Biology subjects

Linden, D.

Publications and source records attributed to Linden, D..

9 recordsLinked to original sources

bioRxiv2025

Toward navigating emotional states using real-time representational similarity analysis fMRI neurofeedback - a feasibility study

Real-time functional magnetic resonance imaging neurofeedback (rt-fMRI-NF) is a promising non-invasive brain-computer-interface (BCI) technique for enhancing self-regulation of affective states in the brain. However, conventional univariate rt-fMRI-NF approaches are limited in their ability to distinguish neural patterns of distinct emotions that involve overlapping brain regions. In this study, we applied an rt-fMRI semantic neurofeedback (rt-fMRI-sNF) paradigm, incorporating real-time representational similarity analysis (rt-RSA) to enable navigation between emotional states. Four emotional patterns were first derived from functional localizer runs, each designed to evoke a specific emotion, and then applied as target patterns during neurofeedback. Using an RSA-informed circular semantic map (CSM), participants received real-time visual feedback indicating both the similarity and intensity of their current brain activity relative to target emotional patterns. Participants were instructed to use mental imagery to shift their brain activity toward the specific target pattern and increase its intensity. Twenty-four healthy participants completed the localizer runs, and two consecutive neurofeedback runs in the same session. Ten participants successfully engaged with both the similarity and intensity components of the CSM, showing effective modulations of their mental states. Analyses of the localizer runs revealed overlapping regional activations across emotions and demonstrated that RSA outperformed univariate analysis in distinguishing between them. For the neurofeedback runs, linear mixed-effects model (LMM) analyses across multiple performance metrics indicated consistent within-run improvements and higher initial performance in the second run, while significant between-run learning effects emerged only in exploratory models with quadratic time terms. A block-wise comparison also showed significantly higher performance at the end of each run compared to the beginning based on the intensity metric. These findings support the usability of RSA in differentiating multiple emotional states and demonstrate the feasibility of the rt-fMRI-sNF paradigm for emotion regulation.

neuroscience↗

bioRxiv2024

Not enough pleasure? Influence of hallucination proneness on sensory feedback processing of positive self-voice

Ample research explored changes in sensory feedback processing of the self-voice as well as the control of attention allocation in voice hearers, including both non-clinical voice hearers and voice hearers with a psychotic disorder. While the attentional bias toward negative emotional information in voice hearers with a psychotic disorder due to heightened sensitivity towards threat/danger is well established, it remains unclear how positive emotion captures or controls attention. Manipulating the certainty of sensory feedback to the self-voice, transitioning from fully neutral to entirely positive (100% neutral, 60-40% neutral-pleasure, 50-50% neutral-pleasure, 40-60% neutral-pleasure, 100% pleasure), provides an opportunity to investigate attentional control and sensory feedback processing in positive self-voice as a function of hallucination proneness (HP). Participants with different HP scores self-generated and passively listened to their own voices during EEG recordings. N100 or P200 responses to self-generated and externally-generated self-voices did not differ. Further, HP did not modulate N100/P200 responses. These null findings might result from the minimal perceptual discriminability among the five types of voices varying in pleasure content. This might have led to less variation in certainty regarding the sensory feedback to self-voice, and consequently a lack of differential engagement of attentional resources. The lack of a global N100 suppression effect prompts inquiry into the association of sense of ownership/agency and pleasure.

neuroscience↗

bioRxiv2023

Exploring Neural Dynamics in Self-Voice Processing and Perception: Implications for Hallucination Proneness.

Altered sensory feedback processing and attention control are assumed to contribute to auditory verbal hallucinations, which are experienced by the general population and patients with psychosis, implying a continuum of hallucination proneness (HP). However, the interaction of altered sensory feedback processing and attention control along this HP continuum remains unclear. Manipulating the level of certainty of sensory feedback by changing self-voice quality (100% neutral, 60-40% neutral-angry, 50-50% neutral-angry, 40-60% neutral-angry, 100% angry) in individuals varying in HP, we tested this interaction using electroencephalography while participants self-generated or passively listened to their voices. Regardless of voice quality, HP modulated the N100 and P200 suppression effects. High HP individuals showed an increased N100 response to the self-generated voices and an increased P200 response for externally-generated voices. This may indicate increased error awareness and attention allocation in high HP individuals for self-voice generation stemming from altered sensory feedback processing, and/or attentional control. The current findings suggest that alterations of the sensory feedback processing in self-voice production are a fundamental characteristic of the continuum of HP, regardless of the clinical status of voice hearers. HighlightsO_LIAltered N100 voice suppression in high HP, regardless of the clinical status. C_LIO_LIHigh HP associated with altered sensory feedback processing and attentional control. C_LIO_LICurrent findings support a neurophysiological continuum of HP. C_LI

neuroscience↗

bioRxiv2023

Substrate-Specific Function of PNPLA3 Facilitates Hepatic VLDL-Triglyceride Secretion During Stimulated Lipogenesis

The I148M variant of PNPLA3 is strongly linked to hepatic steatosis. Evidence suggests a gain-of-function role for the I148M mutant as an ATGL inhibitor, leaving the physiological relevance of wild-type PNPLA3 undefined. Here we show that PNPLA3 selectively degrades triglycerides (TGs) enriched in polyunsaturated fatty acids (PUFAs) independently of ATGL in cultured cells and mice. Lipidomics and metabolite tracing analyses demonstrated that PNPLA3 mobilizes PUFAs from intracellular TGs for phospholipid desaturation, supporting hepatic secretion of TG-rich lipoproteins. Consequently, mice with liver-specific knockout or acute knockdown of PNPLA3 both exhibited aggravated liver steatosis and concomitant decreases in plasma VLDL-TG, phenotypes that manifest only under lipogenic conditions. I148M-knockin mice similarly displayed impaired hepatic TG secretion during lipogenic stimulation. Our results highlight a specific context whereby PNPLA3 facilitates the balance between hepatic TG storage and secretion and suggest the potential contributions of I148M variant loss-of-function to the development of hepatic steatosis in humans. Summary StatementWe define the physiological role of wild type PNPLA3 in maintaining hepatic VLDL-TG secretion.

physiology↗

bioRxiv2023

A brief real-time fNIRS-informed neurofeedback training of the prefrontal cortex changes brain activity and connectivity during subsequent working memory challenge

Working memory (WM) represents a building-block of higher cognitive functions and a wide range of mental disorders are associated with WM impairments. Initial studies have shown that several sessions of functional nearinfrared spectroscopy (fNIRS) informed real-time neurofeedback (NF) allow healthy individuals to volitionally increase activity in the dorsolateral prefrontal cortex (DLPFC), a region critically involved in WM. For the translation to therapeutic or neuroenhancement applications, however, it is critical to assess whether fNIRS-NF success transfers into neural and behavioral WM enhancement in the absence of feedback. We therefore combined single-session fNIRS-NF of the left DLPFC with a randomized sham-controlled design (N = 62 participants) and a subsequent WM challenge with concomitant functional MRI. Over four runs of fNIRS-NF, the left DLPFC NF training group demonstrated enhanced neural activity in this region, reflecting successful acquisition of neural selfregulation. During the subsequent WM challenge, we observed no evidence for performance differences between the training and the sham group. Importantly, however, examination of the fMRI data revealed that - compared to the sham group - the training group exhibited significantly increased regional activity in the bilateral DLPFC and decreased left DLPFC - left anterior insula functional connectivity during the WM challenge. Exploratory analyses revealed a negative association between DLPFC activity and WM reaction times in the NF group. Together, these findings indicate that healthy individuals can learn to volitionally increase left DLPFC activity in a single training session and that the training success translates into WM-related neural activation and connectivity changes in the absence of feedback. This renders fNIRS-NF as a promising and scalable WM intervention approach that could be applied to various mental disorders.

neuroscience↗

bioRxiv2022

Age-dependent changes in the dynamic functional organization of the brain at rest - a cross - cultural replication approach

Age-associated changes in brain function play an important role in the development of neurodegenerative diseases. Although previous work has examined age-related changes in static functional connectivity (FC), accumulating evidence suggests that advancing age is especially associated with alterations in the dynamic interactions and transitions between different brain states, which hitherto has received less attention. Moreover, conclusions of previous studies in this domain are limited by suboptimal replicability of resting state fMRI and culturally homogenous cohorts. Here, we investigate the robustness of age-associated changes in dynamic functional connectivity (dFC) by capitalizing on the availability of fMRI cohorts from two cultures (Western European and Chinese). In both cohorts we consistently identify two distinct connectivity states: a more frequent segregated within-network connectivity state (state I) and a less frequent integrated between-network connectivity state (state II). In both cohorts, older (55-80 years) compared to younger participants (20-35 years) exhibited lower occurrence of and spent less time in state I. Moreover, older participants tended to exhibit more transitions between networks and greater variance in global efficiency. Overall, our cross-cultural replication of age-associated changes in key dFC metrics implies that advancing age is robustly associated with a reorganization of dynamic brain activation that favors the use of less functionally-specific networks. HighlightsAging is associated with a reorganization of dynamic functional brain connectivity. Age-dependent dynamic functional connectivity changes are relatively stable across cultures. Dynamic properties are promising neural indexes for brain aging in older healthy populations.

neuroscience↗

bioRxiv2021

Dysregulation of NRSF/REST via EHMT1 is association with psychiatric disorders

Genetic evidence indicates disrupted epigenetic regulation as a major risk factor for psychiatric disorders, but the molecular mechanisms that drive this association are undetermined. EHMT1 is an epigenetic repressor that is causal for Kleefstra Syndrome (KS), a neurodevelopmental disorder (NDD) leading to ID, and is associated with schizophrenia. Here, we show that reduced EHMT1 activity decreases NRSF/REST protein leading to abnormal neuronal gene expression and progression of neurodevelopment in human iPSC. We further show that EHMT1 regulates NRSF/REST indirectly via repression of miRNA leading to aberrant neuronal gene regulation and neurodevelopment timing. Expression of a NRSF/REST mRNA that lacks the miRNA-binding sites restores neuronal gene regulation to EHMT1 deficient cells. Importantly, the EHMT1-regulated miRNA gene set with elevated expression is enriched for NRSF/REST regulators with an association for ID and schizophrenia. This reveals a molecular interaction between H3K9 dimethylation and NSRF/REST contributing to the aetiology of psychiatric disorders.

neuroscience↗

bioRxiv2021

Quality control strategies for brain MRI segmentation and parcellation: practical approaches and recommendations - insights from The Maastricht Study

BackgroundQuality control of brain segmentation is a fundamental step to ensure data quality. Manual quality control is the current gold standard, despite unfeasible in large neuroimaging samples. Several options for automated quality control have been proposed, providing potential time efficient and reproducible alternatives. However, those have never been compared side to side, which prevents to reach consensus in the appropriate QC strategy to use. This study aims to elucidate the changes manual editing of brain segmentations produce in morphological estimates, and to analyze and compare the effects of different quality control strategies in the reduction of the measurement error. MethodsWe used structural MR images from 259 participants of The Maastricht Study. Morphological estimates were automatically extracted using FreeSurfer 6.0. A subsample of the brain segmentations with inaccuracies was manually edited, and morphological estimates were compared before and after editing. In parallel, 11 quality control strategies were applied to the full sample. Those included: a manual strategy, manual-QC, in which images were visually inspected and manually edited; five automated strategies where outliers were excluded based on the tools MRIQC and Qoala-T, and the metrics morphological global measures, Euler numbers and Contrast-to-Noise ratio; and five semi-automated strategies, were the outliers detected through the mentioned tools and metrics were not excluded, but visually inspected and manually edited. We used a regression of morphological brain measures against age as a test case to compare the changes in relative unexplained variance that each quality control strategy produces, using the reduction of relative unexplained variance as a measure of increase in quality. ResultsManually editing brain surfaces produced changes particularly high in subcortical brain volumes and moderate in cortical surface area, thickness and hippocampal volumes. The exclusion of outliers based on Euler numbers yielded a larger reduction of relative unexplained variance for measurements of cortical area, subcortical volumes and hippocampal subfields, while manual editing of brain segmentations performed best for cortical thickness. MRIQC produced a lower, but consistent for all types of measures, reduction in relative unexplained variance. Unexpectedly, the exclusion of outliers based on global morphological measures produced an increase of relative unexplained variance, potentially removing more morphological information than noise from the sample. ConclusionOverall, the automatic exclusion of outliers based on Euler numbers or MRIQC are reliable and time efficient quality control strategies that can be applied in large neuroimaging cohorts.

neuroscience↗

bioRxiv2019

Catecholaminergic axons in the neocortex of adult mice regrow following brain injury

Serotonin axons in the adult rodent brain can regrow and recover their function following several forms of injury including controlled cortical impact (CCI), a neocortical stab wound, or systemic amphetamine toxicity. To assess whether this capacity for regrowth is unique to serotonergic fibers, we used CCI and stab injury models to assess whether fibers from other neuromodulatory systems can also regrow following injury. Using tyrosine-hydoxylase (TH) immunohistochemistry we measured the density of catecholaminergic axons before and at various time points after injury. One week after CCI injury we observed a pronounced loss, across cortical layers, of TH+ axons posterior to the site of injury. One month after CCI injury the same was true of TH+ axons both anterior and posterior to the site of injury. This loss was followed by significant recovery of TH+ fiber density across cortical layers, both anterior and posterior to the site of injury, measured three months after injury. TH+ axon loss and recovery over weeks to months was also observed throughout cortical layers using the stab injury model. Double label immunohistochemistry revealed that nearly all TH+ axons in neocortical layer 1/2 are also dopamine-beta-hyroxylase+ (DBH+; presumed norepinephrine), while TH+ axons in layer 5 are a mixture of DBH+ and dopamine transporter+ types. This suggests that noradrenergic axons can regrow following CCI or stab injury in the adult mouse neocortex and leaves open the question of whether dopaminergic axons can do the same.\n\nHighlightsO_LIWe measured catecholaminergic axon density using tyrosine hydroxylase immunohistochemistry following two forms of brain injury.\nC_LIO_LIBoth controlled cortical impact and cortical stab injuries caused extensive damage to catecholaminergic axons in the neocortex of adult mice.\nC_LIO_LIFollowing both types of injury, axon density slowly returned to control values over many weeks, including, in the case of stab injury, regrowth across the stab rift.\nC_LIO_LITogether with previous results showing serotonin axon regrowth, these findings suggest that monaminergic axons have an unusual capacity for regrowth following injury in the adult mammalian brain\nC_LI

neuroscience↗