rudyvdbrink/CitationDatabase huggingface dataset:
Sensory Deviancy Detection Measured Directly Within the Human Nucleus Accumbens.
Cerebral cortex (New York, N.Y. : 1991), 2016

Rapid changes in the environment evoke a comparison between expectancy and actual outcome to inform optimal subsequent behavior. The nucleus accumbens (NAcc), a key interface between the hippocampus and neocortical regions, is a candidate region for mediating this comparison. Here, we report event-related potentials obtained from the NAcc using direct intracranial recordings in 5 human participants while they listened to trains of auditory stimuli differing in their degree of deviation from repetitive background stimuli. NAcc recordings revealed an early mismatch signal (50-220 ms) in response to all deviants. NAcc activity in this time window was also sensitive to the statistics of stimulus deviancy, with larger amplitudes as a function of the level of deviancy. Importantly, this NAcc mismatch signal also predicted generation of longer latency scalp potentials (300-400 ms). The results provide direct human evidence that the NAcc is a key component of a network engaged in encoding statistics of the sensory environmental.
Reticulospinal plasticity after cervical spinal cord injury in the rat involves withdrawal of projections below the injury.
Experimental neurology, 2013

Restoring voluntary fine motor control of the arm and hand is one of the main goals following cervical spinal cord injury (SCI). Although the functional improvement achievable with rehabilitative training in rat models is frequently accompanied by corticospinal tract (CST) plasticity, CST rewiring alone seems insufficient to account for the observed recovery. Recent investigations in animal models of SCI have suggested that the reticulospinal tract (RtST) might contribute to mediating improved motor performance of the forelimb. Here we investigate whether the spared RtST can compensate for the loss of CST input and whether RtST projections rearrange in response to cervical SCI. Animals underwent unilateral ablation of the dorsal CST and rubrospinal tract at spinal level C4, while the ventral RtST projections were spared. At the end of the six-week recovery period, injured animals had made significant improvements in single pellet reaching. This was not accompanied by increased sprouting of the injured CST above the injury compared to uninjured control animals. Injury-induced changes in RtST fiber density within the gray matter, as well as in the number of RtST collaterals entering the gray matter or crossing the cord midline were minor above the injury. However, all analyses directly below the injured spinal level consistently point to a significant decrease of RtST projections. The mechanism and the functional relevance behind this new finding warrant further study. Our results also suggest that mechanisms other than anatomical plasticity, such as plastic changes on a cellular level, might be responsible for the observed spontaneous recovery.
In utero infection of Zika virus leads to abnormal central nervous system development in mice.
Scientific reports, 2019

The World Health Organization has declared ZIKA virus (ZIKV) a global public health emergency, prompted by the association of ZIKV infections with severe brain abnormalities in the human fetus. ZIKV preferentially targets human neuronal precursor cells (NPCs) in both monolayer and cortical brain organoid culture systems and stunts their growth. Although ZIKV is well recognized to cause microcephaly, there is no systematic analysis to demonstrate the effect of ZIKV on central nervous system (CNS) development, including brain malformations and spinal cord dysfunction. Here, we conducted a longitudinal analysis to show that a novel mouse model (infected in utero and monitored after birth until adulthood) recapitulates the effects of ZIKV infection affecting neural stem cells fate and leads to a thinner cortex and a smaller brain. Furthermore, we demonstrate the effect of ZIKV on spinal cord function. Specifically, we found significant reductions in neuron numbers in the anterior horn of grey matter of the spinal cord and muscle dystrophy with a significant decrease in forepaw grip strength in the ZIKV group. Thus, the established mouse model of ZIKV infection leading to abnormal CNS development will help to further advance our understanding of the disease pathogenesis.
Maternal Rest/Nrsf Regulates Zebrafish Behavior through snap25a/b.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2016

During embryonic development, regulation of gene expression is key to creating the many subtypes of cells that an organism needs throughout its lifetime. Recent work has shown that maternal genetics and environmental factors have lifelong consequences on diverse processes ranging from immune function to stress responses. The RE1-silencing transcription factor (Rest) is a transcriptional repressor that interacts with chromatin-modifying complexes to repress transcription of neural-specific genes during early development. Here we show that in zebrafish, maternally supplied rest regulates expression of target genes during larval development and has lifelong impacts on behavior. Larvae deprived of maternal rest are hyperactive and show atypical spatial preferences. Adult male fish deprived of maternal rest present with atypical spatial preferences in a novel environment assay. Transcriptome sequencing revealed 158 genes that are repressed by maternal rest in blastula stage embryos. Furthermore, we found that maternal rest is required for target gene repression until at least 6 dpf. Importantly, disruption of the RE1 sites in either snap25a or snap25b resulted in behaviors that recapitulate the hyperactivity phenotype caused by absence of maternal rest Both maternal rest mutants and snap25a RE1 site mutants have altered primary motor neuron architecture that may account for the enhanced locomotor activity. These results demonstrate that maternal rest represses snap25a/b to modulate larval behavior and that early Rest activity has lifelong behavioral impacts.
Progressive dopaminergic alterations and mitochondrial abnormalities in LRRK2 G2019S knock-in mice.
Neurobiology of disease, 2015

Mutations in the LRRK2 gene represent the most common genetic cause of late onset Parkinson's disease. The physiological and pathological roles of LRRK2 are yet to be fully determined but evidence points towards LRRK2 mutations causing a gain in kinase function, impacting on neuronal maintenance, vesicular dynamics and neurotransmitter release. To explore the role of physiological levels of mutant LRRK2, we created knock-in (KI) mice harboring the most common LRRK2 mutation G2019S in their own genome. We have performed comprehensive dopaminergic, behavioral and neuropathological analyses in this model up to 24months of age. We find elevated kinase activity in the brain of both heterozygous and homozygous mice. Although normal at 6months, by 12months of age, basal and pharmacologically induced extracellular release of dopamine is impaired in both heterozygous and homozygous mice, corroborating previous findings in transgenic models over-expressing mutant LRRK2. Via in vivo microdialysis measurement of basal and drug-evoked extracellular release of dopamine and its metabolites, our findings indicate that exocytotic release from the vesicular pool is impaired. Furthermore, profound mitochondrial abnormalities are evident in the striatum of older homozygous G2019S KI mice, which are consistent with mitochondrial fission arrest. We anticipate that this G2019S mouse line will be a useful pre-clinical model for further evaluation of early mechanistic events in LRRK2 pathogenesis and for second-hit approaches to model disease progression.
Mood Disorders, Accelerated Aging, and Inflammation: Is the Link Hidden in Telomeres?
Cells, 2019

Mood disorders are associated with an increased risk of aging-related diseases, which greatly contribute to the excess morbidity and mortality observed in affected individuals. Clinical and molecular findings also suggest that mood disorders might be characterized by a permanent state of low-grade inflammation. At the cellular level, aging translates into telomeres shortening. Intriguingly, inflammation and telomere shortening show a bidirectional association: a pro-inflammatory state seems to contribute to aging and telomere dysfunction, and telomere attrition is able to induce low-grade inflammation. Several independent studies have reported shorter telomere length and increased levels of circulating inflammatory cytokines in mood disorders, suggesting a complex interplay between altered inflammatory⁻immune responses and telomere dynamics in the etiopathogenesis of these disorders. In this review, we critically discuss studies investigating the role of telomere attrition and inflammation in the pathogenesis and course of mood disorders, and in pharmacological treatments with psychotropic medications.
Personalized safety measures reduce the adverse event rate of long-term video EEG.
Epilepsia open, 2017

Safety in epilepsy monitoring units (EMUs) has become an increasing concern because adverse events occur in up to 10% of patients undergoing long-term video EEG in EMUs. The aim of this study was to assess the effectiveness of a specific safety protocol in an EMU.
Burst muscle performance predicts the speed, acceleration, and turning performance of Anna's hummingbirds.
eLife, 2015

Despite recent advances in the study of animal flight, the biomechanical determinants of maneuverability are poorly understood. It is thought that maneuverability may be influenced by intrinsic body mass and wing morphology, and by physiological muscle capacity, but this hypothesis has not yet been evaluated because it requires tracking a large number of free flight maneuvers from known individuals. We used an automated tracking system to record flight sequences from 20 Anna's hummingbirds flying solo and in competition in a large chamber. We found that burst muscle capacity predicted most performance metrics. Hummingbirds with higher burst capacity flew with faster velocities, accelerations, and rotations, and they used more demanding complex turns. In contrast, body mass did not predict variation in maneuvering performance, and wing morphology predicted only the use of arcing turns and high centripetal accelerations. Collectively, our results indicate that burst muscle capacity is a key predictor of maneuverability.
Ameliorating spatial neglect with non-invasive brain stimulation: from pathophysiological concepts to novel treatment strategies.
Neuropsychological rehabilitation, 2011

Neglect is a multifaceted, complex syndrome, in which patients fail to detect or respond to stimuli or parts thereof located contralesionally. Non-invasive brain stimulation by means of transcranial magnetic stimulation (TMS) or transcranial direct current stimulation (tDCS) may not only be useful as diagnostic research tools to explore the pathophysiology of neglect, but also for ameliorating its symptoms. Current approaches for modulating neglect non-invasively are mainly based on the neurophysiological concept of interhemispheric inhibition, which suggests a pathological overactivation of the contralesional hemisphere due to reduced inhibitory influences from the lesioned one. Within this framework, non-invasive brain stimulation mainly aims to inhibit the contralesional hemisphere to allow for rebalancing the system. However, facilitatory protocols for enhancing the ipsilesional neural circuitry might also prove useful. In this review, we discuss the contribution of non-invasive brain stimulation to current pathological concepts of neglect, the promising results of the proof-of-principle studies currently available as well as the specific aspects to be systematically investigated before broader clinical trials may eventually suggest a routine clinical application.
Profiles of visuospatial memory dysfunction in opioid-exposed and dependent populations.
Psychological medicine, 2019

Chronic opioid exposure is common world-wide, but behavioural performance remains under-investigated. This study aimed to investigate visuospatial memory performance in opioid-exposed and dependent clinical populations and its associations with measures of intelligence and cognitive impulsivity.
Expression of ALS/FTD-linked mutant CCNF in zebrafish leads to increased cell death in the spinal cord and an aberrant motor phenotype.
Human molecular genetics, 2017

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive, fatal neurodegenerative disease characterised by the death of upper and lower motor neurons. Approximately 10% of cases have a known family history of ALS and disease-linked mutations in multiple genes have been identified. ALS-linked mutations in CCNF were recently reported, however the pathogenic mechanisms associated with these mutations are yet to be established. To investigate possible disease mechanisms, we developed in vitro and in vivo models based on an ALS-linked missense mutation in CCNF. Proteomic analysis of the in vitro models identified the disruption of several cellular pathways in the mutant model, including caspase-3 mediated cell death. Transient overexpression of human CCNF in zebrafish embryos supported this finding, with fish expressing the mutant protein found to have increased levels of cleaved (activated) caspase-3 and increased cell death in the spinal cord. The mutant CCNF fish also developed a motor neuron axonopathy consisting of shortened primary motor axons and increased frequency of aberrant axonal branching. Importantly, we demonstrated a significant correlation between the severity of the CCNF-induced axonopathy and a reduced motor response to a light stimulus (photomotor response). This is the first report of an ALS-linked CCNF mutation in vivo and taken together with the in vitro model identifies the disruption of cell death pathways as a significant consequence of this mutation. Additionally, this study presents a valuable new tool for use in ongoing studies investigating the pathobiology of ALS-linked CCNF mutations.
D-aspartate prevents corticostriatal long-term depression and attenuates schizophrenia-like symptoms induced by amphetamine and MK-801.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2008

Since their discovery in the mammalian CNS, D-aspartate and D-serine have aroused a strong interest with regard to their role as putative neuromodulatory molecules. Whereas the functional role of D-serine as an endogenous coagonist of NMDA receptors (NMDARs) has been elucidated, the biological significance of D-aspartate in the brain is still mostly unclear. In the present study, we demonstrated that nonphysiological high levels of D-aspartate (1) increased in vivo NMDAR activity, (2) attenuated prepulse inhibition deficits induced by amphetamine and MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5,10-imine hydrogen maleate], (3) produced striatal adaptations of glutamate synapses resembling those observed after chronic haloperidol treatment, and (4) enhanced hippocampal NMDAR-dependent memory. This evidence was obtained using two different experimental strategies that produced an abnormal increase of endogenous D-aspartate levels in the mouse: a genetic approach based on the targeted deletion of the D-aspartate oxidase gene and a pharmacological approach based on oral administration of D-aspartate. This work provides in vivo evidence of a neuromodulatory role exerted by D-aspartate on NMDAR signaling and raises the intriguing hypothesis that also this D-amino acid, like D-serine, could be used as a therapeutic agent in the treatment of schizophrenia-related symptoms.
Brain-first versus body-first Parkinson's disease: a multimodal imaging case-control study.
Brain : a journal of neurology, 2020

Parkinson's disease is characterized by the presence of abnormal, intraneuronal α-synuclein aggregates, which may propagate from cell-to-cell in a prion-like manner. However, it remains uncertain where the initial α-synuclein aggregates originate. We have hypothesized that Parkinson's disease comprises two subtypes. A brain-first (top-down) type, where α-synuclein pathology initially arises in the brain with secondary spreading to the peripheral autonomic nervous system; and a body-first (bottom-up) type, where the pathology originates in the enteric or peripheral autonomic nervous system and then spreads to the brain. We also hypothesized that isolated REM sleep behaviour disorder (iRBD) is a prodromal phenotype for the body-first type. Using multimodal imaging, we tested the hypothesis by quantifying neuronal dysfunction in structures corresponding to Braak stages I, II and III involvement in three distinct patient groups. We included 37 consecutive de novo patients with Parkinson's disease into this case-control PET study. Patients with Parkinson's disease were divided into 24 RBD-negative (PDRBD-) and 13 RBD-positive cases (PDRBD+) and a comparator group of 22 iRBD patients. We used 11C-donepezil PET/CT to assess cholinergic (parasympathetic) innervation, 123I-metaiodobenzylguanidine (MIBG) scintigraphy to measure cardiac sympathetic innervation, neuromelanin-sensitive MRI to measure the integrity of locus coeruleus pigmented neurons, and 18F-dihydroxyphenylalanine (FDOPA) PET to assess putaminal dopamine storage capacity. Colon volume and transit times were assessed with CT scans and radiopaque markers. Imaging data from the three groups were interrogated with ANOVA and Kruskal-Wallis tests corrected for multiple comparisons. The PDRBD- and PDRBD+ groups showed similar marked reductions in putaminal FDOPA-specific uptake, whereas two-thirds of iRBD patients had normal scans (P < 10-13, ANOVA). When compared to the PDRBD- patients, the PDRBD+ and iRBD patients showed reduced mean MIBG heart:mediastinum ratios (P < 10-5, ANOVA) and colon 11C-donepezil standard uptake values (P = 0.008, ANOVA). The PDRBD+ group trended towards a reduced mean MRI locus coeruleus: pons ratio compared to PDRBD- (P = 0.07, t-test). In comparison to the other groups, the PDRBD+ group also had enlarged colon volumes (P < 0.001, ANOVA) and delayed colonic transit times (P = 0.01, Kruskal-Wallis). The combined iRBD and PDRBD+ patient data were compatible with a body-first trajectory, characterized by initial loss of cardiac MIBG signal and 11C-colonic donepezil signal followed by loss of putaminal FDOPA uptake. In contrast, the PDRBD- data were compatible with a brain-first trajectory, characterized by primary loss of putaminal FDOPA uptake followed by a secondary loss of cardiac MIBG signal and 11C-donepezil signal. These findings support the existence of brain-first and body-first subtypes of Parkinson's disease.
Current Reports on Perinatal Intimate Partner Violence.
Current psychiatry reports, 2017

The purpose of this study was to review the literature on perinatal intimate partner violence, focusing on recent knowledge to guide mental health professionals on the best approaches to identify and treat women exposed to perinatal intimate partner violence.
Reproducibility in Computational Neuroscience Models and Simulations.
IEEE transactions on bio-medical engineering, 2016

Like all scientific research, computational neuroscience research must be reproducible. Big data science, including simulation research, cannot depend exclusively on journal articles as the method to provide the sharing and transparency required for reproducibility.
Anodal transcranial direct current stimulation does not influence the neural adjustments associated with fatiguing contractions in a hand muscle.
European journal of applied physiology, 2019

The objective of the current study was to investigate the mechanisms responsible for the briefer time to failure of a submaximal contraction (C2) when performed 60 min after a similar contraction (C1), and the influence of anodal transcranial direct current stimulation (a-tDCS) applied over the motor cortex on these mechanisms.
Asynchronous Event-Based Motion Processing: From Visual Events to Probabilistic Sensory Representation.
Neural computation, 2019

In this work, we propose a two-layered descriptive model for motion processing from retina to the cortex, with an event-based input from the asynchronous time-based image sensor (ATIS) camera. Spatial and spatiotemporal filtering of visual scenes by motion energy detectors has been implemented in two steps in a simple layer of a lateral geniculate nucleus model and a set of three-dimensional Gabor kernels, eventually forming a probabilistic population response. The high temporal resolution of independent and asynchronous local sensory pixels from the ATIS provides a realistic stimulation to study biological motion processing, as well as developing bio-inspired motion processors for computer vision applications. Our study combines two significant theories in neuroscience: event-based stimulation and probabilistic sensory representation. We have modeled how this might be done at the vision level, as well as suggesting this framework as a generic computational principle among different sensory modalities.
Synchronization of multi-frequency noise-induced oscillations.
Chaos (Woodbury, N.Y.), 2011

Using a model system of FitzHugh-Nagumo type in the excitable regime, the similarity between synchronization of self-sustained and noise-induced oscillations is studied for the case of more than one main frequency in the spectrum. It is shown that this excitable system undergoes the same frequency lockings as a self-sustained quasiperiodic oscillator. The presence of noise-induced both stable and unstable limit cycles and tori, as well as their tangential bifurcations, are discussed. As the FitzHugh-Nagumo oscillator represents one of the basic neural models, the obtained results are of high importance for neuroscience.
Searching for Inflammatory and Oxidative Stress Markers Capable of Clustering Severe Asthma.
Archivos de bronconeumologia, 2021

Asthma inflammation may feature an imbalance between oxidative stress and antioxidant defenses. Oxidative stress induces propagation of airways inflammation and corticosteroid insensitivity contributing to poor asthma control, and frequent severe acute exacerbations. This study assessed inflammation and oxidative stress in severe asthmatic subjects and evaluated the possible correlations between inflammatory and oxidative stress markers investigated and asthma severity.
A wireless system with stimulation and recording capabilities for interfacing peripheral nerves in rodents.
Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference, 2016

Considerable progress has been made in the last decade in implantable bioelectronic neurosystems. Yet most neural implants are used in acute and tethered experimental conditions. Here, we present a preliminary prototype of a multichannel system for simultaneous peripheral nerve stimulation and neural recording. The system comprises miniaturized electronics with a total volume of less then 1.4cm3 including a 3.7V battery which is expected to last for 94 days of standby operation or 18 hours of continuous recording and stimulation. Data read-out and device configuration are wireless. Visceral nerves in rodents are interfaced with compliant extraneural electrodes. The 100×350μm2 electrodes display a low impedance (1.8kn at 1kHz) with a PEDOT:PSS coating. We validated the prototype in acute experiments by applying electrical stimulation to the aortic depressor nerve (ADN), resulting in effective and reproducible decrease in blood pressure and heart rate. The combination of miniaturized electronics and flexible electrodes makes the presented system a versatile platform for future implantable devices interfacing small peripheral nerves and potentially enables new applications in the field of neuroscience.