rudyvdbrink/CitationDatabase huggingface dataset:
Increased matrix metalloproteinases expression in tuberous sclerosis complex: modulation by microRNA 146a and 147b in vitro.
Neuropathology and applied neurobiology, 2020

Matrix metalloproteinases (MMPs) and their endogenous tissue inhibitors (TIMPs) control proteolysis within the extracellular matrix (ECM) of the brain. Dysfunction of this enzymatic system due to brain inflammation can disrupt the blood-brain barrier (BBB) and has been implicated in the pathogenesis of epilepsy. However, this has not been extensively studied in the epileptogenic human brain.
Neurovascular emergencies in the elderly.
Radiologic clinics of North America, 2008

Neurovascular diseases are major causes of disability and death in the elderly; many present as medical emergencies. With the continuing growth of the geriatric population, there has been increasing interest in the impact of aging on the cerebrovascular system. Recent advances in the clinical neurosciences have demonstrated that neurovascular emergencies in the elderly often are amenable to treatment; neuroimaging plays a critical role in diagnosis and neurointerventional techniques are becoming increasingly important therapeutic options. This article provides an overview of some of the common neurovascular disorders in the elderly that require urgent evaluation and treatment, with an emphasis on the expanding role for interventional neuroradiology in their management.
Male and female sex hormones in primary headaches.
The journal of headache and pain, 2018

The three primary headaches, tension-type headache, migraine and cluster headache, occur in both genders, but all seem to have a sex-specific prevalence. These gender differences suggest that both male and female sex hormones could have an influence on the course of primary headaches. This review aims to summarise the most relevant and recent literature on this topic.
Reduced α-MSH Underlies Hypothalamic ER-Stress-Induced Hepatic Gluconeogenesis.
Cell reports, 2015

Alterations in ER homeostasis have been implicated in the pathophysiology of obesity and type-2 diabetes (T2D). Acute ER stress induction in the hypothalamus produces glucose metabolism perturbations. However, the neurobiological basis linking hypothalamic ER stress with abnormal glucose metabolism remains unknown. Here, we report that genetic and induced models of hypothalamic ER stress are associated with alterations in systemic glucose homeostasis due to increased gluconeogenesis (GNG) independent of body weight changes. Defective alpha melanocyte-stimulating hormone (α-MSH) production underlies this metabolic phenotype, as pharmacological strategies aimed at rescuing hypothalamic α-MSH content reversed this phenotype at metabolic and molecular level. Collectively, our results posit defective α-MSH processing as a fundamental mediator of enhanced GNG in the context of hypothalamic ER stress and establish α-MSH deficiency in proopiomelanocortin (POMC) neurons as a potential contributor to the pathophysiology of T2D.
Direct comparison of cortical excitability to transcranial magnetic stimulation in obstructive sleep apnea syndrome and restless legs syndrome.
Sleep medicine, 2015

Changes to transcranial magnetic stimulation (TMS) have been reported in obstructive sleep apnea syndrome (OSAS) and restless legs syndrome (RLS), although no direct comparison study is available. The aim of this new investigation is to assess and compare cortical excitability of OSAS and RLS patients using the same methodology and under the same experimental conditions.
MRI patterns of muscle involvement in type 2 and 3 spinal muscular atrophy patients.
Journal of neurology, 2020

Only few studies have reported muscle involvement in spinal muscular atrophy using muscle MRI but this has not been systematically investigated in a large cohort of both pediatric and adult patients with type 2 and type 3 spinal muscular atrophy. The aim of the present study was to define possible patterns of muscle involvement on MRI, assessing both fatty replacement and muscle atrophy, in a cohort of type 2 and type 3 spinal muscular atrophy children and adults (age range 2-45 years), including both ambulant and non-ambulant patients. Muscle MRI protocol consisted in T1-weighted sequences acquired on axial plane covering the pelvis, the thigh, and the leg with contiguous slices. Each muscle was examined through its whole extension using a grading system that allows a semiquantitative evaluation of fatty infiltration. Thigh muscles were also grouped in anterior, posterior, and medial compartment for classification of global atrophy. The results showed a large variability in both type 2 and type 3 spinal muscular atrophy, with a various degree of proximal to distal gradient. Some muscles, such us the adductor longus and gracilis were always selectively spared. In all patients, the involvement was a combination of muscle atrophy and muscle infiltration. The variability observed may help to better understand both natural history and response to new treatments.
Uniting adolescent neuroimaging and treatment research: Recommendations in pursuit of improved integration.
Neuroscience and biobehavioral reviews, 2016

Many clinicians who provide mental health treatment find developmental neuroscience discoveries to be exciting. However, the utility of these findings often seem far removed from everyday clinical care. Thus, the goal of this article is to offer a bridge to connect the fields of applied adolescent treatment and developmental neuroscience investigation. An overview of the relevance of developmental neuroscience in adolescent direct practice and a rationale for how and why this integration could benefit adolescent treatment outcomes is provided. Finally, a series of practical suggestions is generated for enhancing collaborative, interdisciplinary work that ultimately advances treatment response for this important clinical population.
Evaluation of state and trait biomarkers in healthy volunteers for the development of novel drug treatments in schizophrenia.
Journal of psychopharmacology (Oxford, England), 2011

Antipsychotic drugs are the mainstay of treatment for schizophrenia but they have little effect on core negative symptoms or cognitive impairment. To meet the deficiencies of current treatments, novel potential compounds are emerging from preclinical research but translation to clinical success has been poor. This article evaluates the possibility that cognitive and physiological abnormalities in schizophrenia can be used as central nervous system biomarkers to predict, in healthy volunteers, the likely efficacy of entirely new pharmacological approaches to treatment. Early detection of efficacy would focus resource on rapidly developing, effective drugs. We review the relevance of selected cognitive and physiological abnormalities as biomarkers in schizophrenia and three of its surrogate populations: (i) healthy volunteers with high trait schizotypy; (ii) unaffected relatives of patients; and (iii) healthy volunteers in a state of cortical glutamate disinhibition induced by low-dose ketamine. Several biomarkers are abnormal in these groups and in some instances there has been exploratory work to determine their sensitivity to drug action. They are generally insensitive to current antipsychotics and therefore their predictive validity cannot be established until novel, therapeutically useful drugs are discovered. Until then such biomarker studies can provide evidence of drugs engaging with the mechanism of interest and encouragement of the concept.
Role of PDGF-D and PDGFR-β in neuroinflammation in experimental ICH mice model.
Experimental neurology, 2016

Inflammation plays a key role in the pathophysiological processes after intracerebral hemorrhage (ICH). Post-ICH macrophages infiltrate the brain and release pro-inflammatory factors (tumor necrosis factor-α), amplifying microglial activation and neutrophil infiltration. Platelet-derived growth factor receptor-β (PDGFR-β) is expressed on macrophages and it's activation induces the recruitment of macrophages. Platelet-derived growth factor-D (PDGF-D) is an agonist with a significantly higher affinity to the PDGFR-β compared to another isoform of the receptor. In this study, we investigated the role of PDGF-D in the pro-inflammatory response after ICH in mice.
Lateral prefrontal model-based signatures are reduced in healthy individuals with high trait impulsivity.
Translational psychiatry, 2015

High impulsivity is an important risk factor for addiction with evidence from endophenotype studies. In addiction, behavioral control is shifted toward the habitual end. Habitual control can be described by retrospective updating of reward expectations in 'model-free' temporal-difference algorithms. Goal-directed control relies on the prospective consideration of actions and their outcomes, which can be captured by forward-planning 'model-based' algorithms. So far, no studies have examined behavioral and neural signatures of model-free and model-based control in healthy high-impulsive individuals. Fifty healthy participants were drawn from the upper and lower ends of 452 individuals, completing the Barratt Impulsiveness Scale. All participants performed a sequential decision-making task during functional magnetic resonance imaging (fMRI) and underwent structural MRI. Behavioral and fMRI data were analyzed by means of computational algorithms reflecting model-free and model-based control. Both groups did not differ regarding the balance of model-free and model-based control, but high-impulsive individuals showed a subtle but significant accentuation of model-free control alone. Right lateral prefrontal model-based signatures were reduced in high-impulsive individuals. Effects of smoking, drinking, general cognition or gray matter density did not account for the findings. Irrespectively of impulsivity, gray matter density in the left dorsolateral prefrontal cortex was positively associated with model-based control. The present study supports the idea that high levels of impulsivity are accompanied by behavioral and neural signatures in favor of model-free behavioral control. Behavioral results in healthy high-impulsive individuals were qualitatively different to findings in patients with the same task. The predictive relevance of these results remains an important target for future longitudinal studies.
Emotional arousal to negative information after traumatic experiences: an event-related brain potential study.
Neuroscience, 2011

Event-related brain potentials (ERPs) during an emotional Stroop task were measured in two groups of participants: 14 participants who had experienced the great Sichuan earthquake (earthquake group) and 14 participants who did not experience the earthquake (control group). ERP data showed that negative words elicited a more negative P2 than positive words in the earthquake group. Moreover, negative words also elicited a more negative ERP deflection (N280-380 effect) than positive words in the earthquake group, while this effect was not found in the control group. We suggest that the N280-380 effect may reflect heightened emotional arousal to negative words due to personal experience of a traumatic event. Dipole analysis localized the N280-380 to the parahippocampal gyrus and the cuneus, which we suggest may be related to the automatic recollection of the traumatic experience.
The bench is closer to the bedside than we think: Uncovering the ethical ties between preclinical researchers in translational neuroscience and patients in clinical trials.
PLoS biology, 2018

Millions of people worldwide currently suffer from serious neurological diseases and injuries for which there are few, and often no, effective treatments. The paucity of effective interventions is, no doubt, due in large part to the complexity of the disorders, as well as our currently limited understanding of their pathophysiology. The bleak picture for patients, however, is also attributable to avoidable impediments stemming from quality concerns in preclinical research that often escape detection by research regulation efforts. In our essay, we connect the dots between these concerns about the quality of preclinical research and their potential ethical impact on the patients who volunteer for early trials of interventions informed by it. We do so in hopes that a greater appreciation among preclinical researchers of these serious ethical consequences can lead to a greater commitment within the research community to adopt widely available tools and measures that can help to improve the quality of research.
A common theme in interaction of bacterial immunoglobulin-binding proteins with immunoglobulins illustrated in the equine system.
The Journal of biological chemistry, 2008

The M protein of Streptococcus equi subsp. equi known as fibrinogen-binding protein (FgBP) is a cell wall-associated protein with antiphagocytic activity that binds IgG. Recombinant versions of the seven equine IgG subclasses were used to investigate the subclass specificity of FgBP. FgBP bound predominantly to equine IgG4 and IgG7, with little or no binding to the other subclasses. Competitive binding experiments revealed that FgBP could inhibit the binding of staphylococcal protein A and streptococcal protein G to both IgG4 and IgG7, implicating the Fc interdomain region in binding to FgBP. To identify which of the two IgG Fc domains contributed to the interaction with FgBP, we tested two human IgG1/IgA1 domain swap mutants and found that both domains are required for full binding, with the CH3 domain playing a critical role. The binding site for FgBP was further localized using recombinant equine IgG7 antibodies with single or double point mutations to residues lying at the CH2-CH3 interface. We found that interaction of FgBP with equine IgG4 and IgG7 was able to disrupt C1q binding and antibody-mediated activation of the classical complement pathway, demonstrating an effective means by which S. equi may evade the immune response. The mode of interaction of FgBP with IgG fits a common theme for bacterial Ig-binding proteins. Remarkably, for those interactions studied in detail, it emerges that all the Ig-binding proteins target the CH2-CH3 domain interface, regardless of specificity for IgG or IgA, streptococcal or staphylococcal origin, or host species (equine or human).
Functional connections between activated and deactivated brain regions mediate emotional interference during externally directed cognition.
Human brain mapping, 2018

Recent evidence shows that task-deactivations are functionally relevant for cognitive performance. Indeed, higher cognitive engagement has been associated with higher suppression of activity in task-deactivated brain regions - usually ascribed to the Default Mode Network (DMN). Moreover, a negative correlation between these regions and areas actively engaged by the task is associated with better performance. DMN regions show positive modulation during autobiographical, social, and emotional tasks. However, it is not clear how processing of emotional stimuli affects the interplay between the DMN and executive brain regions. We studied this interplay in an fMRI experiment using emotional negative stimuli as distractors. Activity modulations induced by the emotional interference of negative stimuli were found in frontal, parietal, and visual areas, and were associated with modulations of functional connectivity between these task-activated areas and DMN regions. A worse performance was predicted both by lower activity in the superior parietal cortex and higher connectivity between visual areas and frontal DMN regions. Connectivity between right inferior frontal gyrus and several DMN regions in the left hemisphere was related to the behavioral performance. This relation was weaker in the negative than in the neutral condition, likely suggesting less functional inhibitions of DMN regions during emotional processing. These results show that both executive and DMN regions are crucial for the emotional interference process and suggest that DMN connections are related to the interplay between externally-directed and internally-focused processes. Among DMN regions, superior frontal gyrus may be a key node in regulating the interference triggered by emotional stimuli.
N1366S mutation of human skeletal muscle sodium channel causes paramyotonia congenita.
The Journal of physiology, 2017

Paramyotonia congenita is a hereditary channelopathy caused by missense mutations in the SCN4A gene, which encodes the α subunit of the human skeletal muscle voltage-gated sodium channel NaV1.4. Affected individuals suffered from myotonia and paralysis of muscles, which were aggravated by exposure to cold. We report a three-generation Chinese family with patients presenting paramyotonia congenita and identify a novel N1366S mutation of NaV1.4. Whole-cell electrophysiological recordings of the N1366S channel reveal a gain-of-function change of gating in response to cold. Modelling and molecular dynamic simulation data suggest that an arginine-to-serine substitution at position 1366 increases the distance from N1366 to R1454 and disrupts the hydrogen bond formed between them at low temperature. We demonstrate that N1366S is a disease-causing mutation and that the temperature-sensitive alteration of N1366S channel activity may be responsible for the pronounced paramyotonia congenita symptoms of these patients.
Pain reduces sexual motivation in female but not male mice.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014

Chronic pain is often associated with sexual dysfunction, suggesting that pain can reduce libido. We find that inflammatory pain reduces sexual motivation, measured via mounting behavior and/or proximity in a paced mating paradigm, in female but not male laboratory mice. Pain was produced by injection of inflammogens zymosan A (0.5 mg/ml) or λ-carrageenan (2%) into genital or nongenital (hind paw, tail, cheek) regions. Sexual behavior was significantly reduced in female mice experiencing pain (in all combinations); male mice similarly treated displayed unimpeded sexual motivation. Pain-induced reductions in female sexual behavior were observed in the absence of sex differences in pain-related behavior, and could be rescued by the analgesic, pregabalin, and the libido-enhancing drugs, apomorphine and melanotan-II. These findings suggest that the well known context sensitivity of the human female libido can be explained by evolutionary rather than sociocultural factors, as female mice can be similarly affected.
Long-range connections enrich cortical computations.
Neuroscience research, 2021

The cerebral cortex can perform powerful computations, including those involved in higher cognitive functions. Cortical processing for such computations is executed by local circuits and is further enriched by long-range connectivity. This connectivity is activated under specific conditions and modulates local processing, providing flexibility in the computational performance of the cortex. For instance, long-range connectivity in the primary visual cortex exerts facilitatory impacts when the cortex is silent but suppressive impacts when the cortex is strongly sensory-stimulated. These dual impacts can be captured by a divisive gain control model. Recent methodological advances such as optogenetics, anatomical tracing, and two-photon microscopy have enabled neuroscientists to probe the circuit and synaptic bases of long-range connectivity in detail. Here, I review a series of evidence indicating essential roles of long-range connectivity in visual and hierarchical processing involving numerous cortical areas. I also describe an overview of the challenges encountered in investigating underlying synaptic mechanisms and highlight recent technical approaches that may overcome these difficulties and provide new insights into synaptic mechanisms for cortical processing involving long-range connectivity.
Memory control ability modulates intrusive memories after analogue trauma.
Journal of affective disorders, 2016

Most people suffer from intrusive memories in the aftermath of trauma. For survivors' well-being, it is key that these intrusions are controlled. Memory control can be exerted through retrieval suppression. Poor retrieval suppression, however, should be associated with persistent distressing intrusions and posttraumatic stress disorder (PTSD). This study tested the hypothesis that individual differences in retrieval suppression predict intrusive memories after trauma. Retrieval suppression was examined with the think/no-think task (TNT) using behavioral and event related potential (ERP) measures.
Web-accessible digital brain atlas of the common marmoset (Callithrix jacchus).
Neuroscience research, 2009

Here we describe a web-accessible digital brain atlas of the common marmoset (Callithrix jacchus) at http://marmoset-brain.org:2008. We prepared the histological sections of the marmoset brain using various staining techniques. For virtual microscopy, high-resolution digital images of sections were obtained with Aperio Scanscope. The digital images were then converted to Zoomify files (zoomable multiresolution image files). Thereby, we could provide the multiresolution images of the marmoset brains for fast interactive viewing on the web via the Internet. In addition, we describe an automated method to obtain drawings of Nissl-stained sections.
Mandibular ramus shape variation and ontogeny in Homo sapiens and Homo neanderthalensis.
Journal of human evolution, 2018

As the interface between the mandible and cranium, the mandibular ramus is functionally significant and its morphology has been suggested to be informative for taxonomic and phylogenetic analyses. In primates, and particularly in great apes and humans, ramus morphology is highly variable, especially in the shape of the coronoid process and the relationship of the ramus to the alveolar margin. Here we compare ramus shape variation through ontogeny in Homo neanderthalensis to that of modern and fossil Homo sapiens using geometric morphometric analyses of two-dimensional semilandmarks and univariate measurements of ramus angulation and relative coronoid and condyle height. Results suggest that ramus, especially coronoid, morphology varies within and among subadult and adult modern human populations, with the Alaskan Inuit being particularly distinct. We also identify significant differences in overall anterosuperior ramus and coronoid shapes between H. sapiens and H. neanderthalensis, both in adults and throughout ontogeny. These shape differences are subtle, however, and we therefore suggest caution when using ramus morphology to diagnose group membership for individual specimens of these taxa. Furthermore, we argue that these morphologies are unlikely to be representative of differences in masticatory biomechanics and/or paramasticatory behaviors between Neanderthals and modern humans, as has been suggested by previous authors. Assessments of ontogenetic patterns of shape change reveal that the typical Neanderthal ramus morphology is established early in ontogeny, and there is little evidence for divergent postnatal ontogenetic allometric trajectories between Neanderthals and modern humans as a whole. This analysis informs our understanding of intraspecific patterns of mandibular shape variation and ontogeny in H. sapiens and can shed further light on overall developmental and life history differences between H. sapiens and H. neanderthalensis.