Biology subjects

Ekstrand, C.

Publications and source records attributed to Ekstrand, C..

10 recordsLinked to original sources

bioRxiv2024

Coordinated variation in the immune systems and microbiomes of healthy humans is linked to tonic interferon states

Human immune systems are highly variable, with most variation attributable to non-genetic sources. The gut microbiome crucially shapes the immune system; however, its relationship with the baseline immune states of healthy humans remains incompletely understood. Therefore, we performed multi-omic profiling of 110 healthy participants through the ImmunoMicrobiome study. A factor-based integrative approach identified coordinated variation, revealing that the tonic interferon response was amongst the most variable immune features in healthy participants. Microbiome composition, pathways, and stool metabolites varied concomitantly with interferon response pathways. Distinct transcriptional programs involving inflammation and TGF-{beta} in SIGLEC-1high monocytes and CD69high activated MAIT and NK cells were representative of these programs. Our study provides extensive data to examine the relationship between the immune states and microbiomes of healthy individuals at steady state, which paves the way for delineating inter-individual differences relevant for disease susceptibility and responses to therapy.

immunology↗

bioRxiv2024

Single-cell spatial transcriptomics of fixed, paraffin-embedded biopsies reveals colitis-associated cell networks

Background & AimsImaging-based, single-cell spatial transcriptomics (iSCST) using formalin-fixed, paraffin-embedded (FFPE) tissue could transform translational research by retaining all tissue cell subsets and spatial locations while enabling the analysis of archived specimens. We aimed to develop a robust framework for applying iSCST to archived clinical FFPE mucosal biopsies from patients with inflammatory bowel disease (IBD). MethodsWe performed a comprehensive benchmarking comparison of three iSCST platforms capable of analyzing FFPE specimens. We analyzed FFPE mucosal biopsies (n=57) up to 5 years old from non-IBD controls (HC; n=9) and patients with ulcerative colitis (UC;n=11). After platform-specific cell segmentation, we applied a uniform data processing pipeline to all datasets, including transcript detection, cell annotation, differential gene expression, and neighborhood enrichment. Transcriptomic signatures identified with iSCST were validated using external, publicly available bulk transcriptomic datasets. ResultsA custom 290-plex Xenium gene panel exhibited the highest sensitivity and specificity for transcript detection, enabling precise identification and quantification of diverse cell subsets and differentially expressed genes across cell types and disease states. We mapped transcriptionally distinct fibroblast subsets to discrete spatial locations and identified inflammation-associated fibroblasts (IAFs) and monocytes as a colitis-associated cellular neighborhood. We also identified signatures associated with Vedolizumab (VDZ) responsiveness. VDZ non-responders were characterized by an IAF-monocyte transcriptional signature, while responders exhibited enrichment of epithelial gene sets. ConclusionsOur optimized iSCST framework for archived FFPE biopsies provides unique advantages for assessing the role of colitis-associated cellular networks in routinely collected clinical samples. FFPE-based biomarkers could integrate with existing clinical workflows and potentially aid in risk-stratifying patients.

immunology↗

bioRxiv2024

Lower perceived stress enhances neural synchrony in perceptual and attentional cortices during naturalistic processing

Perceived stress is the subjective appraisal of the level of stress experienced by an individual in response to external or internal demands. Recent research on perceived stress has highlighted its role in influencing cognition, leading to a disruption in cognitive processes, such as emotional processing, attention, and perception. However, most neuroimaging studies examining stress have used static stimuli (e.g., still images) that do not encapsulate real-life multimodal processing in the brain. The current research uses data from the Naturalistic Neuroimaging Database (v2.0; Aliko et al., 2020) to examine differences in neural synchrony (as measured by intersubject correlations; ISCs) associated with perceived stress using functional magnetic resonance imaging (fMRI). We evaluated how self-reported perceived stress levels influence neural synchrony patterns in response to different naturalistic stimuli by examining the differences in neural synchrony between individuals with low and high perceived stress levels. We determined that lower perceived stress was observed with greater neural synchrony areas associated with perceptual and attention processing, including the lateral occipital cortex, superior temporal gyrus, superior parietal lobule, orbital frontal cortex, and the occipital pole. These results indicate that high levels of perceived stress heavily alter neural processing of complex audiovisual stimuli. Together, these results provide evidence that perceived stress influences cognitive processing in everyday life.

neuroscience↗

bioRxiv2023

Psychological well-being modulates neural synchrony during naturalistic fMRI

Psychological well-being (PWB) is a combination of self-acceptance, life purpose, personal growth, positive relationships, and autonomy, and has a significant relationship with physical and mental health. Previous studies using resting-state functional magnetic resonance imaging (fMRI) and static picture stimuli have implicated the anterior cingulate cortex (ACC), posterior cingulate cortex (PCC), orbitofrontal cortex (OFC), insula and thalamus in PWB, however, the replication of associations across studies is scarce, both in strength and direction, resulting in the absence of a model of how PWB impacts neurological processing. Naturalistic stimuli better encapsulate everyday experiences and can elicit more "true-to-life" neurological responses, and therefore may be a more appropriate tool to study PWB. The current study seeks to identify how differing levels of PWB modulate neural synchrony in response to an audiovisual film. With consideration of the inherent variability of the literature, we aim to ascertain the validity of the regions previously mentioned and their association with PWB. We identified that higher levels of PWB were associated with heightened neural synchrony in the bilateral OFC and left PCC, and that lower levels of PWB were associated with heightened neural synchrony in the right temporal parietal junction (TPJ) and left superior parietal lobule (SPL), regions related to narrative processing. Taken together, this research confirms the validity of several regions in association with PWB and suggests that varying levels of PWB produce differences in the processing of a narrative during complex audiovisual processing.

neuroscience↗

bioRxiv2023

Trait level somatic arousal modulates fMRI neural synchrony to naturalistic stimuli

Somatic arousal refers to the physiological and bodily responses that occur in reaction to different emotional and psychological stimuli and is a crucial component of the fight or flight response. Symptoms associated with higher levels of somatic arousal such as higher heart and respiration rates have been shown to impact the blood oxygenation level dependent (BOLD) signal during functional magnetic resonance imaging (fMRI) studies. Differences in baseline levels of somatic arousal may therefore modulate the brains response to incoming stimuli during fMRI. Previous studies typically investigate somatic arousal as a state, rather than as a trait, in which some individuals are more likely to have heightened physiological responses to psychological stimuli, causing the neurological mechanisms behind baseline somatic arousal levels to remain poorly understood. The current study seeks to identify how differing levels of baseline somatic arousal modulate neural synchrony in response to an audiovisual film. We hypothesize that individuals with higher levels of somatic arousal will show overall heightened neural synchrony in response to a complex audiovisual stimulus. We identified that higher levels of somatic arousal are associated with widespread neural synchrony across the brain, including frontal gyri, parietal and temporo-occipital cortices. Taken together, this research suggests that baseline somatic arousal levels should be measured during naturalistic fMRI paradigms, as baseline somatic arousal levels may have a profound influence on synchronous neural activity.

neuroscience↗

bioRxiv2023

Mapping the Changing Neural Architecture of Narrative Processing Using Naturalistic Stimuli: an fMRI Study

A narrative is a coherent representation of actual or fictional events designed to connect experiences. Narratives provide a unique opportunity to investigate brain functions in scenarios more closely resembling real-world experiences. However, most neuroimaging studies examining narrative formation have utilized static stimuli that fail to capture the intricacies of narrative construction in everyday life, particularly how cognitive demands change over the course of narrative processing. The current research uses functional magnetic resonance imaging (fMRI) to examine dynamic narrative processing over the course of a full-length audiovisual narrative. We examined changes in neural synchrony (as quantified by intersubject correlations) in areas related to semantic memory, episodic memory, and visuospatial attention between the beginning, middle, and end of the narrative. Results from two experiments identified two core narrative processing networks responsible for constructing coherent representations across extended timescales. The first network is associated with the early narrative construction, and includes the right intraparietal sulcus/superior parietal lobule, bilateral angular gyrus, bilateral precuneus, and left fusiform gyrus. The second network consists of the right ventral frontal cortex and bilateral parahippocampal cortices, and is associated with longer term narrative integration. Together, these regions provide the framework for successful narrative processing during naturalistic stimuli.

neuroscience↗

bioRxiv2023

A novel 4D fMRI clustering technique to examine event-related spatiotemporal dynamics of face processing in naturalistic stimuli

Cortical function is complex, nuanced, and involves information processing in a multimodal and dynamic world. However, previous functional magnetic resonance imaging (fMRI) research has generally characterized static activation differences between strictly controlled proxies of real-world stimuli that do not encapsulate the complexity of everyday multimodal experiences. Of primary importance to the field of neuroimaging is the development of techniques that distill complex spatiotemporal information into simple, behaviorally relevant representations of neural activation. Herein, we present a novel 4D spatiotemporal clustering method to examine dynamic neural activity associated with events (specifically the onset of human faces in audiovisual movies). Results from this study showed that 4D spatiotemporal clustering can extract clusters of fMRI activation over time that closely resemble the known spatiotemporal pattern of human face processing without the need to model a hemodynamic response function. Overall, this technique provides a new and exciting window into dynamic functional processing across both space and time using fMRI that has wide applications across the field of neuroscience.

neuroscience↗

bioRxiv2023

Females exhibit smaller and less variable patterns of brain activation across a range of motor tasks

Past work has shown that brain structure and function differ between females and males. Males have larger cortical and sub-cortical volume and surface area (both total and subregional), while females have greater cortical thickness in most brain regions. Functional differences are also reported in the literature, yet to date little work has systematically considered whether patterns of brain activity indexed with functional magnetic resonance imaging (fMRI) differ between females and males. Recently, an attempt to modernize and improve our understanding of the homunculus, a somatotopic representation of the human body within the brain, was made. Still, in the decades since it was introduced, no research has considered sex differences in the somatotopic representation. The current study sought to remediate this issue by employing brain somatotopic motor mapping from a previously published and openly available dataset. We tested differences in patterns of functional brain activity associated with 12 voluntary movement patterns in females versus males. Results suggest that females exhibited smaller volumes of brain activation across all 12 movement tasks, and lower patterns of variability in 10 of the 12 movements. We also observed that females had greater cortical thickness, which is in alignment with previous analyses of structural differences. Overall, these findings provide a basis for considering biological sex in future fMRI research and provide a foundation of understanding differences in how neurological pathologies present in females vs males.

neuroscience↗

bioRxiv2021

Considering unique, shared, and dominant brain activation in the Visual Word Form Area and Lateral Occipital Cortex: A comparison of separate and combined word reading and picture naming

Identifying printed words and pictures concurrently is ubiquitous in daily tasks, and so it is important to consider the extent to which reading words and naming pictures may share a cognitive-neurophysiological functional architecture. Two functional magnetic resonance imaging (fMRI) experiments examined whether reading along the left ventral occipitotemporal region (vOT; often referred to as a visual word form area, VWFA) has activation that is overlapping with referent pictures (i.e., both conditions significant and shared, or with one significantly more dominant) or unique (i.e., one condition significant, the other not), and whether picture naming along the right lateral occipital complex (LOC) has overlapping or unique activation relative to referent words. Experiment 1 used familiar regular and exception words (to force lexical reading) and their corresponding pictures in separate naming blocks, and showed dominant activation for pictures in the LOC, and shared activation in the VWFA for exception words and their corresponding pictures (regular words did not elicit significant VWFA activation). Experiment 2 controlled for visual complexity by superimposing the words and pictures and instructing participants to either name the word or the picture, and showed primarily shared activation in the VWFA and LOC regions for both word reading and picture naming, with some dominant activation for pictures in the LOC. Overall, these results highlight the importance of including exception words to force lexical reading when comparing to picture naming, and the significant shared activation in VWFA and LOC serves to challenge specialized models of reading or picture naming.

neuroscience↗

bioRxiv2019

Brain structural connectivity predicts brain functional complexity: DTI derived centrality accounts for variance in fractal properties of fMRI signal

The complexity of brain activity has recently been investigated using the Hurst (H) exponent, which describes the extent to which functional magnetic resonance imaging (fMRI) blood oxygen-level dependent (BOLD) activity is self-similar vs. complex. For example, research has demonstrated that fMRI activity is more complex before than after consumption of alcohol and during task than resting state. The measurement of H in fMRI is a novel method that requires the investigation of additional factors contributing to complexity. Graph theory metrics of centrality can assess how centrally important to the brain network each region is, based on diffusion tensor imaging (DTI) counts of probabilistic white matter (WM) tracts. DTI derived centrality was hypothesized to account for the complexity of functional activity, based on the supposition that more sources of information to integrate should result in more complex activity. FMRI BOLD complexity as measured by H was associated with five brain region centrality measures: degree, eigenvector, PageRank, current flow betweenness, and current flow closeness centrality. Multiple regression analyses demonstrated that degree centrality was the most robust predictor of complexity, whereby greater centrality was associated with increased complexity (lower H). Regions known to be highly connected, including the thalamus and hippocampus, notably were among the highest in centrality and complexity. This research has led to a greater understanding of how brain region characteristics such as DTI centrality relate to the novel Hurst exponent approach for assessing brain activity complexity, and implications for future research that employ these measures are discussed.

neuroscience↗