rudyvdbrink/CitationDatabase huggingface dataset:
Transsaccadic Perception Deficits in Schizophrenia Reflect the Improper Internal Monitoring of Eye Movement Rather Than Abnormal Sensory Processing.
Biological psychiatry. Cognitive neuroscience and neuroimaging, 2018

Symptoms of psychosis in schizophrenia reflect disturbances in sense of agency-difficulty distinguishing internally from externally generated sensory and perceptual experiences. One theory attributes these anomalies to a disruption in corollary discharge (CD), an internal copy of generated motor commands used to distinguish self-movement-generated sensations from externally generated stimulation.
Role of Nurr1 and Ret in inducing rat embryonic neural precursors to dopaminergic neurons.
Neurological research, 2009

Nurr1, a member of the nuclear receptor superfamily of transcription factors, is highly expressed in midbrain dopaminergic (DA) neurons. Ret is a member of the receptor tyrosine kinase (RTK) superfamily and a critical signal transducing subunit of receptors for glial cell line-derived neurotrophic factor (GDNF). Both Nurr1 and Ret play important roles in the development of DA neurons.
Cocaine-mediated induction of microglial activation involves the ER stress-TLR2 axis.
Journal of neuroinflammation, 2016

Neuroinflammation associated with advanced human immunodeficiency virus (HIV)-1 infection is often exacerbated by chronic cocaine abuse. Cocaine exposure has been demonstrated to mediate up-regulation of inflammatory mediators in in vitro cultures of microglia. The molecular mechanisms involved in this process, however, remain poorly understood. In this study, we sought to explore the underlying signaling pathways involved in cocaine-mediated activation of microglial cells.
Anti-Nogo-A antibody treatment does not prevent cell body shrinkage in the motor cortex in adult monkeys subjected to unilateral cervical cord lesion.
BMC neuroscience, 2008

After unilateral cervical cord lesion at the C7/C8 border interrupting the dorsolateral funiculus in adult monkeys, neutralization of Nogo-A using a specific monoclonal antibody promoted sprouting of corticospinal (CS) axons rostral and caudal to the lesion and, in parallel, improved functional recovery. In monkeys lesioned but not treated with the anti-Nogo-A antibody, the CS neurons in the contralesional primary motor cortex (M1) survived to the axotomy, but their soma shrank. Because the anti-Nogo-A treatment induces regeneration and/or sprouting of CS axons, it may improve access to neurotrophic factors. The question therefore arises as to whether anti-Nogo-A treatment prevents the soma shrinkage observed in the contralesional M1?
Using stimulus form change to understand memorial familiarity for pictures and words in patients with mild cognitive impairment and Alzheimer's disease.
Neuropsychologia, 2010

Although it is generally accepted that patients with amnestic mild cognitive impairment (aMCI) and patients with Alzheimer's disease (AD) have significantly impaired recollection, recent evidence has been mixed as to whether these patients demonstrate impaired memorial familiarity. Recent work suggests that familiarity may remain intact for pictures, but not for words. Further, a recent event-related potential (ERP) study suggests that enhanced conceptual processing of pictures may underlie this intact familiarity. However, to date there has been no direct comparison of perceptual and conceptual-based familiarity for pictures and words in patients with aMCI and AD. To investigate this issue, patients with aMCI, patients with AD, and healthy older adults underwent four study-test conditions of word-word, picture-picture, word-picture, and picture-word. When stimuli undergo form change, it has been suggested that only conceptual processing can help support recognition in the absence of recollection. Our results showed that patients successfully relied on perceptual and conceptual-based familiarity to improve recognition for the within format conditions over the across format conditions. Further, results suggested that patients with aMCI and AD are able to use enhanced conceptual processing of pictures compared to words to allow them to overcome the deleterious effects of form change in a similar manner as controls. These results help us begin to understand which aspects of memory are impaired and which remain relatively intact in patients with aMCI and AD. This understanding can then in turn help us to assess, conceptualize, and build behavioral interventions to help treat these patients.
A Propensity Score Analysis of the Impact of Invasive Intracranial Pressure Monitoring on Outcomes after Severe Traumatic Brain Injury.
Journal of neurotrauma, 2016

Although a recent clinical trial (BEST TRIP) demonstrated no improvement in outcomes with invasive intracranial pressure (ICP) monitoring (ICPM) following severe traumatic brain injury (TBI), its generalizability has been called into question. In several global settings ICPM is not the standard of care and is used at the discretion of the attending neurosurgeon. Our objective was to determine the impact of ICPM on mortality and 6-month functional outcomes following severe TBI. The setting was a referral trauma center with 36 intensive care unit (ICU) beds and 300-600 TBI admissions per year. During a 2-year period data were prospectively entered into a severe TBI registry. Patients with severe TBI aged >12 years meeting Brain Trauma Foundation (BTF) criteria for ICPM were included in the study. Outcomes of interest were in-hospital mortality and poor 6-month functional outcome defined as Glasgow Outcome Scale (GOS) score of 3 or lower. A propensity score based analysis incorporating known predictors of outcome in TBI was utilized to examine the impact of ICPM on outcomes. Of 1345 patients meeting study criteria 497 (37%) underwent ICPM. In-hospital mortality was 35% (471/1345). Of 454 patients for whom 6-month outcome was available, 161 (35%) suffered a poor functional outcome. Following propensity score analysis ICPM use was associated with an 8% (p = 0.002) decrease in mortality but no significant effect (p = 0.2) on functional outcome. The use of ICPM following severe TBI was associated with decreased in-hospital mortality. Further clinical trials of ICPM in TBI may be warranted.
Why should neuroscientists worry about iron? The emerging role of ferroptosis in the pathophysiology of neuroprogressive diseases.
Behavioural brain research, 2018

Ferroptosis is a unique form of programmed death, characterised by cytosolic accumulation of iron, lipid hydroperoxides and their metabolites, and effected by the fatal peroxidation of polyunsaturated fatty acids in the plasma membrane. It is a major driver of cell death in neurodegenerative neurological diseases. Moreover, cascades underpinning ferroptosis could be active drivers of neuropathology in major psychiatric disorders. Oxidative and nitrosative stress can adversely affect mechanisms and proteins governing cellular iron homeostasis, such as the iron regulatory protein/iron response element system, and can ultimately be a source of abnormally high levels of iron and a source of lethal levels of lipid membrane peroxidation. Furthermore, neuroinflammation leads to the upregulation of divalent metal transporter1 on the surface of astrocytes, microglia and neurones, making them highly sensitive to iron overload in the presence of high levels of non-transferrin-bound iron, thereby affording such levels a dominant role in respect of the induction of iron-mediated neuropathology. Mechanisms governing systemic and cellular iron homeostasis, and the related roles of ferritin and mitochondria are detailed, as are mechanisms explaining the negative regulation of ferroptosis by glutathione, glutathione peroxidase 4, the cysteine/glutamate antiporter system, heat shock protein 27 and nuclear factor erythroid 2-related factor 2. The potential role of DJ-1 inactivation in the precipitation of ferroptosis and the assessment of lipid peroxidation are described. Finally, a rational approach to therapy is considered, with a discussion on the roles of coenzyme Q
Effect of JWH-250, JWH-073 and their interaction on "tetrad", sensorimotor, neurological and neurochemical responses in mice.
Progress in neuro-psychopharmacology & biological psychiatry, 2016

JWH-250 and JWH-073 are two synthetic cannabinoid agonists with nanomolar affinity at CB1 and CB2 receptors. They are illegally marketed within "herbal blend" for theirs psychoactive effects greater than those produced by Cannabis. Recently, we analyzed an "herbal" preparation containing a mixture of both JWH-250 and JWH-073. The present study was aimed at investigating the in vitro and in vivo pharmacological activity of JWH-250 and JWH-073 in male CD-1 mice. In vitro competition binding experiments performed on mouse and human CB1 and CB2 receptors revealed a nanomolar affinity and potency of the JWH-250 and JWH-073. In vivo studies showed that JWH-250 and JWH-073, administered separately, induced a marked hypothermia, increased pain threshold to both noxious mechanical and thermal stimuli, caused catalepsy, reduced motor activity, impaired sensorimotor responses (visual, acoustic and tactile), caused seizures, myoclonia, hyperreflexia and promote aggressiveness in mice. Moreover, microdialysis study in freely moving mice showed that systemic administration of JWH-250 and JWH-073 stimulated dopamine release in the nucleus accumbens in a dose-dependent manner. Behavioral, neurological and neurochemical effects were fully prevented by the selective CB1 receptor antagonist/inverse agonist AM 251. Co-administration of ineffective doses of JWH-250 and JWH-073 impaired visual sensorimotor responses, improved mechanical pain threshold and stimulated mesolimbic DA transmission in mice, living unchanged all other behavioral and physiological parameters. For the first time the present study demonstrates the overall pharmacological effects induced by the administration of JWH-250 and JWH-073 in mice and it reveals their potentially synergistic action suggesting that co-administration of different synthetic cannabinoids may potentiate the detrimental effects of individual compounds increasing their dangerousness and abuse potential.
Perspectives in Diagnosis and Treatment of Rabies Viral Encephalitis: Insights from Pathogenesis.
Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 2016

Rabies viral encephalitis, though one of the oldest recognized infectious disease of humans, remains an incurable, fatal encephalomyelitis, despite advances in understanding of its pathobiology. Advances in science have led us on the trail of the virus in the host, but the sanctuaries in which the virus remains hidden for its survival are unknown. Insights into host-pathogen interactions have facilitated evolving immunologic therapeutic strategies, though we are far from a cure. Most of the present-day knowledge has evolved from in vitro studies using fixed (attenuated) laboratory strains that may not be applicable in the clinical setting. Much remains to be unraveled about this elusive virus. This review attempts to re-examine the current advances in understanding of the pathobiology of the rabies virus that modulate the diagnosis, treatment, and prevention of this fatal disease.
Neural Mechanisms of Attentional Control for Objects: Decoding EEG Alpha When Anticipating Faces, Scenes,and Tools.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2020

Attentional selection mechanisms in visual cortex involve changes in oscillatory activity in the EEG alpha band (8-12 Hz), with decreased alpha indicating focal cortical enhancement and increased alpha indicating suppression. This has been observed for spatial selective attention and attention to stimulus features such as color versus motion. We investigated whether attention to objects involves similar alpha-mediated changes in focal cortical excitability. In experiment 1, 20 volunteers (8 males; 12 females) were cued (80% predictive) on a trial-by-trial basis to different objects (faces, scenes, or tools). Support vector machine decoding of alpha power patterns revealed that late (>500 ms latency) in the cue-to-target foreperiod, only EEG alpha differed with the to-be-attended object category. In experiment 2, to eliminate the possibility that decoding of the physical features of cues led to our results, 25 participants (9 males; 16 females) performed a similar task where cues were nonpredictive of the object category. Alpha decoding was now only significant in the early (<200 ms) foreperiod. In experiment 3, to eliminate the possibility that task set differences between the different object categories led to our experiment 1 results, 12 participants (5 males; 7 females) performed a predictive cuing task where the discrimination task for different objects was identical across object categories. The results replicated experiment 1. Together, these findings support the hypothesis that the neural mechanisms of visual selective attention involve focal cortical changes in alpha power not only for simple spatial and feature attention, but also for high-level object attention in humans.
Violent victimization and health service utilization in a forensic psychiatric context: a comparison between offenders with mental disorders and matched controls.
BMC psychiatry, 2017

Offenders with mental disorders constitute a particularly exposed group in society, with high rates of morbidity, mortality, and social deprivation. Often thought of primarily as perpetrators, these individuals may also be subjected to violence. Previous research indicates that violent victimization during lifespan is a risk factor for violent perpetration among psychiatric patients, but victimization studies on the group of offenders with mental disorders are scarce. Health services are pivotal to this group, but although most individuals do utilize these services, their vulnerability seems to remain. This study aimed at exploring the rates of victimization and health service utilization, including perceptions of unmet health care needs, among offenders with mental disorders.
Biophysically grounded mean-field models of neural populations under electrical stimulation.
PLoS computational biology, 2020

Electrical stimulation of neural systems is a key tool for understanding neural dynamics and ultimately for developing clinical treatments. Many applications of electrical stimulation affect large populations of neurons. However, computational models of large networks of spiking neurons are inherently hard to simulate and analyze. We evaluate a reduced mean-field model of excitatory and inhibitory adaptive exponential integrate-and-fire (AdEx) neurons which can be used to efficiently study the effects of electrical stimulation on large neural populations. The rich dynamical properties of this basic cortical model are described in detail and validated using large network simulations. Bifurcation diagrams reflecting the network's state reveal asynchronous up- and down-states, bistable regimes, and oscillatory regions corresponding to fast excitation-inhibition and slow excitation-adaptation feedback loops. The biophysical parameters of the AdEx neuron can be coupled to an electric field with realistic field strengths which then can be propagated up to the population description. We show how on the edge of bifurcation, direct electrical inputs cause network state transitions, such as turning on and off oscillations of the population rate. Oscillatory input can frequency-entrain and phase-lock endogenous oscillations. Relatively weak electric field strengths on the order of 1 V/m are able to produce these effects, indicating that field effects are strongly amplified in the network. The effects of time-varying external stimulation are well-predicted by the mean-field model, further underpinning the utility of low-dimensional neural mass models.
Neonatal estradiol exposure to female rats changes GABA
Hormones and behavior, 2017

Exposure of female rats to estradiol during the perinatal period has profound effects on GABAergic neurotransmission that are crucial to establish sexually dimorphic brain characteristics. We previously showed that neonatal β-estradiol 3-benzoate (EB) treatment decreases brain concentrations of the neurosteroid allopregnanolone, a potent positive modulator of extrasynaptic GABA
Dystrophin is expressed in smooth muscle and afferent nerve fibers in the rat urinary bladder.
Muscle & nerve, 2019

With increasing life expectancy, comorbidities become overt in Duchenne muscular dystrophy (DMD). Although micturition problems are common, bladder function is poorly understood in DMD. We studied dystrophin expression and multiple isoform involvement in the bladder during maturation to gain insights into their roles in micturition.
Factor XIII deficiency related recurrent spontaneous intracerebral hemorrhage: a case and literature review.
Clinical neurology and neurosurgery, 2011

Spontaneous intracerebral hemorrhage (ICH) in young adults under 50 years of age is an uncommon occurrence associated with considerable morbidity and mortality. The differential diagnosis of ICH in this population differs from that of older individuals and includes vascular, toxic, inflammatory, oncologic, infectious and hematologic conditions. We present a case based observation of a spontaneous and recurrent ICH in a 25-year-old female secondary to undetected Factor XIII (FXIII) deficiency with no prior associated stigmata of hematologic disturbance admitted to a tertiary care neuroscience intensive care unit (NICU). Our patient was admitted after spontaneous development of left thalamic hemorrhage with ventricular extension. Initial management included external drain placement (EVD) and fresh frozen plasma administration. Diagnostic evaluation was unrevealing including CT angiography, magnetic resonance imaging (MRI) with venography, conventional cerebral angiogram, and hematologic and rheumatologic screens. Our patient recovered but represented 6 months later with five foci of spontaneous ICH. She underwent vascular, infectious, oncologic, hematologic, and rheumatologic evaluations. She expired secondary to ICH expansion with uncal herniation. The results of our investigation revealed markedly diminished FXIII activity. The pathophysiology, diagnosis and treatment of this disease are reviewed. FXIII deficiency should be considered in a case of cryptogenic ICH presenting with multifocal, recurrent ICH and a normal coagulation profile. Early diagnosis and initiation of factor replacement therapy offer the best strategies to reduce the morbidities associated with this disease.
NGF-induced mechanical sensitization of the masseter muscle is mediated through peripheral NMDA receptors.
Neuroscience, 2014

Intramuscular injection of nerve growth factor (NGF) in healthy humans mimics some of the symptoms of myofascial temporomandibular disorders (M-TMD). We hypothesized that NGF induces a prolonged myofascial mechanical sensitization by increasing peripheral N-methyl-d-aspartate (NMDA) receptor expression, leading to an enhanced response of muscle nociceptors to endogenous glutamate. Behavioral experiments with an injection of NGF (25 μg/ml, 10 μl) into the masseter muscle reduced the mechanical withdrawal threshold for 1 day in male rats and 5 days in female rats. These results mirror the sex-related differences found in NGF-induced mechanical sensitization in humans. Intramuscular injection with the competitive NMDA receptor antagonist dl-2-amino-5-phosphonovaleric acid (APV, 0.020 g/ml, 10 μl) reversed the mechanical sensitization in male but not in female rats. NGF increased the number of NMDA receptor subtype 2B (NR2B)-expressing rat trigeminal masseter ganglion neurons in both sexes, which peaked at 3 days post injection. There was an association between the levels of NR2B expression and NGF-induced mechanical sensitization. The average soma size of NR2B-expressing neurons increased significantly. Increased expression of neuropeptides (CGRP and SP) was observed in NR2B-expressing masseter ganglion neurons in female but not in male rats. In healthy men and women, comparable basal expression levels of NR2B and SP were found in peripheral fibers from masseter muscle microbiopsies. This study suggests that NGF-induced sensitization of masseter nociceptors is mediated, in part, by enhanced peripheral NMDA receptor expression. Measurement of peripheral NMDA receptor expression may be useful as a biomarker for M-TMD pain.
Deregulation of TLR4 signaling pathway characterizes Bicuspid Aortic valve syndrome.
Scientific reports, 2019

Bicuspid aortic valve (BAV) disease is recognized to be a syndrome with a complex and multifaceted pathophysiology. Its progression is modulated by diverse evolutionary conserved pathways, such as Notch-1 pathway. Emerging evidence is also highlighting the key role of TLR4 signaling pathway in the aortic valve pathologies and their related complications, such as sporadic ascending aorta aneurysms (AAA). Consistent with these observations, we aimed to evaluate the role of TLR4 pathway in both BAV disease and its common complication, such as AAA. To this aim, 70 subjects with BAV (M/F 50/20; mean age: 58.8 ± 14.8 years) and 70 subjects with tricuspid aortic valve (TAV) (M/F 35/35; mean age: 69.1 ± 12.8 years), with and without AAA were enrolled. Plasma assessment, tissue and gene expression evaluations were performed. Consistent with data obtained in the previous study on immune clonotypic T and B altered responses, we found reduced levels of systemic TNF-α, IL-1, IL-6, IL-17 cytokines in BAV cases, either in the presence or absence of AAA, than TAV cases (p < 0.0001 by ANOVA test). Interestingly, we also detected reduced levels of s-TLR4 in BAV cases with or without AAA in comparison to the two groups of TAV subjects (p < 0.0001 by ANOVA test). These results may suggest a deregulation in the activity or in the expression of TLR4 signaling pathway in all BAV cases. Portrait of these data is, indeed, the significantly decreased gene expression of inflammatory cytokines and TLR4, in both normal and aneurysmatic tissue samples, from BAV with AAA than TAV with AAA. In conclusion, our study demonstrates that subjects with BAV display a significant deregulation of TLR4 signaling pathway paralleled by a deregulation of Notch-1 pathway, as previously showed. This data suggests that the crosstalk between the Notch-1 and TLR4 signaling pathways may play a crucial role in both physiological embryological development, and homeostasis and functionality of aortic valve in adult life.
GABA
Current opinion in pharmacology, 2017

Metabotropic GABAB receptors clearly modify cognitive performance in preclinical animal models, yet translation to treating human disease has been elusive. Compared to their ionotropic GABAA receptor counterpart GABAB receptors not only regulate postsynaptic excitability but also regulate diverse synaptic inputs by presynaptically inhibiting neurotransmitter release. As such, the choice of agonist, antagonist, -ve or +ve modulator as well as CNS exposure level, timing of delivery and longevity of action strongly influence the probability of unlocking the procognitive potential of GABAB receptors in human disease. Quantitative clinical analysis of target/mechanistic engagement of GABAB receptors within cognitive circuits at the level of distinct pre-synaptic and post-synaptic subpopulations is required to determine the optimal pharmacological/dosing profile for different cognitive disorders.