AIC) scores. This shows that the cerebrovascular response increases across development in a brain network-specific manner. Therefore, fMRI studies investigating the developmental period should account for cerebrovascular changes which occur with age.

neuroscience↗

bioRxiv2022

Allosteric feedback inhibition of deoxy-D-xylulose-5-phosphate synthase involves monomerization of the active dimer.

Isoprenoids are a very large and diverse family of metabolites required by all living organisms. All isoprenoids derive from the double-bond isomers isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP), which are produced by the methylerythritol 4-phosphate (MEP) pathway in bacteria and plant plastids. Understanding the regulation of the MEP pathway, probably the main metabolic pathway elucidated in this century, is a must for the rational design of biotechnological endeavors aimed at increasing isoprenoid contents in microbial and plant systems. It has been reported that IPP and DMAPP feedback regulate the activity of deoxyxylulose 5-phosphate (DXS), a dimeric enzyme catalyzing the main flux-controlling step of the MEP pathway. Here we provide experimental insights on the underlying mechanism. Our data show that direct allosteric binding of IPP and DMAPP to bacterial and plant DXS promotes monomerization of the enzyme. This allows a fast response to a sudden increase or decrease in IPP/DMAPP supply by rapidly shifting the dimer-monomer equilibrium accordingly. DXS monomers expose hydrophobic domains that are hidden in the dimer, resulting in aggregation and eventual degradation. Removal of monomers that would otherwise be available for dimerization and enzyme reactivation appears as a more drastic response in case of persistent IPP/DMAPP overabundance (e.g., by a blockage in their conversion to downstream isoprenoids). Our model provides a mechanistic explanation of how IPP and DMAPP supply can be adapted to changes in their demand and it also explains the changes in DXS protein levels observed after long-term interference of the MEP pathway flux. Significance StatementIsoprenoids are a vast family of organic compounds with essential roles in respiration, photosynthesis, photoprotection, membrane structure, and signaling. Many of them have great economic and nutritional relevance as pigments, aromas, drugs or phytonutrients. Despite their functional and structural diversity, they all derive from the same five-carbon precursors. We show that these precursors feedback-regulate their own synthesis in bacteria and plant plastids by allosterically shifting the dimer:monomer equilibrium of the enzyme that catalyzes the first step of their biosynthetic pathway towards the inactive monomeric form. This evolutionary conserved mechanism allows for both short-term (immediate) and long-term (sustained) control of the pathway flux, and its manipulation could be critical for the rational engineering of high-value isoprenoid products in bacterial and plant systems.

biochemistry↗

bioRxiv2022

Spatiotemporally Mapping Thermodynamics of Lysosomes and Mitochondria using Cascade Organelle-Targeting Upconversion Nanoparticles

The intracellular metabolism of organelles, like lysosomes and mitochondria, are highly coordinated spatiotemporally and functionally. The activities of lysosomal enzymes significantly rely on the cytoplasmic temperature, and heat is constantly released by mitochondria as the byproduct of ATP generation during active metabolism. Here, we develop temperature-sensitive LysoDots and MitoDots to monitor the in situ thermodynamics of lysosomes and mitochondria. The design is based on upconversion nanoparticles (UCNPs) with high-density surface modifications to achieve the exceptionally high sensitivity of 2.7% K-1 and accuracy of 0.8 K for nanothermometry to be used in living cells. We show the measurement is independent of the intracellular ion concentrations- and pH values. With Ca2+ ion shock, the temperatures of both lysosomes and mitochondria increased by 2[~]4 {degrees}C. Intriguingly, with Chloroquine treatment, the lysosomal temperature was observed to decrease by up to [~]3 {degrees}C, while mitochondria remained relatively stable. Lastly, with oxidative phosphorylation inhibitor treatment, we observed a 3[~]7 {degrees}C thermal increase and transition from mitochondria to lysosomes. These observations indicate different metabolic pathways and thermal transitions between lysosomes and mitochondria inside HeLa cells. The nanothermometry probes provide a powerful tool for multi-modality functional imaging of subcellular organelles and interactions with high spatial, temporal and thermal dynamics resolutions. Graphical AbstractCascade organelle-targeted nano-thermometers based on upconversion LysoDots and MitoDots. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=159 SRC="FIGDIR/small/480800v1_ufig1.gif" ALT="Figure 1"> View larger version (93K): org.highwire.dtl.DTLVardef@13b8124org.highwire.dtl.DTLVardef@19b78a8org.highwire.dtl.DTLVardef@e866corg.highwire.dtl.DTLVardef@19b51d3_HPS_FORMAT_FIGEXP M_FIG C_FIG

biophysics↗

bioRxiv2022

Assessing functional connectivity differences and work-related fatigue in surviving COVID-negative patients.

The Coronavirus Disease 2019 (COVID-19) has affected all aspects of life around the world. Neuroimaging evidence suggests the novel coronavirus can attack the central nervous system (CNS), causing cerebro-vascular abnormalities in the brain. This can lead to focal changes in cerebral blood flow and metabolic oxygen consumption rate in the brain. However, the extent and spatial locations of brain alterations in COVID-19 survivors are largely unknown. In this study, we have assessed brain functional connectivity (FC) using resting-state functional MRI (RS-fMRI) in 38 (25 males) COVID patients two weeks after hospital discharge, when PCR negative and 31 (24 males) healthy subjects. FC was estimated using independent component analysis (ICA) and dual regression. When compared to the healthy group, the COVID group demonstrated significantly enhanced FC in the basal ganglia and precuneus networks (family wise error (fwe) corrected, pfwe < 0.05), while, on the other hand, reduced FC in the language network (pfwe < 0.05). The COVID group also experienced higher fatigue levels during work, compared to the healthy group (p < 0.001). Moreover, within the precuneus network, we noticed a significant negative correlation between FC and fatigue scores across groups (Spearmans {rho} = - 0.47, p = 0.001, r2 = 0.22). Interestingly, this relationship was found to be significantly stronger among COVID survivors within the left parietal lobe, which is known to be structurally and functionally associated with fatigue in other neurological disorders. Significance StatementEarly neuroimaging studies have mostly focused on structural MRI imaging to report brain abnormalities in acutely ill COVID-19 patients. It is not clear whether functional abnormalities co-exist with structural alterations in patients who have survived the infection and have been discharged from the hospital. A few recent studies have emerged which attempted to address the structural/functional alterations. However, further investigations across different sites are necessary for more conclusive inference. More importantly, fatigue is a highly prevalent symptom among COVID survivors, therefore, the relations of brain imaging abnormalities to fatigue should be investigated. In this study, we try to address these gaps, by collecting imaging data from COVID survivors, now PCR negative, and healthy subjects from a single site - the Indian Institute of Technology (IIT), Delhi, India. Furthermore, this is a continuation of an ongoing study. We have recently shown structural abnormalities and stronger gray matter volume (GMV) correlates of self-reported fatigue in this group of COVID survivors compared to healthy subjects (Hafiz et al., 2022).

neuroscience↗

bioRxiv2021

Regional Topological Aberrances of White Matter- and Gray Matter-based Functional Networks for Attention Processing may Foster Traumatic Brain Injury-Related Attention Deficits in Adults

Traumatic brain injury (TBI) is highly prevalent in adults. TBI-related functional brain alterations have been linked with common post-TBI neurobehavioral sequelae, with unknown neural sub-strates. This study examined the systems-level functional brain alterations in white matter (WM) and gray matter (GM) for visual sustained attention processing, their interactions, and contribution to post-TBI attention deficits. Task-based functional MRI data were collected from 42 adults with TBI and 43 group-matched normal controls (NCs), and analyzed using the graph theoretic tech-nique. Global and nodal topological properties were calculated and compared between the two groups. Correlation analyses were conducted between the neuroimaging measures that showed significant between-group differences and the behavioral symptom measures in attention domain in the groups of TBI and NCs, respectively. Significantly altered nodal efficiency and/or degree in several WM and GM nodes were reported in the TBI group, including the posterior corona radiata (PCR), posterior thalamic radiation (PTR), postcentral gyrus (PoG), and superior temporal sulcus (STS). Subjects with TBI also demonstrated abnormal systems-level functional synchronization between the PTR and STS in the right hemisphere, hypo-interaction between PCR and PoG in the left hemisphere; as well as the involvement of systems-level functional aberrances in PCR in TBI-related behavioral impairments in the attention domain. Findings of the current study suggest that TBI-related systems-level functional alterations associated with these two major association WM tracts and their anatomically connected GM regions may play critical role in TBI-related behavioral deficits in attention domain.

neuroscience↗

bioRxiv2021

Dynamic and stable brain connectivity during movie watching as revealed by functional MRI

Spatially remote brain regions show synchronized activity as typically revealed by correlated functional MRI (fMRI) signals. An emerging line of research has focused on the temporal fluctuations of connectivity; however, its relationships with stationary connectivity have not been clearly illustrated. We examined dynamic and stationary connectivity when the participants watched four different movie clips. We calculated point-by-point multiplication between two regional time series to estimate the time-resolved dynamic connectivity, and estimated the inter-individual consistency of the dynamic connectivity time series. Widespread consistent dynamic connectivity was observed for each movie clip, which also showed differences between the clips. For example, a cartoon movie clip, Wall-E, showed more consistent of dynamic connectivity with the posterior cingulate cortex and supramarginal gyrus, while a court drama clip, A Few Good Men, showed more consistent of dynamic connectivity with the auditory cortex and temporoparietal junction, which might suggest the involvement of specific brain processing for different movie contents. In contrast, the stationary connectivity as measured by the correlations between regional time series was highly similar among the movie clips, and showed fewer statistically significant differences. The patterns of consistent dynamic connectivity could be used to classify different movie clips with higher accuracy than the stationary connectivity and regional activity. These results support the functional significance of dynamic connectivity in reflecting functional brain changes, which could provide more functionally relevant information than stationary connectivity.

neuroscience↗

bioRxiv2021

Frequency-specific coactivation patterns in resting-state and their alterations in schizophrenia: an fMRI study

The resting-state human brain is a dynamic system that shows frequency-specific characteristics. Coactivation pattern (CAP) analysis has been recently used to identify recurring brain states sharing similar coactivation configurations. However, whether and how CAPs differ across different sub-frequency bands are unknown. In the current study, in addition to the typical low-frequency range (0.01 - 0.08 Hz), the spatial and temporal characteristics of CAPs in four sub-frequency bands, slow-5 (0.01 - 0.027 Hz), slow-4 (0.027 - 0.073 Hz), slow-3 (0.073 - 0.198 Hz), and slow-2 (0.198 - 0.25 Hz), were studied. Six CAP states were obtained for each band., The CAPs from the typical frequency range were spatially largely overlapped with those in slow-5, slow-4 and slow-3 but not with those in slow-2. With the increase of frequency, the CAP state became more unstable and resulted in an overall shorter persistence. The spatial and temporal characteristics of slow-4 and slow-5 were further compared, because they constitute most power of the resting-state fMRI signals. In general, slow-4 showed stronger coactivations or co-deactivations in subcortical regions, while slow-5 showed stronger coactivations or co-deactivations in large-scale cortical networks such as the dorsal attention network. Lastly, frequency-dependent dynamic alterations were also observed in schizophrenia patients. Combining the information obtained from both slow-5 and slow-4 increased the classification accuracy of schizophrenia patients than only using the typical range. In conclusion, our results revealed that the spatial and temporal characteristics of CAP state varied at different frequency bands, which could be helpful for identifying brain alterations in schizophrenia.

neuroscience↗

bioRxiv2021

Clinical Strains of Pseudomonas aeruginosa secret LasB protease to induce hemorrhagic diffused alveolar damage and acute lung injury in mice

BackgroundAcute lung injury and acute respiratory distress syndrome are most often caused by bacterial pneumonia, characterized by severe dyspnea and high mortality. Knowledge about the lung injury effects of current clinical bacteria strains is lacking. The aim of this study was to investigate the ability of representative pathogenic bacteria isolated from patients to cause ALI/ARDS in mice and identify the virulent factors. Method7 major bacteria species were isolated from clinical sputum and instilled in to mice airway unilaterally. Histology study was used to judge the lung injury effect. Virulence genes were examined by PCR. Sequence type of P. aeruginosa strains were identified by MLST. LC-MS/MS was used to identify the suspicious protein bands. LasB was purified through DEAE-cellulose column and its toxicity was tested both in vitro and in vivo. ResultsStaphylococcus aureus, Streptococcus pneumoniae, Streptococcus agalactiae, Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa and Escherichia coli were randomly separated and tested 3 times. Among them, gram-negative bacteria are more potential than gram-positive bacteria to cause acute lung injury. However, P. aeruginosa is the only pathogen which induced diffused alveolar damage, hemorrhage and hyaline membrane in the lung of mice. The lung injury effect is associated to the excreted matrix metalloproteinase LasB of P. aeruginosa. Purified LasB recapitulated hemorrhagic acute lung injury identical to P. aeruginosa infection in vivo. We found this was due to the powerful degradation effect of LasB on both lung extracellular matrix and key proteins in coagulation cascade without inducing cellular apoptosis. ConclusionP. aeruginosa strains are most capable to induce ALI/ARDS among major clinical pathogenic bacteria, this ability is specifically attributed to their LasB production.

microbiology↗

bioRxiv2021

Reproducible Coactivation Patterns of Functional Brain Networks Reveal the Aberrant Dynamic State Transition in Schizophrenia

It is well documented that massive dynamic information is contained in the resting-state fMRI. Recent studies have identified recurring states dominated by similar coactivation patterns (CAP) and revealed their temporal dynamics. However, the reproducibility and generalizability of the CAP analysis is unclear. To address this question, the effects of methodological pipelines on CAP are comprehensively evaluated in this study, including preprocessing, network construction, cluster number and three independent cohorts. The CAP state dynamics are characterized by fraction of time, persistence, counts, and transition probability. Results demonstrate six reliable CAP states and their dynamic characteristics are also reproducible. The state transition probability is found to be positively associated with the spatial similarity. Furthermore, the aberrant CAP in schizophrenia has been investigated by using the reproducible method on three cohorts. Schizophrenia patients spend less time in CAP states that involve the fronto-parietal network, but more time in CAP states that involve the default mode and salience network. The aberrant dynamic characteristics of CAP are correlated with the symptom severity. These results reveal the reproducibility and generalizability of the CAP analysis, which can provide novel insights into the neuropathological mechanism associated with aberrant brain network dynamics of schizophrenia. HighlightsO_LIThree coactivation patterns (CAPs) pairs with opposite coactivation profiles were identified, and the between-state transition probability was positively correlated with their spatial similarity. C_LIO_LIGood spatial and temporal reproducibility and generalizability of CAPs were achieved under varied analytic methods and independent cohorts. C_LIO_LISchizophrenia patients showed altered temporal dynamics not only within the triple-network but also other primary and higher-order networks. C_LI

neuroscience↗

bioRxiv2020

Quantitatively Monitoring in situ Mitochondrial Thermal Dynamics by Upconversion Nanoparticles

Temperature dynamics reflect the physiological conditions of cells and organisms. Mitochondria regulates temperature dynamics in living cells, as they oxidize the respiratory substrates and synthesize ATP, with heat being released as a by-product of active metabolism. Here, we report an upconversion nanoparticles based thermometer that allows in situ thermal dynamics monitoring of mitochondria in living cells. We demonstrate that the upconversion nanothermometers can efficiently target mitochondria and the temperature responsive feature is independent of probe concentration and medium conditions. The relative sensing sensitivity of 3.2% K-1 in HeLa cells allows us to measure the mitochondrial temperature difference through the stimulations of high glucose, lipid, Ca2+ shock and the inhibitor of oxidative phosphorylation. Moreover, cells display distinct response time and thermal dynamic profiles under different stimulations, which highlights the potential applications of this thermometer to study in situ vital processes related to mitochondrial metabolism pathways and interactions between organelles.

cell biology↗

bioRxiv2020

Glycopeptidomics Analysis of a Cell Line Model Revealing Pathogenesis and Potential Marker Molecules for the Early Diagnosis of Gastric MALT Lymphoma

BackgroundGastric mucosa-associated lymphoma (GML) is a mature B cell tumor related to Helicobacter pylori (H.pylori) infection. The clinical manifestations of GML are not specific, so GML commonly escapes diagnosis or is misdiagnosed, leading to excessive treatment. The pathogenesis of H.pylori-induced GML is not well understood and there are no molecular markers for early GML diagnosis. MethodsGlycopeptidomics analyses of host cell lines (a BCG823 cell line, C823) and C823 cells infected by H. pylori isolated from patients with GML (GMALT823), gastritis (GAT823), gastric ulcer (GAU823) and gastric cancer (GAC823) were carried out to clarify the host reaction mechanism against GML and identify potential molecular criteria for the early diagnosis of GML. FindingsThirty-three samples were analyzed and approximately 2000 proteins, 200 glycoproteins and 500 glycopeptides were detected in each sample. O-glycans were the dominant glycoforms in GMALT823 cells only. Four specific glycoforms in GMALT823 cells and 2 specific glycoforms in C823 and GMALT823 cells were identified. Eight specific glycopeptides of from 7 glycoproteins were found in GMALT823 cells; of these glycopeptides, 6 and 3 specific glycopeptides had high affinity for T cell epitopes and have conformational B cell epitopes, respectively. InterpretationThe relationship between the predominant glycoforms of host cells and the development of host disease was determined, and the glycoproteins, glycosylation sites and glycoforms might be closely related to the formation of GML, which provides new insight into the pathogenic mechanisms of H. pylori infection and suggests molecular indicators for the early diagnosis of GML.

microbiology↗

bioRxiv2020

Dissecting individual differences in responses to naturalistic stimuli in functional MRI: effects of development and gender

Functional MRI (fMRI) study of naturalistic conditions, e.g. movie watching, usually focuses on shared responses across subjects. However, individual differences have been attracting increasing attention in search of group differences or associations with behavioral outcomes. Individual differences are typically studied by directly modeling the pair-wise intersubject correlation matrix or projecting the relations onto a single dimension. We contend that it is critical to examine whether there are one or more consistent responses underlying the whole sample, because multiple components, if exist, may undermine the intersubject relations using the previous methods. We propose to use principal component analysis (PCA) to examine the heterogeneity of brain responses across subjects and project the individual variability into higher dimensions. By analyzing an fMRI dataset of children and adults watching a cartoon movie, we showed evidence of two consistent responses in the supramarginal gyrus and other regions. While the first components in many regions represented a response pattern mostly in older children and adults, the second components mainly represented the younger children. The second components in the supramarginal network resembled a delayed version of the first PCs for 4 seconds (2 TR), indicating slower responses in the younger children than the older children and adults. The analyses highlight the importance of identifying multiple consistent responses in responses to naturalistic stimuli. This PCA-based approach could be complementary to the commonly used intersubject correlation to analyze movie watching data.

neuroscience↗

bioRxiv2020

Common and separable neural alterations in substance use disorders: evidence from coordinate-based meta-analyses of functional neuroimaging studies in human

Delineating common and separable neural alterations in substance use disorders (SUD) is imperative to understand the neurobiological basis of the addictive process and to inform substance-specific treatment strategies. Given numerous functional MRI (fMRI) studies in different SUDs, meta-analysis could provide an opportunity to determine robust shared and substance-specific alterations. The present study employed a coordinate-based meta-analysis covering fMRI studies in individuals with addictive cocaine, cannabis, alcohol, and nicotine use. The primary meta-analysis demonstrated common alterations in primary dorsal striatal, and frontal circuits engaged in reward/salience processing, habit formation, and executive control across different substances and task-paradigms. Subsequent sub-analyses revealed substance-specific alterations in frontal and limbic regions, with marked frontal and insula-thalamic alterations in alcohol and nicotine use disorders respectively. Finally, examining task-specific alterations across substances revealed pronounced frontal alterations during cognitive processes yet stronger striatal alterations during reward-related processes. Together the findings emphasize the role of dysregulations in striato-frontal circuits and dissociable contributions of these systems in the domains of reward-related and cognitive processes which may contribute to substance-specific behavioral alterations.

neuroscience↗

bioRxiv2019

Intersubject consistent dynamic connectivity during natural vision revealed by functional MRI

The functional communications between brain regions are thought to be dynamic. However, it is usually difficult to elucidate whether the observed dynamic connectivity is functionally meaningful or simply due to noise during unconstrained task conditions such as resting-state. During naturalistic conditions, such as watching a movie, it has been shown that local brain activities, e.g. in the visual cortex, are consistent across subjects. Following similar logic, we propose to study intersubject correlations of the time courses of dynamic connectivity during naturalistic conditions to extract functionally meaningful dynamic connectivity patterns. We analyzed a functional MRI (fMRI) dataset when the subjects watched a short animated movie. We calculated dynamic connectivity by using sliding window technique, and quantified the intersubject correlations of the time courses of dynamic connectivity. Although the time courses of dynamic connectivity are thought to be noisier than the original signals, we found similar level of intersubject correlations of dynamic connectivity to those of regional activity. Most importantly, highly consistent dynamic connectivity could occur between regions that did not show high intersubject correlations of regional activity, and between regions with little stable functional connectivity. The analysis highlighted higher order brain regions such as the default mode network that dynamically interacted with posterior visual regions during the movie watching, which may be associated with the understanding of the movie. HighlightsO_LIIntersubject consistency may provide a complementary approach to study brain dynamic connectivity C_LIO_LIWidespread brain regions showed highly consistent dynamic connectivity during movie watching, while these regions themselves did not show highly consistent regional activity C_LIO_LIConsistent dynamic connectivity often occurred between regions from different functional systems C_LI

neuroscience↗

bioRxiv2019

Anterior cingulate cortex differently modulates fronto-parietal functional connectivity between resting-state and working memory tasks

The brain fronto-parietal regions and the functional communications between them are critical in supporting working memory and other executive functions. The functional connectivity between fronto-parietal regions are modulated by working memory loads, and are shown to be modulated by a third brain region in resting-state. However, it is largely unknown that whether the third-region modulations remain the same during working memory tasks or were largely modulated by task demands. In the current study, we collected functional MRI (fMRI) data when the subjects were performing n-back tasks and in resting-state. We first used a block-designed localizer to define the fronto-parietal regions that showed higher activations in the 2-back than the 1-back condition. Next, we performed physiophysiological interaction (PPI) analysis using left and right middle frontal gyrus (MFG) and superior parietal lobule (SPL) regions, respectively, in three continuous-designed runs of resting-state, 1-back, and 2-back conditions. No regions showed consistent modulatory interactions with the seed pairs in the three conditions. Instead, the anterior cingulate cortex (ACC) showed different modulatory interactions with the right MFG and SPL among the three conditions. While increased activity of the ACC was associated with decreased functional coupling between the right MFG and SPL in resting-state, it was associated with increased functional coupling in the 2-back condition. The observed task modulations support the functional significance of the modulations of the ACC on fronto-parietal connectivity.

neuroscience↗