rudyvdbrink/CitationDatabase huggingface dataset:
Population Receptive Field Shapes in Early Visual Cortex Are Nearly Circular.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2021

The visual field region where a stimulus evokes a neural response is called the receptive field (RF). Analytical tools combined with functional MRI (fMRI) can estimate the RF of the population of neurons within a voxel. Circular population RF (pRF) methods accurately specify the central position of the pRF and provide some information about the spatial extent (diameter) of the RF. A number of investigators developed methods to further estimate the shape of the pRF, for example, whether the shape is more circular or elliptical. There is a report that there are many pRFs with highly elliptical pRFs in early visual cortex (V1-V3; Silson et al., 2018). Large aspect ratios (>2) are difficult to reconcile with the spatial scale of orientation columns or visual field map properties in early visual cortex. We started to replicate the experiments and found that the software used in the publication does not accurately estimate RF shape: it produces elliptical fits to circular ground-truth data. We analyzed an independent data set with a different software package that was validated over a specific range of measurement conditions, to show that in early visual cortex the aspect ratios are <2. Furthermore, current empirical and theoretical methods do not have enough precision to discriminate ellipses with aspect ratios of 1.5 from circles. Through simulation we identify methods for improving sensitivity that may estimate ellipses with smaller aspect ratios. The results we present are quantitatively consistent with prior assessments using other methodologies.
Sonic hedgehog pathway activation is induced by acute brain injury and regulated by injury-related inflammation.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2009

The adult mammalian brain responds to injury by activating a program of cell proliferation during which many oligodendrocyte precursors, microglia, and some astrocytes proliferate. Another common response to brain injury is the induction of reactive gliosis, a process whereby dormant astrocytes undergo morphological changes and alter their transcriptional profiles. Although brain injury-induced reactive gliosis is concurrent with the proliferation of surrounding cells, a functional relationship between reactive gliosis and this cell proliferation has not been clearly demonstrated. Here, we show that the mitogen sonic hedgehog (SHH) is produced in reactive astrocytes after injury to the cerebral cortex and participates in regulating the proliferation of Olig2-expressing (Olig2(+)) cells after brain injury. Using a cortical freeze injury to induce reactive gliosis in a Gli-luciferase reporter mouse, we show that the SHH pathway is maximally active 3 d after brain injury and returns to baseline levels by 14 d. SHH expression parallels Gli activation and localizes to glial fibrillary acidic protein-expressing reactive astrocytes. Inhibition of the SHH pathway with cyclopamine blocks the Gli response and significantly reduces both the proliferating and overall number of Olig2(+) cells in the injured cortex. To provide mechanistic insight into SHH pathway activation in astrocytes, we show that proinflammatory stimuli activate SHH-expressing reactive astrocytes, whereas inhibition of inflammation-induced reactive gliosis by macrophage depletion abolishes SHH activation after brain injury and dampens cell proliferation after injury. Our data describes a unique reactive astrocyte-based, SHH-expressing niche formed in response to injury and inflammation that regulates the proliferation of Olig2(+) cells.
In-depth behavioral characterization of the corticosterone mouse model and the critical involvement of housing conditions.
Physiology & behavior, 2016

Depression and anxiety are disabling and highly prevalent psychiatric disorders. To better understand the neurobiological basis of mood and anxiety disorders, relevant animal models are needed. The corticosterone mouse model is frequently used to study depression. Chronic stress and accompanying glucocorticoid elevation causes pathological changes in the central nervous system, which are related to psychiatric symptoms. Exogenous administration of corticosterone is therefore often used to induce depressive-like behavior in mice and in some cases also features of anxiety-like behavior are shown. However, a thorough characterization of this model has never been conducted and housing conditions of the used subjects often differ between the implemented protocols. We chronically administered a subcutaneous corticosterone bolus injection to single- and group-housed mice, and we subsequently evaluated the face validity of this model by performing a battery of behavioral tests (forced swim test, mouse-tail suspension test, saccharin intake test, novelty-suppressed feeding test, elevated plus maze, light/dark paradigm and open field test). Our results show that corticosterone treatment has a substantial overall effect on depressive-like behavior. Increases in anxiety-like behavior on the other hand are mainly seen in single housed animals, independent of treatment. The current study therefore does not only show a detailed behavioral characterization of the corticosterone mouse model, but furthermore also elucidates the critical influence of housing conditions on the behavioral outcome in this model.
Cultural influences on neural systems of intergroup emotion perception: An fMRI study.
Neuropsychologia, 2020

Cultural factors, such as cultural group membership, have been shown to affect neural bases of face and emotion perception. However, little is known about how cultural factors influence neural processing of emotional faces expressed by in-group and out-group members. In this study, we examined cultural influences on neural activation during the intergroup perception of negative emotional faces. We used functional magnetic resonance imaging to compare neural activation during intergroup emotion processing across cultures in three participants groups; two monocultural groups (i.e. Caucasian-Americans and native Japanese) and a bicultural group (i.e. Japanese-Americans). During scanning, the participants completed an emotional match-to-sample task consisting of negative facial expressions of Japanese and Caucasians. Our results show cultural modulation of neural response in the bilateral amygdala as a function of in-group biases and collectivistic values. Additionally, bicultural Japanese-Americans showed enhanced neural responses in the ventral medial prefrontal and posterior cingulate cortices, which had been related to self-related processing, during the perception of negative facial expression of Japanese. Neural activation in the ventral and posterior cingulate cortices reflected individuals' collectivistic tendencies only in the Japanese-American group, possibly due to greater sensitivity to ingroup biases in bicultural individuals. Our results demonstrate the influence of culture on neural responses during the perception of intergroup emotion from faces.
Opposite effects of noradrenergic arousal on amygdala processing of fearful faces in men and women.
NeuroImage, 2013

Fear-related disorders are significantly more prevalent in women than in men. Stress may modulate the neurocircuitry of fear and is a critical factor in the pathogenesis of fear-related disorders. Therefore, we tested in the present experiment the hypothesis that noradrenaline and glucocorticoids, two major stress mediators, have differential effects on fear processing in men and women. In a placebo-controlled, double-blind between-subject design, 80 healthy men and women were administered orally the α2-adrenoceptor antagonist yohimbine and/or the synthetic glucocorticoid hydrocortisone before they rated images of neutral and fearful faces with respect to the degree of fearfulness of the facial expression. During presentation of facial expressions, functional magnetic resonance images were collected. Yohimbine increased subjective ratings of the fearfulness of the faces in women but reduced fearfulness ratings in men. Neuroimaging data showed that yohimbine increased amygdala activity in response to fearful faces in women, whereas it attenuated amygdala responsivity to fearful faces in men. Moreover, yohimbine decreased orbitofrontal activity while viewing fearful faces in women. Hydrocortisone did not affect fear processing, neither in men nor in women. Our findings suggest that noradrenergic arousal may have opposite effects on fear processing in men and women. These sex differences may represent a biological mechanism that contributes to the differential prevalence of fear-related disorders in men and women.
A method for quantifying visual field inhomogeneities.
Vision research, 2014

It is well known that performance is not homogeneous across the visual field, even at isoeccentric locations. Several inhomogeneities in particular have been identified - a Horizontal-Vertical Anisotropy (HVA - better performance in the horizontal than in the vertical direction); a Vertical Asymmetry (VA - better performance in the lower than the upper visual field); and a Vertical Meridian Asymmetry (VMA - better performance below than above the point of fixation on the vertical meridian). Performance has also been reported to be particularly poor at the location directly above the point of fixation, i.e., the "North" (N) location and sometimes at the location directly below the point of fixation, i.e., the "South" (S) location. These phenomena are typically characterized by statistics that compare performance across the visual field to a homogeneous (circular) model. Here we propose an alternative method for assessing visual field inhomogeneities, which involves comparing performance to an elliptical model of the visual field. We maintain that this method provides a more robust analysis of visual field inhomogeneities because it does not overestimate the North and South effects.
Evidence of a role for orbital prefrontal cortex in preventing over-generalization to moderate predictors of biologically significant events.
Neuroscience, 2017

The mammalian brain is specialized to acquire information about environmental predictors of biologically significant events. However, environments contain an array of stimuli from which animals must ascertain which ones are meaningful in the current situation. This kind of uncertainty is inherent in the discriminative fear conditioning to context task (DFCTC) during which rats are trained to associate one context with foot-shock and another distinct context with no event. Although the contexts differ on several dimensions, they also share similarities making some cues perfect predictors, but others moderate predictors. Appropriate responding requires animals to determine which cues are relevant in the current situation and the ability to constrain their responses only to those perfect predictors. The orbital prefrontal cortex (OPFC) is thought to modulate this function as OPFC lesions result in over-generalization during DFCTC. Two experiments were conducted; the first was intended to dissociate the role of the OPFC in acquisition and expression of DFCTC, and the second intended to determine if the OPFC will also function to constrain responses during an appetitive version of DFCTC. We found that inactivation of the OPFC prior to assessment measures resulted in generalized responses on the appetitive and aversive task, however, these effects may be more prominent during the aversive task. Despite generalization during activity testing, rats were able to discriminate between the two contexts during preference. These results point to a broader role for the OPFC constraining responses to perfect predictors of biologically significant events in uncertain contexts.
Muscle Expression of SOD1
Antioxidants & redox signaling, 2018

Neuromuscular junction (NMJ) represents the morphofunctional interface between muscle and nerve. Several chronic pathologies such as aging and neurodegenerative diseases, including muscular dystrophy and amyotrophic lateral sclerosis, display altered NMJ and functional denervation. However, the triggers and the molecular mechanisms underlying the dismantlement of NMJ remain unclear.
Science is 1% inspiration and 99% biomarkers.
Multiple sclerosis (Houndmills, Basingstoke, England), 2017

Neurodegeneration plays a key role in multiple sclerosis (MS) contributing to long-term disability in patients. The prognosis is, however, unpredictable coloured by complex disease mechanisms which can only be clearly appreciated using biomarkers specific to pathobiology of the underlying process. Here, we describe six promising neurodegenerative biomarkers in MS (neurofilament proteins, neurofilament antibodies, tau, N-acetylaspartate, chitinase and chitinase-like proteins and osteopontin), critically evaluating the evidence using a modified Bradford Hill criteria.
Genes for a 'Wellderly' Life.
Trends in molecular medicine, 2016

A long, healthy life is a desire and priority for most people. Genetic factors for longevity do not fully explain healthy aging. Recent research suggests that, in addition to other factors, healthy aging is at least in part the result of protective genetic variants for Alzheimer's disease (AD) and coronary artery disease (CAD).
IL10RB as a key regulator of COVID-19 host susceptibility and severity.
medRxiv : the preprint server for health sciences, 2021

Recent efforts have identified genetic loci that are associated with coronavirus disease 2019 (COVID-19) infection rates and disease outcome severity. Translating these genetic findings into druggable genes and readily available compounds that reduce COVID-19 host susceptibility is a critical next step.
Cystatin C Plays a Sex-Dependent Detrimental Role in Experimental Autoimmune Encephalomyelitis.
Cell reports, 2020

The cysteine protease inhibitor Cystatin C (CST3) is highly expressed in the brains of multiple sclerosis (MS) patients and C57BL/6J mice with experimental autoimmune encephalomyelitis (EAE; a model of MS), but its roles in the diseases are unknown. Here, we show that CST3 plays a detrimental function in myelin oligodendrocyte glycoprotein 35-55 (MOG
Effects of Promotility Agents on Gastric Emptying and Symptoms: A Systematic Review and Meta-analysis.
Gastroenterology, 2019

Studies have reported a lack of association between improvements in gastric emptying (GE) and upper gastrointestinal (UGI) symptoms with promotility drugs. However, GE test methods were suboptimal in some studies. We assessed improvements in GE and UGI symptoms in patients given promotility agents in studies with optimal or moderate test methods (scintigraphy or breath test, solid meal, >2 hours duration) compared to studies with suboptimal GE test methods.
Engaging across dimensions of diversity: A cross-national perspective on mHealth tools for managing relapsing remitting and progressive multiple sclerosis.
Multiple sclerosis and related disorders, 2019

Smartphone apps and wearable devices could augment clinical practice by detecting changes in health status for multiple sclerosis (MS). This study sought to investigate potential barriers and facilitators for uptake and sustained use in (i) people with both relapsing remitting MS (RRMS) and progressive MS (PMS) and (ii) across different countries.
Low levels of Survival Motor Neuron protein are sufficient for normal muscle function in the SMNΔ7 mouse model of SMA.
Human molecular genetics, 2015

Spinal Muscular Atrophy (SMA) is an autosomal recessive disorder characterized by loss of lower motor neurons. SMA is caused by deletion or mutation of the Survival Motor Neuron 1 (SMN1) gene and retention of the SMN2 gene. The loss of SMN1 results in reduced levels of the SMN protein. SMN levels appear to be particularly important in motor neurons; however SMN levels above that produced by two copies of SMN2 have been suggested to be important in muscle. Studying the spatial requirement of SMN is important in both understanding how SMN deficiency causes SMA and in the development of effective therapies. Using Myf5-Cre, a muscle-specific Cre driver, and the Cre-loxP recombination system, we deleted mouse Smn in the muscle of mice with SMN2 and SMNΔ7 transgenes in the background, thus providing low level of SMN in the muscle. As a reciprocal experiment, we restored normal levels of SMN in the muscle with low SMN levels in all other tissues. We observed that decreasing SMN in the muscle has no phenotypic effect. This was corroborated by muscle physiology studies with twitch force, tetanic and eccentric contraction all being normal. In addition, electrocardiogram and muscle fiber size distribution were also normal. Replacement of Smn in muscle did not rescue SMA mice. Thus the muscle does not appear to require high levels of SMN above what is produced by two copies of SMN2 (and SMNΔ7).
Methods of the pharmacological imaging of the cannabinoid system (PhICS) study: towards understanding the role of the brain endocannabinoid system in human cognition.
International journal of methods in psychiatric research, 2011

Various lines of (pre)clinical research indicate that cannabinoid agents carry the potential for therapeutic application to reduce symptoms in several psychiatric disorders. However, direct testing of the involvement of cannabinoid brain systems in psychiatric syndromes is essential for further development. In the Pharmacological Imaging of the Cannabinoid System (PhICS) study, the involvement of the endocannabinoid system in cognitive brain function is assessed by comparing acute effects of the cannabinoid agonist Δ9-tetrahydrocannabinol (THC) on brain function between healthy controls and groups of psychiatric patients showing cognitive dysfunction. This article describes the objectives and methods of the PhICS study and presents preliminary results of the administration procedure on subjective and neurophysiological parameters. Core elements in the methodology of PhICS are the administration method (THC is administered by inhalation using a vaporizing device) and a comprehensive use of pharmacological magnetic resonance imaging (phMRI) combining several types of MRI scans including functional MRI (fMRI), Arterial Spin Labeling (ASL) to measure brain perfusion, and resting-state fMRI. Additional methods like neuropsychological testing further specify the exact role of the endocannabinoid system in regulating cognition. Preliminary results presented in this paper indicate robust behavioral and subjective effects of THC. In addition, fMRI paradigms demonstrate activation of expected networks of brain regions in the cognitive domains of interest. The presented administration and assessment protocol provides a basis for further research on the involvement of the endocannabionoid systems in behavior and in psychopathology, which in turn may lead to development of therapeutic opportunities of cannabinoid ligands.
Cell Type-Specific Decrease of the Intrinsic Excitability of Motor Cortical Pyramidal Neurons in Parkinsonism.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2021

The hypokinetic motor symptoms of Parkinson's disease (PD) are closely linked with a decreased motor cortical output as a consequence of elevated basal ganglia inhibition. However, whether and how the loss of dopamine (DA) alters the cellular properties of motor cortical neurons in PD remains undefined. We induced parkinsonism in adult C57BL/6 mice of both sexes by injecting neurotoxin, 6-hydroxydopamine (6-OHDA), into the medial forebrain bundle. By using
Prothrombotic genetic variants and atherosclerosis in patients with cerebral ischemia of arterial origin.
Atherosclerosis, 2009

Prothrombotic genetic variants associated with arterial disease probably affect arterial thrombus formation but may also promote atherosclerosis. We hypothesized that specific prothrombotic variants lead to advanced atherosclerosis in patients with cerebral ischemia of arterial origin.
Looking Forward in Candidate Gene Research: Concerns and Suggestions.
Journal of marriage and the family, 2015

Candidate Gene × Environment (cGxE) interaction research holds promise for helping us understand for whom and why environments matter for families and development. In their commentary on our target article (G. L. Schlomer, G. M. Fosco, H. H. Cleveland, D. J. Vandenbergh, & M. E. Feinberg, 2015), J. E. Salvatore and D. M. Dick (2015) present their view of the current state and future of cGxE research and frame the debate regarding its merits for advancing knowledge of gene-environment interplay. In this reply, we discuss points of agreement and departure and provide a list of 5 domains by which the quality of cGxE research should be evaluated. Our hope is that researchers will use this list as a guide for their own work.
Proliferation of hippocampal progenitors relies on p27-dependent regulation of Cdk6 kinase activity.
Cellular and molecular life sciences : CMLS, 2018

Neural stem cells give rise to granule dentate neurons throughout life in the hippocampus. Upon activation, these stem cells generate fast proliferating progenitors that complete several rounds of divisions before differentiating into neurons. Although the mechanisms regulating the activation of stem cells have been intensively studied, little attention has been given so far to the intrinsic machinery allowing the expansion of the progenitor pool. The cell cycle protein Cdk6 positively regulates the proliferation of hippocampal progenitors, but the mechanism involved remains elusive. Whereas Cdk6 functions primarily as a cell cycle kinase, it can also act as transcriptional regulator in cancer cells and hematopoietic stem cells. Using mouse genetics, we show here that the function of Cdk6 in hippocampal neurogenesis relies specifically on its kinase activity. The present study also reveals a specific regulatory mechanism for Cdk6 in hippocampal progenitors. In contrast to the classical model of the cell cycle, we observe that the Cip/Kip family member p27, rather than the Ink4 family, negatively regulates Cdk6 in the adult hippocampus. Altogether, our data uncover a unique, cell type-specific regulatory mechanism controlling the expansion of hippocampal progenitors, where Cdk6 kinase activity is modulated by p27.
Testing the repression hypothesis: effects of emotional valence on memory suppression in the think - no think task.
Consciousness and cognition, 2010

It has been proposed that performance in the think - no think (TNT) task represents a laboratory analogue of the voluntary form of memory repression. The central prediction of this repression hypothesis is that performance in the TNT task will be influenced by emotional characteristics of the material to be remembered. This prediction was tested in two experiments by asking participants to learn paired associates in which the first item was either emotionally positive (e.g. joy) or emotionally negative (e.g. hatred). The second word was always emotionally neutral (e.g. socks). Consistent with the repression hypothesis, significant memory suppression was observed in both experiments following 'no think' instructions for memories associated with emotionally negative material. No suppression was observed for memories associated with emotionally positive information. Implications of these findings for the relationship between performance in the TNT task and the controversial notion of memory repression are considered.