rudyvdbrink/CitationDatabase huggingface dataset:
Theta-band functional connectivity in the dorsal fronto-parietal network predicts goal-directed attention.
Neuropsychologia, 2016

Functional imaging studies have identified a dorsal fronto-parietal network whose activity reflects shifts of attention in space and is sensitive to the behavioural relevance of stimuli. In patients with severe deficits of spatial attention this network is often structurally preserved. Here, we show that resting-state EEG functional connectivity in the dorsal fronto-parietal network predicts impaired goal-directed processing in stroke patients with spatial attention deficits. Eleven right-hemisphere damaged patients with different degrees of contralesional spatial deficits and sixteen age-matched healthy controls performed a visuo-spatial task which required them to react to a central target while ignoring task-relevant distracters presented left or right of fixation. Unlike controls, performance of patients was not modulated by the goal-relevance of peripheral distracters. Compared to controls patients showed a significant decrease in theta-band connectivity between the right dorsolateral prefrontal cortex and the right superior parietal region. Moreover, in both groups we observed a significant correlation between fronto-parietal connectivity and the behavioural effect of distracter relevance. These findings indicate that fronto-parietal functional connectivity is impaired in patients with spatial attention deficits and predicts effects of goal-relevant information on target processing.
From virus to diabetes therapy: Characterization of a specific insulin-degrading enzyme inhibitor for diabetes treatment.
FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2021

Inhibition of insulin-degrading enzyme (IDE) is a possible target for treating diabetes. However, it has not yet evolved into a medical intervention, mainly because most developed inhibitors target the zinc in IDE's catalytic site, potentially causing toxicity to other essential metalloproteases. Since IDE is a cellular receptor for the varicella-zoster virus (VZV), we constructed a VZV-based inhibitor. We computationally characterized its interaction site with IDE showing that the peptide specifically binds inside IDE's central cavity, however, not in close proximity to the zinc ion. We confirmed the peptide's effective inhibition on IDE activity in vitro and showed its efficacy in ameliorating insulin-related defects in types 1 and 2 diabetes mouse models. In addition, we suggest that inhibition of IDE may ameliorate the pro-inflammatory profile of CD4
Stereotaxic endoscopy for the ocular imaging of awake, freely moving animal models.
Journal of biophotonics, 2020

Stereotaxic instruments are increasingly used in research animals for the study of disease, but typically require restraints and anesthetic procedures. A stereotaxic head mount that enables imaging of the anterior chamber of the eye in alert and freely mobile mice is presented in this study. The head mount is fitted based on computed tomography scans and manufactured using 3D printing. The system is placed noninvasively using temporal mount bars and a snout mount, without breaking the skin or risking suffocation, while an instrument channel stabilizes the ocular probes. With a flexible micro-endoscopic probe and a confocal scanning laser microscopy system, <20 μm resolution is achieved in vivo with a field of view of nearly 1 mm. Discomfort is minimal, and further adaptations for minimally invasive neuroscience, optogenetics and auditory studies are possible.
Neuroprotective effect of lithium on hippocampal volumes in bipolar disorder independent of long-term treatment response.
Psychological medicine, 2014

Neuroimaging studies have demonstrated an association between lithium (Li) treatment and brain structure in human subjects. A crucial unresolved question is whether this association reflects direct neurochemical effects of Li or indirect effects secondary to treatment or prevention of episodes of bipolar disorder (BD).
Evidence for oral agmatine sulfate safety--a 95-day high dosage pilot study with rats.
Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association, 2013

Agmatine, decarboxylated arginine, exerts beneficial effects in various experimental disease models. Clinical trials indicate the safety and effectiveness of short-term (up to 21 days) high dose regimens of oral agmatine sulfate, but longer term studies are lacking. This pilot study undertook to assess the safety of a longer term high dosage oral agmatine sulfate in laboratory rats. Adult Wistar rats consumed 5.3 g/l agmatine sulfate in their drinking water for 95 days, a regimen estimated to result in a daily dosage of absorbed agmatine of about 100mg/kg. Animals' body weight, water consumption and blood pressure were periodically measured, and general cage behavior, fur appearance, urination and feces appearance monitored. These parameters were also determined at 20 days after treatment cessation (day 115). On days 95 and 115, animals were euthanized for gross necropsy assessment. Agmatine-treated rats showed slight, but significant reductions in body weight and blood pressure, and reduced water consumption during treatment, which recovered completely within 20 days after treatment cessation. Otherwise, no abnormal behaviors or organ pathologies were observed. These findings are first to suggest apparent safety of sub-chronic high dosage dietary agmatine sulfate in laboratory rats, thus lending further support to the therapeutic applications of agmatine.
The role of DNA methylation in the pathophysiology and treatment of bipolar disorder.
Neuroscience and biobehavioral reviews, 2016

Bipolar disorder (BD) is a multifactorial illness thought to result from an interaction between genetic susceptibility and environmental stimuli. Epigenetic mechanisms, including DNA methylation, can modulate gene expression in response to the environment, and therefore might account for part of the heritability reported for BD. This paper aims to review evidence of the potential role of DNA methylation in the pathophysiology and treatment of BD. In summary, several studies suggest that alterations in DNA methylation may play an important role in the dysregulation of gene expression in BD, and some actually suggest their potential use as biomarkers to improve diagnosis, prognosis, and assessment of response to treatment. This is also supported by reports of alterations in the levels of DNA methyltransferases in patients and in the mechanism of action of classical mood stabilizers. In this sense, targeting specific alterations in DNA methylation represents exciting new treatment possibilities for BD, and the 'plastic' characteristic of DNA methylation accounts for a promising possibility of restoring environment-induced modifications in patients.
Association of perceived health and depression with older adults' subjective memory complaints: contrasting a specific questionnaire with general complaints questions.
European journal of ageing, 2014

The objectives of this paper were to evaluate the association of subjective memory complaints (SMC) with perceived state of health, mood and episodic memory (associative and everyday memory). We studied these areas using two different complaint assessment methods (three general questions and a validated scale). The study included 269 older adults (aged 65-87) with age-related memory changes, but without cognitive impairment. They were evaluated with Mini-cognitive Exam, Rivermead Behavioural Memory Test (a test of everyday memory), Paired Associates Learning Test, Memory Failures of Everyday Questionnaire, three memory complaints questions, Nottingham Health Profile and Geriatric Depression Scale. The results indicated that memory for everyday performance, mood and perceived health were independent predictors of SMC, with mood and perceived health being stronger predictors than actual memory performance. Age was not associated with subjective memory and, with regard to level of education, only the illiterate level was associated with SMC. A specific questionnaire on subjective memory was found to be preferable to an aggregate of complaints questions on self-reported memory; only health profile was found to predict the outcomes on memory complaints questions. Our conclusion is that a group of underlying factors other than everyday memory were playing a role in SMC; these SMC of subjects with age-related memory changes were mainly associated with subjective evaluations of their health.
Intracellular and computational evidence for a dominant role of internal network activity in cortical computations.
Current opinion in neurobiology, 2011

The mammalian cerebral cortex is characterized by intense spontaneous activity, depending on brain region, age, and behavioral state. Classically, the cortex is considered as being driven by the senses, a paradigm which corresponds well to experiments in quiescent or deeply anesthetized states. In awake animals, however, the spontaneous activity cannot be considered as 'background noise', but is of comparable-or even higher-amplitude than evoked sensory responses. Recent evidence suggests that this internal activity is not only dominant, but also it shares many properties with the responses to natural sensory inputs, suggesting that the spontaneous activity is not independent of the sensory input. Such evidence is reviewed here, with an emphasis on intracellular and computational aspects. Statistical measures, such as the spike-triggered average of synaptic conductances, show that the impact of internal network state on spiking activity is major in awake animals. Thus, cortical activity cannot be considered as being driven by the senses, but sensory inputs rather seem to modulate and modify the internal dynamics of cerebral cortex. This view offers an attractive interpretation not only of dreaming activity (absence of sensory input), but also of several mental disorders.
Oncogenic viruses and tumor glucose metabolism: like kids in a candy store.
Molecular cancer therapeutics, 2012

Oncogenic viruses represent a significant public health burden in light of the multitude of malignancies that result from chronic or spontaneous viral infection and transformation. Although many of the molecular signaling pathways that underlie virus-mediated cellular transformation are known, the impact of these viruses on metabolic signaling and phenotype within proliferating tumor cells is less well understood. Whether the interaction of oncogenic viruses with metabolic signaling pathways involves enhanced glucose uptake and glycolysis (both hallmark features of transformed cells) or dysregulation of molecular pathways that regulate oxidative stress, viruses are adept at facilitating tumor expansion. Through their effects on cell proliferation pathways, such as the PI3K and MAPK pathways, the cell cycle regulatory proteins p53 and ATM, and the cell stress response proteins HIF-1α and AMPK, viruses exert control over critical metabolic signaling cascades. Additionally, oncogenic viruses modulate the tumor metabolomic profile through direct and indirect interactions with glucose transporters, such as GLUT1, and specific glycolytic enzymes, including pyruvate kinase, glucose 6-phosphate dehydrogenase, and hexokinase. Through these pathways, oncogenic viruses alter the phenotypic characteristics and energy-use methods of transformed cells; therefore, it may be possible to develop novel antiglycolytic therapies to target these dysregulated pathways in virus-derived malignancies.
Applying economic models to estimate local economic benefits of improved coverage of early intervention for psychosis.
Early intervention in psychiatry, 2019

Early Intervention Psychosis Services (EIPS) for people experiencing First Episode Psychosis (FEP) offer important clinical and non-clinical benefits over standard care. Similarly, intervention for Clinical High Risk for Psychosis state (CHR-P) can prevent psychosis, ameliorate symptoms and have non-clinical benefits. This study aimed to estimate associated local economic benefits of FEP and CHR-P services compared with standard care.
Genetics and genetic counseling in psychiatry: Results from an opinion survey of professionals and users.
Molecular genetics & genomic medicine, 2019

The heritability of several psychiatric disorders is high, and specific at-risk variants have been identified. Therefore, genetic counseling and genetic testing can be prescribed to some psychiatric patients, but these services are not standardized for most of the population. The aims of the study were to gather opinions from mental health professionals and users regarding (a) the genetics of psychiatric disorders and (b) the usefulness of a genetic counseling unit in psychiatry.
Changes of oscillatory activity in the subthalamic nucleus during obsessive-compulsive disorder symptoms: two case reports.
Cortex; a journal devoted to the study of the nervous system and behavior, 2014

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has positive and negative effects on mood and cognition, as shown in patients suffering from Parkinson's disease (PD) and severe obsessive-compulsive disorders (OCD). Such behavioural and clinical effects suggest that the STN has an important function in limbic circuitry, which still needs to be clarified from electrophysiological recordings. Here we report two exceptional cases of OCD patients in whom local field potentials (LFP) of the anterior STN were directly recorded during acute obsessive-compulsive symptoms. We found significant symptom-related changes in different frequency bands, with no clear preferential oscillatory pattern. The overall modified STN activity during OCD symptoms suggests a mixture of both pathological and compensatory mechanisms that would reflect the maintenance of an over stable motor/cognitive/emotional set. Whether this activity propagates throughout the entire cognitive-limbic loops that are impaired in OCD is an interesting question for future research in larger series of patients.
Planning and management of SEEG.
Neurophysiologie clinique = Clinical neurophysiology, 2018

Stereoelectroencephalography (SEEG) aims to define the epileptogenic zone (EZ), to study its relationship with functional areas and the causal lesion and to evaluate the possibility of surgical therapy. Planning of exploration is based on the validity of the hypotheses developed from electroclinical and imaging correlations. Further investigations can refine the implantation plan (e.g. fluorodeoxyglucose positron emission tomography [FDG-PET], single photon emission computerized tomography [SPECT], magnetoencephalography [MEG] and high resolution electroencephalography [EEG-HR]). The scheme is individualized according to the features of each clinical case, but a general approach can be systematized according to the regions involved (temporal versus extra-temporal), the existence of a lesion, its type and extent. It takes account of the hemispheric dominance for language if this can be determined. In "temporal plus" epilepsies, perisylvian and insular regions are among the key structures to investigate in addition to mesial and neocortical temporal areas. In frontal lobe epilepsies, determining the functional and anatomical organization of seizures (anterior versus posterior, mesial versus dorsolateral) allows better targeting of the implantation. Posterior epilepsies tend to have a complex organization leading to multilobar and often bilateral explorations. In lesional cases, it may be useful to implant one or several intralesional electrode(s), except in cases of vascular lesions or cyst. The strategy of implantation can be modified if thermocoagulations are considered. The management of SEEG implies continuous monitoring in a dedicated environment to determine the EZ with optimal safety conditions. This methodology includes spontaneous seizure recordings, low and high frequency stimulations and, if possible, sleep recording. SEEG is applicable in children, even the very young. Specific training of medical and paramedical teams is required.
NADPH oxidase 2-dependent oxidative stress, mitochondrial damage and apoptosis in the ventral cochlear nucleus of D-galactose-induced aging rats.
Neuroscience, 2015

Aging has been associated with oxidative stress and the accumulation of mitochondrial DNA (mtDNA) mutation. The previous study has established a mimetic rat model of aging using D-galactose (D-gal) and revealed that chronic injection of D-gal can increase NADPH oxidase (NOX)-dependent oxidative stress, mitochondrial damage and apoptosis in the peripheral auditory system. However, the effects of NOXs in the central auditory system (CAS) were still obscure. The current study was designed to investigate potential causative mechanisms of central presbycusis by using the D-gal-induced aging rats. We found that the levels of H2O2 and the expression of NADPH oxidase 2 (NOX2) and its corresponding subunits P22(phox), P47(phox) and P67(phox) were greatly increased in the ventral cochlear nucleus (VCN) of D-gal-treated rats as compared with controls. And, the levels of a typical biomarker of oxidative stress, 8-hydroxy-2-deoxyguanosine (8-OHdG), and the accumulation of mtDNA common deletion (CD) were also increased in the VCN of D-gal-treated rats as compared with controls. Moreover, the damage of mitochondrial ultrastructure, a decline in ATP levels, the loss of mitochondrial membrane potential (MMP), an increase in the amount of cytochrome c (cyt c) translocated to the cytoplasm and caspase-3 activation were observed in the VCN induced by D-gal. In addition, we also found that the terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) nick-end-labeling (TUNEL)-positive cells in the VCN were increased in D-gal-treated rats. Taken together, these findings suggest that NOX2-dependent oxidative stress may contribute to mitochondrial damage and activate a caspase-3-dependent apoptosis pathway in the CAS during aging. This study also provides new insights into the development of presbycusis.
Are intracranial pressure wave amplitudes measurable through lumbar puncture?
Acta neurologica Scandinavica, 2013

The aim of this study was to investigate whether pulsations measured in the brain correspond to those measured in lumbar space, and subsequently whether lumbar punctures could replace invasive recordings.
Comparison of the cytokine profiles of patients with neuronal-antibody-associated central nervous system disorders.
The International journal of neuroscience, 2012

Levels of several cytokines were evaluated in the sera of patients with neuromyelitis optica (NMO) and paraneoplastic or nonparaneoplastic autoimmune encephalitis (AE) and healthy controls (HC). AE patients had higher serum interleukin-17 (IL-17), interferon-gamma (IFN-γ), and IL-12 levels than NMO patients and HC. Also, AE patients with antibodies to cell surface antigens (voltage-gated potassium channel, N-methyl-d-aspartate receptor) displayed increased serum Th17 cytokine (IL-17, IL-23) levels as compared with AE patients with antibodies to intracellular antigens (Hu, Yo), NMO patients, and HC. Aquaporin-4 (Aqp-4) antibody positive NMO patients had higher serum IL-9 levels than Aqp-4 antibody negative NMO patients. IL-17, IL-23, IL-12, and antibody levels were significantly correlated in AE patients with antibodies to cell surface antigens. Our results support the notion that different pathogenic mechanisms are involved in central nervous system diseases associated with antibodies to intracellular and cell surface neuronal antigens. T helper 1 (Th1)-/Th17-type immunities and IL-9 might be important therapeutic targets in AE and NMO, respectively.
Prefrontal neuromodulation reverses spatial associations of non-numerical sequences, but not numbers.
Biological psychology, 2017

Numerical and non-numerical sequence items interact with spatial responding, pointing towards mental representations that are grounded in space and referred to as SNARC effects (spatial-numerical association of response codes). An ongoing controversy pertains to the universal origin of different SNARC effects and whether their underpinning is a spatial arrangement of cardinal magnitude (mental number line) or a sequential arrangement of ordinal elements in working memory. Recent results from prefrontal neuromodulation with transcranial direct current stimulation (tDCS) were supportive of the unified working memory account. The current tDCS experiment was designed to empirically test the generalizability of the prefrontal modulation effects previously found for numbers in a non-numerical sequence (weekdays) and to examine predictions from the universal account. Participants performed a series of classification tasks with numerical and non-numerical sequences (1-5, Monday-Friday) before and concurrent to a prefrontal stimulation with either anodal (N=24) or cathodal polarity (N=24). Results show a dissociation of SNARC effects for numbers and weekdays by anodal tDCS: Spatial associations of weekdays were reversed by stimulation, when order was relevant for the task, but SNARC effects with number symbols were emphasized in the regular left-to-right direction, corroborating previous results. A control experiment showed that the polarity-dependent neuromodulation effects were absent in order-irrelevant font color classification, supporting the tDCS principle of activity-dependence. We discuss differences in linguistic markedness between temporal and magnitude-related classifications in an integrative account explaining the full pattern. We suggest that stimulation-enhanced psycholinguistic processing can evoke space-number associations whose direction is opposite to cultural visuospatial experience.
Rat strain differences in restraint stress-induced brain cytokines.
Neuroscience, 2011

Induction of brain cytokines during times of stress has potent effects on altering behavior, mood, and cognitive functioning. Currently, it is unknown why exposure to some stressors such as tailshock and footshock elevate brain cytokines, while exposure to swim, predator odor, and restraint stress do not. Recent data indicate that brain noradrenergic signaling mediates brain cytokine production suggests magnitude of norepinephrine release during stress may be critical in initiating brain cytokine production. The aim of the current study was to investigate stress-induced brain cytokines between rat strains that differ in their magnitude of stress responsiveness as measured by brain norepinephrine and HPA responses. Sprague-Dawley and Fischer rats were placed in a restraint bag for 1 h or 2 h and sacrificed immediately following stressor termination. Exposure to restraint significantly elevated hypothalamic interleukin (IL)-1β and IL-1 receptor type (R) 2 mRNA after 1 h and IL-1β protein after 2 h in the high stress responsive Fischer rats, but not in Sprague-Dawley rats. IL-6, IL-1R1, Il-1 receptor antagonist (RA), and cyclooxygenase (Cox)-2 mRNA were not altered and neither there was expression of any cytokines in the hippocampus or circulating cytokines in either strain. Administration of desipramine (a norepinephrine reuptake inhibitor) to Sprague-Dawley rats was sufficient either alone or in combination with stress to increase IL-1β mRNA in the hypothalamus and desipramine combined with stress was sufficient to increase IL-1R2 mRNA in the hypothalamus. These data support our hypothesis that there is a critical threshold of brain norepinephrine necessary to stimulate brain cytokines, which may help to explain why severe stressors are more commonly reported to induce brain cytokines. These data also suggest an organisms' susceptibility to stress-induced brain cytokine production, depends on responsiveness and regulation of noradrenergic neurons.