Biology subjects

Sandberg, K.

Publications and source records attributed to Sandberg, K..

11 recordsLinked to original sources

bioRxiv2025

The Neural Architecture of Dream Recall Frequency: Insights from Interindividual Variations in Brain Structure and Function

Dreaming represents a complex and universal aspect of human sleep, yet it remains an intriguing phenomenon, with the neural mechanisms underlying dream experiences and their frequency not fully understood. This study employs a multimodal neuroimaging approach, integrating quantitative multi-parameter mapping, diffusion tensor imaging, and resting-state functional MRI, to investigate the neural correlates of dream recall frequency (DRF) in a large cohort of 258 healthy individuals. By employing Linked Independent Component Analysis (LICA), we were able to discern distinctive patterns of brain structure and function that correlated with variations in DRF. Our findings elucidate a complex relationship between dream recall and brain microstructure integrity, particularly in white matter regions of the orbitofrontal cortex, parahippocampal gyrus, superior parietal lobule, and occipital cortex. Higher DRF was related to increased white matter microstructure integrity in these regions and decreased gray matter volume in occipital and temporal areas. In terms of functional measures, higher DRF was associated with reduced connectivity across a range of resting-state networks, including the default mode, visual, and dorsal attention networks. This was particularly evident in the right precuneus and posterior cingulate cortex. These results suggest that enhanced dream recall may be related to the organization of higher-order visual and cognitive processing areas, supporting a top-down model of dreaming. This study contributes to a more comprehensive understanding of the neural substrates underlying individual differences in dream recall, offering a foundation for future investigations into the neurobiology and causal relationships of dreaming.

neuroscience↗

bioRxiv2024

NSAID-mediated cyclooxygenase inhibition disrupts ectodermal derivative formation in axolotl embryos

Embryonic exposures to non-steroidal anti-inflammatory drugs (NSAIDs) have been linked to preterm birth, neural tube closure defects, abnormal enteric innervation, and craniofacial malformations, potentially due to disrupted neural tube or neural crest (NC) cell development. Naproxen (NPX), a common non-steroidal anti-inflammatory drug (NSAID) used to relieve pain and inflammation, exerts its effects through non-selective cyclooxygenase (COX) inhibition. Our lab has identified that the cyclooxygenase (COX-1 and COX-2) isoenzymes are expressed during the early stages of vertebrate embryonic development, and that global inhibition of COX-1 and COX-2 function disrupts NC cell migration and differentiation in Ambystoma mexicanum (axolotl) embryos. NC cells differentiate into various adult tissues including craniofacial cartilage, bone, and neurons in the peripheral and enteric nervous systems. To investigate the specific phenotypic and molecular effects of NPX exposure on NC development and differentiation, and to identify molecular links between COX inhibition and NC derivative anomalies, we exposed late neurula and early tailbud stage axolotl embryos to various concentrations of NPX and performed immunohistochemistry (IHC) for markers of migratory and differentiating NC cells. Our results reveal that NPX exposure impairs the migration of SOX9+ NC cells, leading to abnormal development of craniofacial cartilage structures, including Meckels cartilage in the jaw. NPX exposure also alters the expression of markers associated with peripheral and central nervous system (PNS and CNS) development, suggesting concurrent neurodevelopmental changes.

developmental biology↗

bioRxiv2024

Neural correlates of nightmares revisited: findings from large-scale fMRI cohorts

Study ObjectivesNightmares are linked to daytime distress and psychiatric and neurological disorders. However, knowledge about the brain regions involved in nightmare production is sparse. This study aimed to examine the relationship between nightmare frequency and the functional connectivity of the amygdala with the prefrontal cortex, which is central to emotional regulation. Additionally, the study sought to replicate previous findings on the neural correlates of nightmares using two large cohorts. Methods464 participants underwent functional and structural MRI recordings and answered questions assessing nightmare and dream recall frequency. A general linear model assessed the voxelwise correlation between the amygdala-prefrontal cortex connectivity with nightmare frequency. Additionally, regional homogeneity (ReHo) maps were calculated, high and low nightmare frequency and the entire nightmare frequency spectrum contrasts were determined while controlling for age, sex, and dream recall frequency. ResultsThe study did not find a significant correlation between nightmare frequency and amygdala-prefrontal cortex connectivity. Previous ReHo findings of group differences between high and low nightmare frequency could not be replicated. However, parametric analysis revealed an association between nightmare frequency and ReHo differences in the cerebellum. ConclusionsThis failure to confirm hypothesized and previously reported results, especially with a larger sample size, suggests a need to reevaluate the existing knowledge of the neural correlates of nightmares and consider individual differences such as personality, trauma history, and cognitive processes. Overall, our findings highlight the complexities of interpreting neuroimaging data in sleep research.

neuroscience↗

bioRxiv2024

Identification of unique and potent inhibitors of SARS-CoV-2 main protease from DNA-encoded chemical libraries

In vitro screening of large compounds libraries with automated high-throughput screening is expensive, time consuming and requires dedicated infrastructures. Conversely, the selection of DNA-encoded chemical libraries (DECL) can be rapidly performed with routine equipment available in most laboratories. In this study we identified novel inhibitors of SARS-CoV-2 main protease (Mpro) through the affinity-based selection of the DELopen library (open access for academics), containing 4.2 billion compounds. The identified inhibitors were peptide-like compounds containing an N-terminal electrophilic group able to form a covalent bond with the nucleophilic Cys145 of Mpro, as confirmed by x-ray crystallography. This DECL selection campaign enabled the discovery of the unoptimized compound SLL11 displaying an IC50 of 30 nM, proving that the rapid exploration of large chemical spaces enabled by DECL technology, allows for the direct identification of potent inhibitors avoiding several rounds of iterative medicinal chemistry. Compound MP1, a close analogue of SLL11, showed antiviral activity against SARS-CoV-2 in the low micromolar range when tested in Caco-2 and Calu-3 (EC50 = 2.3 {micro}M) cell lines. As peptide-like compounds can suffer from low cell permeability and metabolic stability, the cyclization of the compounds as well as the substitution of selected residues with D-enantiomers will be explored in the future to improve the antiviral activity of these novel compounds.

microbiology↗

bioRxiv2024

Vividness of Visual Imagery Supported by Intrinsic Structural-Functional Brain Network Dynamics

Vividness of visual imagery is subject to individual variability, a phenomenon with largely unexplored neurobiological underpinnings. By analyzing data from 273 participants we explored the link between the structural-functional organization of brain connectomes and the reported intensity of visual imagery (measured with VVIQ-2). Employing graph theory analyses we investigated both the structural (DTI) and functional (rs-fMRI) connectomes within a network of regions often implicated in visual imagery. Our results indicate a relationship between increased local efficiency and clustering coefficients in the structural connectome in individuals who experience more vivid visual imagery. Increased local efficiency and clustering coefficients were mirrored in the functional connectome with increases in left inferior temporal regions, a region frequently identified as a critical hub in the visual imagery literature. Furthermore, individuals with more vivid imagery were found to have lower levels of global efficiency in their functional connectome. We propose that the clarity and intensity of visual imagery are optimized by a network organization characterized by heightened localized information transfer and interconnectedness. Conversely, an excessively globally integrated network might dilute the specific neural activity crucial for generating vivid visual images, leading to less locally concentrated resource allocation in key regions involved in visual imagery vividness.

neuroscience↗

bioRxiv2023

Temporal Contrast Enhancement in Thermosensation: A Framework for Understanding Paradoxical Heat Sensation

Paradoxical Heat Sensation (PHS) is the remarkable feeling of warmth or heat pain while the skin is cooling. Despite its initial documentation over 100 years ago, a unified explanation for this perplexing experience remains elusive. Here we apply contrast enhancement principles, known for their instrumental role in understanding visual illusions, to the domain of thermosensation. Contrast enhancement describes the amplification of two contrasting visual features, such as the enhanced perception of an edge between a light and dark bar. In thermosensation, this encompasses an enhancement of the difference between sequential warming and cooling of the skin, and is defined as the normalised difference between successive temporal warm and cold temperatures. Remarkably, thermal contrast predicts the occurrence of PHS. Our findings reveal compelling evidence supporting the role of thermal contrast in the generation of PHS, shedding light on its underlying mechanism and offering a framework for broader encoding principles in thermosensation and pain.

neuroscience↗

bioRxiv2020

Illusory size perception with stimuli from animal experiments of surround modulation.

Visual illusions have long been studied because the illusory effect they induce is believed to tell us something important on how the visual system processes visual information. Here, we modified a classic visual illusion, the Delboeuf illusion, so that it resembled a type of stimulus commonly used in experiments investigating surround modulation. We then performed a small set of psychophysical experiments in order to determine if the classical Delboeuf illusion effect, i.e. a change in the perceived size of an object, could be observed in these altered stimuli. In four conditions, we created stimuli that either had a high or low frequency surround in addition to being presented with a proximal thin surround or a distal thick surround. We found a significant difference in perceived object size for all four conditions compared to control indicating the presence of an illusion, and we discuss these findings in relation to existing literature from electrophysiological animal studies.

neuroscience↗

bioRxiv2019

TMS-induced motor activation increases visual awareness

The influence of non-visual information on visual awareness judgments has recently gained substantial interest. Using single-pulse Transcranial Magnetic Stimulation (TMS), we investigate the potential contribution of evidence from the motor system to judgment of visual awareness. We hypothesized that TMS-induced activity in the primary motor cortex (M1) would increase reported visual awareness as compared to the control condition. Additionally, we investigated whether TMS-induced motor-evoked potential could measure accumulated evidence for stimulus perception. Following stimulus presentation and TMS, participants first rated their visual awareness verbally using the Perceptual Awareness Scale, after which they responded manually to a Gabor orientation identification task. Delivering TMS to M1 resulted in higher average awareness ratings as compared to the control condition, in both correct and incorrect identification task response trials, when the hand with which participants responded was contralateral to the stimulated hemisphere (TMS-response-congruent trials). This effect was accompanied by longer Perceptual Awareness Scale response times, irrespective of the congruence between TMS and identification response. Moreover, longer identification response times were observed in TMS-response-congruent trials in the M1 condition as compared to the control condition. Additionally, the amplitudes of motor-evoked potentials were related to the awareness ratings when response congruence was taken into account. We argue that motor-evoked potential can serve as an indirect measure of evidence accumulated for stimulus perception and that longer Perceptual Awareness Scale response times and higher amplitudes of motor-evoked potentials in the M1 condition reflect integration of additional evidence with visual awareness judgment. In conclusion, we advocate that motor activity influences perceptual awareness judgments.

neuroscience↗

bioRxiv2019

An organisational principle for cortical receptive fields

The response to visual stimulation of population receptive fields (pRF) in the human visual cortex can be accurately modelled with a Difference of Gaussians model, yet many aspects of their organisation remain poorly understood. Here, we examined the theoretical underpinnings of this model and argue that the DC-balanced Difference of Gaussians (DoG) holds a number of advantages over a DC-biased DoG. Through functional magnetic resonance imaging (fMRI) pRF mapping, we compared performance of DC-balanced and DC-biased models in human primary visual cortex and found that when model complexity is taken into account, the DC-balanced model is preferred. Finally, we present evidence indicating that the BOLD signal DC-offset contains information related to the processing of visual stimuli. Taken together, the results indicate that V1 neurons are at least frequently organised in the exact constellation that allows them to function as bandpass-filters, which allows for the separation of stimulus contrast and luminance. We further speculate that if the DoG models stimulus contrast, the DC-offset may reflect stimulus luminance. These findings suggest that it may be possible to separate contrast and luminance processing in fMRI experiments and this could lead to new insights on the haemodynamic response.

neuroscience↗

bioRxiv2018

Novel regression methods for metacognition

Metacognition is an important component in basic science and clinical psychology, often studied through complex, cognitive experiments. While Signal Detection Theory (SDT) provides a popular and pervasive framework for modelling responses from such experiments, a shortfall remains that it cannot in a straightforward manner account for the often complex designs. Additionally, SDT does not provide direct estimates of metacognitive ability. This latter shortcoming has recently been sought remedied by introduction of a measure for metacognitive sensitivity dubbed meta-d. The need for a flexible regression model framework remains, however, which should also incorporate the new sensitivity measure. In the present paper, we argue that a straightforward extension of SDT is obtained by identifying the model with the proportional odds model, a widely implemented, ordinal regression technique. We go on to develop a formal statistical framework for metacognitive sensitivity by defining a model that combines standard SDT with meta-d in a latent variable model. We show how this agrees with the literature on meta-d and constitutes a practical framework for extending the model. We supply several teoretical considerations on the model, including closed-form approximate estimates of meta-d and optimal weighing of response-specific meta-sensitivities. We discuss regression analysis as an application of the obtained model and illustrate our points through simulations. Lastly, we present R-software that implements the model. Our methods and their implementation extend the computational possibilities of SDT and meta-d and are useful for theoretical and practical researchers of metacognition.

neuroscience↗

bioRxiv2017

Is whole-brain functional connectivity a neuromarker of sustained attention? Comment on Rosenberg & al. (2016)

Identification of neuromarkers accurately predicting cognitive characteristics from a single, standardised MRI scan could be tremendously useful in basic psychology and clinical practise. In a recent article, Rosenberg et al. (Nat Neurosci, 19, 165-171, 2016) argue that whole-brain functional network strength is a broadly applicable neuromarker of sustained attention. They claim that this marker accurately predicts performance from task related as well as resting state activity. Here, we discuss the applicability and generalizability in the context of three methodological concerns: Simulations show that the statistical methods for the 1) initial validation analyses as well as 2) internal validation using leave-one-out cross validation, are biased towards significance; 3) simple and complex models are compared suboptimally. Overall, we find that the article of Rosenberg et al. provides sufficient proof that network strength is associated with attentional capacity that it is not possible to say to which extent, and for this reason we argue that it cannot be concluded that the network is a broadly applicable neuromarker.

neuroscience↗