rudyvdbrink/CitationDatabase huggingface dataset:
Cysticercosis of midbrain presenting with fluctuating ptosis.
Annals of Indian Academy of Neurology, 2011

Fluctuating ptosis is usually caused by Myasthenia gravis. There are a few case reports of central causes of fluctuating ptosis. A 58-year-old man presented with fluctuating ptosis of one year duration. He was diagnosed as having ocular myasthenia and investigated. On evaluation, his electrophysiological tests revealed negative decremental response and results of neostigmine test was negative. During follow-up, patient developed headache. Imaging of the brain revealed midbrain cysticercosis granuloma. The focal encephalitis and edema was responsible for fluctuating ptosis. It is therefore essential to be aware of conditions that cause such pseudomyasthenic features. Patients with ptosis need to be evaluated for other rare central cause especially when neostigmine test is negative.
Winter is coming: nightmares and sleep problems during seasonal affective disorder.
Journal of sleep research, 2016

Sleep problems, especially nightmares and insomnia, often accompany depression. This study investigated how nightmares, symptoms of insomnia, chronotype and sleep duration associate with seasonal affective disorder, a special form of depression. Additionally, it was noted how latitude, a proxy for photoperiod, and characteristics of the place of residence affect the prevalence of seasonal affective disorder and sleep problems. To study these questions, data from FINRISK 2012 study were used. FINRISK 2012 consists of a random population sample of Finnish adults aged 25-74 years (n = 4905) collected during winter from Finnish urban and rural areas spanning the latitudes of 60°N to 66°N. The Seasonal Pattern Assessment Questionnaire was used to assess symptoms of seasonal affective disorder. Participants with symptoms of seasonal affective disorder had significantly increased odds of experiencing frequent nightmares and symptoms of insomnia, and they were more often evening chronotypes. Associations between latitude, population size and urbanicity with seasonal affective disorder symptoms and sleep disturbances were generally not significant, although participants living in areas bordering urban centres had less sleep problems than participants from other regions. These data show that the prevalence of seasonal affective disorder was not affected by latitude.
Early rescue of interneuron disease trajectory in developmental epilepsies.
Current opinion in neurobiology, 2016

The discovery of over 150 monogenic epilepsies and advances in early genetic diagnoses have launched a search for molecular strategies and developmental timetables to reverse or even prevent the course of these debilitating brain disorders. Orthologous rodent models of key disease genes are providing important examples of the range of targets, and serve as valuable test systems for perinatal therapeutic approaches. While gene-specific analyses of single rare 'orphan' diseases are each narrow in scope, they illuminate downstream pathways converging onto interneurons, and treatments that strengthen inhibition during cortical maturation may provide broad protection against these seemingly disparate gene errors. Several genes, even those linked to malformations, show promise for postnatal correction before the onset of their clinical phenotype.
Hepatitis C testing and infection rates in bipolar patients with and without comorbid substance use disorders.
Bipolar disorders, 2008

To determine and compare hepatitis C (HCV) screening and testing rates among four groups: those with (i) bipolar disorder [BD group (history of BD but no substance use disorder)]; (ii) substance use disorders [SUD group (history of SUD but no BD)]; (iii) co-occurring disorders [DD group (history of both BD and an SUD)]; and (iv) a control group (no history of either bipolar disorder or substance use disorder). Our hypothesis was that HCV antibody testing rates and HCV prevalence would be higher in the BD, SUD, and DD groups than the control group.
Monoclonal antibody therapy for neuromyelitis optica spectrum disorder: current and future.
The International journal of neuroscience, 2017

Monoclonal-antibody has been used for patients with autoimmune disorders for several years, and efficacy and safety were appreciated for these patients. Neuromyelitis optica specturm disorder (NMOSD) has been defined as an autoimmune demyelination disorder of the central nervous system (CNS) with a course of relapse-remission. Treatment of prevention is important for patients with NMOSD because of the increased disability after several attacks. Multiple factors were involved in the pathogenesis of NMOSD. Currently, targeting specific factor was favored in the research into the treatment for NMOSD. Previous studies reported the efficacy and tolerance in NMOSD for drugs such as rituximab, tocilizumab, and eculizumab. The aim of this article is to review the current monoclonal therapies for NMOSD patients, and also future alternative options.
Methylene blue upregulates Nrf2/ARE genes and prevents tau-related neurotoxicity.
Human molecular genetics, 2014

Methylene blue (MB, methylthioninium chloride) is a phenothiazine that crosses the blood brain barrier and acts as a redox cycler. Among its beneficial properties are its abilities to act as an antioxidant, to reduce tau protein aggregation and to improve energy metabolism. These actions are of particular interest for the treatment of neurodegenerative diseases with tau protein aggregates known as tauopathies. The present study examined the effects of MB in the P301S mouse model of tauopathy. Both 4 mg/kg MB (low dose) and 40 mg/kg MB (high dose) were administered in the diet ad libitum from 1 to 10 months of age. We assessed behavior, tau pathology, oxidative damage, inflammation and numbers of mitochondria. MB improved the behavioral abnormalities and reduced tau pathology, inflammation and oxidative damage in the P301S mice. These beneficial effects were associated with increased expression of genes regulated by NF-E2-related factor 2 (Nrf2)/antioxidant response element (ARE), which play an important role in antioxidant defenses, preventing protein aggregation, and reducing inflammation. The activation of Nrf2/ARE genes is neuroprotective in other transgenic mouse models of neurodegenerative diseases and it appears to be an important mediator of the neuroprotective effects of MB in P301S mice. Moreover, we used Nrf2 knock out fibroblasts to show that the upregulation of Nrf2/ARE genes by MB is Nrf2 dependent and not due to secondary effects of the compound. These findings provide further evidence that MB has important neuroprotective effects that may be beneficial in the treatment of human neurodegenerative diseases with tau pathology.
[Genetic factors of alcohol-dependence].
L'Encephale, 2009

Alcohol dependence is a complex and multifactorial disease resulting both from neurobiological mechanisms and environmental factors. It is frequently associated with comorbid psychiatric disorders or with specific personality or behavioral features. Although action can be taken on the environment in order to decrease the risk of the illness, current methods used to prevent or to treat this pathology show moderate efficacy: problematic consumption of ethanol in the general population as well as relapse rates under treatment in dependent patients remain indeed very high.
How to test for phasic modulation of neural and behavioural responses.
NeuroImage, 2019

Research on whether perception or other processes depend on the phase of neural oscillations is rapidly gaining popularity. However, it is unknown which methods are optimally suited to evaluate the hypothesized phase effect. Using a simulation approach, we here test the ability of different methods to detect such an effect on dichotomous (e.g., "hit" vs "miss") and continuous (e.g., scalp potentials) response variables. We manipulated parameters that characterise the phase effect or define the experimental approach to test for this effect. For each parameter combination and response variable, we identified an optimal method. We found that methods regressing single-trial responses on circular (sine and cosine) predictors perform best for all of the simulated parameters, regardless of the nature of the response variable (dichotomous or continuous). In sum, our study lays a foundation for optimized experimental designs and analyses in future studies investigating the role of phase for neural and behavioural responses. We provide MATLAB code for the statistical methods tested.
A portable site: a binding element for 17β-estradiol can be placed on any subunit of a nicotinic α4β2 receptor.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011

Endogenous steroids can modulate the activity of transmitter-gated channels by directly interacting with the receptor. 17β-Estradiol potentiates activation of neuronal nicotinic α4β2 receptors by interacting with a 4 aa sequence at the extreme C terminus of the α4 subunit, but it is not known whether potentiation requires that the sequence be placed on a specific subunit (e.g., an α4 subunit that is involved in forming an acetylcholine-binding site). By using concatemers of subunits and chimeric subunits, we have found that the C-terminal domain can be moved from the α4 to the β2 subunit and still result in potentiation. In addition, the sequence can be placed on a subunit that contributes to an acetylcholine-binding site or on the structural subunit. The data indicate that this estradiol-binding element is a discrete sequence and suggest that the effect of 17β-estradiol is mediated by actions on single subunits and that the overall consequences for gating occur because of the summation of independent energetic contributions to overall gating of this receptor.
A novel method to simultaneously record spinal cord electrophysiology and electroencephalography signals.
NeuroImage, 2021

The brain and the spinal cord together make up the central nervous system (CNS). The functions of the human brain have been the focus of neuroscience research for a long time. However, the spinal cord is largely ignored, and the functional interaction of these two parts of the CNS is only partly understood. This study developed a novel method to simultaneously record spinal cord electrophysiology (SCE) and electroencephalography (EEG) signals and validated its performance using a classical resting-state study design with two experimental conditions: eyes-closed (EC) and eyes-open (EO). We recruited nine postherpetic neuralgia patients implanted with a spinal cord stimulator, which was modified to record SCE signals simultaneously with EEG signals. For both EEG and SCE, similar differences were found in delta- and alpha-band oscillations between the EC and EO conditions, and the spectral power of these frequency bands was able to predict EC/EO behaviors. Moreover, causal connectivity analysis suggested a top-down regulation in delta-band oscillations from the brain to the spinal cord. Altogether, this study demonstrates the validity of simultaneous SCE-EEG recording and shows that the novel method is a valuable tool to investigate the brain-spinal interaction. With this method, we can better unite knowledge about the brain and the spinal cord for a deeper understanding of the functions of the whole CNS.
What would a synthetic connectome look like?
Physics of life reviews, 2020

A major challenge of contemporary neuroscience is to unravel the structure of the connectome, the ensemble of neural connections that link between different functional units of the brain, and to reveal how this structure relates to brain function. This thriving area of research largely follows the general tradition in biology of reverse-engineering, which consists of first observing and characterizing a biological system or process, and then deconstructing it into its fundamental building blocks in order to infer its modes of operation. However, a complementary form of biology has emerged, synthetic biology, which emphasizes construction-based forward-engineering. The synthetic biology approach comprises the assembly of new biological systems out of elementary biological parts. The rationale is that the act of building a system can be a powerful method for gaining deep understanding of how that system works. As the fields of connectomics and synthetic biology are independently growing, I propose to consider the benefits of combining the two, to create synthetic connectomics, a new form of neuroscience and a new form of synthetic biology. The goal of synthetic connectomics would be to artificially design and construct the connectomes of live behaving organisms. Synthetic connectomics could serve as a unifying platform for unraveling the complexities of brain operation and perhaps also for generating new forms of artificial life, and, in general, could provide a valuable opportunity for empirically exploring theoretical predictions about network function. What would a synthetic connectome look like? What purposes would it serve? How could it be constructed? This review delineates the novel notion of a synthetic connectome and aims to lay out the initial steps towards its implementation, contemplating its impact on science and society.
The delayed reproduction of long time intervals defined by innocuous thermal sensation.
Experimental brain research, 2016

The presence of discrete events during an interval to be estimated generally causes a dilation of perceived duration (event-filling effect). Here, we investigated this phenomenon in the thermal modality using multi-seconds (19 s) innocuous cool stimuli that were either constant (continuous interval) or fluctuating to create three discrete sensory events (segmented interval). Moreover, we introduced a delay following stimulus offset, before the reproduction phase, to allow for a direct comparison with our recent study showing an underestimation of duration in a delayed reproduction task of heat pain sensations (Khoshnejad et al. in Pain 155:581-590, 2014. doi: 10.1016/j.pain.2013.12.015 ). The event-filling effect was tested by comparing the delayed reproduction of the segmented and the continuous stimuli in experimental conditions asking participants to (1) reproduce the dynamics of the sensation (i.e., changes in sensory intensity over time) or (2) reproduce only the interval duration (i.e., sensation onset-to-offset). A perceptual (control) condition required participants to report changes in sensation concurrently with the stimulus. Results of the dynamic task confirmed the underestimation of duration in the delayed reproduction task, but this effect was only found with the continuous and not with the segmented stimulus. This implies that the dilation of duration produced by segmentation might compensate for the underestimation of duration in this delayed reproduction task. However, this temporal dilation effect was only observed when participants were required to attend and reproduce the dynamics of sensation. These results suggest that the event-filling effect can be observed in the thermal sensory modality and that attention directed toward changes in sensory intensity might contribute to this effect.
Combined adaptiveness of specific motor cortical ensembles underlies learning.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2010

Learning motor skills entails adaptation of neural computations that can generate or modify associations between sensations and actions. Indeed, humans can use different strategies when adapting to dynamic loads depending on available sensory feedback. Here, we examined how neural activity in motor cortex was modified when monkeys made arm reaches to a visual target and locally adapted to curl force field with or without visual trajectory feedback. We found that firing rates of a large subpopulation of cells were consistently modulated depending on the distance of their preferred direction from the learned movement direction. The newly acquired activity followed a cosine-like function, with maximal increase in directions that opposed the perturbing force and decrease in opposite directions. As a result, the combined neuronal activity generated an adapted population vector. The results suggest that this could be achieved without changing the tuning properties of the cells. This population directional signal was however altered in the absence of visual feedback; while the cosine pattern of modulation was maintained, the population distributions of modulated cells differed across feedback consistent with the different trajectory shapes. Finally, we predicted generalization patterns of force-field learning based on the cosine-like modulation. These conformed to reported features of generalization in humans, suggesting that the generalization function was related to the observed rate modulations in the motor cortex. Overall, the findings suggest that the new combined activation of neuronal ensembles could underlie the change in the internal model of movement dynamics in a way that depends on available sensory feedback and chosen strategy.
Effect of amniotic-fluid ingestion on vaginal-cervical-stimulation-induced Fos expression in female rats during estrus.
Brain research, 2011

Placental Opioid-Enhancing Factor (POEF) is a substance found in amniotic fluid (AF) that, when ingested, potentiates opioid-mediated, but not non-opioid-mediated, hypoalgesia. Vaginal-cervical stimulation (VCS) produces a stimulus-bound, partially opioid-mediated hypoalgesia that previous research has shown to be potentiated by AF ingestion. To understand the mechanism of opioid enhancement by POEF we investigated the pattern of neural activation after a bout of VCS that produced hypoalgesia, with and without co-administration of AF. Specifically, virgin Long-Evans rats showing vaginal estrus were handled briefly (control) or received VCS (75g pressure, 1 min), in a pattern that approximated early parturition rather than copulation, using a spring-loaded glass-rod probe. Rats were given an orogastric infusion (0.25 ml) of either AF or 0.9% saline resulting in four groups (VCS or handling; AF or saline). Rats were perfused 90 min after treatment and tissue was processed by immunohistochemistry for Fos. The number of Fos-immunoreactive cells was counted in structures previously shown to express Fos in response to VCS (the medial preoptic area, MPOA; the ventrolateral portion of the ventromedial hypothalamic nucleus, vlVMH; the arcuate nucleus, ARC). We found that this pattern of VCS did not produce a significant increase in Fos expression in the MPOA and vlVMH unless it was paired with AF. VCS produced a significant increase in Fos in the ARC. The interaction of AF and VCS on Fos expression in the MPOA suggests that POEF may enhance vaginal-cervical sensory input at parturition to facilitate sensitization of the MPOA, and presumably facilitate maternal-behavior onset.
SPG7 and Impaired Emotional Communication.
Cerebellum (London, England), 2017

The goal of this report is to describe the genetic mutations of a patient with cerebellar degeneration who had ataxia and impaired emotional communication that led to damage of family relationships. We extracted genomic DNA from peripheral blood lymphocytes and performed whole exome sequencing (WES) in this patient and his unaffected parents and siblings. Found mutations were confirmed by Sanger sequencing in each individual. We found compound heterozygous mutations in the paraplegin (SPG7) gene. One mutated allele has been previously described as a disease-causing missense mutation for spastic paraplegia type 7 (SPG7) (c.1529C > T, p.Ala510Val). The second mutated allele involved a single nucleotide deletion which results in a frameshift in the coding sequence (c.2271delG, p.Met757fs*65). The second allele is similar to, but unique from, other described, SPG7-linked truncation mutations. The abnormal emotional communication in this patient broadens the phenotypic boundary of SPG7.
Tau aggregates are RNA-protein assemblies that mislocalize multiple nuclear speckle components.
Neuron, 2021

Tau aggregates contribute to neurodegenerative diseases, including frontotemporal dementia and Alzheimer's disease (AD). Although RNA promotes tau aggregation in vitro, whether tau aggregates in cells contain RNA is unknown. We demonstrate, in cell culture and mouse brains, that cytosolic and nuclear tau aggregates contain RNA with enrichment for small nuclear RNAs (snRNAs) and small nucleolar RNAs (snoRNAs). Nuclear tau aggregates colocalize with and alter the composition, dynamics, and organization of nuclear speckles, membraneless organelles involved in pre-mRNA splicing. Moreover, several nuclear speckle components, including SRRM2, mislocalize to cytosolic tau aggregates in cells, mouse brains, and brains of individuals with AD, frontotemporal dementia (FTD), and corticobasal degeneration (CBD). Consistent with these alterations, we observe that the presence of tau aggregates is sufficient to alter pre-mRNA splicing. This work identifies tau alteration of nuclear speckles as a feature of tau aggregation that may contribute to the pathology of tau aggregates.
Sub-acute systemic erythropoietin administration reduces ischemic brain injury in an age-dependent manner.
Oncotarget, 2016

Stroke is associated with neuroinflammation, neuronal loss and blood-brain barrier (BBB) breakdown. Thus far, recombinant tissue-type plasminogen activator (rtPA), the only approved treatment for acute ischemic stroke, increases the risk of intracerebral hemorrhage and is poorly efficient in disaggregating platelet-rich thrombi. Therefore, the development of safer and more efficient therapies is highly awaited. Encouraging neuroprotective effects were reported in mouse models of ischemic stroke following administration of erythropoietin (EPO). However, previous preclinical studies did not investigate the effects of EPO in focal ischemic stroke induced by a platelet-rich thrombus and did not consider the implication of age. Here, we performed middle cerebral artery occlusion by inducing platelet-rich thrombus formation in chimeric 5- (i.e. young) and 20- (i.e. aged) months old C57BL/6 mice, in which hematopoietic stem cells carried the green fluorescent protein (GFP)-tag. Recombinant human EPO (rhEPO) was administered 24 hours post-occlusion and blood-circulating monocyte populations were studied by flow cytometry 3 hours post-rhEPO administration. Twenty-four hours following rhEPO treatment, neuronal loss and BBB integrity were assessed by quantification of Fluoro-Jade B (FJB)-positive cells and extravasated serum immunoglobulins G (IgG), respectively. Neuroinflammation was determined by quantifying infiltration of GFP-positive bone marrow-derived cells (BMDC) and recruitment of microglial cells into brain parenchyma, along with monocyte chemotactic protein-1 (MCP-1) brain protein levels. Here, rhEPO anti-inflammatory properties rescued ischemic injury by reducing neuronal loss and BBB breakdown in young animals, but not in aged littermates. Such age-dependent effects of rhEPO must therefore be taken into consideration in future studies aiming to develop new therapies for ischemic stroke.