rudyvdbrink/CitationDatabase huggingface dataset:
A model of amygdala function following plastic changes at specific synapses during extinction.
Neurobiology of stress, 2019

The synaptic networks in the amygdala have been the subject of intense interest in recent times, primarily because of the role of this structure in emotion. Fear and its extinction depend on the workings of these networks, with particular interest in extinction because of its potential to ameliorate adverse symptoms associated with post-traumatic stress disorder. Here we place emphasis on the extinction networks revealed by recent techniques, and on the probable plasticity properties of their synaptic connections. We use modules of neurons representing each of the principal components identified as involved in extinction. Each of these modules consists of neural networks, containing specific ratios of excitatory and specialized inhibitory neurons as well as synaptic plasticity mechanisms appropriate for the component of the amygdala they represent. While these models can produce dynamic output, here we concentrate on the equilibrium outputs and do not model the details of the plasticity mechanisms. Pavlovian fear conditioning generates a fear memory in the lateral amygdala module that leads to activation of neurons in the basal nucleus fear module but not in the basal nucleus extinction module. Extinction protocols excite infralimbic medial prefrontal cortex neurons (IL) which in turn excite so-called extinction neurons in the amygdala, leading to the release of endocannabinoids from them and an increase in efficacy of synapses formed by lateral amygdala neurons on them. The model simulations show how such a mechanism could explain experimental observations involving the role of IL as well as endocannabinoids in different temporal phases of extinction.
Pharmacological DNA Demethylation Weakens Inhibitory Synapses in the Auditory Cortex and Re-opens the Critical Period for Frequency Map Plasticity.
Neuroscience, 2020

The critical period is a time of maximal plasticity within the cortex. The progression of the critical period is marked by experience-dependent transcriptional alterations in cortical neurons, which in turn shifts the excitatory-inhibitory balance in the brain, and accordingly reduces plasticity. Epigenetic mechanisms, such as DNA methylation, control the transcriptional state of neurons, and have been shown to be dynamically regulated during the critical period. Here we show that adult animals have a significantly higher concentration of DNA methylation than critical period animals. Pharmacological reduction of DNA methylation in adult animals re-establishes critical period auditory map plasticity. Furthermore, the reduction of DNA methylation in adult animals, reverted intrinsic characteristics of inhibitory synapses to an immature state. Our data suggest that accumulation of DNA methylation during the critical period confers a mature phenotype to cortical neurons, which in turn, facilitates the reduction in plasticity seen after the critical period.
Commute Time as a Method to Explore Brain Functional Connectomes.
Brain connectivity, 2019

Graph theory has been extensively applied to investigate complex brain networks in current neuroscience research. Many metrics derived from graph theory, such as local and global efficiencies, are based on the path length between nodes. These approaches are commonly used in analyses of brain networks assessed by resting-state functional magnetic resonance imaging, although relying on the strong assumption that information flow throughout the network is restricted to the shortest paths. In this study, we propose the utilization of commute time as a tool to investigate regional centrality on the functional connectome. Our initial hypothesis was that an alternative approach that considers alternative routes (such as commute time) could provide further information into the organization of functional networks. However, our empirical findings on the ADHD-200 database suggest that at the group level, the commute time and shortest path are highly correlated. In contrast, at the subject level, we discovered that commute time is much less susceptible to head motion artifacts when compared with metrics based on shortest paths. Given the overall similarity between the measures, we argue that commute time might be advantageous particularly for connectomic studies in populations where motion artifacts are a major issue.
Development of an Intervention to Create a Supportive Work Environment for Employees with Chronic Conditions: An Intervention Mapping Approach.
Journal of occupational rehabilitation, 2020

Purpose This study describes the development of an evidence-based intervention to create a supportive work environment for employees with chronic conditions. Occupational physicians (OPs) play an important role in guiding organizations in this process of organizational change. Supportive work environments can aid in preventing work-related problems and facilitate sustainable employment. Current workplace interventions for employees with chronic conditions are mainly focused on return to work or a reduction in sick leave at the individual worker's level. This study contributes to the literature an organizational-level intervention which utilizes a preventive approach. Methods Intervention mapping (IM) is a six-step, structured protocol that was used to develop this intervention. In step 1, a needs assessment was conducted to define the problem and explore the perspectives of all stakeholders involved. The program outcomes and the performance objectives of employees with chronic conditions and occupational physicians were specified in step 2. In step 3, appropriate methods and practical applications were chosen. Step 4 describes the actual development of the intervention, consisting of (1) a training for occupational physicians to teach them how to guide organizations in creating a supportive work environment; (2) a practical assignment; and (3) a follow-up meeting. The intervention will be implemented in a pilot study in which occupational physicians will put their acquired knowledge and skills into practice within one of their organizations, which is delineated in step 5. Conclusions IM proved to be a valuable and practical tool for the development of this intervention, aiming to facilitate sustainable employment for employees with chronic conditions.
Eyes Wide Open on AMPAR Trafficking during Motor Learning.
Neuron, 2020

In this issue of Neuron, Roth et al. (2020) report that the content of GluA1-containing AMPAR at spines and dendrites in vivo in the motor and visual cortex increases proportionally to the learning of a motor task. Visual cortex activity is necessary for increasing AMPAR content and learning in light.
In vivo γ-aminobutyric acid increase as a biomarker of the epileptogenic zone: An unbiased metabolomics approach.
Epilepsia, 2021

Following surgery, focal seizures relapse in 20% to 50% of cases due to the difficulty of delimiting the epileptogenic zone (EZ) by current imaging or electrophysiological techniques. Here, we evaluate an unbiased metabolomics approach based on ex vivo and in vivo nuclear magnetic resonance spectroscopy (MRS) methods to discriminate the EZ in a mouse model of mesiotemporal lobe epilepsy (MTLE).
Pharma TARP: a troubled asset relief program for novel, abandoned projects in the pharmaceutical industry.
TheScientificWorldJournal, 2011

Within days of each other, Pfizer, Merck, and GlaxoSmithKline announced that they will focus on a few therapeutic areas only and abandon others entirely. Pfizer alone will close well over a hundred drug development projects that have reached two-thirds of the way to launch. The programs are deemed to be too risky and not lucrative enough for Big Pharma in the current climate. Society has a real need for the drugs that are no longer going to be developed for, among others, drug-resistant epilepsy, neuropathic and cancer pain, type-2 diabetes, obesity, and schizophrenia. The authors propose a radical response by the U.S. government and the National Institutes of Health to rescue these abandoned projects, and to continue selected programs for drug approval by the U.S. Food and Drug Administration and the European Medicines Agency. The investment required is small compared to the Troubled Asset Relief Program bank bail out, but the return on investment in financial terms and in satisfying societal needs makes this proposal attractive.
Candesartan in migraine prevention: results from a retrospective real-world study.
Journal of neurology, 2020

Randomized studies have reported a positive effect of candesartan, an angiotensin II receptor antagonist, in migraine prevention. The aim of our study was to explore patient subjective efficacy of candesartan in a real-world sample of migraine patients and try to identify predictors of candesartan response. We audited the clinical records of 253 patients who attended the King's College Hospital, London, from February 2015 to December 2017, looking specifically at their response to candesartan. Univariate and multivariate logistic regression models were used to identify predictors of headache benefit. Odds ratios (OR) with confidence intervals (CI) 95% were calculated. Eighty-one patients (chronic migraine, n = 68) were included in the final analysis. Thirty-eight patients reported a positive response to candesartan, while 43 patients did not have a meaningful therapeutic effect. The median dose of candesartan was 8 mg and the median treatment period was 6 months. In a univariate logistic regression model, the presence of daily headache was associated with reduced odds of headache benefit (OR 0.39, 95% CI 0.16-0.96, p = 0.04). In multivariate logistic regression model, younger age (OR 0.92, 95% CI 0.87-0.98, p = 0.006) and longer disease duration (OR 1.06, 95% CI 1.01-1.12, p = 0.03) were associated with a good response to candesartan, while the presence of daily headache was associated with reduced odds of headache benefit (OR 0.16, 95% CI 0.04-0.71, p = 0.01). Having failed up to nine preventives in patients did not predict a treatment failure with candesartan as well. Candesartan yields clinical benefits in difficult-to-treat migraine patients, irrespective of previous failed preventives.
C5-C6 Cervical Spinal Cord Cavernous Malformation Microsurgical Resection: 2-Dimensional Operative Video.
Operative neurosurgery (Hagerstown, Md.), 2019

We describe the case of a previously healthy 44-yr-old female patient presenting with a sudden onset of numbness, paresthesias, and decreased sensation in her lower limbs. Physical examination revealed a decreased sensation to vibration and light touch in her lower extremities, primarily in the left limb. Impaired proprioception was also evident primarily in the left toe. Full strength with 2+ reflexes was observed in all extremities. Magnetic resonance imaging demonstrated an exophytic lesion in the posterior aspect of the cervical spinal cord at the C5-C6 level, with a hemosiderin halo, consistent with a cavernous malformation. Given the evidence of past hemorrhage and the location of the lesion, microsurgical intervention was indicated. A midline cervical C5-C6 laminectomy under neurophysiologic monitoring was performed, and complete resection of the lesion was achieved with mild improvement of the sensitive symptoms and no evidence of new motor deficits. Any microsurgical resection of a cervical spinal cord lesion can be technically difficult and adequate patient selection with evaluation of the accessibility to the lesion is key.1 Surgical resection of cavernous malformations in selected patients eliminates the risk of future hemorrhage and may achieve satisfactory outcomes comparable to patients who undergo conservative management.2 In the following video illustration, we narrate this operative case, and highlight the nuances of this approach. Patient consent was obtained for the submission of the video to this journal.
[Species Differences in the Brain between Human and Non-Human Primates].
Brain and nerve = Shinkei kenkyu no shinpo, 2019

Cognitive abilities of humans are superior to that of non-human primates (NHP). Differences in genes, gene expression, cellular composition and response, neural circuit, and brain volume between humans and NHP underlying cognitive abilities are discussed, with a focus on cortical expansion, prefrontal expansion, language-related areas, and the adaptation of longer life spans in humans.
Research on the synchronous detection of neuronal signals under a nerve stimulation system control.
Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference, 2017

Deep brain stimulation (DBS) provides a recognized research intervention for neurological disease currently. However, there is a lack of traditional electrical stimulator to observe neuronal firing activity synchronously. The aim of the present study was to realize concurrent detection of neuronal signals better under a nerve stimulation system control. Herein, we designed an integrated software, which could control not only neuro-stimulator but also detection instrument at the same time. Moreover, the actual stimulation signals applied to the experiment object could be collected back to data acquisition card and in consistent with the electrophysiological signals. As to basic performance of self-building stimulator, the accuracy of output square signal was verified to be greater than 99.05 % with the change of voltage amplitude. Practicably, combined with homemade microelectrode array (MEA) detecting device, medial forebrain bundle (MFB) DBS effects were observed significantly through the changes of electrophysiological signals in caudate putamen (CPu) of Sprague-Dawley (SD) rat, and the signal-to-noise ratio (SNR) was 5:1 after stimulation. Therefore, the comprehensive nerve stimulation system, which consists of neuro-stimulator and integrated software, could be widely used in the field of neuroscience research with high precision and synchronization.
Noradrenaline Release from Locus Coeruleus Terminals in the Hippocampus Enhances Excitation-Spike Coupling in CA1 Pyramidal Neurons Via β-Adrenoceptors.
Cerebral cortex (New York, N.Y. : 1991), 2020

Release of the neuromodulator noradrenaline signals salience during wakefulness, flagging novel or important experiences to reconfigure information processing and memory representations in the hippocampus. Noradrenaline is therefore expected to enhance hippocampal responses to synaptic input; however, noradrenergic agonists have been found to have mixed and sometimes contradictory effects on Schaffer collateral synapses and the resulting CA1 output. Here, we examine the effects of endogenous, optogenetically driven noradrenaline release on synaptic transmission and spike output in mouse hippocampal CA1 pyramidal neurons. We show that endogenous noradrenaline release enhances the probability of CA1 pyramidal neuron spiking without altering feedforward excitatory or inhibitory synaptic inputs in the Schaffer collateral pathway. β-adrenoceptors mediate this enhancement of excitation-spike coupling by reducing the charge required to initiate action potentials, consistent with noradrenergic modulation of voltage-gated potassium channels. Furthermore, we find the likely effective concentration of endogenously released noradrenaline is sub-micromolar. Surprisingly, although comparable concentrations of exogenous noradrenaline cause robust depression of slow afterhyperpolarization currents, endogenous release of noradrenaline does not, indicating that endogenous noradrenaline release is targeted to specific cellular locations. These findings provide a mechanism by which targeted endogenous release of noradrenaline can enhance information transfer in the hippocampus in response to salient events.
[Potential interest of ocular saccades for detection of suicidal behavior in depressed elderly].
Geriatrie et psychologie neuropsychiatrie du vieillissement, 2019

Elderly people, especially those with depression, represent the population most at risk for suicide. In addition to commonly used neuropsychological, psychiatric and biological tests, ocular saccadic analysis can be an interesting tool for identifying suicidal behaviors (SB). These SBs could be associated with an alteration of the cortical structures involved in the executive functions. This alteration is particularly manifested by a decrease in the ability to control eye movements (EM). Thus, depressed elderly people with SB may have a greater impairment of oculomotor performance than those without SB. The purpose of this article is to summarize the literature allowing us to support this hypothesis.
Prenatal pregabalin is associated with sex-dependent alterations in some behavioral parameters in valproic acid-induced autism in rat offspring.
International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience, 2020

This study was performed to evaluate the effects of prenatal exposure to pregabalin (PGB) on behavioral changes of rat offspring in an animal model of valproic acid (VPA)-induced autism-like symptoms. Pregnant rats received VPA (600 mg/kg/i.p.) once at 12.5 gestational days for autism-like symptom induction in offspring. After the delivery single male and single female offspring from each mother were randomly selected for behavioral test (anxiety, pain response, pleasure, and motor function) at 60th day adulthood (n = 7). Offspring received prenatal PGB (15 & 30 mg/kg/i.p.) during gestational days 9.5 to 15.5 either alone or in combination with VPA (PGB15, PGB30, PGB15 + VPA, and PGB30 + VPA). Control offspring received normal saline during the same period. The result showed that prenatal VPA exposure was associated with autism-like behaviors in rat offspring. PGB treatment during the gestational period revealed significant reduction in sucrose preference test and anxiety in elevated plus maze and open field test in offspring. Also, PGB treatments exhibited a dose-dependent increase in pain threshold in prenatally VPA exposed rats in tail-flick and hot plate test. Also, there was a sex-related significant impairment in motor function in beam balance and open field test, and male rats were affected more than females. However, no significant sex differences in sucrose preference and pain sensitivity were observed in prenatal PGB-treated rat offspring. In conclusion, prenatal exposure to VPA increased the risk of autism-like behaviors in the offspring rats, and PGB treatment during the gestational period was associated with some beneficial effects, including anxiety reduction and motor impairment in autism-like symptoms in rat offspring.
Singing under the influence: examining the effects of nutrition and addiction on a learned vocal behavior.
Molecular neurobiology, 2011

The songbird model is widely established in a number of laboratories for the investigation of the neurobiology and development of vocal learning. While vocal learning is rare in the animal kingdom, it is a trait that songbirds share with humans. The neuroanatomical and physiological organization of the brain circuitry that controls learned vocalizations has been extensively characterized, particularly in zebra finches (Taeniopygia guttata). Recently, several powerful molecular and genomic tools have become available in this organism, making it an attractive choice for neurobiologists interested in the neural and genetic basis of a complex learned behavior. Here, we briefly review some of the main features of vocal learning and associated brain structures in zebra finches and comment on some examples that illustrate how themes related to nutrition and addiction can be explored using this model organism.
Sex and handedness differences in eye-hand visual reaction times in handball players.
The International journal of neuroscience, 2003

Sex and handedness differences in the eye-dominant hand, the right eye-right hand and the left eye-left hand visual reaction times were studied in 270 right-handed and 56 left -handed young handball players. Reaction time was assessed by a software package. All visual reaction times were longer in women than in men. In the eye-dominant hand and the left eye- left hand visual reaction times, the left-handers had a superiority over the right handers, but there was no difference between the right eye-right hand visual reaction times of the right- and left-handers. In right-handers, all visual reaction times were longer in women than in men, but there was no sex difference in left-handers. The results suggest that left-handed players have probably an intrinsic neurological advantage.
Competing inhibition-stabilized networks in sensory and memory processing.
Conference record. Asilomar Conference on Signals, Systems & Computers, 2018

In simplified models of neocortical circuits, inhibition is either modeled in a feedforward manner or through mutual inhibitory interactions that provide for competition between neuronal populations. By contrast, recent work has suggested a critical role for recurrent inhibition as a negative feedback element that stabilizes otherwise unstable recurrent excitation. Here, we show how models based upon a motif of recurrently connected "E-I" pairs of excitatory and inhibitory units can be used to describe experimental observations in sensory and memory networks. In a sensory network model of binocular rivalry, a model based on competing E-I motifs captures psychophysical observations about how incongruous images presented to the two eyes compete. In a model of cortical working memory, an architecturally similar model with modified synaptic time constants can mathematically accumulate signals into a working memory buffer in a manner that is robust to the abrupt removal of cells. These results suggest the inhibition-stabilized E-I motif as a fundamental building block for models of a wide array of neocortical dynamics.
Deep Neck Space Infection in HIV-Infected Children: A Case Series.
Cureus, 2020

Background Deep neck space infections (DNSIs) in children may lead to airway compromise and damage to the great vessels in the neck. They occur more commonly in the HIV-infected population. To our knowledge, this is the first case series of DNSI in HIV-infected children Objectives The aim of this study was to describe the demography and document the sites of infection; organisms identified and resistance patterns in HIV-infected children with DNSI. Methods We retrospectively reviewed the clinical records of children (<16 years) diagnosed with deep neck infections at the teaching hospitals for the Department of Otolaryngology, Head and Neck Surgery, University of the Witwatersrand, between January 2010 and December 2018. Results We identified 17 patients with DNSI of which six children had concomitant HIV infection. The average age at presentation was six years (range: 0.35-13 years); there were four males and two females. The most common site involved was the submandibular space, which was affected in four patients. The detected organisms included: Coagulase-negative staphylococcus, Streptococcus viridans, Prevotella, Proteus mirabilis and Bacteroides fragilis. The organisms were universally resistant to penicillin and ampicillin resistance was documented in all but one patient. Conclusion Our findings on microbiology, resistance and tuberculosis culture are significant even in the face of a small series and have implications for the diagnosis and treatment of DNSI in HIV-infected children. Tuberculosis should routinely be considered in high burden settings. We recommend the empiric use of a β-lactamase-resistant antibiotic until targeted therapy based on culture and sensitivity can be instituted.