rudyvdbrink/CitationDatabase huggingface dataset:
Transient serotonin depletion at adolescence, but not at early infancy, reduced subsequent anxiety-like behavior and alcohol intake in female mice.
Psychopharmacology, 2021

Serotonin (5-HT) plays an important role in the organization of the central nervous system and in the development of social interaction deficits and psychiatric disorders, including anxiety, depression, and addiction disorders. Notably, disruption of the 5-HT system during sensitive periods of development exerts long-term consequences, including altered anxiety response and problematic use of alcohol.
Age-related differences in the structural and effective connectivity of cognitive control: a combined fMRI and DTI study of mental arithmetic.
Neurobiology of aging, 2019

Cognitive changes with aging are highly variable across individuals. This study investigated whether cognitive control performance might depend on preservation of structural and effective connectivity in older individuals. Specifically, we tested inhibition following working memory (WM) updating and maintenance. We analyzed diffusion tensor imaging and functional magnetic resonance imaging data in thirty-four young adults and thirty-four older adults, who performed an arithmetic verification task during functional magnetic resonance imaging. Results revealed larger arithmetic interference in older adults relative to young adults after WM updating, whereas both groups showed similar interference after WM maintenance. In both groups, arithmetic interference was associated with larger activations and stronger effective connectivity among bilateral anterior cingulate, bilateral inferior frontal gyrus, and left angular gyrus, with larger activations of frontal regions in older adults than in younger adults. In older adults, preservation of frontoparietal structural microstructure, especially involving the inferior frontaloccipital fasciculus, was associated with reduced interference, and stronger task-related effective connectivity. These results highlight how both structural and functional changes in the cognitive control network contribute to individual variability in performance during aging.
N-terminal heterogeneity of parenchymal and vascular amyloid-β deposits in Alzheimer's disease.
Neuropathology and applied neurobiology, 2020

The deposition of amyloid-β (Aβ) peptides in the form of extracellular plaques in the brain represents one of the classical hallmarks of Alzheimer's disease (AD). In addition to 'full-length' Aβ starting with aspartic acid (Asp-1), considerable amounts of various shorter, N-terminally truncated Aβ peptides have been identified by mass spectrometry in autopsy samples from individuals with AD.
Remote platelet function testing using P-selectin expression in patients with recent cerebral ischaemia on clopidogrel.
Stroke and vascular neurology, 2021

Antiplatelet agents reduce recurrence after cerebral ischaemia but are not effective in all patients, in part because of treatment resistance. The primary aim was to assess the proportion of patients who are insensitive to clopidogrel. The secondary aim was to assess the association between insensitivity to clopidogrel and recurrent cerebrovascular events.
Role of Feedback Connections in Central Visual Processing.
Annual review of vision science, 2020

The physiological response properties of neurons in the visual system are inherited mainly from feedforward inputs. Interestingly, feedback inputs often outnumber feedforward inputs. Although they are numerous, feedback connections are weaker, slower, and considered to be modulatory, in contrast to fast, high-efficacy feedforward connections. Accordingly, the functional role of feedback in visual processing has remained a fundamental mystery in vision science. At the core of this mystery are questions about whether feedback circuits regulate spatial receptive field properties versus temporal responses among target neurons, or whether feedback serves a more global role in arousal or attention. These proposed functions are not mutually exclusive, and there is compelling evidence to support multiple functional roles for feedback. In this review, the role of feedback in vision will be explored mainly from the perspective of corticothalamic feedback. Further generalized principles of feedback applicable to corticocortical connections will also be considered.
Substrate reduction therapy with Miglustat in pediatric patients with GM1 type 2 gangliosidosis delays neurological involvement: A multicenter experience.
Molecular genetics & genomic medicine, 2020

In GM1 gangliosidosis the lack of function of β-galactosidase results in an accumulation of GM1 ganglioside and related glycoconjugates in visceral organs, and particularly in the central nervous system, leading to severe disability and premature death. In the type 2 form of the disease, early intervention would be important to avoid precocious complications. To date, there are no effective therapeutic options in preventing progressive neurological deterioration. Substrate reduction therapy with Miglustat, a N-alkylated sugar that inhibits the enzyme glucosylceramide synthase, has been proposed for the treatment of several lysosomal storage disorders such as Gaucher type 1 and Niemann Pick Type C diseases. However, data on Miglustat therapy in patients with GM1 gangliosidosis are still scarce.
Growth-Promoting Treatment Screening for Corticospinal Neurons in Mouse and Man.
Cellular and molecular neurobiology, 2020

Neurons of the central nervous system (CNS) that project long axons into the spinal cord have a poor axon regenerative capacity compared to neurons of the peripheral nervous system. The corticospinal tract (CST) is particularly notorious for its poor regeneration. Because of this, traumatic spinal cord injury (SCI) is a devastating condition that remains as yet uncured. Based on our recent observations that direct neuronal interleukin-4 (IL-4) signaling leads to repair of axonal swellings and beneficial effects in neuroinflammation, we hypothesized that IL-4 acts directly on the CST. Here, we developed a tissue culture model for CST regeneration and found that IL-4 promoted new growth cone formation after axon transection. Most importantly, IL-4 directly increased the regenerative capacity of both murine and human CST axons, which corroborates its regenerative effects in CNS damage. Overall, these findings serve as proof-of-concept that our CST regeneration model is suitable for fast screening of new treatments for SCI.
N-Methyl-D-aspartate (NMDA) receptor involvement in central nervous system prostaglandin production during the relapse phase of chronic relapsing experimental autoimmune encephalomyelitis (CR EAE).
Fundamental & clinical pharmacology, 2013

Our previous studies have established that major changes in central nervous system (CNS) prostaglandin (PG) levels occur during the relapse phase of chronic relapsing experimental autoimmune encephalomyelitis (CR EAE), an animal model of the human demyelinating disease multiple sclerosis. PG production is controlled through a series of enzymic pathways that, in EAE, are influenced by neuroantigen-driven autoimmune events. In non-immune-based models of CNS disease, endogenous glucocorticoids have been proposed as instigators of PG synthesis via activation of the N-methyl-D-aspartate (NMDA) receptor. Glucocorticoids have an important regulatory role in the pathogenesis EAE and the NMDA receptor is intimately involved in many of the characteristic neuroinflammatory processes that govern the disease. Therefore, the alterations in prostanoid concentrations during the relapse stage of CR EAE may ultimately be governed by glucocorticoid-induced NMDA receptor activation. The current investigation has examined the proposed glucocorticoid-NMDA receptor link by determining the effects of the receptor antagonist, (+) MK-801, on CNS PGE 2 and PGD 2 levels in Biozzi mice with relapse symptoms of CR EAE. Prostanoid concentrations in the cerebral cortex were not altered by drug administration, and in cerebellar tissues, a vehicle effect negated any drug-induced changes. However, the level of PGD 2 in spinal cords from (+) MK-801-dosed mice was significantly lower, compared to controls, but PGE 2 concentrations remained unchanged. The results suggest that glucocorticoid-NMDA receptor-linked events are not primarily responsible for PG generation in the brain but may influence prostanoid production in discrete areas of the CNS.
Health and criminal justice system involvement among African American siblings.
SSM - population health, 2019

Health disparities between African Americans and Whites have persisted in the United States. Researchers have recently hypothesized that the relatively poor health of African Americans may be caused, in part, by African American overrepresentation in the criminal justice system.
Use of spontaneous ventilation to monitor the effects of posterior fossa surgery in the sitting position.
Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia, 2009

We describe the successful excision, guided by spontaneous ventilation, of a cervico-medullary hemangioblastoma in a 22-year-old female in the sitting position. A balanced anesthesia technique comprising an oxygen, nitrous oxide, sevoflurane, fentanyl and vecuronium mixture was used. Apart from routine monitors, electroencephalographic spectral entropy monitoring was used to determine the depth of anesthesia and transesophageal echocardiography for detection of venous air embolism. The patient remained in spontaneous ventilation for 235min during tumor excision. The intraoperative and postoperative course were uneventful. The patient recovered without any major neurological deficit.
The Application of Digital Platforms in Supporting UK International Medical Graduates.
Cureus, 2020

Although international medical graduates (IMGs) constitute considerable percentage of doctors in the National Health Service (NHS), they face several challenges in acclimatizing to the NHS health system. Communication skills, language subtleties, and career progression difficulties are among the most important challenges that overseas doctors face. Some resources are already available to support these doctors and several trusts across the UK have developed local interventions and educational programs to help their doctors bridge the gaps in their knowledge. However, there is no proof of the external validity of these programs and none are identified as effective on a national level. Senior IMGs are leading very popular and inspiring projects using digital platforms, especially social media. We identified several social media pages, groups, and websites subscribed to by hundreds of thousands of doctors in the UK and around the world, including doctors who are planning a future career in the UK. These platforms provide information, resources, support, and answers to questions posed by junior IMGs. Inspired by these projects and also by an Australian project that transformed a local IMG education program, we studied whether using digital platforms and transforming evidence-based local programs to national ones would be the best way forward to support IMGs.
A Regions of Interest Voxel-Based Morphometry Study of the Human Brain During High-Frequency Spinal Cord Stimulation in Patients With Failed Back Surgery Syndrome.
Pain practice : the official journal of World Institute of Pain, 2020

The effectiveness of spinal cord stimulation (SCS) as pain-relieving treatment for failed back surgery syndrome (FBSS) has already been demonstrated. However, potential structural and functional brain alterations resulting from subsensory SCS are less clear. The aim of this study was to test structural volumetric changes in a priori chosen regions of interest related to chronic pain after 1 month and 3 months of high-frequency SCS in patients with FBSS.
An Accurate and Robust Method for Spike Sorting Based on Convolutional Neural Networks.
Brain sciences, 2020

In the fields of neuroscience and biomedical signal processing, spike sorting is a crucial step to extract the information of single neurons from extracellular recordings. In this paper, we propose a novel deep learning approach based on one-dimensional convolutional neural networks (1D-CNNs) to implement accurate and robust spike sorting. The results of the simulated data demonstrated that the clustering accuracy in most datasets was greater than 99%, despite the multiple levels of noise and various degrees of overlapped spikes. Moreover, the proposed method performed significantly better than the state-of-the-art method named "WMsorting" and a deep-learning-based multilayer perceptron (MLP) model. In addition, the experimental data recorded from the primary visual cortex of a macaque monkey were used to evaluate the proposed method in a practical application. It was shown that the method could successfully isolate most spikes of different neurons (ranging from two to five) by training the 1D-CNN model with a small number of manually labeled spikes. Considering the above, the deep learning method proposed in this paper is of great advantage for spike sorting with high accuracy and strong robustness. It lays the foundation for application in more challenging works, such as distinguishing overlapped spikes and the simultaneous sorting of multichannel recordings.
The effect of anaesthetic dose on response and remission in electroconvulsive therapy for major depressive disorder: nationwide register-based cohort study.
BJPsych open, 2021

Electroconvulsive therapy (ECT) is a safe and effective treatment for major depressive disorder (MDD). ECT treatment effect relies on induced generalised seizures. Most anaesthetics raise the seizure threshold and shorten seizure duration. There are no conclusive studies on the effect of anaesthetic dose on response and remission rates with ECT for MDD.
Decision analysis in the clinical neurosciences: a systematic review of the literature.
European journal of neurology, 1995

Clinical decision analysis can be a useful scientific tool for individual patient management, for planning of clinical research and for reaching consensus about clinical problems. We systematically reviewed the decision analytic studies in the clinical neurosciences that were published between 1975 and July 1994. All studies were assessed on aspects of clinical applicability: presence of case and context description, completeness of the analysed strategies from a clinical point of view, extendibility of the analyses to different patient profiles, and up-to-date-ness. Fifty-nine decision analyses of twenty-eight different clinical problems were identified. Twenty-eight analyses were based on the theory of subjective expected utility, twelve on cost-effectiveness analysis. Four studies used ROC analysis, and fifteen were risk-, or risk-benefit analyses. At least six studies could have been improved by more elaborately disclosing the context of the clinical problem that was addressed. In eleven studies, the effect of different, yet plausible assumptions was not explored, and in eighteen studies the reader was not informed how to extend the results of the analysis to patients with (slightly) different clinical characterisitics. All studies had, by nature, the potential to promote insight into the clinical problem and focus the discussion on clinically important aspects, and gave clinically useful advice. We conclude that clinical decision analysis, as an explicit, quantitative approach to uncertainty in decision making in the clinical neurosciences will fulfill a growing need in the near future.
A maximum flow-based network approach for identification of stable noncoding biomarkers associated with the multigenic neurological condition, autism.
BioData mining, 2021

Machine learning approaches for predicting disease risk from high-dimensional whole genome sequence (WGS) data often result in unstable models that can be difficult to interpret, limiting the identification of putative sets of biomarkers. Here, we design and validate a graph-based methodology based on maximum flow, which leverages the presence of linkage disequilibrium (LD) to identify stable sets of variants associated with complex multigenic disorders.
Uncovering memory-related gene expression in contextual fear conditioning using ribosome profiling.
Progress in neurobiology, 2021

Contextual fear conditioning (CFC) in rodents is the most widely used behavioural paradigm in neuroscience research to elucidate the neurobiological mechanisms underlying learning and memory. It is based on the pairing of an aversive unconditioned stimulus (US; e.g. mild footshock) with a neutral conditioned stimulus (CS; e.g. context of the test chamber) in order to acquire associative long-term memory (LTM), which persists for days and even months. Using genome-wide analysis, several studies have generated lists of genes modulated in response to CFC in an attempt to identify the "memory genes", which orchestrate memory formation. Yet, most studies use naïve animals as a baseline for assessing gene-expression changes, while only few studies have examined the effect of the US alone, without pairing to context, using genome-wide analysis of gene-expression. Herein, using the ribosome profiling methodology, we show that in male mice an immediate shock, which does not lead to LTM formation, elicits pervasive translational and transcriptional changes in the expression of Immediate Early Genes (IEGs) in dorsal hippocampus (such as Fos and Arc), a fact which has been disregarded by the majority of CFC studies. By removing the effect of the immediate shock, we identify and validate a new set of genes, which are translationally and transcriptionally responsive to the association of context-to-footshock in CFC, and thus constitute salient "memory genes".
Neuropeptide Y family receptors Y1 and Y2 from sea lamprey, Petromyzon marinus.
General and comparative endocrinology, 2015

The vertebrate gene family for neuropeptide Y (NPY) receptors expanded by duplication of the chromosome carrying the ancestral Y1-Y2-Y5 gene triplet. After loss of some duplicates, the ancestral jawed vertebrate had seven receptor subtypes forming the Y1 (including Y1, Y4, Y6, Y8), Y2 (including Y2, Y7) and Y5 (only Y5) subfamilies. Lampreys are considered to have experienced the same chromosome duplications as gnathostomes and should also be expected to have multiple receptor genes. However, previously only a Y4-like and a Y5 receptor have been cloned and characterized. Here we report the cloning and characterization of two additional receptors from the sea lamprey Petromyzon marinus. Sequence phylogeny alone could not with certainty assign their identity, but based on synteny comparisons of P. marinus and the Arctic lamprey, Lethenteron camtschaticum, with jawed vertebrates, the two receptors most likely are Y1 and Y2. Both receptors were expressed in human HEK293 cells and inositol phosphate assays were performed to determine the response to the three native lamprey peptides NPY, PYY and PMY. The three peptides have similar potencies in the nanomolar range for Y1. No obvious response to the three peptides was detected for Y2. Synteny analysis supports identification of the previously cloned receptor as Y4. No additional NPY receptor genes could be identified in the presently available lamprey genome assemblies. Thus, four NPY-family receptors have been identified in lampreys, orthologs of the same subtypes as in humans (Y1, Y2, Y4 and Y5), whereas many other vertebrate lineages have retained additional ancestral subtypes.
The Persistence of Privilege for a Healthy Retina.
Immunity, 2020

A minor haplotype of chromosome 10q26 accounts for much of the genetic risk of age-related macular degeneration (AMD). In this issue of Immunity, Beguier et al. demonstrate that carriers of the 10q26 AMD-risk haplotype overexpress the peptidase HTRA1, which in turns results in mononuclear phagocyte persistence in an immune privileged site and pathogenic inflammation.
Transcription factor EB overexpression prevents neurodegeneration in experimental synucleinopathies.
JCI insight, 2019

The synucleinopathies Parkinson's disease (PD) and Multiple system atrophy (MSA) - characterized by α-synuclein intracytoplasmic inclusions into, respectively, neurons and oligodendrocytes - are associated with impairment of the autophagy-lysosomal pathways (ALP). Increased expression of the master regulator of ALP, transcription factor EB (TFEB), is hypothesized to promote the clearance of WT α-synuclein and survival of dopaminergic neurons. Here, we explore the efficacy of targeted TFEB overexpression either in neurons or oligodendrocytes to reduce the pathological burden of α-synuclein in a PD rat model and a MSA mouse model. While TFEB neuronal expression was sufficient to prevent neurodegeneration in the PD model, we show that only TFEB oligodendroglial overexpression leads to neuroprotective effects in the MSA model. These beneficial effects were associated with a decreased accumulation of α-synuclein into oligodendrocytes through recovery of the ALP machinery. Our study demonstrates that the cell type where α-synuclein aggregates dictates the target of TFEB overexpression in order to be protective, paving the way for adapted therapies.
The extended autonomic system, dyshomeostasis, and COVID-19.
Clinical autonomic research : official journal of the Clinical Autonomic Research Society, 2020

The pandemic viral illness COVID-19 is especially life-threatening in the elderly and in those with any of a variety of chronic medical conditions. This essay explores the possibility that the heightened risk may involve activation of the "extended autonomic system" (EAS). Traditionally, the autonomic nervous system has been viewed as consisting of the sympathetic nervous system, the parasympathetic nervous system, and the enteric nervous system. Over the past century, however, neuroendocrine and neuroimmune systems have come to the fore, justifying expansion of the meaning of "autonomic." Additional facets include the sympathetic adrenergic system, for which adrenaline is the key effector; the hypothalamic-pituitary-adrenocortical axis; arginine vasopressin (synonymous with anti-diuretic hormone); the renin-angiotensin-aldosterone system, with angiotensin II and aldosterone the main effectors; and cholinergic anti-inflammatory and sympathetic inflammasomal pathways. A hierarchical brain network-the "central autonomic network"-regulates these systems; embedded within it are components of the Chrousos/Gold "stress system." Acute, coordinated alterations in homeostatic settings (allostasis) can be crucial for surviving stressors such as traumatic hemorrhage, asphyxiation, and sepsis, which throughout human evolution have threatened homeostasis; however, intense or long-term EAS activation may cause harm. While required for appropriate responses in emergencies, EAS activation in the setting of chronically decreased homeostatic efficiencies (dyshomeostasis) may reduce thresholds for induction of destabilizing, lethal vicious cycles. Testable hypotheses derived from these concepts are that biomarkers of EAS activation correlate with clinical and pathophysiologic data and predict outcome in COVID-19 and that treatments targeting specific abnormalities identified in individual patients may be beneficial.