rudyvdbrink/CitationDatabase huggingface dataset:
Growth/differentiation factor 3 signals through ALK7 and regulates accumulation of adipose tissue and diet-induced obesity.
Proceedings of the National Academy of Sciences of the United States of America, 2008

Growth/differentiation factor 3 (GDF3) is highly expressed in adipose tissue, and previous overexpression experiments in mice have suggested that it may act as an adipogenic factor under conditions of high lipid load. GDF3 has been shown to signal via the activin receptor ALK4 during embryogenesis, but functional receptors in adipose tissue are unknown. In this study, we show that Gdf3(-/-) mutant mice accumulate less adipose tissue than WT animals and show partial resistance to high-fat diet-induced obesity despite similar food intake. We also demonstrate that GDF3 can signal via the ALK4-homolog ALK7 and the coreceptor Cripto, both of which are expressed in adipose tissue. In agreement with a role for ALK7 in GDF3 signaling in vivo, mutant mice lacking ALK7 also showed reduced fat accumulation and partial resistance to diet-induced obesity. We propose that GDF3 regulates adipose-tissue homeostasis and energy balance under nutrient overload in part by signaling through the ALK7 receptor.
The association between psychotic experiences and traumatic life events: the role of the intention to harm.
Psychological medicine, 2018

Previous work showed traumatic life events (TLE) with intention to harm, like bullying and abuse, to be more strongly associated with psychotic experiences (PE) than other types of trauma, like accidents. However, this association is subject to reporting bias and can be confounded by demographic characteristics and by differences in dose of exposure across different trauma categories. We studied the association between TLE with and without intention to harm and PE, taking into account potential confounders and biases.
Functional capacity scale in assessment of patients with intracranial aneurysms: reliability and validity.
The Journal of neuroscience nursing : journal of the American Association of Neuroscience Nurses, 2014

The aim of the study was to investigate the use of the Functional Capacity Scale (FCS) to measure functional outcome of patients who had undergone surgical removal of an intracranial aneurysm in the early postoperative period. Reliability and validity of the tool were tested as well as its utility in nursing practice. The study included 120 patients, operated on for intracranial aneurysm. Phase I included 23 patients. Reliability of FCS and the amount of time used for the assessment were tested using observation and direct measurement methods. Phase II included 97 patients, and the tool was administered along with standard outcome assessment tools (Barthel Index, Functional Index "Repty," Glasgow Outcome Score, and Rankin Scale) to determine concurrent validity. Kendall's coefficients of concordance (W) between particular care markers of FCS ranged from 0.910 to 1.000. Mean amount of time used for assessment was 90 seconds. Differences between time used for measurements by individual examiners were insignificant (p > .05). Correlation of FCS with the following scales was statistically significant: Functional Index "Repty" (p < .001), Glasgow Outcome Score (p < .01), Rankin Scale (p < .01), and Barthel Index (p < .001). The FCS appears to be a reliable, valid, and practical assessment tool for neuroscience nurses to use with patients who have undergone surgical removal of an intracranial aneurysm.
Impact of Zika Virus on adult human brain structure and functional organization.
Annals of clinical and translational neurology, 2018

To determine the impact of Zika virus (ZIKV) infection on brain structure and functional organization of severely affected adult patients with neurological complications that extend beyond Guillain-Barré Syndrome (GBS)-like manifestations and include symptoms of the central nervous system (CNS).
Improvement of Health-Related Quality of Life After Roux-en-Y Gastric Bypass Related to Weight Loss.
Obesity surgery, 2017

Effect of bariatric surgery on health-related quality of life (HRQOL) varies greatly. This might be caused by the diversity in questionnaires used to assess HRQOL and the weight loss of the studied population. This study assesses the relationship between weight loss and HRQOL in primary Roux-en-Y gastric bypass (RYGB) patients by using an obesity-specific (impact of weight on quality of life-lite, IWQOL-lite) and a generic (RAND-36) questionnaire.
Hand Motion Detection in fNIRS Neuroimaging Data.
Healthcare (Basel, Switzerland), 2017

As the number of people diagnosed with movement disorders is increasing, it becomes vital to design techniques that allow the better understanding of human brain in naturalistic settings. There are many brain imaging methods such as fMRI, SPECT, and MEG that provide the functional information of the brain. However, these techniques have some limitations including immobility, cost, and motion artifacts. One of the most emerging portable brain scanners available today is functional near-infrared spectroscopy (fNIRS). In this study, we have conducted fNIRS neuroimaging of seven healthy subjects while they were performing wrist tasks such as flipping their hand with the periods of rest (no movement). Different models of support vector machine is applied to these fNIRS neuroimaging data and the results show that we could classify the action and rest periods with the accuracy of over 80% for the fNIRS data of individual participants. Our results are promising and suggest that the presented classification method for fNIRS could further be applied to real-time applications such as brain computer interfacing (BCI), and into the future steps of this research to record brain activity from fNIRS and EEG, and fuse them with the body motion sensors to correlate the activities.
Chronic mild stress eliminates the neuroprotective effect of Copaxone after CNS injury.
Brain, behavior, and immunity, 2013

Copolymer (Cop)-1, also known as glatiramer acetate, is an active compound of Copaxone, a drug widely used by patients with multiple sclerosis (MS). Copaxone functions in MS through two mechanisms of action, namely immunomodulation and neuroprotection. Because the immune system is suppressed or altered in depressed individuals, and since depression is often associated with neurological conditions, we were interested in examining whether the neuroprotective effect of Copaxone persists under conditions of stress-induced depressive behavior. We exposed mice to unpredictable chronic mild stress for 4 weeks and then treated them with three doses of Copaxone at 3-day intervals, with the last dose given immediately before the mice underwent a crush injury to the optic nerve. Whereas nonstressed mice exhibited a strong neuroprotective response after Copaxone treatment, this effect was completely absent in mice that underwent chronic mild stress. Interestingly, when Copaxone was combined with Prozac, the neuroprotective effect of Copaxone was regained, suggesting that chronic mild stress interferes with the neuroprotective effect of Copaxone. These results may shed a light on mechanism of action of Copaxone and lead to new combined therapies for neurodegenerative and neuroinflammatory disorders.
NeuroD Factors Discriminate Mineralocorticoid From Glucocorticoid Receptor DNA Binding in the Male Rat Brain.
Endocrinology, 2017

In the limbic brain, mineralocorticoid receptors (MRs) and glucocorticoid receptors (GRs) both function as receptors for the naturally occurring glucocorticoids (corticosterone/cortisol) but mediate distinct effects on cellular physiology via transcriptional mechanisms. The transcriptional basis for specificity of these MR- vs GR-mediated effects is unknown. To address this conundrum, we have identified the extent of MR/GR DNA-binding selectivity in the rat hippocampus using chromatin immunoprecipitation followed by sequencing. We found 918 and 1450 nonoverlapping binding sites for MR and GR, respectively. Furthermore, 475 loci were co-occupied by MR and GR. De novo motif analysis resulted in a similar binding motif for both receptors at 100% of the target loci, which matched the known glucocorticoid response element (GRE). In addition, the Atoh/NeuroD consensus sequence was found in co-occurrence with all MR-specific binding sites but was absent for GR-specific or MR-GR overlapping sites. Basic helix-loop-helix family members Neurod1, Neurod2, and Neurod6 showed hippocampal expression and were hypothesized to bind the Atoh motif. Neurod2 was detected at rat hippocampal MR binding sites but not at GR-exclusive sites. All three NeuroD transcription factors acted as DNA-binding-dependent coactivators for both MR and GR in reporter assays in heterologous HEK293 cells, likely via indirect interactions with the receptors. In conclusion, a NeuroD family member binding to an additional motif near the GRE seems to drive specificity for MR over GR binding at hippocampal binding sites.
Aberrant striatal plasticity is specifically associated with dyskinesia following levodopa treatment.
Movement disorders : official journal of the Movement Disorder Society, 2010

Chronic levodopa treatment for Parkinson's disease often results in the development of abnormal involuntary movement, known as L-dopa-induced dyskinesia (LIDs). Studies suggest that LIDs may be associated with aberrant corticostriatal plasticity. Using in vivo extracellular recordings from identified Type I and Type II medium spiny striatal neurons, chronic L-dopa treatment was found to produce abnormal corticostriatal information processing. Specifically, after chronic L-dopa treatment in dopamine-depleted rats, there was a transition from a cortically evoked long-term depression (LTD) to a complementary but opposing form of plasticity, long-term potentiation, in Type II "indirect" pathway neurons. In contrast, LTD could still be induced in Type I neurons. Interestingly, the one parameter that correlated best with dyskinesias was the inability to de-depress established LTD in Type I medium spiny striatal neurons. Taken as a whole, we propose that the induction of LIDs is due, at least in part, to an aberrant induction of plasticity within the Type II indirect pathway neurons combined with an inability to de-depress established plastic responses in Type I neurons. Such information is critical for understanding the cellular mechanisms underlying one of the major caveats to L-dopa therapy.
Methamphetamine Induces Anhedonic-Like Behavior and Impairs Frontal Cortical Energetics in Mice.
CNS neuroscience & therapeutics, 2017

We recently showed that a single high dose of methamphetamine (METH) induces a persistent frontal cortical monoamine depletion that is accompanied by helpless-like behavior in mice. However, brain metabolic alterations underlying both neurochemical and mood alterations remain unknown.
Ceftriaxone-mediated upregulation of the glutamate transporter GLT-1 contrasts neurotoxicity evoked by kainate in rat organotypic spinal cord cultures.
Neurotoxicology, 2017

Excitotoxicity is a major pathological trigger of neurodegenerative diseases like amyotrophic lateral sclerosis. This process is caused by excessive release of the transmitter glutamate that overwhelms the capacity of astroglia transporters to maintain a low extracellular level of this aminoacid and strongly stimulates neurons. Using an in vitro model of rat organotypic spinal slice culture, we explored if the excitotoxicity caused by the potent glutamate analogue kainate, widely employed as a paradigm to evoke neurotoxicity in the central nervous system, was prevented by the antibiotic ceftriaxone known to enhance glutamate transporter expression. We also tested if excitotoxicity was made worse by inhibiting glutamate uptake with dl-threo-β-benzyloxyaspartate (TBOA). These experiments were aimed at clarifying the relative contribution to neurotoxicity by kainate-activation of glutamate receptors or kainate-mediated release of glutamate. Neither ceftriaxone nor TBOA alone had adverse effects. Ceftriaxone (10μM; 3days) significantly decreased delayed cell death induced by kainate (100μM; 1h) and limited neuronal damage especially to motoneurons. This effect was associated to stronger astrocytic immunostaining of the glutamate transporter GLT-1. Conversely, pharmacological inhibition of glutamate uptake with TBOA was per se unable to induce neurotoxicity, yet it intensified cell death evoked by kainate. These data indicate that kainate-mediated glutamate release was critical to damage neurons, an effect prevented by up regulating glutamate uptake. These data suggest that modulating glutamate uptake is an important strategy to preserve neuronal networks.
Temporal dynamics of saccades explained by a self-paced process.
Scientific reports, 2017

Sensory organs are thought to sample the environment rhythmically thereby providing periodic perceptual input. Whisking and sniffing are governed by oscillators which impose rhythms on the motor-control of sensory acquisition and consequently on sensory input. Saccadic eye movements are the main visual sampling mechanism in primates, and were suggested to constitute part of such a rhythmic exploration system. In this study we characterized saccadic rhythmicity, and examined whether it is consistent with autonomous oscillatory generator or with self-paced generation. Eye movements were tracked while observers were either free-viewing a movie or fixating a static stimulus. We inspected the temporal dynamics of exploratory and fixational saccades and quantified their first-order and high-order dependencies. Data were analyzed using methods derived from spike-train analysis, and tested against mathematical models and simulations. The findings show that saccade timings are explained by first-order dependencies, specifically by their refractory period. Saccade-timings are inconsistent with an autonomous pace-maker but are consistent with a "self-paced" generator, where each saccade is a link in a chain of neural processes that depend on the outcome of the saccade itself. We propose a mathematical model parsimoniously capturing various facets of saccade-timings, and suggest a possible neural mechanism producing the observed dynamics.
Is Model Fitting Necessary for Model-Based fMRI?
PLoS computational biology, 2015

Model-based analysis of fMRI data is an important tool for investigating the computational role of different brain regions. With this method, theoretical models of behavior can be leveraged to find the brain structures underlying variables from specific algorithms, such as prediction errors in reinforcement learning. One potential weakness with this approach is that models often have free parameters and thus the results of the analysis may depend on how these free parameters are set. In this work we asked whether this hypothetical weakness is a problem in practice. We first developed general closed-form expressions for the relationship between results of fMRI analyses using different regressors, e.g., one corresponding to the true process underlying the measured data and one a model-derived approximation of the true generative regressor. Then, as a specific test case, we examined the sensitivity of model-based fMRI to the learning rate parameter in reinforcement learning, both in theory and in two previously-published datasets. We found that even gross errors in the learning rate lead to only minute changes in the neural results. Our findings thus suggest that precise model fitting is not always necessary for model-based fMRI. They also highlight the difficulty in using fMRI data for arbitrating between different models or model parameters. While these specific results pertain only to the effect of learning rate in simple reinforcement learning models, we provide a template for testing for effects of different parameters in other models.
Unsupervised clustering method to detect microsaccades.
Journal of vision, 2014

Microsaccades, small involuntary eye movements that occur once or twice per second during attempted visual fixation, are relevant to perception, cognition, and oculomotor control and present distinctive characteristics in visual and oculomotor pathologies. Thus, the development of robust and accurate microsaccade-detection techniques is important for basic and clinical neuroscience research. Due to the diminutive size of microsaccades, however, automatic and reliable detection can be difficult. Current challenges in microsaccade detection include reliance on set, arbitrary thresholds and lack of objective validation. Here we describe a novel microsaccade-detecting method, based on unsupervised clustering techniques, that does not require an arbitrary threshold and provides a detection reliability index. We validated the new clustering method using real and simulated eye-movement data. The clustering method reduced detection errors by 62% for binocular data and 78% for monocular data, when compared to standard contemporary microsaccade-detection techniques. Further, the clustering method's reliability index was correlated with the microsaccade-detection error rate, suggesting that the reliability index may be used to determine the comparative precision of eye-tracking devices.
Numerical rule coding in the prefrontal, premotor, and posterior parietal cortices of macaques.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012

Switching flexibly between behavioral goals is a hallmark of executive control and requires integration of external and internal information. We recorded single-neuron correlates of different numerical representations (sensory-, working memory-, and rule-related activity) in the dorsal premotor area (PMd), the cingulate motor areas (CMA), and the ventral intraparietal sulcus (VIP) and compared them to previous recordings in the lateral prefrontal cortex (PFC). Two monkeys were trained to encode and memorize numerosities and flexibly switch between two abstract quantitative rules based on rule cues. Almost 20% of randomly selected PFC and PMd neurons significantly represented the numerical rule in a behaviorally relevant manner, approximately twice as many as in the CMA and VIP. Rule selectivity was significantly better for PMd neurons than for PFC cells. Seemingly at the expense of rule selectivity, however, sensory- and memory-related numerosity activity was greatly diminished compared with previous delayed match-to-numerosity studies. These findings suggest the involvement of the frontal premotor areas in strategic planning such as rule following. Moreover, the results emphasize that the coding capacities of neurons in association cortical areas are far more dynamic depending on task demands than previously thought.
Enhancing maternal and infant wellbeing: study protocol for a feasibility trial of the Baby Triple P Positive Parenting programme for mothers with severe mental health difficulties (the IMAGINE study).
Trials, 2018

There is a strong evidence base for the benefits of parenting interventions for parents without severe mental illness (SMI). As the impact of maternal SMI can be significant on child development, mothers need support to maximise outcomes for themselves and their children. Some mothers with SMI require admission jointly with their baby to a Mother and Baby Unit (MBU), a psychiatric inpatient ward, for assessment and treatment. However, MBUs do not yet offer formally evaluated, evidence-based parenting interventions as a matter of routine. This paper describes a study to investigate the feasibility and acceptability of conducting a randomised controlled trial (RCT) to evaluate a parenting and psychological intervention targeting the mother's and infant's wellbeing for mothers admitted to a MBU.
A template-matching algorithm for laminar identification of cortical recording sites from evoked response potentials.
Journal of neurophysiology, 2020

In recent years, the advent of the so-called silicon probes has made it possible to homogeneously sample spikes and local field potentials (LFPs) from a regular grid of cortical recording sites. In principle, this allows inferring the laminar location of the sites based on the spatiotemporal pattern of LFPs recorded along the probe, as in the well-known current source-density (CSD) analysis. This approach, however, has several limitations, since it relies on visual identification of landmark features (i.e., current sinks and sources) by human operators - features that can be absent from the CSD pattern if the probe does not span the whole cortical thickness, thus making manual labelling harder. Furthermore, as any manual annotation procedure, the typical CSD-based workflow for laminar identification of recording sites is affected by subjective judgment undermining the consistency and reproducibility of results. To overcome these limitations, we developed an alternative approach, based on finding the optimal match between the LFPs recorded along a probe in a given experiment and a template LFP profile that was computed using 18 recording sessions, in which the depth of the recording sites had been recovered through histology. We show that this method can achieve an accuracy of 79 µm in recovering the cortical depth of recording sites and a 76% accuracy in inferring their laminar location. As such, our approach provides an alternative to CSD that, being fully automated, is less prone to the idiosyncrasies of subjective judgment and works reliably also for recordings spanning a limited cortical stretch.
Aβ-dependent reduction of NCAM2-mediated synaptic adhesion contributes to synapse loss in Alzheimer's disease.
Nature communications, 2015

Alzheimer's disease (AD) is characterized by synapse loss due to mechanisms that remain poorly understood. We show that the neural cell adhesion molecule 2 (NCAM2) is enriched in synapses in the human hippocampus. This enrichment is abolished in the hippocampus of AD patients and in brains of mice overexpressing the human amyloid-β (Aβ) precursor protein carrying the pathogenic Swedish mutation. Aβ binds to NCAM2 at the cell surface of cultured hippocampal neurons and induces removal of NCAM2 from synapses. In AD hippocampus, cleavage of the membrane proximal external region of NCAM2 is increased and soluble extracellular fragments of NCAM2 (NCAM2-ED) accumulate. Knockdown of NCAM2 expression or incubation with NCAM2-ED induces disassembly of GluR1-containing glutamatergic synapses in cultured hippocampal neurons. Aβ-dependent disassembly of GluR1-containing synapses is inhibited in neurons overexpressing a cleavage-resistant mutant of NCAM2. Our data indicate that Aβ-dependent disruption of NCAM2 functions in AD hippocampus contributes to synapse loss.