rudyvdbrink/CitationDatabase huggingface dataset:
NMDA receptors in the CeA and BNST differentially regulate fear conditioning to predictable and unpredictable threats.
Neurobiology of learning and memory, 2020

Considerable work demonstrates that Pavlovian fear conditioning depends on N-methyl-D-aspartate (NMDA) receptor-dependent plasticity within the amygdala. In addition, the bed nucleus of the stria terminalis (BNST) has also been implicated in fear conditioning, particularly in the expression of fear to poor predictors of threat. We recently found that the expression of backward (BW) fear conditioning, in which an auditory conditioned stimulus (CS) follows a footshock unconditioned stimulus (US), requires the BNST; the expression of forward (FW) fear conditioning was not disrupted by BNST inactivation. However, whether NMDA receptors within the BNST contribute to the acquisition of fear conditioning is unknown. Moreover, the central nucleus of the amygdala (CeA), which has extensive connections with the BNST, is critically involved in FW conditioning, however whether it participates in BW conditioning has not been explored. Here we test the specific hypothesis that the CeA and the BNST mediate the acquisition of FW and BW fear conditioning, respectively. Adult female and male rats were randomly assigned to receive bilateral infusions of the NMDA receptor antagonist, D,L-2-amino-5-phosphonovalerate (APV), into the CeA or BNST prior to FW or BW fear conditioning. We found that intra-CeA APV impaired the acquisition of both FW and BW conditioning, whereas intra-BNST APV produced selective deficits in BW conditioning. Moreover, APV in the BNST significantly reduced contextual freezing, whereas CeA NMDA receptor antagonism impeded early but not long-lasting contextual fear. Collectively, these data reveal that CeA and BNST NMDA receptors have unique roles in fear conditioning.
A lifetime of dedication to the old in his Kentucky home.
Neuromolecular medicine, 2011

He spent tens of thousands of hours peering through the oculars of a microscope at stained brain tissue sections from thousands of patients who died with or without a neurodegenerative disorder; most of those patients he had himself cared for and had removed and processed their brain tissues upon their death. His discerning mind, humble demeanor, optimism and patience were fundamental features of his character. Through his research discoveries and advocacy, Dr. William R. Markesbery fought for those millions of elderly Americans with Alzheimer's disease (AD) and their families and friends. For over a decade, my laboratory was located directly above Dr. Markesbery's in the Sanders-Brown Research Center on Aging at the University of Kentucky in Lexington. In this article, I first provide several examples of how he moved research on AD forward on multiple fronts, not only by building one of the best AD Research Centers in the world, but also by providing a helping hand to the tens of thousands of Kentuckian's and their families to ease their suffering as best he could. Also described below are the results of several research projects on which I had the good fortune of collaborating with Dr. Markesbery.
A View from the Top: Prefrontal Control of Object Recognition.
Neuron, 2021

In this issue of Neuron, Kar and DiCarlo (2021) demonstrate that feedback from ventrolateral prefrontal cortex (VLPFC) to inferotemporal cortex (IT) is required for object recognition. They show that inactivating VLPFC selectively degrades object recognition performance and population encoding of object identity in IT.
Identification of a Signaling Mechanism by Which the Microbiome Regulates Th17 Cell-Mediated Depressive-Like Behaviors in Mice.
The American journal of psychiatry, 2020

Microbiota dysbiosis has been linked to major depressive disorder, but the mechanisms whereby the microbiota modulates mood remain poorly understood. The authors tested whether specific changes in the microbiome modulate depressive-like behaviors.
Brain metastasis in a patient with multiple malignancies.
JAAPA : official journal of the American Academy of Physician Assistants, 2021

Brain metastases originate from other primary cancers within the body, most commonly lung, breast, and melanoma. Because patients with brain metastasis, stroke, or intracranial hemorrhage may present with similar acute neurologic symptoms, clinicians must have a high suspicion for brain metastasis and perform an immediate workup to rule out life-threatening conditions. This case report focuses on the clinical symptoms, diagnostics, and treatment options for brain metastasis in a patient with multiple malignancies.
Time- and frequency-resolved covariance analysis for detection and characterization of seizures from intracraneal EEG recordings.
Biological cybernetics, 2020

The amount of power in different frequency bands of the electroencephalogram (EEG) carries information about the behavioral state of a subject. Hence, neurologists treating epileptic patients monitor the temporal evolution of the different bands. We propose a covariance-based method to detect and characterize epileptic seizures operating on the band-filtered EEG signal. The algorithm is unsupervised and performs a principal component analysis of intra-cranial EEG recordings, detecting transient fluctuations of the power in each frequency band. Its simplicity makes it suitable for online implementation. Good sampling of the non-ictal periods is required, while no demands are imposed on the amount of data during ictal activity. We tested the method with 32 seizures registered in 5 patients. The area below the resulting receiver-operating characteristic curves was 87% for the detection of seizures and 91% for the detection of recruited electrodes. To identify the behaviorally relevant correlates of the physiological signal, we identified transient changes in the variance of each band that were correlated with the degree of loss of consciousness, the latter assessed by the so-called Consciousness Seizure Scale, summarizing the performance of the subject in a number of behavioral tests requested during seizures. We concluded that those crisis with maximal impairment of consciousness tended to exhibit an increase in variance approximately 40 s after seizure onset, with predominant power in the theta and alpha bands and reduced delta and beta activity.
Naphthoquinone-Dopamine Hybrids Inhibit α-Synuclein Aggregation, Disrupt Preformed Fibrils, and Attenuate Aggregate-Induced Toxicity.
Chemistry (Weinheim an der Bergstrasse, Germany), 2020

Accumulation and aggregation of the intrinsically disordered protein α-synuclein (α-Syn) into amyloid fibrils are hallmarks of a series of heterogeneous neurodegenerative disorders, known as synucleinopathies and most notably Parkinson's disease (PD). The crucial role of α-Syn aggregation in PD makes it an attractive target for the development of disease-modifying therapeutics that would inhibit α-Syn aggregation or disrupt its preformed fibrillar assemblies. To this end, we have designed and synthesized two naphthoquinone-dopamine-based hybrid small molecules, NQDA and Cl-NQDA, and demonstrated their ability to inhibit in vitro amyloid formation by α-Syn using ThT assay, CD, TEM, and Congo red birefringence. Moreover, these hybrid molecules efficiently disassembled preformed fibrils of α-Syn into nontoxic species, as evident from LUV leakage assay. NQDA and Cl-NQDA were found to have low cytotoxicity and they attenuated the toxicity induced by α-Syn towards SH-SY5Y neuroblastoma cells. NQDA was found to efficiently cross an in vitro human blood-brain barrier model. These naphthoquinone-dopamine based derivatives can be an attractive scaffold for therapeutic design towards PD.
CREB Participates in Paclitaxel-Induced Neuropathic Pain Genesis Through Transcriptional Activation of Dnmt3a in Primary Sensory Neurons.
Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 2021

Chemotherapy-induced peripheral neuropathic pain (CIPNP) often occurs in cancer patients treated with antineoplastic drugs. Therapeutic management of CIPNP is very limited, at least in part due to the largely unknown mechanisms that underlie CIPNP genesis. Here, we showed that systemic administration of the chemotherapeutic drug paclitaxel significantly and time-dependently increased the levels of cyclic AMP response element-binding protein (CREB) in dorsal root ganglion (DRG) neurons. Blocking this increase through DRG microinjection of Creb siRNA attenuated paclitaxel-induced mechanical, heat, and cold nociceptive hypersensitivities. Mimicking this increase through DRG microinjection of the adeno-associated virus 5 expressing full-length Creb mRNA led to enhanced responses to basal mechanical, heat, and cold stimuli in mice in absence of paclitaxel treatment. Mechanically, paclitaxel-induced increase of DRG CREB protein augmented Dnmt3a promoter activity and participated in the paclitaxel-induced upregulation of DNMT3a protein in the DRG. CREB overexpression also elevated the expression of DNMT3a in in vivo and in vitro DRG neurons of naïve mice. Given that DNMT3a is an endogenous instigator of CIPNP and that CREB co-expresses with DNMT3a in DRG neurons, CREB may be a key player in CIPNP through transcriptional activation of the Dnmt3a gene in primary sensory neurons. CREB is thus a likely potential target for the therapeutic management of this disorder.
The Gigantocellular Reticular Nucleus Plays a Significant Role in Locomotor Recovery after Incomplete Spinal Cord Injury.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2020

Traditionally, the brainstem has been seen as hardwired and poorly capable of plastic adaptations following spinal cord injury (SCI). Data acquired over the past decades, however, suggest differently: following SCI in various animal models (lamprey, chick, rodents, nonhuman primates), different forms of spontaneous anatomic plasticity of reticulospinal projections, many of them originating from the gigantocellular reticular nucleus (NRG), have been observed. In line with these anatomic observations, animals and humans with incomplete SCI often show various degrees of spontaneous motor recovery of hindlimb/leg function. Here, we investigated the functional relevance of two different modes of reticulospinal fiber growth after cervical hemisection, local rewiring of axotomized projections at the lesion site versus compensatory outgrowth of spared axons, using projection-specific, adeno-associated virus-mediated chemogenetic neuronal silencing. Detailed assessment of joint movements and limb kinetics during overground locomotion in female adult rats showed that locally rewired as well as compensatory NRG fibers were responsible for different aspects of recovered forelimb and hindlimb functions (i.e., stability, strength, coordination, speed, or timing). During walking and swimming, both locally rewired as well as compensatory NRG plasticity were crucial for recovered function, while the contribution of locally rewired NRG plasticity to wading performance was limited. Our data demonstrate comprehensively that locally rewired as well as compensatory plasticity of reticulospinal axons functionally contribute to the observed spontaneous improvement of stepping performance after incomplete SCI and are at least partially causative to the observed recovery of function, which can also be observed in human patients with spinal hemisection lesions.
Sample Preparation for Metabolic Profiling using MALDI Mass Spectrometry Imaging.
Journal of visualized experiments : JoVE, 2020

Metabolomics, the study to identify and quantify small molecules and metabolites present in an experimental sample, has emerged as an important tool to investigate the biological activities during development and diseases. Metabolomics approaches are widely employed in the study of cancer, nutrition/diet, diabetes, and other physiological and pathological conditions involving metabolic processes. An advantageous tool that aids in metabolomic profiling advocated in this paper is matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI). Its ability to detect metabolites in situ without labeling, structural modifications, or other specialized reagents, such as those used in immunostaining, makes MALDI MSI a unique tool in advancing methodologies relevant in the field of metabolomics. An appropriate sample preparation process is critical to yield optimal results and will be the focus of this paper.
[On the necessity to distinguishing judgment from subjective choice in the cognitive neuroscience of morality].
Medecine sciences : M/S, 2011

Recently, cognitive neuroscience has shed new light on our understanding of the neural underpinning of humans' morality. These findings allow for a fundamental questioning and rethinking of the alleged dichotomy between reason and emotion, that has profoundly shaped both moral philosophy and moral psychology. Functional neuroimaging and neuropsychology studies have provided strong arguments favoring a dynamic and interdependent interaction between rational and emotional processes in the brain. Yet another fundamental issue remains largely unexplored: the dissociation between certain behaviours and the moral judgments that seem to precede them. The importance of this dissociation was highlighted in a study of psychopathic patients during which they preserved their moral judgments while frequently engaging in completely non moral behaviour. Such dissociation could result from the cognitive difference between an objective moral judgement with no personal consequence, and a subjective behavioural choice that has effective or potential personal consequences. Consequently, the results of moral dilemma experiments would differ widely depending whether they explore objective or subjective moral evaluations. That these evaluations involve two distinct neural processes should be taken into account when exploring the neural bases of human morality.
Intranasal oxytocin decreases self-oriented learning.
Psychopharmacology, 2021

Oxytocin has been found to play an important role in human social cognition and social interaction. Over the last two decades, surge studies have been conducted to investigate how oxytocin impacts other-oriented processes, such as trust and generosity (Zak et al. in PLoS ONE 2(11):e1128, 2007); however, the examination of the effect of oxytocin on self-related processes was relatively inadequate. Appropriate and efficient social interactions require both self- and other-related information processing. Recent studies have found that intranasal oxytocin (IN-OT) influences the self-related process, although the results have been mixed. The computational process underlying the effects of IN-OT on self-processing remains unknown.
Simvastatin-induced rhabdomyolysis.
European journal of neurology, 1994

At a time of increasing use of simvastatin and other "statin" drugs for cholesterol lowering, we report a case of simvastatin-induced acute massive rhabdomyolysis with renal failure in a woman with primary biliary cirrhosis, occurring 2 years after starting the drug. The differential diagnosis is highlighted and the literature reviewed.
Increased sensitivity to strong perturbations in a whole-brain model of LSD.
NeuroImage, 2021

Lysergic acid diethylamide (LSD) is a potent psychedelic drug, which has seen a revival in clinical and pharmacological research within recent years. Human neuroimaging studies have shown fundamental changes in brain-wide functional connectivity and an expansion of dynamical brain states, thus raising the question about a mechanistic explanation of the dynamics underlying these alterations. Here, we applied a novel perturbational approach based on a whole-brain computational model, which opens up the possibility to externally perturb different brain regions in silico and investigate differences in dynamical stability of different brain states, i.e. the dynamical response of a certain brain region to an external perturbation. After adjusting the whole-brain model parameters to reflect the dynamics of functional magnetic resonance imaging (fMRI) BOLD signals recorded under the influence of LSD or placebo, perturbations of different brain areas were simulated by either promoting or disrupting synchronization in the regarding brain region. After perturbation offset, we quantified the recovery characteristics of the brain area to its basal dynamical state with the Perturbational Integration Latency Index (PILI) and used this measure to distinguish between the two brain states. We found significant changes in dynamical complexity with consistently higher PILI values after LSD intake on a global level, which indicates a shift of the brain's global working point further away from a stable equilibrium as compared to normal conditions. On a local level, we found that the largest differences were measured within the limbic network, the visual network and the default mode network. Additionally, we found a higher variability of PILI values across different brain regions after LSD intake, indicating higher response diversity under LSD after an external perturbation. Our results provide important new insights into the brain-wide dynamical changes underlying the psychedelic state - here provoked by LSD intake - and underline possible future clinical applications of psychedelic drugs in particular psychiatric disorders.
Epigenome-wide change and variation in DNA methylation in childhood: trajectories from birth to late adolescence.
Human molecular genetics, 2021

DNA methylation (DNAm) is known to play a pivotal role in childhood health and development, but a comprehensive characterization of genome-wide DNAm trajectories across this age period is currently lacking. We have therefore performed a series of epigenome-wide association studies in 5019 blood samples collected at multiple time-points from birth to late adolescence from 2348 participants of two large independent cohorts. DNAm profiles of autosomal CpG sites (CpGs) were generated using the Illumina Infinium HumanMethylation450 BeadChip. Change over time was widespread, observed at over one-half (53%) of CpGs. In most cases, DNAm was decreasing (36% of CpGs). Inter-individual variation in linear trajectories was similarly widespread (27% of CpGs). Evidence for non-linear change and inter-individual variation in non-linear trajectories was somewhat less common (11 and 8% of CpGs, respectively). Very little inter-individual variation in change was explained by sex differences (0.4% of CpGs) even though sex-specific DNAm was observed at 5% of CpGs. DNAm trajectories were distributed non-randomly across the genome. For example, CpGs with decreasing DNAm were enriched in gene bodies and enhancers and were annotated to genes enriched in immune-developmental functions. In contrast, CpGs with increasing DNAm were enriched in promoter regions and annotated to genes enriched in neurodevelopmental functions. These findings depict a methylome undergoing widespread and often non-linear change throughout childhood. They support a developmental role for DNA methylation that extends beyond birth into late adolescence and has implications for understanding life-long health and disease. DNAm trajectories can be visualized at http://epidelta.mrcieu.ac.uk.
Lower pattern recognition memory scores in anorexia nervosa.
Journal of eating disorders, 2021

There is extensive evidence for volumetric reductions in the hippocampus in patients with anorexia nervosa (AN), however the impact on function is unclear. Pattern separation and recognition are hippocampus-dependent forms of learning thought to underlie stimulus discrimination.
Neuroscience: A New Pathway to Make Us Smarter and Happier.
Current biology : CB, 2020

Treatments that improve cognition and decrease depression converge on decreasing phosphorylation of eukaryotic elongation factor 2 (eEF2). This decrease is sufficient to lead to altered levels of proteins that cause an increase in new neurons, improved cognition and less depression.
Odor-Induced Saltiness Enhancement: Insights Into The Brain Chronometry Of Flavor Perception.
Neuroscience, 2021

Flavor perception results from the integration of at least odor and taste. Evidence for such integration is that odors can have taste properties (odor-induced taste). Most brain areas involved in flavor perception are high-level areas; however, primary gustatory and olfactory areas also show activations in response to a combination of odor and taste. While the regions involved in flavor perception are now quite well identified, the network's organization is not yet understood. Using a close to real salty soup model with electroencephalography brain recording, we evaluated whether odor-induced saltiness enhancement would result in differences of amplitude and/or latency in late cognitive P3 peak mostly and/or in P1 early sensory peak. Three target solutions were created from the same base of green-pea soup: i) with a "usual" salt concentration (PPS2), ii) with "reduced" salt (PPS1: -50%), and iii) with reduced salt and a "beef stock" odor (PPS1B). Sensory data showed that the beef odor produced saltiness enhancement in PPS1B in comparison to PPS1. As the main EEG result, the late cognitive P3 peak was delayed by 25 ms in the odor-added solution PPS1B compared to PPS1. The odor alone did not explain this peak amplitude and higher latency in the P3 peak. These results support the classical view that high-level integratory areas process odor-taste interactions with potential top-down effects on primary sensory regions.
Acute surgical management of children with ruptured brain arteriovenous malformation.
Journal of neurosurgery. Pediatrics, 2021

Rupture of brain arteriovenous malformation (AVM) is the main etiology of intracerebral hemorrhage (ICH) in children. Ensuing intracranial hypertension is among the modifiable prognosis factors and sometimes requires emergency hemorrhage evacuation (HE). The authors aimed to analyze variables associated with HE in children with ruptured AVM.
This Is Your Brain on (Low) Glucose.
Trends in neurosciences, 2020

Brain functioning and high-order cognitive functions critically rely on glucose as a metabolic substrate. In a recent study, Kealy et al. investigated the impact of glucose availability on sickness behavior and delirium in mice and humans. They identified disrupted brain carbohydrate metabolism as a key mechanistic driver of these behaviors.
HPV-related papillary squamous cell carcinoma of the tonsil during treatment with fingolimod.
Multiple sclerosis and related disorders, 2018

Fingolimod is a commonly used treatment for highly active relapsing-remitting multiple sclerosis (MS). We describe the case of a 50-year old man on fingolimod since 2011 who presented, in April 2017, with a voluminous swelling of the left tonsil. A left tonsillectomy was performed, and histological exam disclosed a papillary squamous cell carcinoma of the palatine tonsil, with an in situ hybridization positive for human papillomavirus (HPV)-16 DNA. Neither lymph nodes involvement nor other metastases were detected. Fingolimod was stopped as a precautionary measure in May 2017, and the patient currently continues his follow up at our Department. Immunocompromised patients are at risk for developing HPV-related malignancies probably in light of the suppression of T-cell immunity, therefore an increased risk for HPV activation in MS patients treated with disease modifying therapies (DMTs) characterized by a more pronounced immunosuppressant activity cannot be excluded. Given the absence of studies on larger cohorts of MS patients exposed to DMTs, additional monitoring for HPV infection during fingolimod treatment is not currently recommended. However, vigilance for this possible association is warranted.