rudyvdbrink/CitationDatabase huggingface dataset:
Do subitizing deficits in developmental dyscalculia involve pattern recognition weakness?
Developmental science, 2013

The abilities of children diagnosed with developmental dyscalculia (DD) were examined in two types of object enumeration: subitizing, and small estimation (5-9 dots). Subitizing is usually defined as a fast and accurate assessment of a number of small dots (range 1 to 4 dots), and estimation is an imprecise process to assess a large number of items (range 5 dots or more). Based on reaction time (RT) and accuracy analysis, our results indicated a deficit in the subitizing and small estimation range among DD participants in relation to controls. There are indications that subitizing is based on pattern recognition, thus presenting dots in a canonical shape in the estimation range should result in a subitizing-like pattern. In line with this theory, our control group presented a subitizing-like pattern in the small estimation range for canonically arranged dots, whereas the DD participants presented a deficit in the estimation of canonically arranged dots. The present finding indicates that pattern recognition difficulties may play a significant role in both subitizing and subitizing deficits among those with DD.
Hand and Arm Bimanual Intensive Therapy Including Lower Extremity (HABIT-ILE) in Children With Unilateral Spastic Cerebral Palsy: A Randomized Trial.
Neurorehabilitation and neural repair, 2015

Intensive bimanual training results in more improvement in hand function in children with unilateral spastic cerebral palsy (USCP) than lower intensity conventional interventions. However, it is not known whether combined upper and lower extremity training in an intensive protocol is more efficacious for upper and lower functional abilities than conventional therapies provided in usual customary care.
Comparison of nanofiltration efficacy in reducing infectivity of centrifuged versus ultracentrifuged 263K scrapie-infected brain homogenates in "spiked" albumin solutions.
Transfusion, 2012

The safety of plasma-derived products is of concern for possible transmission of variant Creutzfeldt-Jakob disease. The absence of validated screening tests requires the use of procedures to remove or inactivate prions during the manufacture of plasma-derived products to minimize the risk of transmission. These procedures need proper validation studies based on spiking human plasma or intermediate fractions of plasma fractionation with prions in a form as close as possible to that present in blood.
Relationship between whole blood omega-3 fatty acid levels and dorsal cingulate gray matter volume: Sex differences and implications for impulse control.
Nutritional neuroscience, 2020

During adolescence, the prefrontal cortex (PFC) undergoes substantial structural development, including cortical thinning, a process associated with improvements in behavioral control. The cingulate cortex is among the regions recruited in response inhibition and mounting evidence suggests cingulate function may be sensitive to availability of an essential dietary nutrient, omega-3 fatty acids (N3; i.e. EPA + DHA). Our primary aim was to investigate the relationship between a biomarker of omega-3 fatty acids -- percent of whole blood fatty acids as EPA + DHA (N3 Index) -- and cingulate morphology, in typically developing adolescent males (
Repetitive magnetic stimulation induces plasticity of excitatory postsynapses on proximal dendrites of cultured mouse CA1 pyramidal neurons.
Brain structure & function, 2015

Repetitive transcranial magnetic stimulation (rTMS) of the human brain can lead to long-lasting changes in cortical excitability. However, the cellular and molecular mechanisms which underlie rTMS-induced plasticity remain incompletely understood. Here, we used repetitive magnetic stimulation (rMS) of mouse entorhino-hippocampal slice cultures to study rMS-induced plasticity of excitatory postsynapses. By employing whole-cell patch-clamp recordings of CA1 pyramidal neurons, local electrical stimulations, immunostainings for the glutamate receptor subunit GluA1 and compartmental modeling, we found evidence for a preferential potentiation of excitatory synapses on proximal dendrites of CA1 neurons (2-4 h after stimulation). This rMS-induced synaptic potentiation required the activation of voltage-gated sodium channels, L-type voltage-gated calcium channels and N-methyl-D-aspartate-receptors. In view of these findings we propose a cellular model for the preferential strengthening of excitatory synapses on proximal dendrites following rMS in vitro, which is based on a cooperative effect of synaptic glutamatergic transmission and postsynaptic depolarization.
DNA-methylation of the dopamin receptor 2 gene is altered during alcohol withdrawal.
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 2019

The dopaminergic neurotransmission is known to be of crucial importance in addictive behavior. Epigenetic regulation like methylation of DNA influences the function of dopaminergic transmission. The present study investigated alterations of DNA methylation in the dopamine D2 receptor (DRD2)-gene in patients suffering from alcohol dependence. The study sample consists of 99 alcohol dependent males admitted for alcohol withdrawal treatment and a control group of 33 healthy participants. Blood samples underwent bisulfite sequencing to determine levels of DNA-methylation of the promoter region of the DRD2 gene. Mixed linear modeling was used to test differences between patients and controls, course of methylation during detoxification. While DRD2-gene methylation did not differ significantly between patients and controls, we found a significant increase of DRD2-gene methylation during alcohol withdrawal/early abstinence. Craving, measured with the Obsessive Compulsive Drinking Scale (OCDS), was significantly associated with DRD2-gene methylation. Furthermore, smoking significantly influenced DRD2-gene methylation in both, patients and controls. As in other types of addictive disorders, DRD2-gene methylation is altered during alcohol withdrawal/early abstinence. The findings regarding an association with alcohol craving and tobacco consumption point towards a crucial role of DRD2-gene methylation in the neurobiology of addictive behavior.
Sex differences in stress-induced visceral hypersensitivity following early life adversity: a two hit model.
Neurogastroenterology and motility, 2016

Early life adversity (ELA) has been indicated as a risk factor for the development of stress axis dysfunction in adulthood, specifically in females. We previously showed that unpredictable ELA induces visceral hyperalgesia in adult female rats. It remains to be determined whether ELA alters visceral nociceptive responses to stress in adulthood. The current study tested the hypothesis that following ELA, exposure to an adulthood stressor, or second hit, serves as a risk factor for exaggerated stress-induced visceral hypersensitivity that is sex-specific.
GLUT 1 receptor expression and circulating levels of fasting glucose in high grade serous ovarian cancer.
Journal of cellular physiology, 2018

In recent years, the poorly remarkable goals achieved in terms of patients' important outcomes for ovarian cancer have fueled our interest toward the study of its metabolic roots. Within this research pipeline, we assessed the association between the expression of the glucose transporter GLUT1, as expressed at the tumor tissue level, and circulating pre-surgical levels of fasting glucose in a case series including data from 40 patients with high FIGO stage serous ovarian cancer. Patients who provided data to the current analysis were randomly selected from a larger cohort. To our purposes, the procedures related to serum and tissue collection, storage and biomarker assessment were highly standardized and centralized at the institutional laboratories. The GLUT1 antibody SPM498 SPRING (REF. E13810) was used at a 1:500 dilution in 2 µm slides. Staining for GLUT1 was observed at the cell membrane level in all the cases assessed, but strong staining was described in 29 (72.5%) of them. The agreement between the two independent reviewers was 100%. Strong GLUT1 staining was inversely associated with circulating levels of fasting glucose, with a particularly striking difference for patients in the lowest fasting glucose tertile (p = 0.044). These results support the biological plausibility of the association of interest. If confirmed in larger studies, our findings may help clarify the potentials of biomarkers related to energy metabolism in terms of prognosis definition, treatment assignment, and outcome interpretation for patients with high FIGO stage serous ovarian cancer.
Critical role of CA1 muscarinic receptors on memory acquisition deficit induced by total (TSD) and REM sleep deprivation (RSD).
Progress in neuro-psychopharmacology & biological psychiatry, 2017

Despite different theories regarding sleep physiological function, an overall census indicates that sleep is useful for neural plasticity which eventually strengthens cognition and brain performance. Different studies show that sleep deprivation (SD) leads to impaired learning and hippocampus dependent memory. According to some studies, cholinergic system plays an important role in sleep (particularly REM sleep), learning, memory, and its retrieval. So this study has been designed to investigate the effect of CA1 Cholinergic Muscarinic Receptors on memory acquisition deficit induced by total sleep deprivation (TSD) and REM sleep deprivation (RSD).
Notch1 deficiency decreases hepatic lipid accumulation by induction of fatty acid oxidation.
Scientific reports, 2016

Notch signaling pathways modulate various cellular processes, including cell proliferation, differentiation, adhesion, and communication. Recent studies have demonstrated that Notch1 signaling also regulates hepatic glucose production and lipid synthesis. However, the effect of Notch1 signaling on hepatic lipid oxidation has not yet been directly investigated. To define the function of Notch1 signaling in hepatic lipid metabolism, wild type mice and Notch1 deficient antisense transgenic (NAS) mice were fed a high-fat diet. High-fat diet -fed NAS mice exhibited a marked reduction in hepatic triacylglycerol accumulation compared with wild type obese mice. The improved fatty liver was associated with an increased expression of hepatic genes involved in fatty acid oxidation. However, lipogenic genes were not differentially expressed in the NAS liver, suggesting lipolytic-specific regulatory effects by Notch1 signaling. Expression of fatty acid oxidative genes and the rate of fatty acid oxidation were also increased by inhibition of Notch1 signaling in HepG2 cells. In addition, similar regulatory effects on lipid accumulation were observed in adipocytes. Taken together, these data show that inhibition of Notch1 signaling can regulate the expression of fatty acid oxidation genes and may provide therapeutic strategies in obesity-induced hepatic steatosis.
Miniature Untethered EEG Recorder Improves Advanced Neuroscience Methodologies.
IEEE transactions on biomedical circuits and systems, 2019

Rodent electroencephalography (EEG) in preclinical research is frequently conducted in behaving animals. However, the difficulty inherent in identifying EEG epochs associated with a particular behavior or cue is a significant obstacle to more efficient analysis. In this paper we highlight a new solution, using infrared event stamping to accurately synchronize EEG, recorded from superficial sites above the hippocampus and prefrontal cortex, with video motion tracking data in a transgenic Alzheimer's disease (AD) mouse model. Epochs capturing specific behaviors were automatically identified and extracted prior to further analysis. This was achieved by the novel design of an ultra-miniature wearable EEG recorder, the NAT-1 device, and its in-situ IR recording module. The device is described in detail, and its contribution to enabling new neuroscience is demonstrated.
Bridging the gap: a reticulo-propriospinal detour bypassing an incomplete spinal cord injury.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014

Anatomically incomplete spinal cord injuries are often followed by considerable functional recovery in patients and animal models, largely because of processes of neuronal plasticity. In contrast to the corticospinal system, where sprouting of fibers and rearrangements of circuits in response to lesions have been well studied, structural adaptations within descending brainstem pathways and intraspinal networks are poorly investigated, despite the recognized physiological significance of these systems across species. In the present study, spontaneous neuroanatomical plasticity of severed bulbospinal systems and propriospinal neurons was investigated following unilateral C4 spinal hemisection in adult rats. Injection of retrograde tracer into the ipsilesional segments C3-C4 revealed a specific increase in the projection from the ipsilesional gigantocellular reticular nucleus in response to the injury. Substantial regenerative fiber sprouting of reticulospinal axons above the injury site was demonstrated by anterograde tracing. Regrowing reticulospinal fibers exhibited excitatory, vGLUT2-positive varicosities, indicating their synaptic integration into spinal networks. Reticulospinal fibers formed close appositions onto descending, double-midline crossing C3-C4 propriospinal neurons, which crossed the lesion site in the intact half of the spinal cord and recrossed to the denervated cervical hemicord below the injury. These propriospinal projections around the lesion were significantly enhanced after injury. Our results suggest that severed reticulospinal fibers, which are part of the phylogenetically oldest motor command system, spontaneously arborize and form contacts onto a plastic propriospinal relay, thereby bypassing the lesion. These rearrangements were accompanied by substantial locomotor recovery, implying a potential physiological relevance of the detour in restoration of motor function after spinal injury.
Efficiency of structural connectivity networks relates to intrinsic motivation in children born extremely preterm.
Brain imaging and behavior, 2019

Intrinsic motivation is essential for academic success and cognitive growth, but limited work has examined the neuroanatomical underpinnings of intrinsic motivation from a network perspective, particularly in early childhood. Using graph theoretical analysis, this study investigated global and local properties of structural connectivity networks in relation to intrinsic motivation within a vulnerable group of children at early school age. Fifty-three 7 year-old children born extremely preterm (<28 weeks' gestational age)/extremely low birth weight (<1000 g) underwent T1 and diffusion weighted imaging. Structural connectivity networks were generated using 162 cortical and subcortical nodes, and edges were created using constrained spherical deconvolution-based tractography. Global and node-specific network measures were analyzed in association with self-reported aspects of intrinsic motivation for school learning (Mastery, Challenge and Curiosity) using linear regression. Results indicated that increased information transfer across the network was associated with greater Mastery, while increased clustering and small-world topology related to greater Challenge. Increased efficiency and connection strength of the striatum in particular, related to greater intrinsic motivation. These findings suggest that both integrated and segregated network communication support aspects of intrinsic motivation in childhood, and shed new light on structural network properties important for intrinsic motivation orientations in extremely preterm children at early school age.
Glucocorticoid-mediated induction of caveolin-1 disrupts cytoskeletal organization, inhibits cell migration and re-epithelialization of non-healing wounds.
Communications biology, 2021

Although impaired keratinocyte migration is a recognized hallmark of chronic wounds, the molecular mechanisms underpinning impaired cell movement are poorly understood. Here, we demonstrate that both diabetic foot ulcers (DFUs) and venous leg ulcers (VLUs) exhibit global deregulation of cytoskeletal organization in genomic comparison to normal skin and acute wounds. Interestingly, we found that DFUs and VLUs exhibited downregulation of ArhGAP35, which serves both as an inactivator of RhoA and as a glucocorticoid repressor. Since chronic wounds exhibit elevated levels of cortisol and caveolin-1 (Cav1), we posited that observed elevation of Cav1 expression may contribute to impaired actin-cytoskeletal signaling, manifesting in aberrant keratinocyte migration. We showed that Cav1 indeed antagonizes ArhGAP35, resulting in increased activation of RhoA and diminished activation of Cdc42, which can be rescued by Cav1 disruption. Furthermore, we demonstrate that both inducible keratinocyte specific Cav1 knockout mice, and MβCD treated diabetic mice, exhibit accelerated wound closure. Taken together, our findings provide a previously unreported mechanism by which Cav1-mediated cytoskeletal organization prevents wound closure in patients with chronic wounds.
A Bayesian perspective on magnitude estimation.
Trends in cognitive sciences, 2015

Our representation of the physical world requires judgments of magnitudes, such as loudness, distance, or time. Interestingly, magnitude estimates are often not veridical but subject to characteristic biases. These biases are strikingly similar across different sensory modalities, suggesting common processing mechanisms that are shared by different sensory systems. However, the search for universal neurobiological principles of magnitude judgments requires guidance by formal theories. Here, we discuss a unifying Bayesian framework for understanding biases in magnitude estimation. This Bayesian perspective enables a re-interpretation of a range of established psychophysical findings, reconciles seemingly incompatible classical views on magnitude estimation, and can guide future investigations of magnitude estimation and its neurobiological mechanisms in health and in psychiatric diseases, such as schizophrenia.
A commentary on the "eating addiction" versus "food addiction" perspectives on addictive-like food consumption.
Appetite, 2017

The food addiction construct posits that vulnerable individuals may experience an addictive-like response to certain foods, such as those high in fat and refined carbohydrates. Recently, an alternative model to food addiction was proposed, suggesting that the act of eating may be a behavioral addiction that can trigger an addictive-like response in susceptible individuals. One major rationale for the eating addiction framework is that the assessment of food addiction is based on behavioral indicators, such as consuming greater quantities of food than intended and eating certain foods despite negative consequences. It is also suggested that the lack of investigation into which foods and food attributes (e.g., sugar) may have an addictive potential is evidence that food addiction does not parallel a substance-based addiction and more closely resembles a behavioral addiction. The present paper provides a commentary suggesting that the substance-based, food-addiction framework is more appropriate than the behavioral-addiction, eating-addiction perspective to conceptualize addictive-like food consumption. In order to illustrate this point, this manuscript will discuss behavioral components characteristic of all substance-use disorders, preliminary evidence to suggest that all foods are not equally associated with addictive-like eating, and key differences between the hypothesized eating addiction phenotype and the only existing behavioral addiction in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), gambling disorder. Further, this paper will consider implications of applying an addiction label to food versus eating and suggest future research directions to evaluate whether food addiction is a valid and clinically useful construct.
Cytoarchitectonically-driven MRI atlas of nonhuman primate hippocampus: Preservation of subfield volumes in aging.
Hippocampus, 2019

Identification of primate hippocampal subfields in vivo using structural MRI imaging relies on variable anatomical guidelines, signal intensity differences, and heuristics to differentiate between regions (Yushkevich et al., 2015a). Thus, a clear anatomically-driven basis for subfield demarcation is lacking. Recent work, however, has begun to develop methods to use ex vivo histology or ex vivo MRI (Adler et al., 2014; Iglesias et al., 2015) that have the potential to inform subfield demarcations of in vivo images. For optimal results, however, ex vivo and in vivo images should ideally be matched within the same healthy brains, with the goal to develop a neuroanatomically-driven basis for in vivo structural MRI images. Here, we address this issue in young and aging rhesus macaques (young n = 5 and old n = 5) using ex vivo Nissl-stained sections in which we identified the dentate gyrus, CA3, CA2, CA1, subiculum, presubiculum, and parasubiculum guided by morphological cell properties (30 μm thick sections spaced at 240 μm intervals and imaged at 161 nm/pixel). The histologically identified boundaries were merged with in vivo structural MRIs (0.625 × 0.625 × 1 mm) from the same subjects via iterative rigid and diffeomorphic registration resulting in probabilistic atlases of young and old rhesus macaques. Our results indicate stability in hippocampal subfield volumes over an age range of 13 to 32 years, consistent with previous results showing preserved whole hippocampal volume in aged macaques (Shamy et al., 2006). Together, our methods provide a novel approach for identifying hippocampal subfields in non-human primates and a potential 'ground truth' for more accurate identification of hippocampal subfield boundaries on in vivo MRIs. This could, in turn, have applications in humans where accurately identifying hippocampal subfields in vivo is a critical research goal.
Diagnostic Targeted Resequencing in 349 Patients with Drug-Resistant Pediatric Epilepsies Identifies Causative Mutations in 30 Different Genes.
Human mutation, 2017

Targeted resequencing gene panels are used in the diagnostic setting to identify gene defects in epilepsy. We performed targeted resequencing using a 30-genes panel and a 95-genes panel in 349 patients with drug-resistant epilepsies beginning in the first years of life. We identified 71 pathogenic variants, 42 of which novel, in 30 genes, corresponding to 20.3% of the probands. In 66% of mutation positive patients, epilepsy onset occurred before the age of 6 months. The 95-genes panel allowed a genetic diagnosis in 22 (6.3%) patients that would have otherwise been missed using the 30-gene panel. About 50% of mutations were identified in genes coding for sodium and potassium channel components. SCN2A was the most frequently mutated gene followed by SCN1A, KCNQ2, STXBP1, SCN8A, CDKL5, and MECP2. Twenty-nine mutations were identified in 23 additional genes, most of them recently associated with epilepsy. Our data show that panels targeting about 100 genes represent the best cost-effective diagnostic option in pediatric drug-resistant epilepsies. They enable molecular diagnosis of atypical phenotypes, allowing to broaden phenotype-genotype correlations. Molecular diagnosis might influence patients' management and translate into better and specific treatment recommendations in some conditions.