rudyvdbrink/CitationDatabase huggingface dataset:
High Resolution Dissection of Reactive Glial Nets in Alzheimer's Disease.
Scientific reports, 2016

Fixed human brain samples in tissue repositories hold great potential for unlocking complexities of the brain and its alteration with disease. However, current methodology for simultaneously resolving complex three-dimensional (3D) cellular anatomy and organization, as well as, intricate details of human brain cells in tissue has been limited due to weak labeling characteristics of the tissue and high background levels. To expose the potential of these samples, we developed a method to overcome these major limitations. This approach offers an unprecedented view of cytoarchitecture and subcellular detail of human brain cells, from cellular networks to individual synapses. Applying the method to AD samples, we expose complex features of microglial cells and astrocytes in the disease. Through this methodology, we show that these cells form specialized 3D structures in AD that we refer to as reactive glial nets (RGNs). RGNs are areas of concentrated neuronal injury, inflammation, and tauopathy and display unique features around β-amyloid plaque types. RGNs have conserved properties in an AD mouse model and display a developmental pattern coinciding with the progressive accumulation of neuropathology. The method provided here will help reveal novel features of the healthy and diseased human brain, and aid experimental design in translational brain research.
Dynamics of longitudinal dentate gyrus axons associated with seizure.
The Journal of physiology, 2021

Axon collaterals of DG granule neurons project towards neighbouring DG granule cell layer Longitudinal axons in the DG-DG circuit possess denser synapses than transverse axons in the DG-CA3 circuit The size of varicosities of the longitudinal axons, but not transverse ones, is regulated by seizures as measured behaviourally Varicosity size of DG-DG axons can be a symptomatic marker of DG-related brain diseases ABSTRACT: The hippocampus network has captured the attention of neuroscientists as a model for understanding cognition and behaviour. Previously, we have identified interlamellar, namely longitudinal, axons between CA1 pyramidal neurons analogous to recurrent connections between CA3 pyramidal neurons. Currently it is unknown whether longitudinal axons of DG granule neurons are present and how they are associated with the behavioural symptoms of seizure. We found longitudinal axons projections from DG granule cells extending to neighbouring DG granule cell layers. These DG-DG axons have more numerous varicosities and are thinner than the DG-CA3 axons, suggesting heavy synaptic formation along a longitudinal axis. Furthermore, the size of varicosities in the DG-DG but not DG-CA3 axons is regulated by seizures as measured behaviourally. The results suggest that the dynamics of longitudinal DG axons is a symptomatic marker of DG-related brain diseases.
Artery of Percheron infarction: a case report.
Journal of medical case reports, 2017

The artery of Percheron is a rare anatomic variant of arterial supply to the paramedian thalamus and rostral midbrain, and occlusion of the artery of Percheron results in bilateral paramedian thalamic infarcts with or without midbrain involvement. Acute artery of Percheron infarcts represent 0.1 to 2% of total ischemic stroke. However, of thalamic strokes, occlusion of artery of Percheron is the cause in 4 to 35% of cases. Early diagnosis of artery of Percheron infarction can be challenging because it is infrequent and early computed tomography or magnetic resonance imaging may be negative. Thus, it can be confused with other neurological conditions such as tumors and infections.
Entorhinal transformations in abstract frames of reference.
PLoS biology, 2019

Knowing how another's preferences relate to our own is a central aspect of everyday decision-making, yet how the brain performs this transformation is unclear. Here, we ask whether the putative role of the hippocampal-entorhinal system in transforming relative and absolute spatial coordinates during navigation extends to transformations in abstract decision spaces. During functional magnetic resonance imaging (fMRI), subjects learned a stranger's preference for an everyday activity-relative to one of three personally known individuals-and subsequently decided how the stranger's preference relates to the other two individuals' preferences. We observed entorhinal/subicular responses to the absolute distance between the ratings of the stranger and the familiar choice options. Notably, entorhinal/subicular signals were sensitive to which familiar individuals were being compared to the stranger. In contrast, striatal signals increased when accurately determining the ordinal position of choice options in relation to the stranger. Paralleling its role in navigation, these data implicate the entorhinal/subicular region in assimilating relatively coded knowledge within abstract metric spaces.
Hurst entropy: A method to determine predictability in a binary series based on a fractal-related process.
Physical review. E, 2019

Shannon's concept of information is related to predictability. In a binary series, the value of information relies on the frequency of 0's and 1's, or how it is expected to occur. However, information entropy does not consider the bias in randomness related to autocorrelation. In fact, it is possible for a binary temporal series to carry both short- and long-term memories related to the sequential distribution of 0's and 1's. Although the Hurst exponent measures the range of autocorrelation, there is a lack of mathematical connection between information entropy and autocorrelation present in the series. To fill this important gap, we combined numerical simulations and an analytical approach to determine how information entropy changes according to the frequency of 0's and 1's and the Hurst exponent. Indeed, we were able to determine how predictability depends on both parameters. Our findings are certainly useful to several fields when binary times series are applied, such as neuroscience to econophysics.
Nonrandom local circuits in the dentate gyrus.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2008

The dentate hilus has been extensively studied in relation to its potential role in memory and in temporal lobe epilepsy. Little is known, however, about the synapses formed between the two major cell types in this region, glutamatergic mossy cells and hilar interneurons, or the organization of local circuits involving these cells. Using triple and quadruple simultaneous intracellular recordings in rat hippocampal slices, we find that mossy cells evoke EPSPs with high failure rates onto hilar neurons. Mossy cells show profound synapse specificity; 87.5% of their intralamellar connections are onto hilar interneurons. Hilar interneurons also show synapse specificity and preferentially inhibit mossy cells; 81% of inhibitory hilar synapses are onto mossy cells. Hilar IPSPs have low failure rates, are blocked by the GABA(A) receptor antagonist gabazine, and exhibit short-term depression when tested at 17 Hz. Surprisingly, more than half (57%) of the mossy cell synapses we found onto interneurons were part of reciprocal excitatory/inhibitory local circuit motifs. Neither the high degree of target cell specificity, nor the significant enrichment of structured polysynaptic local circuit motifs, could be explained by nonrandom sampling or somatic proximity. Intralamellar hilar synapses appear to function primarily by integrating synchronous inputs and presynaptic burst discharges, allowing hilar cells to respond over a large dynamic range of input strengths. The reciprocal mossy cell/interneuron local circuit motifs we find enriched in the hilus may generate sparse neural representations involved in hippocampal memory operations.
The facial width-to-height ratio determines interpersonal distance preferences in the observer.
Aggressive behavior, 2017

Facial width-to-height ratio (fWHR) is correlated with a number of aspects of aggressive behavior in men. Observers appear to be able to assess aggressiveness from male fWHR, but implications for interpersonal distance preferences have not yet been determined. This study utilized a novel computerized stop-distance task to examine interpersonal space preferences of female participants who envisioned being approached by a man; men's faces photographed posed in neutral facial expressions were shown in increasing size to mimic approach. We explored the effect of the men's fWHR, their behavioral aggression (measured previously in a computer game), and women's ratings of the men's aggressiveness, attractiveness, and masculinity on the preferred interpersonal distance of 52 German women. Hierarchical linear modelling confirmed the relationship between the fWHR and trait judgements (ratings of aggressiveness, attractiveness, and masculinity). There were effects of fWHR and actual aggression on the preferred interpersonal distance, even when controlling statistically for men's and the participants' age. Ratings of attractiveness, however, was the most influential variable predicting preferred interpersonal distance. Our results extend earlier findings on fWHR as a cue of aggressiveness in men by demonstrating implications for social interaction. In conclusion, women are able to accurately detect aggressiveness in emotionally neutral facial expressions, and adapt their social distance preferences accordingly.
GABA(A) receptor agonist and antagonist alter vestibular compensation and different steps of reactive neurogenesis in deafferented vestibular nuclei of adult cats.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013

Strong reactive cell proliferation occurs in the vestibular nuclei after unilateral vestibular neurectomy (UVN). Most of the newborn cells survive, differentiate into glial cells and neurons with GABAergic phenotype, and have been reported to contribute to recovery of the posturo-locomotor functions in adult cats. Because the GABAergic system modulates vestibular function recovery and the different steps of neurogenesis in mammals, we aimed to examine in our UVN animal model the effect of chronic infusion of GABA(A) receptor (R) agonist and antagonist in the vestibular nuclei. After UVN and one-month intracerebroventricular infusions of saline, GABA(A)R agonist (muscimol) or antagonist (gabazine), cell proliferation and differentiation into astrocytes, microglial cells, and neurons were revealed using immunohistochemical methods. We also determined the effects of these drug infusions on the recovery of posturo-locomotor and oculomotor functions through behavioral tests. Our results showed that surprisingly, one month after UVN, newborn cells did not survive in the UVN-muscimol group whereas the number of GABAergic pre-existent neurons increased, and the long-term behavioral recovery of the animals was drastically impaired. Conversely, a significant number of newborn cells survived up to 1 month in the UVN-gabazine group whereas the astroglial population increased, and these animals showed the fastest recovery in behavioral functions. This study reports for the first time that GABA plays multiple roles, ranging from beneficial to detrimental on the different steps of a functional postlesion neurogenesis and further, strongly influences the time course of vestibular function recovery.
Naturalistic stimuli reveal a dominant role for agentic action in visual representation.
NeuroImage, 2020

Naturalistic, dynamic movies evoke strong, consistent, and information-rich patterns of activity over a broad expanse of cortex and engage multiple perceptual and cognitive systems in parallel. The use of naturalistic stimuli enables functional brain imaging research to explore cognitive domains that are poorly sampled in highly-controlled experiments. These domains include perception and understanding of agentic action, which plays a larger role in visual representation than was appreciated from experiments using static, controlled stimuli.
Repeating a strongly masked stimulus increases priming and awareness.
Consciousness and cognition, 2013

Previous studies [Marcel, A. J. (1983). Conscious and unconscious perception: Experiments on visual masking and word recognition. Cognitive Psychology, 15(2), 197-237; Wentura, D., & Frings, C. (2005). Repeated masked category primes interfere with related exemplars: New evidence for negative semantic priming. Journal of Experimental Psychology: Learning, Memory, and Cognition, 31(1), 108-120] suggested that repeatedly presenting a masked stimulus improves priming without increasing perceptual awareness. However, neural theories of consciousness predict the opposite: Increasing bottom-up strength in such a paradigm should also result in increasing availability to awareness. Here, we tested this prediction by manipulating the number of repetitions of a strongly masked digit. Our results do not replicate the dissociation observed in previous studies and are instead suggestive that repeating an unconscious and attended masked stimulus enables the progressive emergence of perceptual awareness.
LRRK2 Facilitates tau Phosphorylation through Strong Interaction with tau and cdk5.
Biochemistry, 2015

Leucine-rich repeat kinase 2 (LRRK2) and tau have been identified as risk factors of Parkinson's disease (PD). As LRRK2 is a kinase and tau is hyperphosphorylated in some LRRK2 mutation carriers of PD patients, the obvious hypothesis is that tau could be a substrate of LRRK2. Previous reports that LRRK2 phosphorylates free tau or tubulin-associated tau provide direct support for this proposition. By comparing LRRK2 with cdk5, we show that wild-type LRRK2 and the G2019S mutant phosphorylate free recombinant full-length tau protein with specific activity 480- and 250-fold lower than cdk5, respectively. More strikingly tau binds to wt LRRK2 or the G2019S mutant 140- or 200-fold more strongly than cdk5. The extremely low activity of LRRK2 but strong binding affinity with tau suggests that LRRK2 may facilitate tau phosphorylation as a scaffold protein rather than as a major tau kinase. This hypothesis is further supported by the observation that (i) cdk5 or tau coimmunoprecipitates with endogenous LRRK2 in SH-SY5Y cells, in mouse brain tissue, and in human PBMCs; (ii) knocking down endogenous LRRK2 by its siRNA in SH-SY5Y cells reduces tau phosphorylation at Ser396 and Ser404; (iii) inhibiting LRRK2 kinase activity by its inhibitors has no effect on tau phosphorylation at these two sites; and (iv) overexpressing wt LRRK2, the G2019S mutant, or the D1994A kinase-dead mutant in SH-SY5Y cells has no effect on tau phosphorylation. Our results suggest that LRRK2 facilitates tau phosphorylation indirectly by recruiting tau or cdk5 rather than by directly phosphorylating tau.
Binaural benefit for speech recognition with spectral mismatch across ears in simulated electric hearing.
The Journal of the Acoustical Society of America, 2011

The present study investigated the effects of binaural spectral mismatch on binaural benefits in the context of bilateral cochlear implants using acoustic simulations. Binaural spectral mismatch was systematically manipulated by simulating changes in the relative insertion depths across ears. Sentence recognition, presented unilaterally and bilaterally, were measured in normal-hearing listeners in quiet and noise at +5 dB signal-to-noise ratio. Significant binaural benefits were observed when the interaural difference in insertion depth was 1 mm or less. This result suggests a dependence of the binaural benefit on redundant speech information, rather than on similarity in performance across ears.
A meta-analysis of functional magnetic resonance imaging studies of eye movements and visual word reading.
Brain and behavior, 2017

The pattern of eye movements during reading is substantially correlated with linguistic factors. While there have been a large number of studies on the neural mechanisms of eye movements and word reading separately, a limited number of studies have compared the activation patterns of these two processes and discussed the associations of their corresponding brain regions within the framework of naturalistic reading.
COveRs to impRove AesthetiC ouTcome after Surgery for Chronic subdural haemAtoma by buRr hole trepanation (CORRECT-SCAR): protocol of a Swiss single-blinded, randomised controlled trial.
BMJ open, 2019

Outcomes rated on impairment scales are satisfactory after burr hole trepanation for chronic subdural haematoma (cSDH). However, the surgery leads to bony defects in the skull with skin depressions above that are frequently considered aesthetically unsatisfactory by the patients. Those defects could be covered by the approved medical devices (burr hole covers), but this is rarely done today. We wish to assess, whether the application of burr hole covers after trepanation for the evacuation of cSDH leads to higher patient satisfaction with the aesthetical result at 90 days postoperative, without worsening disability outcomes or increasing the complication rate.
The dopamine uptake inhibitor 3 alpha-[bis(4'-fluorophenyl)metoxy]-tropane reduces cocaine-induced early-gene expression, locomotor activity, and conditioned reward.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2009

Benztropine (BZT) analogs, a family of high-affinity dopamine transporter ligands, are molecules that exhibit pharmacological and behavioral characteristics predictive of significant therapeutic potential in cocaine addiction. Here, we examined in mice the effects of 3 alpha-[bis(4'-fluorophenyl)metoxy]-tropane (AHN-1055) on motor activity, conditioned place preference (CPP) and c-Fos expression in the striatum. AHN-1055 produced mild attenuation of spontaneous locomotor activity at a low dose (1 mg/kg) and weak stimulation at a higher dose (10 mg/kg). In parallel, the BZT analog significantly increased c-Fos expression in the dorsolateral caudoputamen at the high dose, whereas producing marginal decreases at low and moderate doses (1, 3 mg/kg) in both dorsal and ventral striatum. Interaction assays showed that cocaine's ability to stimulate locomotor activity was decreased by AHN-1055 treatment, but not by treatment with D-amphetamine. Such reduced ability did not result from an increase in stereotyped behavior. Another dopamine uptake inhibitor, nomifensine, decreased cocaine-induced locomotor activity but evoked by itself intense motor stereotypies. Remarkably, the BZT analog dose-dependently blocked cocaine-induced CPP without producing CPP when given alone, and blocked in conditioned mice cocaine-stimulated early-gene activation in the nucleus accumbens and dorsomedial striatum. These observations provide evidence that AHN-1055 does not behave as a classical psychomotor stimulant and that some of its properties, including attenuation of cocaine-induced striatal c-Fos expression, locomotor stimulation, and CPP, support its candidacy, and that of structurally related molecules, as possible pharmacotherapies in cocaine addiction.
Emerging roles of ER stress in the etiology and pathogenesis of Alzheimer's disease.
The FEBS journal, 2018

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by synaptic dysfunction and accumulation of abnormal aggregates formed by amyloid-β peptides or phosphorylated tau proteins. Accumulating evidence suggests that alterations in the buffering capacity of the proteostasis network are a salient feature of AD. The endoplasmic reticulum (ER) is the main compartment involved in protein folding and secretion and is drastically affected in AD neurons. ER stress triggers the activation of the unfolded protein response (UPR), a signal transduction pathway that enforces adaptive programs to recover homeostasis or trigger apoptosis of irreversibly damaged cells. Experimental manipulation of specific UPR signaling modules in preclinical models of AD has revealed a key role of this pathway in regulating protein misfolding and neurodegeneration. Recent studies suggest that the UPR also influences synaptic plasticity and memory through ER stress-independent mechanisms. Consequently, targeting of the UPR in AD is emerging as an interesting therapeutic approach to modify the two pillars of AD, protein misfolding and synaptic failure. Here, we review the functional role of ER stress signaling in AD, discussing the complex involvement of the pathway in controlling neuronal survival, the amyloid cascade, neurodegeneration and synaptic function. Recent intervention efforts to target the UPR with pharmacological and gene therapy strategies are also discussed.
The depressed patient in a biological world: on philosophical and diagnostic strategies.
Journal of evaluation in clinical practice, 2013

We questioned: what kind of relationships between mental and neurobiological levels of complexity is or could become useful in the psychiatric practice? The concept of mind and associated mood states defended here is that they are physically emergent, subjective, qualitative, unified features of the brain. We compared our neurobiological assessment also to psychoanalytical practice (first person's perspective).
What goes through the gate? Exploring interference with visual feature binding.
Neuropsychologia, 2011

A series of experiments explored the mechanisms determining the encoding and storage of features and objects in visual working memory. We contrasted the effects of three types of visual suffix on cued recall of a display of colored shapes. The suffix was presented after the display and before the recall cue. The latter was either the color or shape of one of the objects and signaled recall of the object's other feature. In Experiments 1 and 2, we found a larger effect of 'plausible' suffixes comprising features (color and shape) drawn from the experimental set, relative to the effect of 'implausible' suffixes comprising features outside the experimental set. Experiment 3 extended this pattern by showing that 'semi-plausible' suffixes containing only one feature (either color or shape) from the experimental set had an equivalent effect to those with both features from the set. Reduction in accuracy was mainly due to an increase in recall of suffix features, rather than within-display confusions. The findings suggest a feature-based filtering process in visual working memory, with any stimuli that pass through this filter serving to directly overwrite existing object representations.
The effects of ghrelin antagonists [D-Lys(3) ]-GHRP-6 or JMV2959 on ethanol, water, and food intake in C57BL/6J mice.
Alcoholism, clinical and experimental research, 2014

Alcohol use and abuse patterns have created a need for novel treatment models. Current research has turned its focus on reward pathways associated with intrinsic necessities, such as feeding. Theories suggest that drugs of abuse seize control of natural reward pathways and dysregulate normal function, leading to chronic addiction. One such pathway involving the hunger stimulating peptide, ghrelin, is the focus of our study.