rudyvdbrink/CitationDatabase huggingface dataset:
Neural changes with tactile learning reflect decision-level reweighting of perceptual readout.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013

Despite considerable work, the neural basis of perceptual learning remains uncertain. For visual learning, although some studies suggested that changes in early sensory representations are responsible, other studies point to decision-level reweighting of perceptual readout. These competing possibilities have not been examined in other sensory systems, investigating which could help resolve the issue. Here we report a study of human tactile microspatial learning in which participants achieved >six-fold decline in acuity threshold after multiple training sessions. Functional magnetic resonance imaging was performed during performance of the tactile microspatial task and a control, tactile temporal task. Effective connectivity between relevant brain regions was estimated using multivariate, autoregressive models of hidden neuronal variables obtained by deconvolution of the hemodynamic response. Training-specific increases in task-selective activation assessed using the task × session interaction and associated changes in effective connectivity primarily involved subcortical and anterior neocortical regions implicated in motor and/or decision processes, rather than somatosensory cortical regions. A control group of participants tested twice, without intervening training, exhibited neither threshold improvement nor increases in task-selective activation. Our observations argue that neuroplasticity mediating perceptual learning occurs at the stage of perceptual readout by decision networks. This is consonant with the growing shift away from strictly modular conceptualization of the brain toward the idea that complex network interactions underlie even simple tasks. The convergence of our findings on tactile learning with recent studies of visual learning reconciles earlier discrepancies in the literature on perceptual learning.
Ventral Subiculum Stimulation Promotes Persistent Hyperactivity of Dopamine Neurons and Facilitates Behavioral Effects of Cocaine.
Cell reports, 2015

The ventral subiculum (vSUB) plays a key role in addiction, and identifying the neuronal circuits and synaptic mechanisms by which vSUB alters the excitability of dopamine neurons is a necessary step to understand the motor changes induced by cocaine. Here, we report that high-frequency stimulation of the vSUB (HFSvSUB) over-activates ventral tegmental area (VTA) dopamine neurons in vivo and triggers long-lasting modifications of synaptic transmission measured ex vivo. This potentiation is caused by NMDA-dependent plastic changes occurring in the bed nucleus of the stria terminalis (BNST). Finally, we report that the modification of the BNST-VTA neural circuits induced by HFSvSUB potentiates locomotor activity induced by a sub-threshold dose of cocaine. Our findings unravel a neuronal circuit encoding behavioral effects of cocaine in rats and highlight the importance of adaptive modifications in the BNST, a structure that influences motivated behavior as well as maladaptive behaviors associated with addiction.
Aspects of the narcolepsy-cataplexy syndrome in O/E3-null mutant mice.
Neuroscience, 2011

Orexins (hypocretins) are peptide neurotransmitters produced by a small group of neurons located exclusively in the lateral hypothalamus (LH). Orexins modulate arousal, and as a result, have profound effects on feeding behavior and the sleep-wake cycle. Loss of orexin producing neurons leads to a narcoleptic phenotype, characterized by sudden transitions from vigilance to rapid eye movement (REM) sleep (direct transition to REM, DREM) observed in electroencephalogram (EEG) and electromyogram (EMG) recordings. In this study, we demonstrate that mice lacking the basic helix-loop-helix transcription factor O/E3 (also known as ebf2) have a decrease in orexin-producing cells in the LH, in addition to a severely impaired orexinergic innervation of the pons. These changes in the orexinergic circuit of O/E3-null animals induce a narcoleptic phenotype, similar to the one arising in orexin-deficient and orexin-ataxin-3 mice. Taken together, our results suggest that O/E3 plays a central role during the establishment of a functional orexinergic circuit by controlling the expression of essential hypothalamic neurotransmitter and the correct development of the nerve fibers arising from the hypothalamus. This is the first report regarding the narcolepsy-cataplexy syndrome in O/E3-null mice, which adds the importance of transcription factors in the regulation of neural subpopulations that control the sleep-wake cycle.
Early evolutionary history (from bacteria to hemichordata) of the omnipresent purinergic signalling: A tribute to Geoff Burnstock inquisitive mind.
Biochemical pharmacology, 2021

Purines and pyrimidines are indispensable molecules of life; they are fundamental for genetic code and bioenergetics. From the very early evolution of life purines have acquired the meaning of damage-associated extracellular signaller and purinergic receptors emerged in unicellular organisms. Ancestral purinoceptors are P2X-like ionotropic ligand-gated cationic channels showing 20-40% of homology with vertebrate P2X receptors; genes encoding ancestral P2X receptors have been detected in Protozoa, Algae, Fungi and Sponges; they are also present in some invertebrates, but are absent from the genome of insects, nematodes, and higher plants. Plants nevertheless evolved a sophisticated and widespread purinergic signalling system relying on the idiosyncratic purinoceptor P2K1/DORN1 linked to intracellular Ca
The error processing system in major depressive disorder: cortical phenotypal marker hypothesis.
Biological psychology, 2014

Major depressive disorder (MDD) ensues reduced goal-directed cognition and behaviour. Cognitive and emotional flexibility to disengage and adapt future responses was examined in the error processing system (error-related negativity/ERN, error-positivity/Pe event-related potentials) of 58 depressed patients (21 current, 37 remitted) vs. 27 controls undergoing cognitive and affective Go/NoGo paradigms. ERN was equivalent between patient and controls for the cognitive task, albeit amplitude attenuated in patients during the affective task. Blunted ERN amplitudes were evident between patients and controls in males compared to females, plausibly underpinned by disparities in dopaminergic pathways. Patients displayed enhanced Pe amplitudes for both cognitive and affective tasks. Abberations in cortical error processing in MDD appear specific to affective systems for the pre-attentive ERN, opposed to cognitive and affective processing for the consciously-integrated Pe. Heightened Pe, observed in both current and remitted patients, advocates the possibility of the Pe waveform as a candidate intermediate phenotype of depression.
A decrease in the addition of new cells in the nucleus accumbens and prefrontal cortex between puberty and adulthood in male rats.
Developmental neurobiology, 2014

Adolescence involves shifts in social behaviors, behavioral flexibility, and adaptive risk-taking that coincide with structural remodeling of the brain. We previously showed that new cells are added to brain regions associated with sexual behaviors, suggesting that cytogenesis may be a mechanism for acquiring adult-typical behaviors during adolescence. Whether pubertal cell addition occurs in brain regions associated with behavioral flexibility or motivation and whether these patterns differ between pubertal and adult animals had not been determined. Therefore, we assessed patterns of cell proliferation or survival in the prefrontal cortex and nucleus accumbens. Pubertal and adult male rats were given injections of bromo-deoxyuridine (BrdU). To assess cell proliferation, half of the animals from each group were sacrificed 24 h following the last injection. The remaining animals were sacrificed at Day 30 following the last injection to evaluate cell survival. Adult animals had significantly lower densities of BrdU-immunoreactive (ir) cells in the prefrontal cortex, irrespective of post-BrdU survival time, whereas in the nucleus accumbens, adult animals had a lower density of BrdU-ir cells at the short survival time; however, the density of BrdU-ir cells was equivalent in pubertal and adult animals at the longer survival time. These data provide evidence that cell addition during puberty may contribute to the remodeling of brain regions associated with behavioral flexibility and motivation, and this cell addition continues into adulthood, albeit at lower levels. Higher levels of cell proliferation or survival in younger animals may reflect a higher level of plasticity, possibly contributing to the dynamic remodeling of the pubertal brain.
Improving the clinical efficiency of T2(*) mapping of ligament integrity.
Journal of biomechanics, 2014

Current MR methods use T2(*) relaxation time as a surrogate measure of ligament strength. Currently, a multi-echo voxel-wise least squares fit is the gold standard to create T2(*) maps; however, the post-processing is time-intensive and serves as a stopgap for clinical use. The study objective was to determine if an alternative method could improve post-processing time without sacrificing fidelity of T2(*) values for eventual translational use in the clinic. Using a 6 echo FLASH sequence, three different methods were used to determine intact posterior cruciate ligament (PCL) median T2(*) Two of these methods utilized a voxel-wise method to establish T2(*) maps: (1) a current "gold standard" method using a voxel-wise 6 echo least-squares fit (6LS) and (2) a voxel-wise 2 echo point T2(*) determination (2MM). The third method used median ligament signal intensity and a single nonlinear least-squares fit (6LSROI) instead of a voxel-wise basis. The resulting median T2(*) values of the PCL and computational time were compared. The median T2(*) values were 42% higher using the 2MM compared to the 6LS method (p<0.0001). However, a strong correlation was found for the median T2(*) values between the 2MM and 6LS methods (R(2)=0.80). The median T2(*) values were not significantly different between the 6LS and 6LSROI methods (p=0.519). Using the 2MM (which provides a regional map) and the 6LSROI (which efficiently provides the median T2(*) value) methods in tandem would take only minutes of post-processing computational time compared to the 6LS method (~540 min), and hence would facilitate clinical application of T2(*) maps to predict ligament structural properties as a patient outcome measure.
Increased Risk of Depression in Patients with Parkinson Disease: A Nationwide Cohort Study.
The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry, 2015

The association between Parkinson disease (PD) and depression remains unclear, particularly in the Asian population. The purpose of this study is to investigate the risk of depression in patients with PD using population-based data.
TLR4 activation enhances the PD-L1-mediated tolerogenic capacity of colonic CD90+ stromal cells.
Journal of immunology (Baltimore, Md. : 1950), 2014

Signaling via programmed death ligand-1 (PD-L1) and PD-L2 is crucial for maintaining peripheral tolerance. CD90(+) myofibroblasts/fibroblasts (CMFs) are major programmed cell death-1 (PD-1) ligand-expressing cells in normal human colonic mucosa. CMFs suppress activated CD4(+) T cell proliferation via PD-1 ligands. It is not known whether signaling through TLRs contribute to the regulation PD-1 ligands on CMFs upon colonic mucosal tolerance. In this study, we demonstrated that stimulation of TLR4 on human CMFs upregulates PD-L1, but not PD-L2, and reinforces CMF-mediated suppression of CD4(+) T cell proliferation and IFN-γ production. TLR4-mediated upregulation of PD-L1 on CMFs involved NF-κB pathways and was JAK2 and MyD88 dependent. MyD88-dependent stimulation of TLR1/2 and TLR5 also upregulated PD-L1 expression on CMFs in culture. PD-L1 expression was drastically decreased in vivo in the colonic mucosa of mice devoid of MyD88. Induction of MyD88 deficiency in CMFs in fibroblast-specific MyD88 conditional knockout mice resulted in a strong increase in a mucosal IFN-γ expression concomitantly with the abrogation of PD-L1 expression in CMFs under homeostasis and epithelial injury induced by dextran sodium sulfate. Together, these data suggest that MyD88-dependent TLR stimulation of CMFs in the normal colonic mucosa may reinforce these cells' anti-inflammatory capacity and thus contribute to the maintenance of mucosal tolerance.
Prenatal inhibition of the tryptophan-kynurenine pathway alters synaptic plasticity and protein expression in the rat hippocampus.
Brain research, 2013

Glutamate receptors sensitive to N-methyl-d-aspartate (NMDA) are important in early brain development, influencing cell proliferation and migration, neuritogenesis, axon guidance and synapse formation. The kynurenine pathway of tryptophan metabolism includes an agonist (quinolinic acid) and an antagonist (kynurenic acid) at these receptors. Rats were treated in late gestation with 3,4-dimethoxy-N-[4-(3-nitrophenyl)thiazol-2-yl]-benzene-sulphonamide (Ro61-8048), an inhibitor of kynurenine-3-monoxygenase which diverts kynurenine metabolism to kynurenic acid. Within 5h of drug administration, there was a significant decrease in GluN2A expression and increased GluN2B in the embryo brains, with changes in sonic hedgehog at 24h. When injected dams were allowed to litter normally, the brains of offspring were removed at postnatal day 21 (P21). Recordings of hippocampal field excitatory synaptic potentials (fEPSPs) showed that prenatal exposure to Ro61-8048 increased neuronal excitability and paired-pulse facilitation. Long-term potentiation was also increased, with no change in long-term depression. At this time, levels of GluN2A, GluN2B and postsynaptic density protein PSD-95 were all increased. Among several neurodevelopmental proteins, the expression of sonic hedgehog was increased, but DISC1 and dependence receptors were unaffected, while raised levels of doublecortin and Proliferating Cell Nuclear Antigen (PCNA) suggested increased neurogenesis. The results reveal that inhibiting the kynurenine pathway in utero leads to molecular and functional synaptic changes in the embryos and offspring, indicating that the pathway is active during gestation and plays a significant role in the normal early development of the embryonic and neonatal nervous system.
The potential impact of recruitment method on sample characteristics and treatment outcomes in a psychosocial trial for women with co-occurring substance use disorder and PTSD.
Drug and alcohol dependence, 2012

Recruitment method can impact the sample composition of a clinical trial and, thus, the generalizability of the results, but the importance of recruitment method in substance use disorder trials has received little attention. The present paper sought to address this research gap by evaluating the association between recruitment method and sample characteristics and treatment outcomes in a substance use disorder trial.
Morphine epigenomically regulates behavior through alterations in histone H3 lysine 9 dimethylation in the nucleus accumbens.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012

Dysregulation of histone modifying enzymes has been associated with numerous psychiatric disorders. Alterations in G9a (Ehmt2), a histone methyltransferase that catalyzes the euchromatic dimethylation of histone H3 at lysine 9 (H3K9me2), has been implicated recently in mediating neural and behavioral plasticity in response to chronic cocaine administration. Here, we show that chronic morphine, like cocaine, decreases G9a expression, and global levels of H3K9me2, in mouse nucleus accumbens (NAc), a key brain reward region. In contrast, levels of other histone methyltransferases or demethylases, or of other methylated histone marks, were not affected in NAc by chronic morphine. Through viral-mediated gene transfer and conditional mutagenesis, we found that overexpression of G9a in NAc opposes morphine reward and locomotor sensitization and concomitantly promotes analgesic tolerance and naloxone-precipitated withdrawal, whereas downregulation of G9a in NAc enhances locomotor sensitization and delays the development of analgesic tolerance. We identified downstream targets of G9a by providing a comprehensive chromatin immunoprecipitation followed by massively parallel sequencing analysis of H3K9me2 distribution in NAc in the absence and presence of chronic morphine. These data provide novel insight into the epigenomic regulation of H3K9me2 by chronic morphine and suggest novel chromatin-based mechanisms through which morphine-induced addictive-like behaviors arise.
Simvastatin enhances the hippocampal klotho in a rat model of streptozotocin-induced cognitive decline.
Progress in neuro-psychopharmacology & biological psychiatry, 2017

Brain oxidative status is a crucial factor in the development of sporadic Alzheimer's disease (AD). Klotho, an anti-aging protein, diminishes oxidative stress by the induction of manganese superoxide dismutase (MnSOD). Thus, the substances that increase klotho expression could be considered as a potential treatment for Alzheimer's disease when the oxidative imbalance is present. Statins are suggested to up-regulate klotho expression. We examined the effect of simvastatin (5mg/kg, daily for 3weeks) on hippocampal klotho and MnSOD expression in the cognitive declined animal model induced by intracerebroventricular (ICV)-streptozotocin (STZ) administration. Cognitive assessment was performed by the Morris Water Maze (MWM) test. The results indicated that mean escape latency and distance were prolonged in the ICV-STZ group compared with the control group. The expression of klotho and MnSOD were also down regulated in the hippocampus. Furthermore, improved spatial performance was observed in simvastatin-treated animals. This effect could be related to increase in oxidative stress tolerance as evidenced by klotho and MnSOD up-regulation. Our current study indicates that klotho upregulation may be a neuroprotective mechanism of simvastatin against cognitive decline in AD.
Improving Staffing and Nurse Engagement in a Neuroscience Intermediate Unit.
The Journal of neuroscience nursing : journal of the American Association of Neuroscience Nurses, 2017

The neuroscience intermediate unit is a 23-bed unit that was initially staffed with a nurse-to-patient ratio of 1:4 to 1:5. In time, the unit's capacity to care for the exceeding number of progressively acute patients fell short of the desired goals in the staff affecting the nurse satisfaction. The clinical nurses desired a lower nurse-patient ratio. The purpose of this project was to justify a staffing increase through a return on investment and increased quality metrics.
Functional Brain Networks Are Dominated by Stable Group and Individual Factors, Not Cognitive or Daily Variation.
Neuron, 2018

The organization of human brain networks can be measured by capturing correlated brain activity with fMRI. There is considerable interest in understanding how brain networks vary across individuals or neuropsychiatric populations or are altered during the performance of specific behaviors. However, the plausibility and validity of such measurements is dependent on the extent to which functional networks are stable over time or are state dependent. We analyzed data from nine high-quality, highly sampled individuals to parse the magnitude and anatomical distribution of network variability across subjects, sessions, and tasks. Critically, we find that functional networks are dominated by common organizational principles and stable individual features, with substantially more modest contributions from task-state and day-to-day variability. Sources of variation were differentially distributed across the brain and differentially linked to intrinsic and task-evoked sources. We conclude that functional networks are suited to measuring stable individual characteristics, suggesting utility in personalized medicine.
Study protocol of the ASD-Net, the German research consortium for the study of Autism Spectrum Disorder across the lifespan: from a better etiological understanding, through valid diagnosis, to more effective health care.
BMC psychiatry, 2017

Autism Spectrum Disorder (ASD) is a severe, lifelong neurodevelopmental disorder with early onset that places a heavy burden on affected individuals and their families. Due to the need for highly specialized health, educational and vocational services, ASD is a cost-intensive disorder, and strain on health care systems increases with increasing age of the affected individual.
Differential accumulation of storage bodies with aging defines discrete subsets of microglia in the healthy brain.
eLife, 2020

To date, microglia subsets in the healthy CNS have not been identified. Utilizing autofluorescence (AF) as a discriminating parameter, we identified two novel microglia subsets in both mice and non-human primates, termed autofluorescence-positive (AF
Higher health care use before a clinically isolated syndrome with or without subsequent MS.
Multiple sclerosis and related disorders, 2019

To establish whether a unique multiple sclerosis (MS) prodrome exists by comparing health care utilization in the five-year period before initial presentation with optic neuritis (ON) or transverse myelitis (TM) among those who were and were not subsequently diagnosed with MS.
Involvement of the choroid plexus in multiple sclerosis autoimmune inflammation: a neuropathological study.
Journal of neuroimmunology, 2008

An immunological function has been proposed for the choroid plexus (CP). In multiple sclerosis (MS) brains, CPs show (immunohistochemistry to HLA-DR, CD3, CD20, CD68, VCAM-1, CD138) T lymphocytes in vessels and stroma, VCAM-1 expression on endothelia, intense HLA-DR immunostaining on cells in CP stroma, among CP epithelium and on epiplexus cells. CPs in control or amyotrophic lateral sclerosis brains do not show such inflammatory changes. Intense CP inflammation is observed in viral encephalitis. Changes in MS CPs suggest persisting immune activation, with intensity similar to acute encephalitis, even in MS phases in which neurodegeneration prevails. In MS, CPs could represent a site for lymphocyte entry in the CSF and for CSF antigens presentation.
Mechanism evaluation of a lifestyle intervention for patients with musculoskeletal pain who are overweight or obese: protocol for a causal mediation analysis.
BMJ open, 2017

Low back pain (LBP) and knee osteoarthritis (OA) are highly prevalent and disabling conditions that cause societal and economic impact worldwide. Two randomised controlled trials (RCTs) will evaluate the effectiveness of a multicomponent lifestyle intervention for patients with LBP and knee OA who are overweight or obese. The key targets of this intervention are to improve physical activity, modify diet and correct pain beliefs. These factors may explain how a lifestyle intervention exerts its effects on key patient-relevant outcomes: pain, disability and quality of life. The aim of this protocol is to describe a planned analysis of a mechanism evaluation for a lifestyle intervention for overweight or obese patients with LBP and knee OA.
Trait self-reflectiveness relates to time-varying dynamics of resting state functional connectivity and underlying structural connectomes: Role of the default mode network.
NeuroImage, 2020

Cognitive insight is defined as the ability to reflect upon oneself (i.e. self-reflectiveness), and to not be overly confident of one's own (incorrect) beliefs (i.e. self-certainty). These abilities are impaired in several disorders, while they are essential for the evaluation and regulation of one's behavior. We hypothesized that cognitive insight is a dynamic process, and therefore examined how it relates to temporal dynamics of resting state functional connectivity (FC) and underlying structural network characteristics in 58 healthy individuals.