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BMC Genomics Jun 2024Advances of spatial transcriptomics technologies enabled simultaneously profiling gene expression and spatial locations of cells from the same tissue. Computational...
BACKGROUND
Advances of spatial transcriptomics technologies enabled simultaneously profiling gene expression and spatial locations of cells from the same tissue. Computational tools and approaches for integration of transcriptomics data and spatial context information are urgently needed to comprehensively explore the underlying structure patterns. In this manuscript, we propose HyperGCN for the integrative analysis of gene expression and spatial information profiled from the same tissue. HyperGCN enables data visualization and clustering, and facilitates downstream analysis, including domain segmentation, the characterization of marker genes for the specific domain structure and GO enrichment analysis.
RESULTS
Extensive experiments are implemented on four real datasets from different tissues (including human dorsolateral prefrontal cortex, human positive breast tumors, mouse brain, mouse olfactory bulb tissue and Zabrafish melanoma) and technologies (including 10X visium, osmFISH, seqFISH+, 10X Xenium and Stereo-seq) with different spatial resolutions. The results show that HyperGCN achieves superior clustering performance and produces good domain segmentation effects while identifies biologically meaningful spatial expression patterns. This study provides a flexible framework to analyze spatial transcriptomics data with high geometric complexity.
CONCLUSIONS
HyperGCN is an unsupervised method based on hypergraph induced graph convolutional network, where it assumes that there existed disjoint tissues with high geometric complexity, and models the semantic relationship of cells through hypergraph, which better tackles the high-order interactions of cells and levels of noise in spatial transcriptomics data.
Topics: Humans; Animals; Mice; Gene Expression Profiling; Transcriptome; Deep Learning; Cluster Analysis; Computational Biology; Breast Neoplasms; Olfactory Bulb
PubMed: 38840049
DOI: 10.1186/s12864-024-10469-x -
Cortex; a Journal Devoted To the Study... May 2024Stroke often causes long-term motor and somatosensory impairments. Motor planning and tactile perception rely on spatial body representations. However, the link between...
Stroke often causes long-term motor and somatosensory impairments. Motor planning and tactile perception rely on spatial body representations. However, the link between altered spatial body representations, motor deficit and tactile spatial coding remains unclear. This study investigates the relationship between motor deficits and alterations of anatomical (body) and tactile spatial representations of the hand in 20 post-stroke patients with upper limb hemiparesis. Anatomical and tactile spatial representations were assessed from 10 targets (nails and knuckles) respectively cued verbally by their anatomical name or using tactile stimulations. Two distance metrics (hand width and finger length) and two structural measures (relative organization of targets positions and angular deviation of fingers from their physical posture) were computed and compared to clinical assessments, normative data and lesions sites. Over half of the patients had altered anatomical and/or tactile spatial representations. Metrics of tactile and anatomical representations showed common variations, where a wider hand representation was linked to more severe motor deficits. In contrast, alterations in structural measures were not concomitantly observed in tactile and anatomical representations and did not correlate with clinical assessments. Finally, a preliminary analysis showed that specific alterations in tactile structural measures were associated with dorsolateral prefrontal stroke lesions. This study reveals shared and distinct characteristics of anatomical and tactile hand spatial representations, reflecting different mechanisms that can be affected differently after stroke: metrics and location of tactile and anatomical representations were partially shared while the structural measures of tactile and anatomical representations had distinct characteristics.
PubMed: 38838560
DOI: 10.1016/j.cortex.2024.04.015 -
Cortex; a Journal Devoted To the Study... May 2024How to fairly allocate goods is a key issue of social decision-making. Extensive research demonstrates that people do not selfishly maximize their own benefits, but...
How to fairly allocate goods is a key issue of social decision-making. Extensive research demonstrates that people do not selfishly maximize their own benefits, but instead also consider how others are affected. However, most accounts of the psychological processes underlying fairness-related behavior implicitly assume that assessments of fairness are somewhat stable. In this paper, we present results of a novel task, the Re-Allocation Game, in which two players receive an allocation determined by the computer and, on half of the trials, one player has the subsequent possibility to change this allocation. Importantly, prior to the receipt of the allocation, players were shown either their respective financial situations, their respective performance on a previous simple task, or random information, while being scanned using functional neuroimaging. As expected, our results demonstrate when given the opportunity, participants allocated on average almost half the money to anonymous others. However, our findings further show that participants used the provided information in a dynamic manner, revealing the underlying principle based on which people re-allocate money - namely based on merit, need, or equality - switches dynamically. On the neural level, we identified activity in the right and left dorsolateral prefrontal cortices related to context-independent inequity and context-dependent fairness information respectively when viewing the computer-generated allocations. At the same time, activity in the temporoparietal and precuneus represented these different types of fairness-related information in adjacent and partially overlapping clusters. Finally, we observed that the activity pattern in the precuneus and putamen was most clearly related to participants' subsequent re-allocation decisions. Together, our findings suggest that participants judge an allocation as fair or unfair using a network associated with cognitive control and theory-of-mind, while dynamically switching between what might constitute a fair allocation in a particular context.
PubMed: 38838559
DOI: 10.1016/j.cortex.2024.03.015 -
PloS One 2024Mental fatigue is an early and enduring symptom in persons with autoimmune disease particularly multiple sclerosis (MS). Neuromodulation has emerged as a potential...
INTRODUCTION
Mental fatigue is an early and enduring symptom in persons with autoimmune disease particularly multiple sclerosis (MS). Neuromodulation has emerged as a potential treatment although optimal cortical targets have yet to be determined. We aimed to examine cortical hemodynamic responses within bilateral dorsolateral prefrontal cortex (dlPFC) and frontopolar areas during single and dual cognitive tasks in persons with MS-related fatigue compared to matched controls.
METHODS
We recruited persons (15 MS and 12 age- and sex-matched controls) who did not have physical or cognitive impairment and were free from depressive symptoms. Functional near infrared spectroscopy (fNIRS) registered hemodynamic responses during the tasks. We calculated oxyhemoglobin peak, time-to-peak, coherence between channels (a potential marker of neurovascular coupling) and functional connectivity (z-score).
RESULTS
In MS, dlPFC demonstrated disrupted hemodynamic coherence during both single and dual tasks, as evidenced by non-significant and negative correlations between fNIRS channels. In MS, reduced coherence occurred in left dorsolateral PFC during the single task but occurred bilaterally as the task became more challenging. Functional connectivity was lower during dual compared to single tasks in the right dorsolateral PFC in both groups. Lower z-score was related to greater feelings of fatigue. Peak and time-to-peak hemodynamic response did not differ between groups or tasks.
CONCLUSIONS
Hemodynamic responses were inconsistent and disrupted in people with MS experiencing mental fatigue, which worsened as the task became more challenging. Our findings point to dlPFC, but not frontopolar areas, as a potential target for neuromodulation to treat cognitive fatigue.
Topics: Humans; Female; Male; Adult; Multiple Sclerosis; Hemodynamics; Dorsolateral Prefrontal Cortex; Cognition; Middle Aged; Spectroscopy, Near-Infrared; Fatigue; Case-Control Studies; Mental Fatigue; Prefrontal Cortex
PubMed: 38837991
DOI: 10.1371/journal.pone.0303211 -
Scientific Reports Jun 2024Evidence has shown that both sleep loss and daily caffeine intake can induce changes in grey matter (GM). Caffeine is frequently used to combat sleepiness and impaired... (Randomized Controlled Trial)
Randomized Controlled Trial
Repeated caffeine intake suppresses cerebral grey matter responses to chronic sleep restriction in an A adenosine receptor-dependent manner: a double-blind randomized controlled study with PET-MRI.
Evidence has shown that both sleep loss and daily caffeine intake can induce changes in grey matter (GM). Caffeine is frequently used to combat sleepiness and impaired performance caused by insufficient sleep. It is unclear (1) whether daily use of caffeine could prevent or exacerbate the GM alterations induced by 5-day sleep restriction (i.e. chronic sleep restriction, CSR), and (2) whether the potential impact on GM plasticity depends on individual differences in the availability of adenosine receptors, which are involved in mediating effects of caffeine on sleep and waking function. Thirty-six healthy adults participated in this double-blind, randomized, controlled study (age = 28.9 ± 5.2 y/; F:M = 15:21; habitual level of caffeine intake < 450 mg; 29 homozygous C/C allele carriers of rs5751876 of ADORA2A, an A adenosine receptor gene variant). Each participant underwent a 9-day laboratory visit consisting of one adaptation day, 2 baseline days (BL), 5-day sleep restriction (5 h time-in-bed), and a recovery day (REC) after an 8-h sleep opportunity. Nineteen participants received 300 mg caffeine in coffee through the 5 days of CSR (CAFF group), while 17 matched participants received decaffeinated coffee (DECAF group). We examined GM changes on the 2nd BL Day, 5th CSR Day, and REC Day using magnetic resonance imaging and voxel-based morphometry. Moreover, we used positron emission tomography with [F]-CPFPX to quantify the baseline availability of A adenosine receptors (AR) and its relation to the GM plasticity. The results from the voxel-wise multimodal whole-brain analysis on the Jacobian-modulated T1-weighted images controlled for variances of cerebral blood flow indicated a significant interaction effect between caffeine and CSR in four brain regions: (a) right temporal-occipital region, (b) right dorsomedial prefrontal cortex (DmPFC), (c) left dorsolateral prefrontal cortex (DLPFC), and (d) right thalamus. The post-hoc analyses on the signal intensity of these GM clusters indicated that, compared to BL, GM on the CSR day was increased in the DECAF group in all clusters but decreased in the thalamus, DmPFC, and DLPFC in the CAFF group. Furthermore, lower baseline subcortical AR availability predicted a larger GM reduction in the CAFF group after CSR of all brain regions except for the thalamus. In conclusion, our data suggest an adaptive GM upregulation after 5-day CSR, while concomitant use of caffeine instead leads to a GM reduction. The lack of consistent association with individual AR availability may suggest that CSR and caffeine affect thalamic GM plasticity predominantly by a different mechanism. Future studies on the role of adenosine A receptors in CSR-induced GM plasticity are warranted.
Topics: Humans; Caffeine; Male; Adult; Gray Matter; Receptor, Adenosine A1; Positron-Emission Tomography; Female; Magnetic Resonance Imaging; Double-Blind Method; Sleep Deprivation; Young Adult; Receptor, Adenosine A2A
PubMed: 38830861
DOI: 10.1038/s41598-024-61421-8 -
Bioinformatics Advances 2024The recent spatial transcriptomics (ST) technologies have enabled characterization of gene expression patterns and spatial information, advancing our understanding of...
MOTIVATION
The recent spatial transcriptomics (ST) technologies have enabled characterization of gene expression patterns and spatial information, advancing our understanding of cell lineages within diseased tissues. Several analytical approaches have been proposed for ST data, but effectively utilizing spatial information to unveil the shared variation with gene expression remains a challenge.
RESULTS
We introduce STew, a Spatial Transcriptomic multi-viEW representation learning method, to jointly analyze spatial information and gene expression in a scalable manner, followed by a data-driven statistical framework to measure the goodness of model fit. Through benchmarking using human dorsolateral prefrontal cortex and mouse main olfactory bulb data with true manual annotations, STew achieved superior performance in both clustering accuracy and continuity of identified spatial domains compared with other methods. STew is also robust to generate consistent results insensitive to model parameters, including sparsity constraints. We next applied STew to various ST data acquired from 10× Visium, Slide-seqV2, and 10× Xenium, encompassing single-cell and multi-cellular resolution ST technologies, which revealed spatially informed cell type clusters and biologically meaningful axes. In particular, we identified a proinflammatory fibroblast spatial niche using ST data from psoriatic skins. Moreover, STew scales almost linearly with the number of spatial locations, guaranteeing its applicability to datasets with thousands of spatial locations to capture disease-relevant niches in complex tissues.
AVAILABILITY AND IMPLEMENTATION
Source code and the R software tool STew are available from github.com/fanzhanglab/STew.
PubMed: 38827413
DOI: 10.1093/bioadv/vbae064 -
BioRxiv : the Preprint Server For... May 2024In studying the neural correlates of working memory (WM) ability via functional magnetic resonance imaging (fMRI) in health and disease, it is relatively uncommon for...
BACKGROUND
In studying the neural correlates of working memory (WM) ability via functional magnetic resonance imaging (fMRI) in health and disease, it is relatively uncommon for investigators to report associations between brain activation and measures of task performance. Additionally, how the choice of WM task impacts observed activation-performance relationships is poorly understood. We sought to illustrate the impact of WM task on brain-behavior correlations using two large, publicly available datasets.
METHODS
We conducted between-participants analyses of task-based fMRI data from two publicly available datasets: the Human Connectome Project (HCP; n = 866) and the Queensland Twin Imaging (QTIM) Study (n = 459). Participants performed two distinct variations of the back WM task with different stimuli, timings, and response paradigms. Associations between brain activation ([2-back - 0-back] contrast) and task performance (2-back % correct) were investigated separately in each dataset, as well as across datasets, within the dorsolateral prefrontal cortex (dlPFC), medial prefrontal cortex, and whole cortex.
RESULTS
Global patterns of activation to task were similar in both datasets. However, opposite associations between activation and task performance were observed in bilateral pre-supplementary motor area and left middle frontal gyrus. Within the dlPFC, HCP participants exhibited a significantly greater activation-performance relationship in bilateral middle frontal gyrus relative to QTIM Study participants.
CONCLUSIONS
The observation of diverging activation-performance relationships between two large datasets performing variations of the -back task serves as a critical reminder for investigators to exercise caution when selecting WM tasks and interpreting neural activation in response to a WM task.
PubMed: 38826388
DOI: 10.1101/2024.05.23.595597 -
BioRxiv : the Preprint Server For... May 2024The cell-type specific role of the vascular endothelial growth factors (VEGFs) in the pathogenesis of Alzheimer's disease (AD) is not well characterized. In this study,...
The cell-type specific role of the vascular endothelial growth factors (VEGFs) in the pathogenesis of Alzheimer's disease (AD) is not well characterized. In this study, we utilized a single-nucleus RNA sequencing dataset from Dorsolateral Prefrontal Cortex (DLFPC) of 424 donors from the Religious Orders Study and Memory and Aging Project (ROS/MAP) to investigate the effect of 10 VEGF genes ( , and ) on AD endophenotypes. Mean age of death was 89 years, among which 68% were females, and 52% has AD dementia. Negative binomial mixed models were used for differential expression analysis and for association analysis with β-amyloid load, PHF tau tangle density, and both cross-sectional and longitudinal global cognitive function. Intercellular VEGF-associated signaling was profiled using CellChat. We discovered prefrontal cortical expression was upregulated in AD brains in both endothelial and microglial cells. Higher expression was also associated with worse cross-sectional global cognitive function, longitudinal cognitive trajectories, and β-amyloid load. Similarly, higher endothelial expression was associated with more β-amyloid load. In contrast to the receptors, showed opposing effects on β-amyloid load whereby higher levels in oligodendrocytes was associated with high amyloid burden, while higher levels in inhibitory neurons was associated with lower amyloid burden. Finally, AD cells showed significant reduction in overall VEGF signaling comparing to those from cognitive normal participants. Our results highlight key changes in VEGF receptor expression in endothelial and microglial cells during AD, and the potential protective role of VEGFB in neurons.
PubMed: 38826287
DOI: 10.1101/2024.04.12.589221 -
Brain Stimulation 2024Transcranial magnetic stimulation (TMS) is believed to alter ongoing neural activity and cause circuit-level changes in brain function. While the electrophysiological...
BACKGROUND
Transcranial magnetic stimulation (TMS) is believed to alter ongoing neural activity and cause circuit-level changes in brain function. While the electrophysiological effects of TMS have been extensively studied with scalp electroencephalography (EEG), this approach generally evaluates low-frequency neural activity at the cortical surface. However, TMS can be safely used in patients with intracranial electrodes (iEEG), allowing for direct assessment of deeper and more localized oscillatory responses across the frequency spectrum.
OBJECTIVE/HYPOTHESIS
Our study used iEEG to understand the effects of TMS on human neural activity in the spectral domain. We asked (1) which brain regions respond to cortically-targeted TMS, and in what frequency bands, (2) whether deeper brain structures exhibit oscillatory responses, and (3) whether the neural responses to TMS reflect evoked versus induced oscillations.
METHODS
We recruited 17 neurosurgical patients with indwelling electrodes and recorded neural activity while patients underwent repeated trials of single-pulse TMS at either the dorsolateral prefrontal cortex (DLPFC) or parietal cortex. iEEG signals were analyzed using spectral methods to understand the oscillatory responses to TMS.
RESULTS
Stimulation to DLPFC drove widespread low-frequency increases (3-8 Hz) in frontolimbic cortices and high-frequency decreases (30-110 Hz) in frontotemporal areas, including the hippocampus. Stimulation to parietal cortex specifically provoked low-frequency responses in the medial temporal lobe. While most low-frequency activity was consistent with phase-locked evoked responses, anterior frontal regions exhibited induced theta oscillations following DLPFC stimulation.
CONCLUSIONS
By combining TMS with intracranial EEG recordings, our results suggest that TMS is an effective means to perturb oscillatory neural activity in brain-wide networks, including deeper structures not directly accessed by stimulation itself.
Topics: Humans; Transcranial Magnetic Stimulation; Male; Adult; Female; Middle Aged; Electroencephalography; Electrocorticography; Parietal Lobe; Young Adult; Dorsolateral Prefrontal Cortex; Brain Waves
PubMed: 38821396
DOI: 10.1016/j.brs.2024.05.014 -
Journal of Neuroengineering and... May 2024Transcranial alternating current stimulation (tACS) is a prominent non-invasive brain stimulation method for modulating neural oscillations and enhancing human cognitive...
BACKGROUND
Transcranial alternating current stimulation (tACS) is a prominent non-invasive brain stimulation method for modulating neural oscillations and enhancing human cognitive function. This study aimed to investigate the effects of individualized theta tACS delivered in-phase and out-of-phase between the dorsal anterior cingulate cortex (dACC) and left dorsolateral prefrontal cortex (lDLPFC) during inhibitory control performance.
METHODS
The participants engaged in a Stroop task with phase-lagged theta tACS over individually optimized high-density electrode montages targeting the dACC and lDLPFC. We analyzed task performance, event-related potentials, and prestimulus electroencephalographic theta and alpha power.
RESULTS
We observed significantly reduced reaction times following out-of-phase tACS, accompanied by reduced frontocentral N1 and N2 amplitudes, enhanced parieto-occipital P1 amplitudes, and pronounced frontocentral late sustained potentials. Out-of-phase stimulation also resulted in significantly higher prestimulus frontocentral theta and alpha activity.
CONCLUSIONS
These findings suggest that out-of-phase theta tACS potently modulates top-down inhibitory control, supporting the feasibility of phase-lagged tACS to enhance inhibitory control performance.
Topics: Humans; Transcranial Direct Current Stimulation; Male; Female; Adult; Inhibition, Psychological; Young Adult; Electroencephalography; Evoked Potentials; Gyrus Cinguli; Reaction Time; Theta Rhythm; Stroop Test; Dorsolateral Prefrontal Cortex
PubMed: 38816860
DOI: 10.1186/s12984-024-01385-y