rudyvdbrink/CitationDatabase huggingface dataset:
Auditory nerve perinodal dysmyelination in noise-induced hearing loss.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014

Exposure to loud sound (acoustic overexposure; AOE) induces hearing loss and damages cellular structures at multiple locations in the auditory pathway. Whether AOE can also induce changes in myelin sheaths of the auditory nerve (AN) is an important issue particularly because these changes can be responsible for impaired action potential propagation along the AN. Here we investigate the effects of AOE on morphological and electrophysiological features of the centrally directed part of the rat AN projecting from the cochlear spiral ganglion to brainstem cochlear nuclei. Using electron microscopy and immunocytochemistry, we show that AOE elongates the AN nodes of Ranvier and triggers notable perinodal morphological changes. Compound action potential recordings of the AN coupled to biophysical modeling demonstrated that these nodal and perinodal structural changes were associated with decreased conduction velocity and conduction block. Furthermore, AOE decreased the number of release sites in the cochlear nuclei associated with the reduced amplitudes of EPSCs evoked by AN stimulation. In conclusion, AN dysmyelination may be of fundamental importance in auditory impairment following exposure to loud sound.
Neurocognitive Functioning in Unoperated Adults with Chiari Malformation Type I.
World neurosurgery, 2019

Adults with Chiari malformation type 1 (CM1) often report cognitive impairment. This cross-sectional study investigates the cognitive and emotional functioning of a sample of adults with CM1 who presented for neurosurgical evaluation prior to intervention.
Lesion evidence for the critical role of the intraparietal sulcus in spatial attention.
Brain : a journal of neurology, 2011

Based on lesion mapping studies, the inferior parietal lobule and temporoparietal junction are considered the critical parietal regions for spatial-attentional deficits. Lesion evidence for a key role of the intraparietal sulcus, a region featuring prominently in non-human primate studies and human functional imaging studies of the intact brain, is still lacking, probably due to the exceptional nature of isolated intraparietal sulcus lesions. We combined behavioural testing and functional imaging in two patients with a focal intraparietal sulcus lesion sparing the inferior parietal lobule and temporoparietal junction to examine the critical contribution of the intraparietal sulcus to spatial attention. Case H.H. had a focal ischaemic lesion (1.8 cm3) that was confined to the posterior segment of the left intraparietal sulcus, whereas Case N.V. had a partially reversible lesion of the middle segment of the right intraparietal sulcus extending into the superior parietal lobule (13.8 cm3). The performance of these cases was contrasted with five cases with a classical inferior parietal lesion, as well as with a group of 31 age-matched controls. In the behavioural study, the patients performed an orientation discrimination task on a peripheral target (eccentricity 7.6°) that was preceded by a central spatial cue. We manipulated both the cue validity (17% trials with an invalid spatial cue) and the presence of a competing distracter in the visual field contralateral to the target (17% double stimulation trials). The ability of the patients with an intraparietal sulcus lesion to reorient their spatial focus of attention and to select between competing stimuli was impaired for contralesional targets compared with controls, similarly to what we saw in the inferior parietal group. Furthermore, we could observe that the deficit in Case N.V. resolved with regression of the lesion. To further evaluate the correspondence between spatial-attentional deficits and the intraparietal sulcus lesions, we ascertained the functional integrity of the inferior parietal lobule and temporoparietal junction in Case H.H. using event-related functional magnetic resonance imaging with the same task as in the behavioural study. The intraparietal sulcus lesion of this patient did not affect the task-related activation of the inferior parietal lobule or temporoparietal junction. Additionally, a resting-state functional magnetic resonance imaging study in Case H.H. and 62 controls revealed that the lesion in Case H.H. did not affect the topology of the ventral attention network nor the strength of its main inter- and intrahemispheric connections. Our findings demonstrate that the human superior parietal cortex critically contributes to spatially selective attention.
Interventions for Children Affected by Armed Conflict: a Systematic Review of Mental Health and Psychosocial Support in Low- and Middle-Income Countries.
Current psychiatry reports, 2016

Over one billion children under the age of 18 live in countries affected by armed conflict. This systematic review replicates an earlier study, aiming to provide a comprehensive update of the most current developments in interventions for children affected by armed conflict. For the period 2009-2015, a total of 1538 records were collected from PubMed, PsycINFO, and PILOTS. Twenty-four studies met the inclusion criteria, and the included interventions involve data from 4858 children. Although the number of publications and level of evidence has improved since the previous review, there is still a general lack of rigor and clarity in study design and reported results. Overall, interventions appeared to show promising results demonstrating mostly moderate effect sizes on mental health and psychosocial well-being. However, these positive intervention benefits are often limited to specific subgroups. There is a need for increased diversification in research focus, with more attention to interventions that focus at strengthening community and family support, and to young children, and improvements in targeting and conceptualizing of interventions.
Hand dexterity and direct disease related cost in multiple sclerosis.
Journal of the neurological sciences, 2014

The nine hole peg test (9HPT) is an emerging outcome measure in clinical trials in multiple sclerosis (MS). In this study we investigated how performance on the 9HPT at baseline is related to annualized direct MS related cost.
Investigation of patient and observer agreement on description of seizures at initial clinical visit.
Annals of clinical and translational neurology, 2019

There have been few studies of agreement between seizure descriptions obtained from patients and observers. We investigated 220 patients and observers who completed structured questionnaires about patients' semiological seizure features at the initial clinical visit. Inter-rater reliability was assessed using Cohen's kappa and indices of positive and negative agreement. Patients and observers had excellent agreement on the presence of memory impairment and generalized shaking and stiffness during seizures. In addition, patients under-reported seizure descriptions more easily observed externally, whereas observers under-reported change in patient location at seizure end. These findings may guide interpretation of clinical histories obtain in epilepsy care.
Right Brodmann area 18 predicts tremor arrest after Vim radiosurgery: a voxel-based morphometry study.
Acta neurochirurgica, 2018

Drug-resistant essential tremor (ET) can benefit from open standard stereotactic procedures, such as deep-brain stimulation or radiofrequency thalamotomy. Non-surgical candidates can be offered either high-focused ultrasound (HIFU) or radiosurgery (RS). All procedures aim to target the same thalamic site, the ventro-intermediate nucleus (e.g., Vim). The mechanisms by which tremor stops after Vim RS or HIFU remain unknown. We used voxel-based morphometry (VBM) on pretherapeutic neuroimaging data and assessed which anatomical site would best correlate with tremor arrest 1 year after Vim RS.
Brain responses to anticipating and receiving beer: Comparing light, at-risk, and dependent alcohol users.
Addiction biology, 2020

Impaired brain processing of alcohol-related rewards has been suggested to play a central role in alcohol use disorder. Yet, evidence remains inconsistent and mainly originates from studies in which participants passively observe alcohol cues or taste alcohol. Here, we designed a protocol in which beer consumption was predicted by incentive cues and contingent on instrumental action closer to real life situations. We predicted that anticipating and receiving beer (compared with water) would elicit activity in the brain reward network and that this activity would correlate with drinking level across participants. The sample consisted of 150 beer-drinking males, aged 18 to 25 years. Three groups were defined based on alcohol use disorders identification test (AUDIT) scores: light drinkers (n = 39), at-risk drinkers (n = 64), and dependent drinkers (n = 47). fMRI measures were obtained while participants engaged in the beer incentive delay task involving beer- and water-predicting cues followed by real sips of beer or water. During anticipation, outcome notification and delivery of beer compared with water, higher activity was found in a reward-related brain network including the dorsal medial prefrontal cortex, orbitofrontal cortex, and amygdala. Yet, no activity was observed in the striatum, and no differences were found between the groups. Our results reveal that anticipating, obtaining, and tasting beer activates parts of the brain reward network, but that these brain responses do not differentiate between different drinking levels.
Retinotopy and attention in human occipital, temporal, parietal, and frontal cortex.
Cerebral cortex (New York, N.Y. : 1991), 2008

Novel mapping stimuli composed of biological motion figures were used to study the extent and layout of multiple retinotopic regions in the entire human brain and to examine the independent manipulation of retinotopic responses by visual stimuli and by attention. A number of areas exhibited retinotopic activations, including full or partial visual field representations in occipital cortex, the precuneus, motion-sensitive temporal cortex (extending into the superior temporal sulcus), the intraparietal sulcus, and the vicinity of the frontal eye fields in frontal cortex. Early visual areas showed mainly stimulus-driven retinotopy; parietal and frontal areas were driven primarily by attention; and lateral temporal regions could be driven by both. We found clear spatial specificity of attentional modulation not just in early visual areas but also in classical attentional control areas in parietal and frontal cortex. Indeed, strong spatiotopic activity in these areas could be evoked by directed attention alone. Conversely, motion-sensitive temporal regions, while exhibiting attentional modulation, also responded significantly when attention was directed away from the retinotopic stimuli.
Caloric restriction and the adipokine leptin alter the SDF-1 signaling axis in bone marrow and in bone marrow derived mesenchymal stem cells.
Molecular and cellular endocrinology, 2015

Growing evidence suggests that the chemokine stromal cell-derived factor-1 (SDF-1) is essential in regulating bone marrow (BM) derived mesenchymal stromal/stem cell (BMSC) survival, and differentiation to either a pro-osteogenic or pro-adipogenic fate. This study investigates the effects of caloric restriction (CR) and leptin on the SDF-1/CXCR4 axis in bone and BM tissues in the context of age-associated bone loss. For in vivo studies, we collected bone, BM cells and BM interstitial fluid from 12 and 20 month-old C57Bl6 mice fed ad-libitum (AL), and 20-month-old mice on long-term CR with, or without, intraperitoneal injection of leptin for 10 days (10 mg/kg). To mimic conditions of CR in vitro, 18 month murine BMSCs were treated with (1) control (Ctrl): normal proliferation medium, (2) nutrient restriction (NR): low glucose, low serum medium, or (3) NR + leptin: NR medium + 100 ng/ml leptin for 6-48 h. In BMSCs both protein and mRNA expression of SDF-1 and CXCR4 were increased by CR and CR + leptin. In contrast, the alternate SDF-1 receptor CXCR7 was decreased, suggesting a nutrient signaling mediated change in SDF-1 axis signaling in BMSCs. However, in bone SDF-1, CXCR4 and 7 gene expression increase with age and this is reversed with CR, while addition of leptin returns this to the "aged" level. Histologically bone formation was lower in the calorically restricted mice and BM adipogenesis increased, both effects were reversed with the 10 day leptin treatment. This suggests that in bone CR and leptin alter the nutrient signaling pathways in different ways to affect the local action of the osteogenic cytokine SDF-1. Studies focusing on the molecular interaction between nutrient signaling by CR, leptin and SDF-1 axis may help to address age-related musculoskeletal changes.
Acetylation of microtubules influences their sensitivity to severing by katanin in neurons and fibroblasts.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2010

Here we investigated whether the sensitivity of microtubules to severing by katanin is regulated by acetylation of the microtubules. During interphase, fibroblasts display long microtubules with discrete regions rich in acetylated tubulin. Overexpression of katanin for short periods of time produced breaks preferentially in these regions. In fibroblasts with experimentally enhanced or diminished microtubule acetylation, the sensitivity of the microtubules to severing by katanin was increased or decreased, respectively. In neurons, microtubules are notably more acetylated in axons than in dendrites. Experimental manipulation of microtubule acetylation in neurons yielded similar results on dendrites as observed on fibroblasts. However, under these experimental conditions, axonal microtubules were not appreciably altered with regard to their sensitivity to katanin. We hypothesized that this may be attributable to the effects of tau on the axonal microtubules, and this was validated by studies in which overexpression of tau caused microtubules in dendrites and fibroblasts to be more resistant to severing by katanin in a manner that was not dependent on the acetylation state of the microtubules. Interestingly, none of these various findings apply to spastin, because the severing of microtubules by spastin does not appear to be strongly influenced by either the acetylation state of the microtubules or tau. We conclude that sensitivity to microtubule severing by katanin is regulated by a balance of factors, including the acetylation state of the microtubules and the binding of tau to the microtubules. In the neuron, this contributes to regional differences in the microtubule arrays of axons and dendrites.
The distinct roles of two GPCRs, MrgprC11 and PAR2, in itch and hyperalgesia.
Science signaling, 2011

Itch has been defined as an unpleasant skin sensation that triggers the urge to scratch. Primary sensory dorsal root ganglia neurons detect itch stimuli through peripheral axons in the skin, playing an important role in generating itch. Itch is broadly categorized as histaminergic (sensitive to antihistamines) or nonhistaminergic. The peptide Ser-Leu-Ile-Gly-Arg-Leu (SLIGRL) is an itch-inducing agent widely used to study histamine-independent itch. Here, we show that Mrgprs (Mas-related G protein-coupled receptors), particularly MrgprC11, rather than PAR2 (protease-activated receptor 2) as previously thought, mediate this type of itch. A shorter peptide, SLIGR, which specifically activates PAR2 but not MrgprC11, induced thermal pain hypersensitivity in mice but not a scratch response. Therefore, although both Mrgpr and PAR2 are SLIGRL-responsive G protein-coupled receptors present in dorsal root ganglia, each plays a specific role in mediating itch and pain.
A causal role for TRESK loss of function in migraine mechanisms.
Brain : a journal of neurology, 2019

The two-pore potassium channel, TRESK has been implicated in nociception and pain disorders. We have for the first time investigated TRESK function in human nociceptive neurons using induced pluripotent stem cell-based models. Nociceptors from migraine patients with the F139WfsX2 mutation show loss of functional TRESK at the membrane, with a corresponding significant increase in neuronal excitability. Furthermore, using CRISPR-Cas9 engineering to correct the F139WfsX2 mutation, we show a reversal of the heightened neuronal excitability, linking the phenotype to the mutation. In contrast we find no change in excitability in induced pluripotent stem cell derived nociceptors with the C110R mutation and preserved TRESK current; thereby confirming that only the frameshift mutation is associated with loss of function and a migraine relevant cellular phenotype. We then demonstrate the importance of TRESK to pain states by showing that the TRESK activator, cloxyquin, can reduce the spontaneous firing of nociceptors in an in vitro human pain model. Using the chronic nitroglycerine rodent migraine model, we demonstrate that mice lacking TRESK develop exaggerated nitroglycerine-induced mechanical and thermal hyperalgesia, and furthermore, show that cloxyquin conversely is able to prevent sensitization. Collectively, our findings provide evidence for a role of TRESK in migraine pathogenesis and its suitability as a therapeutic target.
The effect of Wi-Fi electromagnetic waves on neuronal response properties in rat barrel cortex.
Somatosensory & motor research, 2019

There is a growing number of studies on the possible biological effects of Wi-Fi radiations on nervous system. In this study we investigated the effect of Wi-Fi exposure on single neuron responses to natural stimuli by using whisker to barrel pathway. This study was done on 29 male Wistar rats. Neuronal spontaneous activity and ON and OFF responses to displacement of principal whisker (PW), adjacent whisker (AW) and combination of PW-AW stimulation (as natural stimuli) were recorded in barrel cortex of anaesthetised rats. A D-link Wi-Fi device was used for 1 h exposure to 2.4 GHz microwaves in data mode (18.2 dBm and 44% for power and duty cycle). A condition test ratio (CTR) was calculated for assessing neuronal integrative properties. Wi-Fi radiations decreased CTR for ON responses. However, neuronal spontaneous activity and ON and OFF responses were not significantly changed following exposure to Wi-Fi signals. The results of this study demonstrated that exposure to Wi-Fi radiation could modulate integrative responses to natural stimuli in barrel cortex.
The role of caveolin-1 in morphine-induced structural plasticity in primary cultured mouse cerebral cortical neurons.
Neuroscience letters, 2018

Long-term repeated application of morphine induces plasticity changes in sensitive neurons, which represents the neurobiological basis of morphine addiction. Caveolin-1 (Cav-1) is an important scaffolding protein that plays a key role in the regulation of neurostructural plasticity. However, in-depth studies focused on the role of Cav-1 in morphine-induced changes in neurostructural plasticity are lacking. The present study explored the effects of Cav-1 on the expression levels of 2 markers of neurite outgrowth, growth association protein 43 (GAP-43) and microtubule-associated protein 2 (MAP-2), during the process of morphine-induced changes in the structural plasticity. A primary mouse cerebral cortical neuron culture was established, and Cav-1 knockdown was achieved. The results showed that morphine at a concentration of 10.0μmol/L had no adverse effect on neuronal viability, but enhanced the Cav-1 and GAP-43 levels and induced the outgrowth of MAP-2-labeled neurites. The qRT-PCR data showed that 10.0μmol/L of morphine increased the Cav-1 mRNA level and promoted Cav-1 expression at the transcriptional level. Moreover, Cav-1 knockdown inhibited the morphine-induced upregulation of GAP-43 expression and the prolongation of MAP-2-labeled neurites. In conclusion, morphine was capable of inducing changes in the structural plasticity of primary cultured mouse cortical neurons, and Cav-1 played an important role in this process. Inhibition of Cav-1 expression reduced the morphine-induced increase in the neuronal growth markers GAP-43 and MAP-2. Thus, Cav-1 may be a potential molecular target for inhibiting morphine-induced neuroplasticity.
Experiences of Improving Access to Psychological Therapy Services for Perinatal Mental Health Difficulties: a Qualitative Study of Women's and Therapists' Views.
Behavioural and cognitive psychotherapy, 2018

Perinatal mental health difficulties are highly prevalent. In England, the Improving Access to Psychological Therapy (IAPT) programme provides evidence-based psychological treatment, predominantly in the form of brief manualized cognitive behavioural therapy (CBT), to people with mild to moderate depression or anxiety. Yet little is known about the experiences of women referred to IAPT with perinatal mental health difficulties.
ADP-Ribosylation Factor-Like 2 (ARL2) regulates cilia stability and development of outer segments in rod photoreceptor neurons.
Scientific reports, 2018

Photoreceptor cells are specialized neurons with a sensory cilium carrying an elaborate membrane structure, the outer segment (OS). Inherited mutations in genes involved in ciliogenesis frequently result in OS malformation and blindness. ADP-ribosylation factor-like 2 (ARL2) has recently been implicated in OS formation through its association with Binder of ARL2 (BART or ARL2BP), a protein linked to inherited blinding disease. To test the role of ARL2 in vision we created a transgenic mouse model expressing a tagged-dominant active form of human ARL2 (ARL2-Q70L) under a rod-specific promoter. Transgenic ARL2-Q70L animals exhibit reduced photoreceptor cell function as early as post-natal day 16 and progressive rod degeneration. We attribute loss of photoreceptor function to the defective OS morphogenesis in the ARL2-Q70L transgenic model. ARL2-Q70L expression results in shortened inner and outer segments, shortened and mislocalized axonemes and cytoplasmic accumulation of rhodopsin. In conclusion, we show that ARL2-Q70L is crucial for photoreceptor neuron sensory cilium development. Future research will expand upon our hypothesis that ARL2-Q70L mutant interferes with microtubule maintenance and tubulin regulation resulting in impaired growth of the axoneme and elaboration of the photoreceptor outer segment.
Narp regulates homeostatic scaling of excitatory synapses on parvalbumin-expressing interneurons.
Nature neuroscience, 2010

Homeostatic synaptic scaling alters the strength of synapses to compensate for prolonged changes in network activity and involves both excitatory and inhibitory neurons. The immediate-early gene Narp (neuronal activity-regulated pentraxin) encodes a secreted synaptic protein that can bind to and induce clustering of AMPA receptors (AMPARs). We found that Narp prominently accumulated at excitatory synapses on parvalbumin-expressing interneurons (PV-INs). Increasing network activity resulted in a homeostatic increase of excitatory synaptic strength onto PV-INs that increased inhibitory drive and this response was absent in neurons cultured from Narp-/- mice. Activity-dependent changes in the strength of excitatory inputs on PV-INs in acute hippocampal slices were also dependent on Narp and Narp-/- mice had increased sensitivity to kindling-induced seizures. We propose that Narp recruits AMPARs at excitatory synapses onto PV-INs to rebalance network excitation/inhibition dynamics following episodes of increased circuit activity.