rudyvdbrink/CitationDatabase huggingface dataset:
Lower-frequency event-related desynchronization: a signature of late mismatch responses to sounds, which is reduced or absent in children with specific language impairment.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2010

Poor discrimination of nonlinguistic sounds has been implicated in language-learning problems in children, but research evidence has been inconsistent. This study included 32 participants with specific language impairment (SLI) and 32 typically developing controls aged 7-16 years. Frequency discrimination thresholds were estimated in a task where participants had to distinguish a higher-frequency tone from a 1000 Hz tone. Neurophysiological responses were assessed in an oddball paradigm. Stimuli were either 1030 or 1200 Hz pure tones (deviants) presented in a series of standard 1000 Hz tones, or syllables (deviant [da] or [bi] in a series of standard /ba/). On the behavioral task, children (7- to 11-year-olds) had high thresholds, regardless of language status, but teenagers (12-16 years) with SLI had higher thresholds than their controls. Conventional analysis of electrophysiological responses showed no difference between groups for the mismatch negativity (MMN), but the late discriminative negativity (LDN) was reduced in amplitude for smaller deviants in participants with SLI. Time-frequency analysis revealed that, whereas the MMN reflected enhanced intertrial coherence in the theta frequency band, the LDN corresponded to a period of event-related desynchronization extending across a wide low-frequency band including delta, theta, and alpha. This manifested as a drop in power in those frequencies, which was marked in the controls but reduced or absent in children with SLI across all stimulus types. This provides compelling evidence for a low-level auditory perceptual impairment in SLI that affects a processing stage after initial detection of a sound change.
Aspirin prevents colorectal cancer metastasis in mice by splitting the crosstalk between platelets and tumor cells.
Oncotarget, 2016

We investigated whether platelets prime colon cancer cells for metastasis and whether pharmacological inhibition of platelet function may prevent it. Coculturing HT29 human colon carcinoma cells with human platelets led to the induction of mesenchymal-like cancer cells characterized by downregulation of E-cadherin and upregulation of Twist1, enhanced cell mobility and a proaggregatory action on platelets. These changes were prevented by different antiplatelet agents, aspirin[an inhibitor of cyclooxygenase(COX)-1], DG-041[an antagonist of prostaglandin(PG)E2 EP3 receptor] and ticagrelor (a P2Y12 receptor antagonist). The injection of HT29 cells, exposed to platelets in vitro, into the tail vein of humanized immunodeficient mice led to higher incidence of lung metastasis compared to the injection of untreated HT29 cells. This effect was associated with enhanced systemic biosynthesis of thromboxane(TX)A2 and PGE2in vivo. Platelet COX-1 inhibition by aspirin administration to mice prevented the increased rate of metastasis as well as the enhanced production of TXA2 and PGE2 induced by the in vitro priming of HT29 cells by platelets. In conclusion, targeting platelet COX-1 with low-dose aspirin exerts an antimetastatic action by averting the stem cell mimicry of cancer cells associated with enhanced proaggregatory effects induced by platelet-tumor cell interactions. These effects may be shared by other antiplatelet drugs.
Additive neuroprotection by metabotropic glutamate receptor subtype-selective ligands in a rat Parkinson's model.
Neuroreport, 2008

Pharmacological activation of group III metabotropic glutamate receptors (mGluR) or inhibition of group I mGluR by subtype-selective ligands is neuroprotective in experimental models of Parkinson's disease. The aim of this study was to investigate whether targeting both receptor subtypes simultaneously produces enhanced neuroprotection. Rodents bearing a 6-hydroxydopamine lesion were intranigrally administered either the group III mGluR agonist L-(+)-2-amino-4-phosphonobutyric acid or the group I mGluR antagonist 2-methyl-6-(phenylethynyl)pyridine, alone or in combination. Coadministration of L-(+)-2-amino-4-phosphonobutyric acid and 2-methyl-6-(phenylethynyl)pyridine resulted in robust nigrostriatal neuroprotection that was significantly increased compared with either compound alone. These data suggest that targeting multiple mGluR subtypes with low doses of selective ligands may provide an enhanced therapeutic response in experimental models of Parkinson's disease.
Validated multi-step approach for in vivo recording and analysis of optogenetically evoked glutamate in the mouse globus pallidus.
Journal of neurochemistry, 2018

Precise quantification of extracellular glutamate concentrations upon neuronal activation is crucial for the understanding of brain function and neurological disorders. While optogenetics is an outstanding method for the correlation between distinct neurons and their role in circuitry and behavior, the electrochemically inactive nature of glutamate has proven challenging for recording upon optogenetic stimulations. This difficulty is due to the necessity for using enzyme-coated microelectrodes and the risk for light-induced artifacts. In this study, we establish a method for the combination of in vivo optogenetic stimulation with selective measurement of glutamate concentrations using enzyme-coated multielectrode arrays and amperometry. The glutamatergic subthalamic nucleus (STN), which is the main electrode target site in deep brain stimulation treatment of advanced Parkinson's disease, has recently proven opotogenetically targetable in Pitx2-Cre-transgenic mice and was here used as model system. Upon stereotactic injection of viral Channelrhodopsin2-eYFP constructs into the STN, amperometric recordings were performed at a range of optogenetic stimulation frequencies in the globus pallidus, the main STN target area, in anesthetized mice. Accurate quantification was enabled through a multi-step analysis approach based on self-referencing microelectrodes and repetition of the experimental protocol at two holding potentials, which allowed for the identification, isolation and removal of photoelectric and photoelectrochemical artifacts. This study advances the field of in vivo glutamate detection with combined optogenetics and amperometric recordings by providing a validated analysis framework for application in a wide variety of glutamate-based approaches in neuroscience.
Amplification of potential thermogenetic mechanisms in cetacean brains compared to artiodactyl brains.
Scientific reports, 2021

To elucidate factors underlying the evolution of large brains in cetaceans, we examined 16 brains from 14 cetartiodactyl species, with immunohistochemical techniques, for evidence of non-shivering thermogenesis. We show that, in comparison to the 11 artiodactyl brains studied (from 11 species), the 5 cetacean brains (from 3 species), exhibit an expanded expression of uncoupling protein 1 (UCP1, UCPs being mitochondrial inner membrane proteins that dissipate the proton gradient to generate heat) in cortical neurons, immunolocalization of UCP4 within a substantial proportion of glia throughout the brain, and an increased density of noradrenergic axonal boutons (noradrenaline functioning to control concentrations of and activate UCPs). Thus, cetacean brains studied possess multiple characteristics indicative of intensified thermogenetic functionality that can be related to their current and historical obligatory aquatic niche. These findings necessitate reassessment of our concepts regarding the reasons for large brain evolution and associated functional capacities in cetaceans.
Initial Experience of the Levodopa-Entacapone-Carbidopa Intestinal Gel in Clinical Practice.
Journal of personalized medicine, 2021

Patients in fluctuating stages of Parkinson's disease (PD) require device-aided treatments. Continuous infusion of levodopa-carbidopa intestinal gel (LCIG) is a well-proven option in clinical practice. We now report the first clinical experience of levodopa-entacapone-carbidopa intestinal gel (LECIG) therapy. An observational study of the first patients to start LECIG in our clinic was performed. Twenty-four patients (11 females, 13 males) were included. The median age was 71.5 years, and the median duration since PD diagnosis was 15.5 years. The median treatment duration was 305 days. Median doses were: 6.0 mL as morning dose, 2.5 mL/h as infusion rate, and 1.0 mL as extra dose. Half of the patients were switched directly from LCIG. These patients express improvements in the size and weight of the pump. Furthermore, most of them considered the new pump to be improved regarding user-friendliness. Six patients discontinued LECIG, three due to diarrhea, one due to hallucinations and two deceased (one cardiac arrest and one COVID-19). LECIG has shown to be possible to use in patients with PD, efficacy and safety as expected. Patients are generally happy with the size and usability of the pump, but some technical improvements of the software are warranted, as well as larger, prospective studies.
Direct current stimulation modulates the excitability of the sensory and motor fibres in the human posterior tibial nerve, with a long-lasting effect on the H-reflex.
The European journal of neuroscience, 2017

Several studies demonstrated that transcutaneous direct current stimulation (DCS) may modulate central nervous system excitability. However, much less is known about how DC affects peripheral nerve fibres. We investigated the action of DCS on motor and sensory fibres of the human posterior tibial nerve, with supplementary analysis in acute experiments on rats. In forty human subjects, electric pulses at the popliteal fossa were used to elicit either M-waves or H-reflexes in the Soleus, before (15 min), during (10 min) and after (30 min) DCS. Cathodal or anodal current (2 mA) was applied to the same nerve. Cathodal DCS significantly increased the H-reflex amplitude; the post-polarization effect lasted up to ~ 25 min after the termination of DCS. Anodal DCS instead significantly decreased the reflex amplitude for up to ~ 5 min after DCS end. DCS effects on M-wave showed the same polarity dependence but with considerably shorter after-effects, which never exceeded 5 min. DCS changed the excitability of both motor and sensory fibres. These effects and especially the long-lasting modulation of the H-reflex suggest a possible rehabilitative application of DCS that could be applied either to compensate an altered peripheral excitability or to modulate the afferent transmission to spinal and supraspinal structures. In animal experiments, DCS was applied, under anaesthesia, to either the exposed peroneus nerve or its Dorsal Root, and its effects closely resembled those found in human subjects. They validate therefore the use of the animal models for future investigations on the DCS mechanisms.
Influence of childhood trauma on the treatment outcomes of pharmacological and/or psychological interventions for adolescents and adults with bipolar disorder: protocol for a systematic review and meta-analysis.
BMJ open, 2021

Despite available pharmacological and psychological treatments, remission rates for bipolar disorder remain relatively low. Current research implicates the experience of childhood trauma as a potential moderator of poor treatment outcomes among individuals with bipolar disorder. To date, the evidence reporting the influence of childhood trauma on the treatment outcomes of pharmacological and/or psychological interventions for adolescents and adults with bipolar disorder has not been systematically reviewed.
Evaluating Cerebrovascular Reactivity during the Early Symptomatic Phase of Sport Concussion.
Journal of neurotrauma, 2019

Cerebrovascular reactivity (CVR) indexes the ability of blood vessels to respond to vasoactive stimuli and may be a sensitive biomarker of concussion. However, alterations in whole-brain CVR remain poorly understood during the early symptomatic phase of injury. In this study, CVR was assessed using blood-oxygenation-level dependent functional magnetic resonance imaging (BOLD fMRI) combined with a respiratory challenge paradigm; resting cerebral blood flow (CBF) was also evaluated using arterial spin labeling (ASL). Imaging data were collected for 77 university-level athletes, including 56 athletic uninjured controls and 21 concussed athletes scanned in the early symptomatic phase of injury (≤7 days post-injury). The normal response to respiratory challenge was assessed in the athletic control group, in which a robust whole-brain response was observed. The concussed athletes were then compared to a matched subset of controls. Concussion was associated with greater reductions in BOLD activity during the early phase of the respiratory task, localized primarily in frontal and pre-frontal areas, whereas no significant effects on resting global CBF were observed. In addition, greater symptom severity was associated with greater reductions in BOLD response, with effects distributed throughout the brain. This study establishes fMRI with respiratory challenge as a robust method for assessing acute concussion-related alterations in CVR. Moreover, it highlights the importance of examining neurovascular response to physiological stressors after a concussion.
Creatine supports propagation and promotes neuronal differentiation of inner ear progenitor cells.
Neuroreport, 2014

Long-term propagation of inner ear-derived progenitor/stem cells beyond the third generation and differentiation into inner ear cell types has been shown to be feasible, but challenging. We investigated whether the known neuroprotective guanidine compound creatine (Cr) promotes propagation of inner ear progenitor/stem cells as mitogen-expanded neurosphere cultures judged from the formation of spheres over passages. In addition, we studied whether Cr alone or in combination with brain-derived neurotrophic factor (BDNF) promotes neuronal differentiation of inner ear progenitors. For this purpose, early postnatal rat spiral ganglia, utricle, and organ of Corti-derived progenitors were grown as floating spheres in the absence (controls) or presence of Cr (5 mM) from passage 3 onward. Similarly, dissociated sphere-derived cultures were differentiated for 14 days in the presence or absence of Cr (5 mM) and spiral ganglia sphere-derived cultures in a combination of Cr with the neurotrophin BDNF (50 ng/ml). We found that the cumulative total number of spheres over all passages was significantly higher after Cr supplementation as compared with controls in all the three inner ear cultures. In contrast, sphere sizes were not affected by the administration of Cr. Administration of Cr during differentiation of spiral ganglia cells resulted in a significantly higher density of β-III-tubulin-positive cells compared with controls, whereas densities of myosin VIIa-positive cells in cultures of utricle and organ of Corti were not affected by the treatment. Importantly, a combination of Cr with the neurotrophin BDNF resulted in further significantly increased densities of β-III-tubulin-positive cells in cultures of spiral ganglia cells as compared with single treatments. In sum, Cr promoted continuing propagation of rat inner ear-derived progenitor cells and supported specifically in combination with BDNF the differentiation of neuronal cell types from spiral ganglion-derived spheres.
Extended-amygdala intrinsic functional connectivity networks: A population study.
Human brain mapping, 2021

Pre-clinical and human neuroimaging research implicates the extended-amygdala (ExtA) (including the bed nucleus of the stria terminalis [BST] and central nucleus of the amygdala [CeA]) in networks mediating negative emotional states associated with stress and substance-use behaviours. The extent to which individual ExtA structures form a functionally integrated unit is controversial. We utilised a large sample (n > 1,000 healthy young adult humans) to compare the intrinsic functional connectivity networks (ICNs) of the BST and CeA using task-free functional magnetic resonance imaging (fMRI) data from the Human Connectome Project. We assessed whether inter-individual differences within these ICNs were related to two principal components representing negative disposition and alcohol use. Building on recent primate evidence, we tested whether within BST-CeA intrinsic functional connectivity (iFC) was heritable and further examined co-heritability with our principal components. We demonstrate the BST and CeA to have discrete, but largely overlapping ICNs similar to previous findings. We found no evidence that within BST-CeA iFC was heritable; however, post hoc analyses found significant BST iFC heritability with the broader superficial and centromedial amygdala regions. There were no significant correlations or co-heritability associations with our principal components either across the ICNs or for specific BST-Amygdala iFC. Possible differences in phenotype associations across task-free, task-based, and clinical fMRI are discussed, along with suggestions for more causal investigative paradigms that make use of the now well-established ExtA ICNs.
Biophysical mechanisms underlying the membrane trafficking of synaptic adhesion molecules.
Neuropharmacology, 2020

Adhesion proteins play crucial roles at synapses, not only by providing a physical trans-synaptic linkage between axonal and dendritic membranes, but also by connecting to functional elements including the pre-synaptic neurotransmitter release machinery and post-synaptic receptors. To mediate these functions, adhesion proteins must be organized on the neuronal surface in a precise and controlled manner. Recent studies have started to describe the mobility, nanoscale organization, and turnover rate of key synaptic adhesion molecules including cadherins, neurexins, neuroligins, SynCAMs, and LRRTMs, and show that some of these proteins are highly mobile in the plasma membrane while others are confined at sub-synaptic compartments, providing evidence for different regulatory pathways. In this review article, we provide a biophysical view of the diffusional trapping of adhesion molecules at synapses, involving both extracellular and intracellular protein interactions. We review the methodology underlying these measurements, including biomimetic systems with purified adhesion proteins, means to perturb protein expression or function, single molecule imaging in cultured neurons, and analytical models to interpret the data. This article is part of the special issue entitled 'Mobility and trafficking of neuronal membrane proteins'.
Actin filaments partition primary cilia membranes into distinct fluid corrals.
The Journal of cell biology, 2018

Physical properties of primary cilia membranes in living cells were examined using two independent, high-spatiotemporal-resolution approaches: fast tracking of single quantum dot-labeled G protein-coupled receptors and a novel two-photon super-resolution fluorescence recovery after photobleaching of protein ensemble. Both approaches demonstrated the cilium membrane to be partitioned into corralled domains spanning 274 ± 20 nm, within which the receptors are transiently confined for 0.71 ± 0.09 s. The mean membrane diffusion coefficient within the corrals,
Hippocampal memory traces are differentially modulated by experience, time, and adult neurogenesis.
Neuron, 2014

Memory traces are believed to be ensembles of cells used to store memories. To visualize memory traces, we created a transgenic line that allows for the comparison between cells activated during encoding and expression of a memory. Mice re-exposed to a fear-inducing context froze more and had a greater percentage of reactivated cells in the dentate gyrus (DG) and CA3 than mice exposed to a novel context. Over time, these differences disappeared, in keeping with the observation that memories become generalized. Optogenetically silencing DG or CA3 cells that were recruited during encoding of a fear-inducing context prevented expression of the corresponding memory. Mice with reduced neurogenesis displayed less contextual memory and less reactivation in CA3 but, surprisingly, normal reactivation in the DG. These studies suggest that distinct memory traces are located in the DG and in CA3 but that the strength of the memory is related to reactivation in CA3.
Tlx3 controls cholinergic transmitter and Peptide phenotypes in a subset of prenatal sympathetic neurons.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013

The embryonic sympathetic nervous system consists of predominantly noradrenergic neurons and a very small population of cholinergic neurons. Postnatal development further allows target-dependent switch of a subset of noradrenergic neurons into cholinergic phenotype. How embryonic cholinergic neurons are specified at the prenatal stages remains largely unknown. In this study, we found that the expression of transcription factor Tlx3 was progressively restricted to a small population of embryonic sympathetic neurons in mice. Immunostaining for vesicular acetylcholine transporter (VAChT) showed that Tlx3 was highly expressed in cholinergic neurons at the late embryonic stage E18.5. Deletion of Tlx3 resulted in the loss of Vacht expression at E18.5 but not E12.5. By contrast, Tlx3 was required for expression of the cholinergic peptide vasoactive intestinal polypeptide (VIP), and somatostatin (SOM) at both E12.5 and E18.5. Furthermore, we found that, at E18.5 these putative cholinergic neurons expressed glial cell line-derived neurotrophic factor family coreceptor Ret but not tyrosine hydroxylase (Ret(+)/TH(-)). Deletion of Tlx3 also resulted in disappearance of high-level Ret expression. Last, unlike Tlx3, Ret was required for the expression of VIP and SOM at E18.5 but not E12.5. Together, these results indicate that transcription factor Tlx3 is required for the acquisition of cholinergic phenotype at the late embryonic stage as well as the expression and maintenance of cholinergic peptides VIP and SOM throughout prenatal development of mouse sympathetic neurons.
Comprehension of computer code relies primarily on domain-general executive brain regions.
eLife, 2020

Computer programming is a novel cognitive tool that has transformed modern society. What cognitive and neural mechanisms support this skill? Here, we used functional magnetic resonance imaging to investigate two candidate brain systems: the multiple demand (MD) system, typically recruited during math, logic, problem solving, and executive tasks, and the language system, typically recruited during linguistic processing. We examined MD and language system responses to code written in Python, a text-based programming language (Experiment 1) and in ScratchJr, a graphical programming language (Experiment 2); for both, we contrasted responses to code problems with responses to content-matched sentence problems. We found that the MD system exhibited strong bilateral responses to code in both experiments, whereas the language system responded strongly to sentence problems, but weakly or not at all to code problems. Thus, the MD system supports the use of novel cognitive tools even when the input is structurally similar to natural language.