rudyvdbrink/CitationDatabase huggingface dataset:
Distinct patterns of default mode and executive control network circuitry contribute to present and future executive function in older adults.
NeuroImage, 2019

Executive function (EF) performance in older adults has been linked with functional and structural profiles within the executive control network (ECN) and default mode network (DMN), white matter hyperintensities (WMH) burden and levels of Alzheimer's disease (AD) pathology. Here, we simultaneously explored the unique contributions of these factors to baseline and longitudinal EF performance in older adults. Thirty-two cognitively normal (CN) older adults underwent neuropsychological testing at baseline and annually for three years. Neuroimaging and AD pathology measures were collected at baseline. Separate linear regression models were used to determine which of these variables predicted composite EF scores at baseline and/or average annual change in composite ΔEF scores over the three-year follow-up period. Results demonstrated that low DMN deactivation, high ECN activation and WMH burden were the main predictors of EF scores at baseline. In contrast, poor DMN and ECN WM microstructure and higher AD pathology predicted greater annual decline in EF scores. Subsequent mediation analysis demonstrated that DMN WM microstructure uniquely mediated the relationship between AD pathology and ΔEF. These results suggest that functional activation patterns within the DMN and ECN and WMHs contribute to baseline EF while structural connectivity within these networks impact longitudinal EF performance in older adults.
Predictors of Long-Term Outcome of Subthalamic Stimulation in Parkinson Disease.
Annals of neurology, 2021

This study was undertaken to identify preoperative predictive factors of long-term motor outcome in a large cohort of consecutive Parkinson disease (PD) patients with bilateral subthalamic nucleus deep brain stimulation (STN-DBS).
Dynamic frontotemporal systems process space and time in working memory.
PLoS biology, 2018

How do we rapidly process incoming streams of information in working memory, a cognitive mechanism central to human behavior? Dominant views of working memory focus on the prefrontal cortex (PFC), but human hippocampal recordings provide a neurophysiological signature distinct from the PFC. Are these regions independent, or do they interact in the service of working memory? We addressed this core issue in behavior by recording directly from frontotemporal sites in humans performing a visuospatial working memory task that operationalizes the types of identity and spatiotemporal information we encounter every day. Theta band oscillations drove bidirectional interactions between the PFC and medial temporal lobe (MTL; including the hippocampus). MTL theta oscillations directed the PFC preferentially during the processing of spatiotemporal information, while PFC theta oscillations directed the MTL for all types of information being processed in working memory. These findings reveal an MTL theta mechanism for processing space and time and a domain-general PFC theta mechanism, providing evidence that rapid, dynamic MTL-PFC interactions underlie working memory for everyday experiences.
Gambling, Substance Use and Violence in Male and Female Adolescents.
Journal of gambling studies, 2020

The study systematically examined the link between history of gambling, and substance-use and violence-related measures in male and female adolescents, and compared association differences between genders in representative youth risk behavior surveillance data. An anonymous survey was administered to 2425 9th- to 12th-grade students in the state of Connecticut to assess risk behaviors that impact health. Reported past-12-months gambling was the independent variable of interest. Chi squares and adjusted odds-ratios were computed to determine gambling associations with demographic variables, substance-use, and violence-related measures, and whether associations were different between genders. Among students, 18.6% reported gambling. Reported gambling in males and females associated with lifetime use of any drugs, marijuana, cocaine, inhalants, heroin, methamphetamines, ecstasy, synthetic marijuana, non-medical pain-relievers, and injected drugs, in addition to past-30-days cigarette smoking, alcohol and heavy alcohol drinking, and marijuana use. Gambling associated with reported weapon-carrying, being threatened or injured with a weapon, forced sexual intercourse, bullying, and electronic bullying in males; physical dating violence in females; and physical fighting and sexual dating violence in both groups. Gambling and gender interaction terms did not associate with outcome measures except synthetic marijuana use, which trended towards significance (P = 0.052). Gambling in adolescence was similarly linked to risk behaviors involving substance-use in males and females, though gambling relationships with different violence-measures varied between genders. Assessing gambling behavior may be important for targeted preventions focused on adolescents at risk for substance-use disorder and physical violence.
Cxcl10 enhances blood cells migration in the sub-ventricular zone of mice affected by experimental autoimmune encephalomyelitis.
Molecular and cellular neurosciences, 2010

The peri-ventricular area of the forebrain constitutes a preferential site of inflammation in multiple sclerosis, and the sub-ventricular zone (SvZ) is functionally altered in its animal model experimental autoimmune encephalomyelitis (EAE). The reasons for this preferential localization are still poorly understood. We show here that, in EAE mice, blood-derived macrophages, T and B cells and microglia (Mg) from the surrounding parenchyma preferentially accumulate within the SvZ, deranging its cytoarchitecture. We found that the chemokine Cxcl10 is constitutively expressed by a subset of cells within the SvZ, constituting a primary chemo-attractant signal for activated T cells. During EAE, T cells and macrophages infiltrating the SvZ in turn secrete pro-inflammatory cytokines such as TNFalpha and IFNgamma capable to induce Mg cells accumulation and SvZ derangement. Accordingly, lentiviral-mediated over-expression of IFNgamma or TNFalpha in the healthy SvZ mimics Mg/microglia recruitment occurring during EAE, while Cxcl10 over-expression in the SvZ is able to increase the frequency of peri-ventricular inflammatory lesions only in EAE mice. Finally, we show, by RT-PCR and in situ hybridization, that Cxcl10 is expressed also in the healthy human SvZ, suggesting a possible molecular parallelism between multiple sclerosis and EAE.
Muscle sympathetic nerve activity-coupled changes in brain activity during sustained muscle pain.
Brain and behavior, 2018

Long-lasting experimental muscle pain elicits divergent muscle sympathetic responses, with some individuals exhibiting a persistent increase in muscle sympathetic nerve activity (MSNA), and others a decrease. These divergent responses are thought to result from sustained functional changes in specific brain regions that modulate the cardiovascular responses to pain.
Lack of Diaph3 relaxes the spindle checkpoint causing the loss of neural progenitors.
Nature communications, 2016

The diaphanous homologue Diaph3 (aka mDia2) is a major regulator of actin cytoskeleton. Loss of Diaph3 has been constantly associated with cytokinesis failure ascribed to impaired accumulation of actin in the cleavage furrow. Here we report that Diaph3 is required before cell fission, to ensure the accurate segregation of chromosomes. Inactivation of the Diaph3 gene causes a massive loss of cortical progenitor cells, with subsequent depletion of intermediate progenitors and neurons, and results in microcephaly. In embryonic brain extracts, Diaph3 co-immunoprecipitates with BubR1, a key regulator of the spindle assembly checkpoint (SAC). Diaph3-deficient cortical progenitors have decreased levels of BubR1 and fail to properly activate the SAC. Hence, they bypass mitotic arrest and embark on anaphase in spite of incorrect chromosome segregation, generating aneuploidy. Our data identify Diaph3 as a major guard of cortical progenitors, unravel novel functions of Diaphanous formins and add insights into the pathobiology of microcephaly.
Activation of 5-HT
Stress (Amsterdam, Netherlands), 2017

Acute activation of the hypothalamic-pituitary-adrenal (HPA) axis, leading to the release of corticosteroid hormones into the circulation, is an adaptive response to perceived threats. Persistent activation of the HPA axis can lead to impaired physiological or behavioral function with maladaptive consequences. Thus, efficient control and termination of stress responses is essential for well-being. However, inhibitory control mechanisms governing the HPA axis are poorly understood. Previous studies suggest that serotonergic systems, acting within the medial hypothalamus, play an important role in inhibitory control of stress-induced HPA axis activity. To test this hypothesis, we surgically implanted chronic jugular cannulae in adult male rats and conducted bilateral microinjection of vehicle or the 5-HT
Spatiotemporally dissociable neural signatures for generating and updating expectation over time in children: A High Density-ERP study.
Developmental cognitive neuroscience, 2016

Temporal orienting (TO) is the allocation of attentional resources in time based on the a priori generation of temporal expectancy of relevant stimuli as well as the a posteriori updating of this expectancy as a function of both sensory-based evidence and elapsing time. These processes rely on dissociable cognitive mechanisms and neural networks. Yet, although there is evidence that TO may be a core mechanism for cognitive functioning in childhood, the developmental spatiotemporal neural dynamics of this mechanism are little understood. In this study we employed a combined approach based on the application of distributed source reconstruction on a high spatial resolution ERP data array obtained from eighteen 8- to 12-year-old children completing a TO paradigm in which both the cue (Temporal vs. Neutral) and the SOA (Short vs. Long) were manipulated. Results show both cue (N1) and SOA (CNV, Omission Detection Potential and Anterior Anticipatory Index) ERP effects, which were associated with expectancy generation and updating, respectively. Only cue-related effects were correlated with age, as revealed by a reduction of the N1 delta effect with increasing age. Our data suggest that the neural correlates underlying TO are already established at least from 8 to 12 years of age.
The immune system and developmental programming of brain and behavior.
Frontiers in neuroendocrinology, 2012

The brain, endocrine, and immune systems are inextricably linked. Immune molecules have a powerful impact on neuroendocrine function, including hormone-behavior interactions, during health as well as sickness. Similarly, alterations in hormones, such as during stress, can powerfully impact immune function or reactivity. These functional shifts are evolved, adaptive responses that organize changes in behavior and mobilize immune resources, but can also lead to pathology or exacerbate disease if prolonged or exaggerated. The developing brain in particular is exquisitely sensitive to both endogenous and exogenous signals, and increasing evidence suggests the immune system has a critical role in brain development and associated behavioral outcomes for the life of the individual. Indeed, there are associations between many neuropsychiatric disorders and immune dysfunction, with a distinct etiology in neurodevelopment. The goal of this review is to describe the important role of the immune system during brain development, and to discuss some of the many ways in which immune activation during early brain development can affect the later-life outcomes of neural function, immune function, mood and cognition.
Socioeconomic factors affect treatment delivery for patients with low grade glioma: a Swedish population-based study.
Journal of neuro-oncology, 2020

Despite aspirations to achieve equality in healthcare we know that socioeconomic differences exist and may affect treatment and patient outcome, also in serious diseases such as cancer. We investigated disparities in neurosurgical care and outcome for patients with low-grade glioma (LGG).
Sulfatides in extracellular vesicles isolated from plasma of multiple sclerosis patients.
Journal of neuroscience research, 2016

Extracellular vesicles (EVs) are membrane nanovesicles of diverse sizes secreted by different cell types and are involved in intercellular communication. EVs shuttle proteins, nucleic acids, and lipids that reflect their cellular origin and could mediate their biological function in recipient cells. EVs circulate in biological fluids and are considered as potential biomarkers that could be used to analyze and characterize disease development, course and response to treatment. EVs exhibit specific distribution of glycolipids and membrane organization, but little is known about the biological significance of this distribution or how it could contribute to pathological conditions such as multiple sclerosis (MS). We provide the first description of sulfatide composition in plasma-derived EVs by ultra-high-performance liquid chromatography tandem mass spectrometry. We found that EVs of different sizes showed C16:0 sulfatide but no detectable levels of C18:0, C24:0, or C24:1 sulfatide species. Small EVs isolated at 100,000 × g-enriched in exosomes-from plasma of patients with MS showed a significant increase of C16:0 sulfatide compared with healthy controls. Nanoparticle tracking analysis showed that the particle size distribution in MS plasma was significantly different compared with healthy controls. Characterization of small EVs isolated from MS plasma showed similar protein content and similar levels of exosomal markers (Alix, Rab-5B) and vesicular marker MHC class I (major histocompatibility complex class I) compared with healthy controls. Our findings indicate that C16:0 sulfatide associated with small EVs is a candidate biomarker for MS that could potentially reflect pathological changes associated with this disease and/or the effects of its treatment. © 2016 Wiley Periodicals, Inc.
Short term memory properties of sensory neural architectures.
Journal of computational neuroscience, 2019

A functional role of the cerebral cortex is to form and hold representations of the sensory world for behavioral purposes. This is achieved by a sheet of neurons, organized in modules called cortical columns, that receives inputs in a peculiar manner, with only a few neurons driven by sensory inputs through thalamic projections, and a vast majority of neurons receiving mainly cortical inputs. How should cortical modules be organized, with respect to sensory inputs, in order for the cortex to efficiently hold sensory representations in memory? To address this question we investigate the memory performance of trees of recurrent networks (TRN) that are composed of recurrent networks, modeling cortical columns, connected with each others through a tree-shaped feed-forward backbone of connections, with sensory stimuli injected at the root of the tree. On these sensory architectures two types of short-term memory (STM) mechanisms can be implemented, STM via transient dynamics on the feed-forward tree, and STM via reverberating activity on the recurrent connectivity inside modules. We derive equations describing the dynamics of such networks, which allow us to thoroughly explore the space of possible architectures and quantify their memory performance. By varying the divergence ratio of the tree, we show that serial architectures, where sensory inputs are successively processed in different modules, are better suited to implement STM via transient dynamics, while parallel architectures, where sensory inputs are simultaneously processed by all modules, are better suited to implement STM via reverberating dynamics.
LMO7 deficiency reveals the significance of the cuticular plate for hearing function.
Nature communications, 2019

Sensory hair cells, the mechanoreceptors of the auditory and vestibular systems, harbor two specialized elaborations of the apical surface, the hair bundle and the cuticular plate. In contrast to the extensively studied mechanosensory hair bundle, the cuticular plate is not as well understood. It is believed to provide a rigid foundation for stereocilia motion, but specifics about its function, especially the significance of its integrity for long-term maintenance of hair cell mechanotransduction, are not known. We discovered that a hair cell protein called LIM only protein 7 (LMO7) is specifically localized in the cuticular plate and the cell junction. Lmo7 KO mice suffer multiple cuticular plate deficiencies, including reduced filamentous actin density and abnormal stereociliar rootlets. In addition to the cuticular plate defects, older Lmo7 KO mice develop abnormalities in inner hair cell stereocilia. Together, these defects affect cochlear tuning and sensitivity and give rise to late-onset progressive hearing loss.
Generalized Myasthenia Gravis: Classification, Clinical Presentation, Natural History, and Epidemiology.
Neurologic clinics, 2018

Myasthenia gravis (MG) is a rare disease, but the most common disorder of the neuromuscular junction. It is the prototypic autoimmune disease most commonly caused by antibodies to the acetylcholine receptor (AChR) leading to characteristic fatigable weakness of the ocular, bulbar, respiratory, axial, and limb muscles. The majority of patients with MG first present with ocular symptoms. Most patients with MG will experience at least 1 exacerbation of symptoms throughout the course of their illness. This article will cover the epidemiology, clinical presentation, classification, and natural history of MG.
Magnetic resonance imaging in dissociated strabismus complex demonstrates generalized hypertrophy of rectus extraocular muscles.
Journal of AAPOS : the official publication of the American Association for Pediatric Ophthalmology and Strabismus, 2017

Dissociated strabismus complex (DSC) is an enigmatic form of strabismus that includes dissociated vertical deviation (DVD) and dissociated horizontal deviation (DHD). We employed magnetic resonance imaging (MRI) to evaluate the extraocular muscles in DSC.
Spontaneous multiple cervical artery dissections after alemtuzumab.
Multiple sclerosis (Houndmills, Basingstoke, England), 2020

We report a case of multiple cervical artery dissections that occurred 4 days after a first course of alemtuzumab in a woman with relapsing-remitting multiple sclerosis and discuss its potential relationship and mechanisms of action. In particular, an arterial inflammatory process, secondary to cytokine release, could potentially lead to intimal thickening, luminal irregularities, stenosis, and ultimately occlusion. Occurrence of an unexpected serious adverse event, in our case, multiple cervical artery dissections, especially in a close time window after drug administration, questions a potential causal relationship with the drug or a simple coincidence.
Early monocular defocus disrupts the normal development of receptive-field structure in V2 neurons of macaque monkeys.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014

Experiencing different quality images in the two eyes soon after birth can cause amblyopia, a developmental vision disorder. Amblyopic humans show the reduced capacity for judging the relative position of a visual target in reference to nearby stimulus elements (position uncertainty) and often experience visual image distortion. Although abnormal pooling of local stimulus information by neurons beyond striate cortex (V1) is often suggested as a neural basis of these deficits, extrastriate neurons in the amblyopic brain have rarely been studied using microelectrode recording methods. The receptive field (RF) of neurons in visual area V2 in normal monkeys is made up of multiple subfields that are thought to reflect V1 inputs and are capable of encoding the spatial relationship between local stimulus features. We created primate models of anisometropic amblyopia and analyzed the RF subfield maps for multiple nearby V2 neurons of anesthetized monkeys by using dynamic two-dimensional noise stimuli and reverse correlation methods. Unlike in normal monkeys, the subfield maps of V2 neurons in amblyopic monkeys were severely disorganized: subfield maps showed higher heterogeneity within each neuron as well as across nearby neurons. Amblyopic V2 neurons exhibited robust binocular suppression and the strength of the suppression was positively correlated with the degree of hereogeneity and the severity of amblyopia in individual monkeys. Our results suggest that the disorganized subfield maps and robust binocular suppression of amblyopic V2 neurons are likely to adversely affect the higher stages of cortical processing resulting in position uncertainty and image distortion.
Biofunctionalized peptide-based hydrogels provide permissive scaffolds to attract neurite outgrowth from spiral ganglion neurons.
Colloids and surfaces. B, Biointerfaces, 2017

Cochlear implants (CI) allow for hearing rehabilitation in patients with sensorineural hearing loss or deafness. Restricted CI performance results from the spatial gap between spiral ganglion neurons and the CI, causing current spread that limits spatially restricted stimulation and impairs frequency resolution. This may be substantially improved by guiding peripheral processes of spiral ganglion neurons towards and onto the CI electrode contacts. An injectable, peptide-based hydrogel was developed which may provide a permissive scaffold to facilitate neurite growth towards the CI. To test hydrogel capacity to attract spiral ganglion neurites, neurite outgrowth was quantified in an in vitro model using a custom-designed hydrogel scaffold and PuraMatrix
Decreased Expression of IFNG-AS1, IFNG and IL-1B Inflammatory Genes in Medicated Schizophrenia and Bipolar Patients.
Scandinavian journal of immunology, 2017

Although aberrant expression of cytokines such as IL-1B and IFNG in blood from psychiatric patients supports a role of inflammation in the pathogenesis of the disease, little is known about mechanisms underlying their regulation. We aimed to evaluate the putative role of IFNG-AS1 long non-coding RNA (lncRNA) in controlling of IFNG locus in patients with schizophrenia (SZ) and bipolar (BP). We analysed the expression levels of IFNG-AS1 long non-coding RNA, and IFNG and IL-1B mRNAs in blood cells from 27 SZ- and 30 BP-medicated patients and in 32 healthy controls. Our data showed that IFNG-AS1 expression dramatically decreased in BP and SZ patients compared with controls and was significantly correlated with IFNG expression in patients specifically. Transcript levels of IL-1B were also significantly reduced in BP and SZ patients compared with controls. No significant differences in the expression of IFNG-AS1, IFNG and IL-1B genes were found between patients with BP and SZ. Our data shed further light on the potential role of inflammation, and more particularly inflammatory lncRNAs, in SZ and BP diseases and their pharmacological treatment.
Ubiquitin Signaling and Degradation of Aggregate-Prone Proteins.
Trends in biochemical sciences, 2019

Mutant protein aggregation and misfolding is often correlated with toxicity in neurodegenerative diseases. Aggregate-prone proteins are tagged by ubiquitin that signals them for destruction by the proteasome or autophagy, two key pathways for protein degradation and proteostasis. Here, we review recent studies showing that the regulation of aggregate-prone proteins by ubiquitin signaling is more complex than initially postulated. We discuss how the ubiquitin code of aggregate-prone proteins is written by specific E3 ubiquitin ligases and edited by deubiquitylating enzymes (DUBs) in cells and in brain tissues, as well as how this affects protein degradation. These studies have advanced our understanding of the specificity of the ubiquitin system and provide new information about its relevance to neurodegenerative diseases and therapy.