rudyvdbrink/CitationDatabase huggingface dataset:
Dynamics of EEG rhythms support distinct visual selection mechanisms in parietal cortex: a simultaneous transcranial magnetic stimulation and EEG study.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2015

Using repetitive transcranial magnetic stimulation (rTMS), we have recently shown a functional anatomical distinction in human parietal cortex between regions involved in maintaining attention to a location [ventral intraparietal sulcus (vIPS)] and a region involved in shifting attention between locations [medial superior parietal lobule (mSPL)]. In particular, while rTMS interference over vIPS impaired target discrimination at contralateral attended locations, interference over mSPL affected performance following shifts of attention regardless of the visual field (Capotosto et al., 2013). Here, using rTMS interference in conjunction with EEG recordings of brain rhythms during the presentation of cues that indicate to either shift or maintain spatial attention, we tested whether this functional anatomical segregation involves different mechanisms of rhythm synchronization. The transient inactivation of vIPS reduced the amplitude of the expected parieto-occipital low-α (8-10 Hz) desynchronization contralateral to the cued location. Conversely, the transient inactivation of mSPL, compared with vIPS, reduced the high-α (10-12 Hz) desynchronization induced by shifting attention into both visual fields. Furthermore, rTMS induced a frequency-specific delay of task-related modulation of brain rhythms. Specifically, rTMS over vIPS or mSPL during maintenance (stay cues) or shifting (shift cues) of spatial attention, respectively, caused a delay of α parieto-occipital desynchronization. Moreover, rTMS over vIPS during stay cues caused a delay of δ (2-4 Hz) frontocentral synchronization. These findings further support the anatomo-functional subdivision of the dorsal attention network in subsystems devoted to shifting or maintaining covert visuospatial attention and indicate that these mechanisms operate in different frequency channels linking frontal to parieto-occipital visual regions.
Evidence for muscle-dependent neuromuscular synaptic site determination in mammals.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2008

Recent evidence challenges the prevalent view that neural factors induce the formation of a de novo postsynaptic apparatus during development of the vertebrate neuromuscular junction. The latest experiments suggest an alternative model in which the muscle fiber induces a nascent postsynaptic apparatus and sets the location of the future synapse. On axonal contact, these sites, laid out in a prepattern in the central area of developing muscle fibers, mature into synapses by the combined action of neural factors such as agrin and ACh. We sought to test in mammals these two models of neuromuscular synaptogenesis. Previously, we showed that continuous prenatal muscle expression of constitutively active ErbB2 (CAErbB2) led to synaptic loss, exuberant axonal sprouting, and lethality at birth. Here, we transiently induced CAErbB2 during midgestation and examined synapse restoration after inducer withdrawal. Centrally enriched ACh receptor (AChR) transcription and clustering were abolished after transient CAErbB2 induction. After inducer withdrawal, synapses were restored but were distributed widely over the entire diaphragm muscle. Under the nerve-dependent model, this distribution is explained by the wide pattern of axonal sprouting triggered by CAErbB2. Yet, in the absence of the nerve, introduced in our animals by mating to Hb9(+/-) mice, a very similar, wide distribution of aneural AChR clusters resulted. Thus, transient expression of CAErbB2 in skeletal muscles leads to reprogramming of the endogenous muscle AChR prepattern. This, and not the nerve, seems primarily responsible for the widely distributed pattern of synapses in our experimental animals.
Mental health problems and fear of childbirth: A cohort study of women in an inner-city maternity service.
Birth (Berkeley, Calif.), 2021

To estimate the population prevalence of severe fear of childbirth (FOC) during pregnancy and investigate its association with: (a) antenatal common mental disorders (depression and anxiety disorder) and (b) elective cesarean birth.
Shisa6 traps AMPA receptors at postsynaptic sites and prevents their desensitization during synaptic activity.
Nature communications, 2016

Trafficking and biophysical properties of AMPA receptors (AMPARs) in the brain depend on interactions with associated proteins. We identify Shisa6, a single transmembrane protein, as a stable and directly interacting bona fide AMPAR auxiliary subunit. Shisa6 is enriched at hippocampal postsynaptic membranes and co-localizes with AMPARs. The Shisa6 C-terminus harbours a PDZ domain ligand that binds to PSD-95, constraining mobility of AMPARs in the plasma membrane and confining them to postsynaptic densities. Shisa6 expressed in HEK293 cells alters GluA1- and GluA2-mediated currents by prolonging decay times and decreasing the extent of AMPAR desensitization, while slowing the rate of recovery from desensitization. Using gene deletion, we show that Shisa6 increases rise and decay times of hippocampal CA1 miniature excitatory postsynaptic currents (mEPSCs). Shisa6-containing AMPARs show prominent sustained currents, indicating protection from full desensitization. Accordingly, Shisa6 prevents synaptically trapped AMPARs from depression at high-frequency synaptic transmission.
The neuroscience of intergroup emotion.
Current opinion in psychology, 2018

What happens to our emotions and in our brains when we experience the world through the lens of our group memberships rather than as individuals? Here we review recent advances in social and affective neuroscience that have identified potential input variables and processing mechanisms underlying one widely studied emotion in intergroup contexts: empathy. There is a well-documented in-group bias in empathy but the mental processes that generate it are poorly understood. Drawing from recent insights in memory research, we suggest that episodic simulation-the ability to imagine events-is an underexplored candidate process that is likely to be involved in shaping emotional experience in intergroup settings.
Novel Alzheimer risk genes determine the microglia response to amyloid-β but not to TAU pathology.
EMBO molecular medicine, 2020

Polygenic risk scores have identified that genetic variants without genome-wide significance still add to the genetic risk of developing Alzheimer's disease (AD). Whether and how subthreshold risk loci translate into relevant disease pathways is unknown. We investigate here the involvement of AD risk variants in the transcriptional responses of two mouse models: APPswe/PS1
Associations of ambulatory blood pressure with urinary caffeine and caffeine metabolite excretions.
Hypertension (Dallas, Tex. : 1979), 2015

Intake of caffeinated beverages might be associated with reduced cardiovascular mortality possibly via the lowering of blood pressure. We estimated the association of ambulatory blood pressure with urinary caffeine and caffeine metabolites in a population-based sample. Families were randomly selected from the general population of Swiss cities. Ambulatory blood pressure monitoring was conducted using validated devices. Urinary caffeine, paraxanthine, theophylline, and theobromine excretions were measured in 24 hours urine using ultrahigh performance liquid chromatography tandem mass spectrometry. We used mixed models to explore the associations of urinary excretions with blood pressure although adjusting for major confounders. The 836 participants (48.9% men) included in this analysis had mean age of 47.8 and mean 24-hour systolic and diastolic blood pressure of 120.1 and 78.0 mm Hg. For each doubling of caffeine excretion, 24-hour and night-time systolic blood pressure decreased by 0.642 and 1.107 mm Hg (both P values <0.040). Similar inverse associations were observed for paraxanthine and theophylline. Adjusted night-time systolic blood pressure in the first (lowest), second, third, and fourth (highest) quartile of paraxanthine urinary excretions were 110.3, 107.3, 107.3, and 105.1 mm Hg, respectively (P trend <0.05). No associations of urinary excretions with diastolic blood pressure were generally found, and theobromine excretion was not associated with blood pressure. Anti-hypertensive therapy, diabetes mellitus, and alcohol consumption modify the association of caffeine urinary excretion with systolic blood pressure. Ambulatory systolic blood pressure was inversely associated with urinary excretions of caffeine and other caffeine metabolites. Our results are compatible with a potential protective effect of caffeine on blood pressure.
Influence of age and posture on spinal and corticospinal excitability.
Experimental gerontology, 2015

This study investigated the modulation of the excitability of spinal and corticospinal pathways from seated to upright standing across adult lifespan. The input-output relations for the Hoffmann (H) reflex and motor-evoked potential (MEP) were recorded in soleus muscle during seated and upright posture in 40 subjects assigned to either young (range: 19-39yrs, n=16), middle-aged (40-59yrs, n=12), and elderly group (60-76yrs, n=12). In seated posture, H reflex and MEP were recorded during voluntary contractions of the ankle plantar flexors inducing similar soleus electromyographic activity that during upright standing. Maximal H-reflex and MEP amplitude (Hmax, MEPmax), and the change in response amplitude from seated to standing were analyzed. The Hmax decreased with age (p=0.001) and from seated to standing (p<0.001). The change in Hmax from seated to standing was greater in elderly (-40.1%; p<0.05) compared with young (-20.7%) and middle-aged groups (-23.7%). MEPmax increased with age and from seated to standing (p<0.001). The change in MEPmax from seated to standing did not differ (p>0.05) between young (+53.6%), middle-aged (+43.2%) and elderly groups (+77.3%). These results indicate a posture-related modulation of the excitability of spinal and corticospinal pathways regardless of age, with a more pronounced modulation of spinal pathway in elderly adults. This study further documents the time course of decrease and increase in spinal and corticospinal excitability, respectively, across adult lifespan.
Metabotropic glutamate receptor 5 is a coreceptor for Alzheimer aβ oligomer bound to cellular prion protein.
Neuron, 2013

Soluble amyloid-β oligomers (Aβo) trigger Alzheimer's disease (AD) pathophysiology and bind with high affinity to cellular prion protein (PrP(C)). At the postsynaptic density (PSD), extracellular Aβo bound to lipid-anchored PrP(C) activates intracellular Fyn kinase to disrupt synapses. Here, we screened transmembrane PSD proteins heterologously for the ability to couple Aβo-PrP(C) with Fyn. Only coexpression of the metabotropic glutamate receptor, mGluR5, allowed PrP(C)-bound Aβo to activate Fyn. PrP(C) and mGluR5 interact physically, and cytoplasmic Fyn forms a complex with mGluR5. Aβo-PrP(C) generates mGluR5-mediated increases of intracellular calcium in Xenopus oocytes and in neurons, and the latter is also driven by human AD brain extracts. In addition, signaling by Aβo-PrP(C)-mGluR5 complexes mediates eEF2 phosphorylation and dendritic spine loss. For mice expressing familial AD transgenes, mGluR5 antagonism reverses deficits in learning, memory, and synapse density. Thus, Aβo-PrP(C) complexes at the neuronal surface activate mGluR5 to disrupt neuronal function.
Nicotinic acetylcholine receptors: Conventional and unconventional ligands and signaling.
Neuropharmacology, 2020

Postsynaptic nAChRs in the peripheral nervous system are critical for neuromuscular and autonomic neurotransmission. Pre- and peri-synaptic nAChRs in the brain modulate neurotransmission and are responsible for the addictive effects of nicotine. Subtypes of nAChRs in lymphocytes and non-synaptic locations may modulate inflammation and other cellular functions. All AChRs that function as ligand-gated ion channels are formed from five homologous subunits organized to form a central cation channel whose opening is regulated by ACh bound at extracellular subunit interfaces. nAChR subtype subunit composition can range from α7 homomers to α4β2α6β2β3 heteromers. Subtypes differ in affinities for ACh and other agonists like nicotine and in efficiencies with which their channels are opened and desensitized. Subtypes also differ in affinities for antagonists and for positive and negative allosteric modulators. Some agonists are "silent" with respect to channel opening, and AChRs may be able to signal metabotropic pathways by releasing G-proteins independent of channel opening. Electrophysiological studies that can resolve single-channel openings and molecular genetic approaches have allowed characterization of the structures of ligand binding sites, the cation channel, and the linkages between them, as well as the organization of AChR subunits and their contributions to function. Crystallography and cryo-electron-microscopy are providing increasing insights into the structures and functions of AChRs. However, much remains to be learned about both AChR structure and function, the in vivo functional roles of some AChR subtypes, and the development of better pharmacological tools directed at AChRs to treat addiction, pain, inflammation, and other medically important issues. This article is part of the special issue on 'Contemporary Advances in Nicotine Neuropharmacology'.
Classics in Chemical Neuroscience: Pramipexole.
ACS chemical neuroscience, 2020

Pramipexole was first manufactured by Pharmacia and Upjohn in July 1997 under the United States brand names of Mirapex and Mirapex ER. Pramipexole is classified as a nonergoline aminobenzothiazole compound that selectively agonizes the dopamine D
A neurally plausible parallel distributed processing model of event-related potential word reading data.
Brain and language, 2012

The Parallel Distributed Processing (PDP) framework has significant potential for producing models of cognitive tasks that approximate how the brain performs the same tasks. To date, however, there has been relatively little contact between PDP modeling and data from cognitive neuroscience. In an attempt to advance the relationship between explicit, computational models and physiological data collected during the performance of cognitive tasks, we developed a PDP model of visual word recognition which simulates key results from the ERP reading literature, while simultaneously being able to successfully perform lexical decision-a benchmark task for reading models. Simulations reveal that the model's success depends on the implementation of several neurally plausible features in its architecture which are sufficiently domain-general to be relevant to cognitive modeling more generally.
The Gist of Juries: Testing a Model of Damage Award Decision Making.
Psychology, public policy, and law : an official law review of the University of Arizona College of Law and the University of Miami School of Law, 2015

Despite the importance of damage awards, juries are often at sea about the amounts that should be awarded, with widely differing awards for cases that seem comparable. We tested a new model of damage award decision making by systematically varying the size, context, and meaningfulness of numerical comparisons or anchors. As a result, we were able to elicit large differences in award amounts that replicated for 2 different cases. Although even arbitrary dollar amounts (unrelated to the cases) influenced the size of award judgments, the most consistent effects of numerical anchors were achieved when the amounts were meaningful in the sense that they conveyed the gist of numbers as small or large. Consistent with the model, the ordinal gist of the severity of plaintiff's damages and defendant's liability predicted damage awards, controlling for other factors such as motivation for the award-judgment task and perceived economic damages. Contrary to traditional dual-process approaches, numeracy and cognitive style (e.g., need for cognition and cognitive reflection) were not significant predictors of these numerical judgments, but they were associated with lower levels of variability once the gist of the judgments was taken into account. Implications for theory and policy are discussed.
An Angiopep2-PAPTP Construct Overcomes the Blood-Brain Barrier. New Perspectives against Brain Tumors.
Pharmaceuticals (Basel, Switzerland), 2021

A developing family of chemotherapeutics-derived from 5-(4-phenoxybutoxy)psoralen (PAP-1)-target mitochondrial potassium channel mtKv1.3 to selectively induce oxidative stress and death of diseased cells. The key to their effectiveness is the presence of a positively charged triphenylphosphonium group which drives their accumulation in the organelles. These compounds have proven their preclinical worth in murine models of cancers such as melanoma and pancreatic adenocarcinoma. In
The lab on lockdown: thinking back and looking ahead.
Nature reviews. Neuroscience, 2020

The shuttering of labs across nations during the COVID-19 pandemic created significant complexities related to remote lab management and ongoing research. The lessons learned may provide opportunities for new ways of working in the post-pandemic era.
The association between metacognitions and the impact of Fibromyalgia in a German sample.
Journal of psychosomatic research, 2016

Fibromyalgia is a chronic condition of unknown aetiology, characterised by widespread pain, sleep disturbances, and fatigue. In this paper we examined the relationship metacognitions and the impact of Fibromyalgia in a German sample, detailing the translation and validation of a self-report metacognitive instrument.
Harnessing region-specific neurovascular signaling to promote germinal matrix vessel maturation and hemorrhage prevention.
Disease models & mechanisms, 2019

Germinal matrix hemorrhage (GMH), affecting about 1 in 300 births, is a major perinatal disease with lifelong neurological consequences. Yet despite advances in neonatal medicine, there is no effective intervention. GMH is characterized by localized bleeding in the germinal matrix (GM), due to inherent vessel fragility unique to this developing brain region. Studies have shown that reduced TGFβ signaling contributes to this vascular immaturity. We have previously shown that a region-specific G-protein-coupled receptor pathway in GM neural progenitor cells regulates integrin β8, a limiting activator of pro-TGFβ. In this study, we use mice to test whether this regional pathway can be harnessed for GMH intervention. We first examined the endogenous dynamics of this pathway and found that it displays specific patterns of activation. We then investigated the functional effects of altering these dynamics by chemogenetics and found that there is a narrow developmental window during which this pathway is amenable to manipulation. Although high-level activity in this time window interferes with vessel growth, moderate enhancement promotes vessel maturation without compromising growth. Furthermore, we found that enhancing the activity of this pathway in a mouse model rescues all GMH phenotypes. Altogether, these results demonstrate that enhancing neurovascular signaling through pharmacological targeting of this pathway may be a viable approach for tissue-specific GMH intervention. They also demonstrate that timing and level are likely two major factors crucial for success. These findings thus provide critical new insights into both brain neurovascular biology and the intervention of GMH.
Intrinsic excitation-inhibition imbalance affects medial prefrontal cortex differently in autistic men versus women.
eLife, 2020

Excitation-inhibition (E:I) imbalance is theorized as an important pathophysiological mechanism in autism. Autism affects males more frequently than females and sex-related mechanisms (e.g., X-linked genes, androgen hormones) can influence E:I balance. This suggests that E:I imbalance may affect autism differently in males versus females. With a combination of in-silico modeling and in-vivo chemogenetic manipulations in mice, we first show that a time-series metric estimated from fMRI BOLD signal, the Hurst exponent (H), can be an index for underlying change in the synaptic E:I ratio. In autism we find that H is reduced, indicating increased excitation, in the medial prefrontal cortex (MPFC) of autistic males but not females. Increasingly intact MPFC H is also associated with heightened ability to behaviorally camouflage social-communicative difficulties, but only in autistic females. This work suggests that H in BOLD can index synaptic E:I ratio and that E:I imbalance affects autistic males and females differently.
Transient relay function of midline thalamic nuclei during long-term memory consolidation in humans.
Learning & memory (Cold Spring Harbor, N.Y.), 2015

To test the hypothesis that thalamic midline nuclei play a transient role in memory consolidation, we reanalyzed a prospective functional MRI study, contrasting recent and progressively more remote memory retrieval. We revealed a transient thalamic connectivity increase with the hippocampus, the medial prefrontal cortex (mPFC), and a parahippocampal area, which decreased with time. In turn, mPFC-parahippocampal connectivity increased progressively. These findings support a model in which thalamic midline nuclei serve as a hub linking hippocampus, mPFC, and posterior representational areas during memory retrieval at an early (2 h) stage of consolidation, extending classical systems consolidation models by attributing a transient role to midline thalamic nuclei.
The regulation and packaging of synaptic vesicles as related to recruitment within glutamatergic synapses.
Neuroscience, 2012

The reserve pool (RP) and readily releasable pool (RRP) of synaptic vesicles within presynaptic nerve terminals, at crayfish and larval Drosophila neuromuscular junctions (NMJs), were examined for physiological differentiation into distinctly separate functional groups. These NMJs are glutamatergic and produce graded excitatory postsynaptic potentials (EPSPs). The packaging of glutamate was perturbed by blocking the vesicular glutamate transporter (VGlut) with bafilomycin A1. Various frequencies of motor nerve stimulation, exposure time, and concentration of bafilomycin A1 were examined. The low-output tonic opener NMJs in crayfish exposed to 4 μM bafilomycin A1 and 20-Hz continuous stimulation decreased the EPSP amplitude to 50% in ∼30 min with controls lasting 3h. After activity and bafilomycin A1-induced synaptic depression, the EPSPs were rapidly revitalized by serotonin (5-HT, 1 μM) in the crayfish preparations. The 5-HT action can be blocked with a PLC inhibitor. We postulate 5-HT recruits unused vesicles from the RP. The perception is the RRP is selectively activated during rapid electrical stimulation (20 Hz) sparing the RP. When stimulation frequency is high (40 Hz) the RP is recruited to the RRP and dampens subsequent recruitment with 5-HT. The higher output synapses of the larval Drosophila NMJ when stimulated at 1 Hz or 5 Hz and exposed to 4 μM of bafilomycin A1 showed a depression rate of 50% within ∼10 min with controls lasting ∼40 min. After low frequency depression and/or exposure to bafilomycin A1 a burst of higher frequency (10 Hz) can recruit vesicles from the RP to the RRP.