rudyvdbrink/CitationDatabase huggingface dataset:
Maximum Tongue Pressure is Associated with Swallowing Dysfunction in ALS Patients.
Dysphagia, 2017

Maximum tongue pressure (MTP) measurement is a convenient, less invasive assessment that has been developed to quantify tongue strength; however, it is unclear whether MTP is useful for the detection of swallowing disorders in amyotrophic lateral sclerosis (ALS) patients. The purpose of this study was to clarify the relationship between MTP and the characteristics of swallowing disorders on videofluorography and to determine the usefulness of tongue pressure measurement for the assessment of swallowing function in ALS patients. Twenty-five ALS patients were evaluated according to the ALS functional rating scale-revised (ALSFRS-R), and their ability to swallow yogurt was observed via videofluorography. MTP was measured using a device (TPM-01, JMS, Hiroshima) equipped with a balloon probe. Then, the relationships between the ALSFRS-R score, swallowing function, and MTP were analyzed. MTP was significantly lower in the subjects with reduced tongue function (p = 0.002) or with pharyngeal residue (p = 0.006) than in the subjects with normal characteristics. Bolus formation and oral transit time and pharyngeal transit time were significantly prolonged among those with reduced MTP. MTP at a cut-off value of 21.0 kPa was associated with a full score on the bulbar-related items of the ALSFRS-R. MTP may serve as a new diagnostic tool for the early detection of swallowing dysfunction in ALS patients, because of its good relationship with their swallowing characteristics.
Association between COMT Val158Met genotype and EEG alpha peak frequency tested in two independent cohorts.
Psychiatry research, 2014

This study could not confirm the association between the Catechol-O-Methyltransferase Val158Met polymorphism (COMT) and electroencephalographic (EEG) alpha peak frequency (APF) in two independent cohorts of 187 (96 depressed and 91 healthy participants) and 413 healthy participants. If COMT and APF play a role in depression or antidepressant treatment response, they do not have a shared pathway. We emphasize the importance of publishing null-findings for obtaining more accurate overall estimates of genetic effects.
Antipsychotics and mortality in a nationwide cohort of 29,823 patients with schizophrenia.
Schizophrenia research, 2018

It has remained controversial if antipsychotic treatment is associated with increased or decreased mortality among patients with schizophrenia, and if there are any clinically meaningful differences between specific agents and routes of administration.
Hypoglycemia-activated GLUT2 neurons of the nucleus tractus solitarius stimulate vagal activity and glucagon secretion.
Cell metabolism, 2014

Glucose-sensing neurons in the brainstem participate in the regulation of energy homeostasis but have been poorly characterized because of the lack of specific markers to identify them. Here we show that GLUT2-expressing neurons of the nucleus of the tractus solitarius form a distinct population of hypoglycemia-activated neurons. Their response to low glucose is mediated by reduced intracellular glucose metabolism, increased AMP-activated protein kinase activity, and closure of leak K(+) channels. These are GABAergic neurons that send projections to the vagal motor nucleus. Light-induced stimulation of channelrhodospin-expressing GLUT2 neurons in vivo led to increased parasympathetic nerve firing and glucagon secretion. Thus GLUT2 neurons of the nucleus tractus solitarius link hypoglycemia detection to counterregulatory response. These results may help identify the cause of hypoglycemia-associated autonomic failure, a major threat in the insulin treatment of diabetes.
Differential activation of the lateral premotor cortex during action observation.
BMC neuroscience, 2010

Action observation leads to neural activation of the human premotor cortex. This study examined how the level of motor expertise (expert vs. novice) in ballroom dancing and the visual viewpoint (internal vs. external viewpoint) influence this activation within different parts of this area of the brain.
Representation of probabilistic outcomes during risky decision-making.
Nature communications, 2020

Goal-directed behaviour requires prospectively retrieving and evaluating multiple possible action outcomes. While a plethora of studies suggested sequential retrieval for deterministic choice outcomes, it remains unclear whether this is also the case when integrating multiple probabilistic outcomes of the same action. We address this question by capitalising on magnetoencephalography (MEG) in humans who made choices in a risky foraging task. We train classifiers to distinguish MEG field patterns during presentation of two probabilistic outcomes (reward, loss), and then apply these to decode such patterns during deliberation. First, decoded outcome representations have a temporal structure, suggesting alternating retrieval of the outcomes. Moreover, the probability that one or the other outcome is being represented depends on loss magnitude, but not on loss probability, and it predicts the chosen action. In summary, we demonstrate decodable outcome representations during probabilistic decision-making, which are sequentially structured, depend on task features, and predict subsequent action.
Rosuvastatin enhances anti-inflammatory and inhibits pro-inflammatory functions in cultured microglial cells.
Neuroscience, 2016

Microglial activation results in profound morphological, functional and gene expression changes that affect the pro- and anti-inflammatory mechanisms of these cells. Although statins have beneficial effects on inflammation, they have not been thoroughly investigated for their ability to affect microglial functions. Therefore the effects of rosuvastatin, one of the most commonly prescribed drugs in cardiovascular therapy, either alone or in combination with bacterial lipopolysaccharide (LPS), were profiled in pure microglial cultures derived from the forebrains of 18-day-old rat embryos. To reveal the effects of rosuvastatin on a number of pro- and anti-inflammatory mechanisms, we performed morphometric, functional and gene expression studies relating to cell adhesion and proliferation, phagocytosis, pro- and anti-inflammatory cytokine (IL-1β, tumor necrosis factor α (TNF-α) and IL-10, respectively) production, and the expression of various inflammation-related genes, including those related to the above morphological parameters and cellular functions. We found that microglia could be an important therapeutic target of rosuvastatin. In unchallenged (control) microglia, rosuvastatin inhibited proliferation and cell adhesion, but promoted microspike formation and elevated the expression of certain anti-inflammatory genes (Cxcl1, Ccl5, Mbl2), while phagocytosis or pro- and anti-inflammatory cytokine production were unaffected. Moreover, rosuvastatin markedly inhibited microglial activation in LPS-challenged cells by affecting both their morphology and functions as it inhibited LPS-elicited phagocytosis and inhibited pro-inflammatory cytokine (IL-1β, TNF-α) production, concomitantly increasing the level of IL-10, an anti-inflammatory cytokine. Finally, rosuvastatin beneficially and differentially affected the expression of a number of inflammation-related genes in LPS-challenged cells by inhibiting numerous pro-inflammatory and stimulating several anti-inflammatory genes. Since the microglia could elicit pro-inflammatory responses leading to neurodegeneration, it is important to attenuate such mechanisms and promote anti-inflammatory properties, and develop prophylactic therapies. By beneficially regulating both pro- and anti-inflammatory microglial functions, rosuvastatin may be considered as a prophylactic agent in the prevention of inflammation-related neurological disorders.
Tangles of neurogenetics, neuroethics, and culture.
Neuron, 2010

Neurogenetics promises rich insights into how the mind works. Researchers investigating the range of topics from normal brain functioning to pathological states are increasingly looking to genetics for clues on human variability and disease etiology. Is it fair to assume this interest in neurogenetics is universal? How should researchers and clinicians approach ideas of consent to research or prediction of disease when a subject or patient understands the mind with concepts or language incompatible with neurogenetics? In this paper we consider how non-Western philosophies bring complexity to ideas of individual and community consent and confidentiality in the context of neurogenetics.
Converging evidence for the association of functional genetic variation in the serotonin receptor 2a gene with prefrontal function and olanzapine treatment.
JAMA psychiatry, 2013

Serotonin (5-hydroxytryptamine) receptor 2a (5-HT2AR) signaling is important for modulation of corticostriatal pathways and prefrontal activity during cognition. Furthermore, newer antipsychotic drugs target 5-HT2AR. A single-nucleotide polymorphism in the 5-HT2AR gene (HTR2A rs6314, C>T; OMIM 182135) has been weakly associated with differential 5-HT2AR signaling and with physiologic as well as behavioral effects.
Are carriers of CYP21A2 mutations less vulnerable to psychological stress? A population-based national cohort study.
Clinical endocrinology, 2017

Congenital adrenal hyperplasia (CAH) is one of the most common monogenic autosomal recessive disorders with an incidence of one in 15 000. About one in 70 individuals in the general population are carriers of a severe CYP21A2 mutation. It has been suggested that this confers a survival advantage, perhaps as a result of increased activity in the hypothalamic-pituitary-adrenal axis. We investigated vulnerability to psychological stress in obligate carriers.
The structure of mania: An overview of factorial analysis studies.
European psychiatry : the journal of the Association of European Psychiatrists, 2020

Operational definitions of mania are based on expert consensus rather than empirical data. The aim of this study is to identify the key domains of mania, as well as the relevance of the different signs and symptoms of this clinical construct.
Cortical remyelination: a new target for repair therapies in multiple sclerosis.
Annals of neurology, 2012

Generation and differentiation of new oligodendrocytes in demyelinated white matter is the best described repair process in the adult human brain. However, remyelinating capacity falters with age in patients with multiple sclerosis (MS). Because demyelination of cerebral cortex is extensive in brains from MS patients, we investigated the capacity of cortical lesions to remyelinate and directly compared the extent of remyelination in lesions that involve cerebral cortex and adjacent subcortical white matter.
Knockdown of TNF‑α alleviates acute lung injury in rats with intestinal ischemia and reperfusion injury by upregulating IL‑10 expression.
International journal of molecular medicine, 2018

Intestinal ischemia and reperfusion (II/R) injury often triggers severe injury in remote organs, with the lungs being considered the main target. Excessive elevation of proinflammatory cytokines is a major contributor in the occurrence and development of II/R‑induced acute lung injury (ALI). Therefore, the present study aimed to investigate whether blocking tumor necrosis factor‑α (TNF‑α) expression could protect the lungs from injury following II/R, and to explore the possible underlying mechanism involving interleukin‑10 (IL‑10). Briefly, II/R was induced in rats by 40 min occlusion of the superior mesenteric artery and celiac artery, followed by 8, 16 or 24 h of reperfusion. Subsequently, lentiviral vectors containing TNF‑α short hairpin (sh)RNA were injected into the right lung tissues, in order to induce TNF‑α knockdown. The severity of ALI was determined according to lung injury scores and lung edema (lung wet/dry weight ratio). The expression levels of TNF‑α were analyzed by quantitative polymerase chain reaction (qPCR), western blotting and immunofluorescence (IF) staining. IL‑10 expression, in response to TNF‑α knockdown, was detected in lung tissues by qPCR and IF. The results detected marked inflammatory responses, and increased levels of lung wet/dry weight ratio and TNF‑α expression, in the lungs of II/R rats. Conversely, treatment with TNF‑α shRNA significantly alleviated the severity of ALI and upregulated the expression levels of IL‑10 in lung tissues. These findings suggested that TNF‑α RNA interference may exert a protective effect on II/R‑induced ALI via the upregulation of IL‑10. Therefore, TNF‑α knockdown may be considered a potential strategy for the prevention or treatment of ALI induced by II/R in future clinical trials.
De novo mutations identified by exome sequencing implicate rare missense variants in SLC6A1 in schizophrenia.
Nature neuroscience, 2020

Schizophrenia is a highly polygenic disorder with important contributions from both common and rare risk alleles. We analyzed exome sequencing data for de novo variants (DNVs) in a new sample of 613 schizophrenia trios and combined this with published data to give a total of 3,444 trios. In this new data, loss-of-function (LoF) DNVs were significantly enriched among 3,471 LoF-intolerant genes, which supports previous findings. In the full dataset, genes associated with neurodevelopmental disorders (n = 159) were significantly enriched for LoF DNVs. Within these neurodevelopmental disorder genes, SLC6A1, which encodes a γ-aminobutyric acid transporter, was associated with missense-damaging DNVs. In 1,122 trios for which genome-wide common variant data were available, schizophrenia and bipolar disorder polygenic risk were significantly overtransmitted to probands. Probands carrying LoF or deletion DNVs in LoF-intolerant or neurodevelopmental disorder genes had significantly less overtransmission of schizophrenia polygenic risk than did non-carriers, which provides a second robust line of evidence that these DNVs increase liability to schizophrenia.
Discovery of ML326: The first sub-micromolar, selective M5 PAM.
Bioorganic & medicinal chemistry letters, 2013

This Letter describes the further chemical optimization of the M5 PAM MLPCN probes ML129 and ML172. A multi-dimensional iterative parallel synthesis effort quickly explored isatin replacements and a number of southern heterobiaryl variations with no improvement over ML129 and ML172. An HTS campaign identified several weak M5 PAMs (M5 EC50 >10μM) with a structurally related isatin core that possessed a southern phenethyl ether linkage. While SAR within the HTS series was very shallow and unable to be optimized, grafting the phenethyl ether linkage onto the ML129/ML172 cores led to the first sub-micromolar M5 PAM, ML326 (VU0467903), (human and rat M5 EC50s of 409nM and 500nM, respectively) with excellent mAChR selectivity (M1-M4 EC50s >30μM) and a robust 20-fold leftward shift of the ACh CRC.
Does early maternal responsiveness buffer prenatal tobacco exposure effects on young children's behavioral disinhibition?
Development and psychopathology, 2019

Children with prenatal tobacco exposure (PTE) exhibit early self-regulatory impairments, reflecting a life-course persistent propensity toward behavioral disinhibition. Previously, we demonstrated the protective role of parental responsiveness for reducing the risk of exposure-related disruptive behavior in adolescence. Here, we expanded this line of inquiry, examining whether responsiveness moderates the relation of PTE to a broader set of behavioral disinhibition features in early childhood and testing alternative diathesis-stress versus differential susceptibility explanatory models. PTE was assessed prospectively using interviews and bioassays in the Midwestern Infant Development Study (MIDS). Mother-child dyads (N = 276) were re-assessed at approximately 5 years of age in a preschool follow-up. We quantified maternal responsiveness and child behavioral disinhibition using a combination of directly observed activities in the lab and developmentally sensitive questionnaires. Results supported a diathesis-stress pattern. Children with PTE and less responsive mothers showed increased disruptive behavior and lower effortful control compared with children without PTE. In contrast, exposed children with more responsive mothers had self-regulatory profiles similar to their non-exposed peers. We did not observe sex differences. Findings provide greater specification of the protective role of maternal responsiveness for self-regulation in children with PTE and help clarify mechanisms that may underscore trajectories of exposure-related behavioral disinhibition.
Stability of facial emotion recognition performance in bipolar disorder.
Psychiatry research, 2016

The aim of this study was to assess the performance in emotional processing over time in a sample of euthymic patients with bipolar disorder (BD). Performance in the facial recognition of the six basic emotions (surprise, anger, sadness, happiness, disgust, and fear) did not change during a follow-up period of almost 7 years. These preliminary results suggest that performance in facial emotion recognition might be stable over time in BD.
Muscle coordination is habitual rather than optimal.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012

When sharing load among multiple muscles, humans appear to select an optimal pattern of activation that minimizes costs such as the effort or variability of movement. How the nervous system achieves this behavior, however, is unknown. Here we show that contrary to predictions from optimal control theory, habitual muscle activation patterns are surprisingly robust to changes in limb biomechanics. We first developed a method to simulate joint forces in real time from electromyographic recordings of the wrist muscles. When the model was altered to simulate the effects of paralyzing a muscle, the subjects simply increased the recruitment of all muscles to accomplish the task, rather than recruiting only the useful muscles. When the model was altered to make the force output of one muscle unusually noisy, the subjects again persisted in recruiting all muscles rather than eliminating the noisy one. Such habitual coordination patterns were also unaffected by real modifications of biomechanics produced by selectively damaging a muscle without affecting sensory feedback. Subjects naturally use different patterns of muscle contraction to produce the same forces in different pronation-supination postures, but when the simulation was based on a posture different from the actual posture, the recruitment patterns tended to agree with the actual rather than the simulated posture. The results appear inconsistent with computation of motor programs by an optimal controller in the brain. Rather, the brain may learn and recall command programs that result in muscle coordination patterns generated by lower sensorimotor circuitry that are functionally "good-enough."
Glutamate/glutamine metabolism coupling between astrocytes and glioma cells: neuroprotection and inhibition of glioma growth.
Biochemical and biophysical research communications, 2014

Glioma glutamate release has been shown to promote the growth of glioma cells and induce neuronal injuries from epilepsy to neuronal death. However, potential counteractions from normal astrocytes against glioma glutamate release have not been fully evaluated. In this study, we investigated the glutamate/glutamine cycling between glioma cells and astrocytes and their impact on neuronal function. Co-cultures of glioma cells with astrocytes (CGA) in direct contact were established under different mix ratio of astrocyte/glioma. Culture medium conditioned in these CGAs were sampled for HPLC measurement, for neuronal ratiometric calcium imaging, and for neuronal survival assay. We found: (1) High levels of glutaminase expression in glioma cells, but not in astrocytes, glutaminase enables glioma cells to release large amount of glutamate in the presence of glutamine. (2) Glutamate levels in CGAs were directly determined by the astrocyte/glioma ratios, indicating a balance between glioma glutamate release and astrocyte glutamate uptake. (3) Culture media from CGAs of higher glioma/astrocyte ratios induced stronger neuronal Ca(2+) response and more severe neuronal death. (4) Co-culturing with astrocytes significantly reduced the growth rate of glioma cells. These results indicate that normal astrocytes in the brain play pivotal roles in glioma growth inhibition and in reducing neuronal injuries from glioma glutamate release. However, as tumor growth, the protective role of astrocytes gradually succumb to glioma cells.
A theoretical account of cue averaging in the rodent head direction system.
Philosophical transactions of the Royal Society of London. Series B, Biological sciences, 2014

Head direction (HD) cell responses are thought to be derived from a combination of internal (or idiothetic) and external (or allothetic) sources of information. Recent work from the Jeffery laboratory shows that the relative influence of visual versus vestibular inputs upon the HD cell response depends on the disparity between these sources. In this paper, we present simulation results from a model designed to explain these observations. The model accurately replicates the Knight et al. data. We suggest that cue conflict resolution is critically dependent on plastic remapping of visual information onto the HD cell layer. This remap results in a shift in preferred directions of a subset of HD cells, which is then inherited by the rest of the cells during path integration. Thus, we demonstrate how, over a period of several minutes, a visual landmark may gain cue control. Furthermore, simulation results show that weaker visual landmarks fail to gain cue control as readily. We therefore suggest a second longer term plasticity in visual projections onto HD cell areas, through which landmarks with an inconsistent relationship to idiothetic information are made less salient, significantly hindering their ability to gain cue control. Our results provide a mechanism for reliability-weighted cue averaging that may pertain to other neural systems in addition to the HD system.
Teaching the cerebellum about reward.
Nature neuroscience, 2019

Selecting the most rewarding action and performing it accurately are two separable brain functions that are thought to rely upon different neural systems. New evidence suggests that the cerebellum could learn to do both.
Insular function in autism: Update and future directions in neuroimaging and interventions.
Progress in neuro-psychopharmacology & biological psychiatry, 2019

The insular cortex, hidden within the lateral sulcus of the human brain, participates in a range of cognitive, affective, and sensory functions. Autism spectrum disorder (ASD), a neurodevelopmental condition affecting all of these functional domains, has increasingly been linked with atypical activation and connectivity of the insular cortices. Here we review the latest research linking atypical insular function to a range of behaviors characteristic of ASD, with an emphasis on neuroimaging findings in the domains of social cognition and executive function. We summarize some of the recent work linking the insula to interventions in autism, including oxytocin-based pharmacological treatments and music therapy. We suggest that future directions likely to yield significant insights into insular pathology in ASD include the analysis of the dynamics of this brain region. We also conclude that more basic research is necessary on the use of oxytocin pharmacotherapy, and larger studies addressing participant heterogeneity are needed on the use of music therapy in ASD. Long-term studies are needed to ascertain sustained effects of these interventions.