rudyvdbrink/CitationDatabase huggingface dataset:
A novel wireless brain stimulation device for long-term use in freely moving mice.
Scientific reports, 2019

Deep brain stimulation (DBS) has been used in clinical settings for many years despite a paucity of knowledge related to the anatomical and functional substrates that lead to benefits and/or side-effects in various disease contexts. In order to maximize the potential of this approach in humans, a better understanding of its mechanisms of action is absolutely necessary. However, the existing micro-stimulators available for pre-clinical models, are limited by the lack of relevant small size devices. This absence prevents sustained chronic stimulation and real time monitoring of animals during stimulation, parameters that are critical for comparison to clinical findings. We therefore sought to develop and refine a novel small wireless micro-stimulator as a means by which to study consequent behavioural to molecular changes in experimental animals. Building on previous work from our group, we refined our implantable micro-stimulator prototype, to be easily combined with intravital 2-photon imaging. Using our prototype we were able to replicate the well described clinical benefits on motor impairment in a mouse model of Parkinson's disease in addition to capturing microglia dynamics live during stimulation. We believe this new device represents a useful tool for performing pre-clinical studies as well as dissecting brain circuitry and function.
Ecological momentary interventions in psychiatry.
Current opinion in psychiatry, 2016

In this review, we discuss feasibility, content, and where possible efficacy of ecological momentary interventions (EMIs) in psychiatry. EMIs adopt mobile devices, such as personal digital assistants or smartphones, for the delivery of treatments in the daily life of patients. We will discuss EMIs in the field of schizophrenia, bipolar disorder and major depression disorder, as well as one generic, transdiagnostic EMI.
Measuring motor coordination in mice.
Journal of visualized experiments : JoVE, 2013

Mice are increasingly being used in behavioral neuroscience, largely replacing rats as the behaviorist's animal of choice. Before aspects of behavior such as emotionality or cognition can be assessed, however, it is vital to determine whether the motor capabilities of e.g. a mutant or lesioned mouse allow such an assessment. Performance on a maze task requiring strength and coordination, such as the Morris water maze, might well be impaired in a mouse by motor, rather than cognitive, impairments, so it is essential to selectively dissect the latter from the former. For example, sensorimotor impairments caused by NMDA antagonists have been shown to impair water maze performance(2). Motor coordination has traditionally been assessed in mice and rats by the rotarod test, in which the animal is placed on a horizontal rod that rotates about its long axis; the animal must walk forwards to remain upright and not fall off. Both set speed and accelerating versions of the rotarod are available. The other three tests described in this article (horizontal bar, static rods and parallel bars) all measure coordination on static apparatus. The horizontal bar also requires strength for adequate performance, particularly of the forelimbs as the mouse initially grips the bar just with the front paws. Adult rats do not perform well on tests such as the static rods and parallel bars (personal observations); they appear less well coordinated than mice. I have only tested male rats, however, and male mice seem generally less well coordinated than females. Mice appear to have a higher strength:weight ratio than rats; the Latin name, Mus musculus, seems entirely appropriate. The rotarod, the variations of the foot fault test(12) or the Catwalk (Noldus)(15) apparatus are generally used to assess motor coordination in rats.
Immunopathology in drug resistant mesial temporal lobe epilepsy with different types of hippocampal sclerosis.
The International journal of neuroscience, 2018

There is evidence that autoimmunity has a specific role in temporal lobe seizures of limbic encephalitis patients. Our aim in this study was to investigate any histopathological clues of autoimmune process in refractory temporal lobe epilepsy (TLE) patients with different pathologically proven hippocampal sclerosis (HS) types.
Design and discovery of 6-[(3S,4S)-4-methyl-1-(pyrimidin-2-ylmethyl)pyrrolidin-3-yl]-1-(tetrahydro-2H-pyran-4-yl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one (PF-04447943), a selective brain penetrant PDE9A inhibitor for the treatment of cognitive disorders.
Journal of medicinal chemistry, 2012

6-[(3S,4S)-4-Methyl-1-(pyrimidin-2-ylmethyl)pyrrolidin-3-yl]-1-(tetrahydro-2H-pyran-4-yl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one (PF-04447943) is a novel PDE9A inhibitor identified using parallel synthetic chemistry and structure-based drug design (SBDD) and has advanced into clinical trials. Selectivity for PDE9A over other PDE family members was achieved by targeting key residue differences between the PDE9A and PDE1C catalytic site. The physicochemical properties of the series were optimized to provide excellent in vitro and in vivo pharmacokinetics properties in multiple species including humans. It has been reported to elevate central cGMP levels in the brain and CSF of rodents. In addition, it exhibits procognitive activity in several rodent models and synaptic stabilization in an amyloid precursor protein (APP) transgenic mouse model. Recent disclosures from clinical trials confirm that it is well tolerated in humans and elevates cGMP in cerebral spinal fluid of healthy volunteers, confirming that it is a quality pharmacological tool for testing clinical hypotheses in disease states associated with impairment of cGMP signaling or cognition.
Neonatal EEG at scalp is focal and implies high skull conductivity in realistic neonatal head models.
NeuroImage, 2014

The potential improvements in spatial resolution of neonatal EEG used in source localization have been challenged by the insufficiencies in realistic neonatal head models. Our present study aimed at using empirical methods to indirectly estimate skull conductivity; the model parameter that is known to significantly affect the behavior of newborn scalp EEG and cause it to be markedly different from that of an adult. To this end, we used 64 channel EEG recordings to study the spatial specificity of scalp EEG by assessing the spatial decays in focal transients using both amplitudes and between-c'hannels linear correlations. The findings showed that these amplitudes and correlations decay within few centimeters from the reference channel/electrode, and that the nature of the decay is independent of the scalp area. This decay in newborn infants was found to be approximately three times faster than the corresponding decay in adult EEG analyzed from a set of 256 channel recordings. We then generated realistic head models using both finite and boundary element methods along with a manually segmented magnetic resonance images to study the spatial decays of scalp potentials produced by single dipole in the cortex. By comparing the spatial decays due to real and simulated EEG for different skull conductivities (from 0.003 to 0.3S/m), we showed that a close match between the empirical and simulated decays was obtained when the selected skull conductivity for newborn was around 0.06-0.2S/m. This is over an order of magnitude higher than the currently used values in adult head modeling. The results also showed that the neonatal scalp EEG is less smeared than that of an adult and this characteristic is the same across the entire scalp, including the fontanel region. These results indicate that a focal cortical activity is generally only registered by electrodes within few centimeters from the source. Hence, the conventional 10 to 20 channel neonatal EEG acquisition systems give a significantly spatially under sampled scalp EEG and may, consequently, give distorted pictures of focal brain activities. Such spatial specificity can only be reconciled by appreciating the anatomy of the neonatal head, especially the still unossified skull structure that needs to be modeled with higher conductivities than conventionally used in the adults.
The Length and Number of Sedentary Bouts Predict Fibrinogen Levels in Postmenopausal Women.
International journal of environmental research and public health, 2020

Menopause is associated with adverse changes in coagulation homeostasis. We aimed to investigate the association between objectively measured sedentary behavior (SB) and SB bouts (i.e., number and length of SB bouts) vs. fibrinogen levels in post-menopausal women. Fifty-three post-menopausal women (age 59.8 ± 6.2 years, BMI 27.3 ± 4.4) wore a multisensory device (Sensewear Mini Armband, BodyMedia, Inc., Pittsburgh, PA) for 5 days, to measure SB and physical activity (PA). Blood samples were collected to measure serum fibrinogen. Fibrinogen was directly correlated with SB (r = -0.48,
N-Lipidated Peptide Dimers: Effective Antibacterial Agents against Gram-Negative Pathogens through Lipopolysaccharide Permeabilization.
Journal of medicinal chemistry, 2015

Treating infections caused by multidrug-resistant Gram-negative pathogens is challenging, and there is concern regarding the toxicity of the most effective antimicrobials for Gram-negative pathogens. We hypothesized that conjugating a fatty acid moiety onto a peptide dimer could maximize the interaction with lipopolysaccharide (LPS) and facilitate the permeabilization of the LPS barrier, thereby improving potency against Gram-negative pathogens. We systematically designed a series of N-lipidated peptide dimers that are active against Gram-negative bacteria, including carbapenem-resistant Enterobacteriaceae (CRE). The optimized lipid length was 6-10 carbons. At these lipid lengths, the N-lipidated peptide dimers exhibited strong LPS permeabilization. Compound 23 exhibited synergy with select antibiotics in most of the combinations tested. 23 and 32 also displayed rapid bactericidal activity. Importantly, 23 and 32 were nonhemolytic at 10 mg/mL, with no cellular or in vivo toxicity. These characteristics suggest that these compounds can overcome the limitations of current Gram-negative-targeted antimicrobials such as polymyxin B.
Neural dynamics and circuit mechanisms of decision-making.
Current opinion in neurobiology, 2012

In this review, I briefly summarize current neurobiological studies of decision-making that bear on two general themes. The first focuses on the nature of neural representation and dynamics in a decision circuit. Experimental and computational results suggest that ramping-to-threshold in the temporal domain and trajectory of population activity in the state space represent a duality of perspectives on a decision process. Moreover, a decision circuit can display several different dynamical regimes, such as the ramping mode and the jumping mode with distinct defining properties. The second is concerned with the relationship between biologically-based mechanistic models and normative-type models. A fruitful interplay between experiments and these models at different levels of abstraction have enabled investigators to pose increasingly refined questions and gain new insights into the neural basis of decision-making. In particular, recent work on multi-alternative decisions suggests that deviations from rational models of choice behavior can be explained by established neural mechanisms.
Occurrence of sickness absence and disability pension in relation to childbirth: A 16-year follow-up study of 6323 Swedish twins.
Scandinavian journal of public health, 2016

Pregnancy, delivery, and the postpartum period may imply morbidity leading to work incapacity; however, this is seldom studied. This study aimed to compare twin sisters giving or not giving birth regarding occurrence of sickness absence (SA) and disability pension (DP).
Lateral fluid percussion: model of traumatic brain injury in mice.
Journal of visualized experiments : JoVE, 2011

Traumatic brain injury (TBI) research has attained renewed momentum due to the increasing awareness of head injuries, which result in morbidity and mortality. Based on the nature of primary injury following TBI, complex and heterogeneous secondary consequences result, which are followed by regenerative processes (1,2). Primary injury can be induced by a direct contusion to the brain from skull fracture or from shearing and stretching of tissue causing displacement of brain due to movement (3,4). The resulting hematomas and lacerations cause a vascular response (3,5), and the morphological and functional damage of the white matter leads to diffuse axonal injury (6-8). Additional secondary changes commonly seen in the brain are edema and increased intracranial pressure (9). Following TBI there are microscopic alterations in biochemical and physiological pathways involving the release of excitotoxic neurotransmitters, immune mediators and oxygen radicals (10-12), which ultimately result in long-term neurological disabilities (13,14). Thus choosing appropriate animal models of TBI that present similar cellular and molecular events in human and rodent TBI is critical for studying the mechanisms underlying injury and repair. Various experimental models of TBI have been developed to reproduce aspects of TBI observed in humans, among them three specific models are widely adapted for rodents: fluid percussion, cortical impact and weight drop/impact acceleration (1). The fluid percussion device produces an injury through a craniectomy by applying a brief fluid pressure pulse on to the intact dura. The pulse is created by a pendulum striking the piston of a reservoir of fluid. The percussion produces brief displacement and deformation of neural tissue (1,15). Conversely, cortical impact injury delivers mechanical energy to the intact dura via a rigid impactor under pneumatic pressure (16,17). The weight drop/impact model is characterized by the fall of a rod with a specific mass on the closed skull (18). Among the TBI models, LFP is the most established and commonly used model to evaluate mixed focal and diffuse brain injury (19). It is reproducible and is standardized to allow for the manipulation of injury parameters. LFP recapitulates injuries observed in humans, thus rendering it clinically relevant, and allows for exploration of novel therapeutics for clinical translation (20). We describe the detailed protocol to perform LFP procedure in mice. The injury inflicted is mild to moderate, with brain regions such as cortex, hippocampus and corpus callosum being most vulnerable. Hippocampal and motor learning tasks are explored following LFP.
Recent progress of drug nanoformulations targeting to brain.
Journal of controlled release : official journal of the Controlled Release Society, 2018

Most of the potential therapeutic agents capable to modulate the pathophysiology or treat the neurological disorders and brain tumors are useless in the current modern and advanced era of neuroscience due to the impeding action of biological barriers. Among various therapeutic strategies applied for translocation of drug delivery across the blood-brain barrier (BBB), nanoformulations set an excellent platform for brain targeting by overcoming the biological and chemical barriers and protecting drug from efflux to promote the optimum therapeutic drug concentration in brain parenchyma tissues. Nanocarriers are the most widely studied delivery vehicles for BBB translocation with the efficiency of selectively targeting or exploiting inherent biological molecules, receptors, carriers or mechanisms of the brain. Nearly all of the available drug delivery nanocarriers explored in recent years for brain therapeutics and theranostics are based on lipid or polymeric materials. Polymeric nanoparticles (NPs) and lipid based nanocarriers including liposomes, solid lipid NPs (SLNs) and micelles, etc. are under the direct focus of neuroscientists due to the promising attributes and vast applications in neurological disorders. Surface modification of nanovehicles with proper targeting moiety or coating with surfactants promotes the interaction with endothelial cells and passage of nanocarriers to the brain. This review comprehensively depicts challenges to the brain targeted drug delivery, mechanisms of drug transportation across the BBB, and potential contributions of endogenous cells as NPs delivery cells and novel targeting ligands decorated nanoformulations in imaging, treating and controlling neurological disorders.
Reducing Astrocyte Calcium Signaling In Vivo Alters Striatal Microcircuits and Causes Repetitive Behavior.
Neuron, 2018

Astrocytes tile the central nervous system, but their functions in neural microcircuits in vivo and their roles in mammalian behavior remain incompletely defined. We used two-photon laser scanning microscopy, electrophysiology, MINIscopes, RNA-seq, and a genetic approach to explore the effects of reduced striatal astrocyte Ca
Effects of emotional maltreatment on semantic network activity during cognitive reappraisal.
Brain imaging and behavior, 2021

Maltreatment experiences alter brain development associated with emotion processing, and dysregulation of emotion may trigger mental health problems in maltreated people. However, studies revealing alterations in brain networks during cognitive reappraisal in victims of maltreatment are strikingly insufficient. In this study, 27 healthy subjects were recruited. The maltreatment experiences and positive reappraisal abilities were measured using the Childhood Trauma Questionnaire-Short Form (CTQ-SF) and Cognitive Emotion Regulation Questionnaire (CERQ), respectively. A cognitive reappraisal task using the International Affective Picture System (IAPS) was designed for functional magnetic resonance imaging (fMRI) experiments. Cognitive reappraisal induced more activities in the bilateral inferior parietal lobes and bilateral middle temporal gyri compared to the condition of "look" (false discovery rate (FDR) corrected p < 0.05). Furthermore, the left inferior parietal lobe and right middle temporal gyrus functionally interacted with components of the default mode network, including the precuneus and the posterior cingulate cortex. In residual analyses after controlling for age and depressive symptoms, the bilateral inferior parietal and middle temporal activities exhibited positive correlations with cognitive reappraisal abilities (all ps < 0.05), and emotional maltreatment experiences were negatively correlated with the left inferior parietal cortex, bilateral middle temporal cortex activities, and left inferior parietal lobe-posterior cingulate cortex connectivity (all ps < 0.05). We found that semantic networks were significant to cognitive reappraisal, especially reinterpretation, and negative effects of emotional maltreatment experiences on semantic network activities.
Reciprocal interactions between circadian clocks and aging.
Mammalian genome : official journal of the International Mammalian Genome Society, 2016

Virtually, all biological processes in the body are modulated by an internal circadian clock which optimizes physiological and behavioral performance according to the changing demands of the external 24-h world. This circadian clock undergoes a number of age-related changes, at both the physiological and molecular levels. While these changes have been considered to be part of the normal aging process, there is increasing evidence that disruptions to the circadian system can substantially impact upon aging and these impacts will have clear health implications. Here we review the current data of how both the physiological and core molecular clocks change with age and how feedback from external cues may modulate the aging of the circadian system.
Cognitive enhancement of healthy older adults using hyperbaric oxygen: a randomized controlled trial.
Aging, 2020

More than half of community-dwelling individuals sixty years and older express concern about declining cognitive abilities. The current study's aim was to evaluate hyperbaric oxygen therapy (HBOT) effect on cognitive functions in healthy aging adults.A randomized controlled clinical trial randomized 63 healthy adults (>64) either to HBOT(n=33) or control arms(n=30) for three months. Primary endpoint included the general cognitive function measured post intervention/control. Cerebral blood flow (CBF) was evaluated by perfusion magnetic resonance imaging.There was a significant group-by-time interaction in global cognitive function post-HBOT compared to control (p=0.0017). The most striking improvements were in attention (net effect size=0.745) and information processing speed (net effect size=0.788).Voxel-based analysis showed significant cerebral blood flow increases in the HBOT group compared to the control group in the right superior medial frontal gyrus (BA10), right and left supplementary motor area (BA6), right middle frontal gyrus (BA6), left middle frontal gyrus (BA9), left superior frontal gyrus (BA8) and the right superior parietal gyrus (BA7).In this study, HBOT was shown to induce cognitive enhancements in healthy aging adults via mechanisms involving regional changes in CBF. The main improvements include attention, information processing speed and executive functions, which normally decline with aging.
Alcohol dependence and treatment utilization in Europe - a representative cross-sectional study in primary care.
BMC family practice, 2015

Alcohol dependence (AD) in Europe is prevalent and causes considerable health burden. Recognition by general practitioners (GPs) and provision of or referral to treatment may contribute to reduce this burden. This paper studied AD prevalence in varying European primary care settings and examined who received treatment.
Trigeminal nerve stimulation induces Fos immunoreactivity in selected brain regions, increases hippocampal cell proliferation and reduces seizure severity in rats.
Neuroscience, 2017

Sites and mechanisms by which trigeminal nerve stimulation (TNS) exerts beneficial effects on symptoms of drug-resistant epilepsy and depression are still unknown. Effects of short-term TNS on brain regions involved in the physiopathology of these disorders were investigated in this study. Forty male rats were assigned to three groups: TNS (undergoing electrical stimulation of the left infraorbitary nerve via surgically implanted cuff electrodes); Sham (undergoing surgical procedure but without a stimulation); Naïve rats. The effects of TNS (3-hour session; 30-s ON, 5-min OFF; 30Hz; 500μs; 2mA) were evaluated on: (i) behavioral pattern of pentylenetetrazole (PTZ)-induced seizures as measured by the Racine scale; (ii) c-Fos-like immunoreactivity in discrete brain areas; (iii) hippocampal cell proliferation by bromodeoxyuridine (BrdU)-like immunoreactivity. In comparison with Sham groups, TNS significantly decreased the duration of PTZ-induced seizures (p<0.05) and promoted a faster recovery (p<0.001) by reducing the most severe seizure types. In the TNS group the number of c-Fos-labeled cells was significantly increased (p<0.001) in the trigeminal nuclear complex, nucleus of the solitary tract, locus coeruleus, dorsal raphe nucleus, hippocampus, amygdala, endopiriform nucleus, entorhinal cortex and sensorimotor cortex. In the TNS group the number of BrdU-positive cells in the dentate gyrus was significantly greater with respect to both Naïve and Sham groups. Data show that acute TNS effectively counteracted PTZ-induced seizures and boosted hippocampal cell proliferation in rats. TNS increased c-Fos-like immunoreactivity in brainstem and forebrain structures which play a pivotal role in the physiopathology of epilepsy and depression.