rudyvdbrink/CitationDatabase huggingface dataset:
Cognitive control and cortisol response to stress in generalised anxiety disorder: a study of working memory capacity with negative and neutral distractors.
Cognition & emotion, 2020

We investigated the association between cognitive control and individual differences in cortisol response to stress in participants with generalised anxiety disorder (GAD) and in never-disordered controls (CTL). To assess cognitive control, participants completed an affective version of the reading span task, which measures working memory capacity (WMC) in the presence of negative and neutral distractors. Participants then completed a standard psychosocial stressor and provided salivary cortisol samples throughout. The relation between WMC and cortisol response to stress was dependent on diagnostic group and distractor valence. Within the GAD group, greater WMC in the presence of neutral distractors was associated with attenuated cortisol response to stress, and greater WMC in the presence of negative distractors was associated with faster cortisol recovery from stress. In contrast, within the CTL group, WMC was unrelated to cortisol stress reactivity or recovery.
Role of the hypothalamus in the neuroendocrine regulation of body weight and composition during energy deficit.
Obesity reviews : an official journal of the International Association for the Study of Obesity, 2012

Energy deficit in lean or obese animals or humans stimulates appetite, reduces energy expenditure and possibly also decreases physical activity, thereby contributing to weight regain. Often overlooked in weight loss trials for obesity, however, is the effect of energy restriction on neuroendocrine status. Negative energy balance in lean animals and humans consistently inhibits activity of the hypothalamo-pituitary-thyroid, -gonadotropic and -somatotropic axes (or reduces circulating insulin-like growth factor-1 levels), while concomitantly activating the hypothalamo-pituitary-adrenal axis, with emerging evidence of similar changes in overweight and obese people during lifestyle interventions for weight loss. These neuroendocrine changes, which animal studies show may result in part from hypothalamic actions of orexigenic (e.g. neuropeptide Y, agouti-related peptide) and anorexigenic peptides (e.g. alpha-melanocyte-stimulating hormone, and cocaine and amphetamine-related transcript), can adversely affect body composition by promoting the accumulation of adipose tissue (particularly central adiposity) and stimulating the loss of lean body mass and bone. As such, current efforts to maximize loss of excess body fat in obese people may inadvertently be promoting long-term complications such as central obesity and associated health risks, as well as sarcopenia and osteoporosis. Future weight loss trials would benefit from assessment of the effects on body composition and key hormonal regulators of body composition using sensitive techniques.
Exome-wide rare variant analysis identifies TUBA4A mutations associated with familial ALS.
Neuron, 2014

Exome sequencing is an effective strategy for identifying human disease genes. However, this methodology is difficult in late-onset diseases where limited availability of DNA from informative family members prohibits comprehensive segregation analysis. To overcome this limitation, we performed an exome-wide rare variant burden analysis of 363 index cases with familial ALS (FALS). The results revealed an excess of patient variants within TUBA4A, the gene encoding the Tubulin, Alpha 4A protein. Analysis of a further 272 FALS cases and 5,510 internal controls confirmed the overrepresentation as statistically significant and replicable. Functional analyses revealed that TUBA4A mutants destabilize the microtubule network, diminishing its repolymerization capability. These results further emphasize the role of cytoskeletal defects in ALS and demonstrate the power of gene-based rare variant analyses in situations where causal genes cannot be identified through traditional segregation analysis.
Relevance of neuronal and glial NPC1 for synaptic input to cerebellar Purkinje cells.
Molecular and cellular neurosciences, 2014

Niemann-Pick type C disease is a rare and ultimately fatal lysosomal storage disorder with variable neurologic symptoms. The disease-causing mutations concern NPC1 or NPC2, whose dysfunction entails accumulation of cholesterol in the endosomal-lysosomal system and the selective death of specific neurons, namely cerebellar Purkinje cells. Here, we investigated whether neurodegeneration is preceded by an imbalance of synaptic input to Purkinje cells and whether neuronal or glial absence of NPC1 has different impacts on synapses. To this end, we prepared primary cerebellar cultures from wildtype or NPC1-deficient mice that are glia-free and highly enriched with Purkinje cells. We report that lack of NPC1 in either neurons or glial cells did not affect the excitability of Purkinje cells, the formation of dendrites or their excitatory synaptic activity. However, simultaneous absence of NPC1 from neuronal and glial cells impaired the presynaptic input to Purkinje cells suggesting a cooperative effect of neuronal and glial NPC1 on synapses.
Ca2+-dependent, phospholipid-binding residues of synaptotagmin are critical for excitation-secretion coupling in vivo.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2008

Synaptotagmin I is the Ca(2+) sensor for fast, synchronous release of neurotransmitter; however, the molecular interactions that couple Ca(2+) binding to membrane fusion remain unclear. The structure of synaptotagmin is dominated by two C(2) domains that interact with negatively charged membranes after binding Ca(2+). In vitro work has implicated a conserved basic residue at the tip of loop 3 of the Ca(2+)-binding pocket in both C(2) domains in coordinating this electrostatic interaction with anionic membranes. Although results from cultured cells suggest that the basic residue of the C(2)A domain is functionally significant, such studies provide contradictory results regarding the importance of the C(2)B basic residue during vesicle fusion. To directly test the functional significance of each of these residues at an intact synapse in vivo, we neutralized either the C(2)A or the C(2)B basic residue and assessed synaptic transmission at the Drosophila neuromuscular junction. The conserved basic residues at the tip of the Ca(2+)-binding pocket of both the C(2)A and C(2)B domains mediate Ca(2+)-dependent interactions with anionic membranes and are required for efficient evoked transmitter release. Our results directly support the hypothesis that the interactions between synaptotagmin and the presynaptic membrane, which are mediated by the basic residues at the tip of both the C(2)A and C(2)B Ca(2+)-binding pockets, are critical for coupling Ca(2+) influx with vesicle fusion during synaptic transmission in vivo. Our model for synaptotagmin's direct role in coupling Ca(2+) binding to vesicle fusion incorporates this finding with results from multiple in vitro and in vivo studies.
Evaluation of a magnetic resonance-compatible dentoalveolar tactile stimulus device.
BMC neuroscience, 2010

Few methods exist to study central nervous system processes following dentoalveolar tactile stimulation using functional magnetic resonance imaging (fMRI), likely due to inherent technical difficulties. Our primary goal was to develop and perform feasibility testing of a novel device capable of delivering valid and reliable dentoalveolar stimuli at dental chair-side and during MRI. Details of a device designed to deliver dentoalveolar dynamic pressure stimuli are described. Device testing took place in three settings: a) laboratory testing to assess range of stimulus force intensities, b) dental chair-side to assess reliability, validity and discriminant ability in force-pain relationship; and c) MRI to evaluate magnetic compatibility and ability to evoke brain activation in painfree subjects similar to those described in the literature.
Prevalence and clinical correlates of sleep disordered breathing in myotonic dystrophy types 1 and 2.
Sleep & breathing = Schlaf & Atmung, 2014

Myotonic dystrophy types 1 (DM1) and 2 (DM2) are the most common muscular dystrophies in adulthood. A high prevalence of excessive daytime sleepiness (EDS) and sleep disordered breathing was documented in DM1; however, there are limited data available regarding DM2. Goals of the study were: (1) to evaluate the prevalence of sleep apnea in a large cohort of patients (71 DM1 and 14 DM2) and (2) to analyze correlations among such disorders and clinical features of myotonic dystrophies.
Fast phasic release properties of dopamine studied with a channel biosensor.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014

Few other neurotransmitters are of as intense interest to neuropsychiatry and neurology as dopamine, yet existing techniques to monitor dopamine release leave an important spatiotemporal gap in our understanding. Electrochemistry and fluorescence imaging tools have been developed to fill the gap, but these methods have important limitations. We circumvent these limitations by introducing a dopamine-gated chloride channel into rat dorsal striatal medium spiny neurons, targets of strong dopamine innervation, thereby transforming dopamine from a slow transmitter into a fast transmitter and revealing new opportunities for studying moment-to-moment regulation of dopamine release. We demonstrate pharmacological and biophysical properties of the channel that make it suitable for fast, local dopamine measurements, and we demonstrate for the first time spontaneous and evoked responses to vesicular dopamine release in the dorsal striatum. Evoked dopamine currents were separated into a fast, monosynaptic component and a slower-rising and decaying disynaptic component mediated by nicotinic receptor activation. In summary, LGC-53 represents a dopamine biosensor with properties suitable for temporal separation of distinct dopamine signals in targets of dopamine innervation.
Synapsins regulate α-synuclein functions.
Proceedings of the National Academy of Sciences of the United States of America, 2019

The normal function of α-synuclein (α-syn) remains elusive. Although recent studies suggest α-syn as a physiologic attenuator of synaptic vesicle (SV) recycling, mechanisms are unclear. Here, we show that synapsin-a cytosolic protein with known roles in SV mobilization and clustering-is required for presynaptic functions of α-syn. Our data offer a critical missing link and advocate a model where α-syn and synapsin cooperate to cluster SVs and attenuate recycling.
Lifting the veil: how to use clinical neuropsychology to assess dementia.
Journal of neurology, neurosurgery, and psychiatry, 2015

Neurologists often struggle to interpret the results of neuropsychological testing, even though cognitive assessments are an integral component of the diagnostic process in dementia syndromes. This article reviews the principles underlying clinical neuropsychology, background on common neuropsychological tests, and tips on how to interpret the results when assessing patients with dementia. General cognitive screening tools, appropriate for use by general neurologists and psychiatrists, as well as specific cognitive tests examining the main cognitive domains (attention and orientation, memory, visuospatial function, language and executive function) in patients with dementia are considered. Finally, the pattern of deficits, helpful in defining clinical dementia phenotypes and sometimes in predicting the underlying molecular pathology, are outlined. Such clinicopathological associations will become invaluable as disease-modifying treatments for dementia are developed and implemented.
Fentanyl Initiated Polymers Prepared by ATRP for Targeted Delivery.
Bioconjugate chemistry, 2017

The targeted delivery of polymers to neurons is a challenging yet important goal for polymer based drug delivery. We prepared a fentanyl based atom transfer radical polymerization (ATRP) initiator to target the Mu opioid receptor (MOR) for neuronal targeting. We incorporated our recently discovered rigid acrylate linking group into the initiator to retain a high degree of binding to the MOR and grafted random or block copolymers of poly(oligo(ethylene oxide) methacrylate)-block-(glycidyl methacrylate). Trifluoroethanol promoted amine ring opening of the glycidyl methacrylate was used for post-polymerization modification of the fentanyl initiated polymers to attach a near-infrared fluorescent dye (ADS790WS) or to build a targeted siRNA delivery system via modification with secondary amines. We examined the biocompatibility, cellular internalization, and siRNA binding properties of our polymer library in a green fluorescent protein expressing SY SH5Y neuroblastoma cell-line.
Developmental changes in NMDA receptor subunit composition at ON and OFF bipolar cell synapses onto direction-selective retinal ganglion cells.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014

In the developing mouse retina, spontaneous and light-driven activity shapes bipolar→ganglion cell glutamatergic synapse formation, beginning around the time of eye-opening (P12-P14) and extending through the first postnatal month. During this time, glutamate release can spill outside the synaptic cleft and possibly stimulate extrasynaptic NMDA-type glutamate receptors (NMDARs) on ganglion cells. Furthermore, the role of NMDARs during development may differ between ON and OFF bipolar synapses as in mature retina, where ON synapses reportedly include extrasynaptic NMDARs with GluN2B subunits. To better understand the function of glutamatergic synapses during development, we made whole-cell recordings of NMDAR-mediated responses, in vitro, from two types of genetically identified direction-selective ganglion cells (dsGCs): TRHR (thyrotropin-releasing hormone receptor) and Drd4 (dopamine receptor 4). Both dsGC types responded to puffed NMDA between P7 and P28; and both types exhibited robust light-evoked NMDAR-mediated responses at P14 and P28 that were quantified by conductance analysis during nicotinic and GABA(A) receptor blockade. For a given cell type and at a given age, ON and OFF bipolar cell inputs evoked similar NMDAR-mediated responses, suggesting that ON-versus-OFF differences in mature retina do not apply to the cell types or ages studied here. At P14, puff- and light-evoked NMDAR-mediated responses in both dsGCs were partially blocked by the GluN2B antagonist ifenprodil, whereas at P28 only TRHR cells remained ifenprodil-sensitive. NMDARs contribute at both ON and OFF bipolar cell synapses during a period of robust activity-dependent synaptic development, with declining GluN2B involvement over time in specific ganglion cell types.
spargel, the PGC-1α homologue, in models of Parkinson disease in Drosophila melanogaster.
BMC neuroscience, 2015

Parkinson disease (PD) is a progressive neurodegenerative disorder presenting with symptoms of resting tremor, bradykinesia, rigidity, postural instability and additional severe cognitive impairment over time. These symptoms arise from a decrease of available dopamine in the striatum of the brain resulting from the breakdown and death of dopaminergic (DA) neurons. A process implicated in the destruction of these neurons is mitochondrial breakdown and impairment. Upkeep and repair of mitochondria involves a number of complex and key components including Pink1, Parkin, and the PGC family of genes. PGC-1α has been characterized as a regulator of mitochondria biogenesis, insulin receptor signalling and energy metabolism, mutation of this gene has been linked to early onset forms of PD. The mammalian PGC family consists of three partially redundant genes making the study of full or partial loss of function difficult. The sole Drosophila melanogaster homologue of this gene family, spargel (srl), has been shown to function in similar pathways of mitochondrial upkeep and biogenesis.
Maturation of shoaling behavior is accompanied by changes in the dopaminergic and serotoninergic systems in zebrafish.
Developmental psychobiology, 2012

The zebrafish has been one of the preferred vertebrate model organisms of developmental biology, and is becoming an important research tool for behavioral neuroscience and behavior genetics. A prominent feature of zebrafish is their strong shoaling tendency. Most recently, the first study investigating the development of shoaling in zebrafish demonstrated that a few days after hatching zebrafish do not shoal, but that shoaling tendency gradually increases during development. The current study investigates this phenomenon using the nearest neighbor distance, a measure most frequently employed for the quantification of shoal cohesion in fish. We demonstrate that shoal cohesion increases with age, while thigmotaxis, "wall hugging," does not show a consistent age-dependent change. The mechanisms underlying the maturation of shoaling are unknown. HPLC analysis of whole brain extracts finds the concentration of dopamine, DOPAC, serotonin, and 5-HIAA normalized to total brain protein weight to increase with age. Although the behavioral and neurochemical results are only correlative at this point, they may open a new avenue into the investigation of the mechanisms and development of social behavior in zebrafish.
Emergent loading dose of antiplatelets for stenting after IV rt-PA in acute ischemic stroke: a feasibility study.
The International journal of neuroscience, 2018

A loading dose of antiplatelets reduces in-stent thrombosis after stent implantation. However, whether it is safe in patients undergoing acute stenting after intravenous recombinant tissue plasminogen activator (rt-PA) is unclear.
Structural graph-based morphometry: A multiscale searchlight framework based on sulcal pits.
Medical image analysis, 2017

Studying the topography of the cortex has proved valuable in order to characterize populations of subjects. In particular, the recent interest towards the deepest parts of the cortical sulci - the so-called sulcal pits - has opened new avenues in that regard. In this paper, we introduce the first fully automatic brain morphometry method based on the study of the spatial organization of sulcal pits - Structural Graph-Based Morphometry (SGBM). Our framework uses attributed graphs to model local patterns of sulcal pits, and further relies on three original contributions. First, a graph kernel is defined to provide a new similarity measure between pit-graphs, with few parameters that can be efficiently estimated from the data. Secondly, we present the first searchlight scheme dedicated to brain morphometry, yielding dense information maps covering the full cortical surface. Finally, a multi-scale inference strategy is designed to jointly analyze the searchlight information maps obtained at different spatial scales. We demonstrate the effectiveness of our framework by studying gender differences and cortical asymmetries: we show that SGBM can both localize informative regions and estimate their spatial scales, while providing results which are consistent with the literature. Thanks to the modular design of our kernel and the vast array of available kernel methods, SGBM can easily be extended to include a more detailed description of the sulcal patterns and solve different statistical problems. Therefore, we suggest that our SGBM framework should be useful for both reaching a better understanding of the normal brain and defining imaging biomarkers in clinical settings.
Cooperative tool-use reveals peripersonal and interpersonal spaces are dissociable.
Cognition, 2017

The space surrounding people is often termed Interpersonal (IPS) in social psychology and Peripersonal (PPS) in neuroscience. In the current debate about their origin, the prevalent opinion is they share common functional characteristics. Bucking the trend, here we report a dissociation between PPS, operationalized as reachable space, and IPS, operationalized as comfort space. To probe their plasticity we introduced a novel type of cooperative long-tool-use that would modify both spaces. Results showed the estimated IPS referred to another individual was reduced, as expected following a positive social interaction. In sharp contrast, the estimated PPS toward the very same cooperative person was actually extended after use of the same long-tool. Control short-tool-use selectively reduced IPS, but not PPS, when performed in the same cooperative set or had no effect on either space estimation, when performed in a neutral set where the other person is not interacting cooperatively, but simply observing. The use of tools to perform actions in social settings allows us to report the first strong evidence that PPS and IPS underlie dissociable plastic representations: the former representation is sensitive to long-tool-dependent plasticity, whereas the latter representation, independently of use of a short or long tool, is sensitive to cooperation-dependent plasticity.
Altered vision destabilizes gait in older persons.
Gait & posture, 2009

This study assessed the effects of dim light and four experimentally induced changes in vision on gait speed and footfall and trunk parameters in older persons walking on level ground. Using a quasi-experimental design, gait characteristics were assessed in full light, dim light, and in dim light combined with manipulations resulting in reduced depth vision, double vision, blurred vision, and tunnel vision, respectively. A convenience sample of 24 home-dwelling older women and men (mean age 78.5 years, SD 3.4) with normal vision for their age and able to walk at least 10 m without assistance participated. Outcome measures were gait speed and spatial and temporal parameters of footfall and trunk acceleration, derived from an electronic gait mat and accelerometers. Dim light alone had no effect. Vision manipulations combined with dim light had effect on most footfall parameters but few trunk parameters. The largest effects were found regarding double and tunnel vision. Men increased and women decreased gait speed following manipulations (p=0.017), with gender differences also in stride velocity variability (p=0.017) and inter-stride medio-lateral trunk acceleration variability (p=0.014). Gender effects were related to differences in body height and physical functioning. Results indicate that visual problems lead to a more cautious and unstable gait pattern even under relatively simple conditions. This points to the importance of assessing vision in older persons and correcting visual impairments where possible.
Perception of animacy and direction from local biological motion signals.
Journal of vision, 2008

We present three experiments that investigated the perception of animacy and direction from local biological motion cues. Coherent and scrambled point-light displays of humans, cats, and pigeons that were upright or inverted were embedded in a random dot mask and presented to naive observers. Observers assessed the animacy of the walker on a six-point Likert scale in Experiment 1, discriminated the direction of walking in Experiment 2, and completed both the animacy rating and the direction discrimination tasks in Experiment 3. We show that like the ability to discriminate direction, the perception of animacy from scrambled displays that contain solely local cues is orientation specific and can be well-elicited within exposure times as short as 200 ms. We show further that animacy ratings attributed to our stimuli are linearly correlated with the ability to discriminate their direction of walking. We conclude that the mechanisms responsible for processing local biological motion signals not only retrieve locomotive direction but also aid in assessing the presence of animate agents in the visual environment.