rudyvdbrink/CitationDatabase huggingface dataset:
Cannabidiol Modulates the Motor Profile and NMDA Receptor-related Alterations Induced by Ketamine.
Neuroscience, 2021

Cannabidiol (CBD) is a non-addictive ingredient of cannabis with antipsychotic potential, while ketamine (KET), an uncompetitive NMDA receptor inhibitor, has been extensively used as a psychotomimetic. Only few studies have focused on the role of CBD on the KET-induced motor profile, while no study has investigated the impact of CBD on KET-induced alterations in NMDA receptor subunit expression and ERK phosphorylation state, in brain regions related to the neurobiology and treatment of schizophrenia. Therefore, the aim of the present study is to evaluate the role of CBD on KET-induced motor response and relevant glutamatergic signaling in the prefrontal cortex, the nucleus accumbens, the dorsal and ventral hippocampus. The present study demonstrated that CBD pre-administration did not reverse KET-induced short-lasting hyperactivity, but it prolonged it over time. CBD alone decreased motor activity at the highest dose tested (30 mg/kg) while KET increased motor activity at the higher doses (30, 60 mg/kg). Moreover, KET induced regionally-dependent alterations in NR1 and NR2B expression and ERK phosphorylation that were reversed by CBD pre-administration. Interestingly, in the nucleus accumbens KET per se reduced NR2B and p-ERK levels, while the CBD/KET combination increased NR2B and p-ERK levels, as compared to control. This study is the first to show that CBD prolongs KET-induced motor stimulation and restores KET-induced effects on glutamatergic signaling and neuroplasticity-related markers. These findings contribute to the understanding of CBD effects on the behavioral and neurobiological profiles of psychotogenic KET.
Neural representation of newly instructed rule identities during early implementation trials.
eLife, 2019

By following explicit instructions, humans instantaneously get the hang of tasks they have never performed before. We used a specially calibrated multivariate analysis technique to uncover the elusive representational states during the first few implementations of arbitrary rules such as 'for coffee, press red button' following their first-time instruction. Distributed activity patterns within the ventrolateral prefrontal cortex (VLPFC) indicated the presence of neural representations specific of individual stimulus-response (S-R) rule identities, preferentially for conditions requiring the memorization of instructed S-R rules for correct performance. Identity-specific representations were detectable starting from the first implementation trial and continued to be present across early implementation trials. The increasingly fluent application of novel rule representations was channelled through increasing cooperation between VLPFC and anterior striatum. These findings inform representational theories on how the prefrontal cortex supports behavioral flexibility specifically by enabling the ad-hoc coding of newly instructed individual rule identities during their first-time implementation.
New considerations on the validity of the Wiener-Granger causality test.
Heliyon, 2020

The Wiener-Granger causality test is used to predict future experimental results from past observations in a purely mathematical way. For instance, in many scientific papers this test has been used to study the causality relations in the case of neuronal activities. Albeit some papers reported repeatedly about problems or open questions related to the application of the Granger causality test on biological systems, these criticisms were always related to some kind of assumptions to be made before the test's application. In our paper instead we investigate the Granger method itself, making use exclusively of fundamental mathematical tools like Fourier transformation and differential calculus. We find that the ARMA method reconstructs any time series from any time series, regardless of their properties, and that the quality of the reconstruction is given by the properties of the Fourier transform. In literature several definitions of "causality" have been proposed in order to maintain the idea that the Granger test might be able to predict future events and prove causality between time series. We find instead that not even the most fundamental requirement underlying any possible definition of causality is met by the Granger causality test. No matter of the details, any definition of causality should refer to the prediction of the future from the past; instead by inverting the time series we find that Granger also allows one to "predict" the past from the future.
Effects of polychlorinated biphenyls exposure on physical growth from birth to childhood and adolescence: A prospective cohort study.
Environmental research, 2020

Given that their traditional lifestyle and diet still relies on fish and other marine species for sustenance, the Inuit are highly exposed to polychlorinated biphenyls (PCBs) and PCBs are increasingly linked to obesity. However, evidence is not consistent regarding which periods of exposure are most relevant. In this study, we examine whether in utero, childhood, and adolescent exposure to PCBs are related to physical growth at adolescence.
Efficient Low-Pass Dendro-Somatic Coupling in the Apical Dendrite of Layer 5 Pyramidal Neurons in the Anterior Cingulate Cortex.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2020

Signal propagation in the dendrites of many neurons, including cortical pyramidal neurons in sensory cortex, is characterized by strong attenuation toward the soma. In contrast, using dual whole-cell recordings from the apical dendrite and soma of layer 5 (L5) pyramidal neurons in the anterior cingulate cortex (ACC) of adult male mice we found good coupling, particularly of slow subthreshold potentials like NMDA spikes or trains of EPSPs from dendrite to soma. Only the fastest EPSPs in the ACC were reduced to a similar degree as in primary somatosensory cortex, revealing differential low-pass filtering capabilities. Furthermore, L5 pyramidal neurons in the ACC did not exhibit dendritic Ca
Deep learning-based behavioral analysis reaches human accuracy and is capable of outperforming commercial solutions.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2020

To study brain function, preclinical research heavily relies on animal monitoring and the subsequent analyses of behavior. Commercial platforms have enabled semi high-throughput behavioral analyses by automating animal tracking, yet they poorly recognize ethologically relevant behaviors and lack the flexibility to be employed in variable testing environments. Critical advances based on deep-learning and machine vision over the last couple of years now enable markerless tracking of individual body parts of freely moving rodents with high precision. Here, we compare the performance of commercially available platforms (EthoVision XT14, Noldus; TSE Multi-Conditioning System, TSE Systems) to cross-verified human annotation. We provide a set of videos-carefully annotated by several human raters-of three widely used behavioral tests (open field test, elevated plus maze, forced swim test). Using these data, we then deployed the pose estimation software DeepLabCut to extract skeletal mouse representations. Using simple post-analyses, we were able to track animals based on their skeletal representation in a range of classic behavioral tests at similar or greater accuracy than commercial behavioral tracking systems. We then developed supervised machine learning classifiers that integrate the skeletal representation with the manual annotations. This new combined approach allows us to score ethologically relevant behaviors with similar accuracy to humans, the current gold standard, while outperforming commercial solutions. Finally, we show that the resulting machine learning approach eliminates variation both within and between human annotators. In summary, our approach helps to improve the quality and accuracy of behavioral data, while outperforming commercial systems at a fraction of the cost.
Current Concepts of Neurophysiological Factors in Central Regulatory Mechanism of Rapid Eye Movement Sleep: A Review.
The West Indian medical journal, 2015

Rapid eye movement (REM) sleep is physiologically different from the other phases of sleep. Most of the postulations by researchers have speculated on the role or significance of the REM sleep stage. Most of the proposed roles that are attributed to REM sleep in vital brain functions are still mere speculations. For example, there is no clear evidence to suggest that REM sleep may play a particular role or may mediate a proposed mechanism for a specific brain function. The aim of this review is to identify those vital processes in brain function believed to be REM sleep driven, and which have featured prominently in the works of researchers in the past. The method adopted in this review was that of information gathering from sources which included published works of past and present researchers, articles on sleep presented in seminars and conferences, published articles on sleep, lecture notes on sleep physiology, textbooks of current editions in neuroscience, reports and published works accessed from the Internet using search engines such as Google, Mamma, PubMed etc. The postulations and hypothesized roles of REM sleep in vital brain function have been clearly highlighted in this review. It is concluded from this review that neural factors involved in the central mechanisms of REM sleep are not fully understood. Nevertheless, information noted in this review lends further credence to the notion that REM sleep is crucial and probably the most important sleep phase. It is hoped that facts in the proposals and postulations chronicled in this review will serve as important information source for neuroscientists and different researchers engaged in the subject of sleep.
Invertebrate vision: peripheral adaptation to repeated object motion.
Current biology : CB, 2013

Visual systems adapt rapidly to objects moving repeatedly within the visual field, because such objects are likely irrelevant. In the crab, the neural switch for such adaptation has been found to take place at a surprisingly early stage of the visual processing pathway.
Transcranial photobiomodulation-induced changes in human brain functional connectivity and network metrics mapped by whole-head functional near-infrared spectroscopy 
Biomedical optics express, 2020

Transcranial photobiomodulation (tPBM) with near-infrared light on the human head has been shown to enhance human cognition. In this study, tPBM-induced effects on resting state brain networks were investigated using 111-channel functional near-infrared spectroscopy over the whole head. Measurements were collected with and without 8-minute tPBM in 19 adults. Functional connectivity (FC) and brain network metrics were quantified using Pearson's correlation coefficients and graph theory analysis (GTA), respectively, for the periods of pre-, during, and post-tPBM. Our results revealed that tPBM (1) enhanced information processing speed and efficiency of the brain network, and (2) increased FC significantly in the frontal-parietal network, shedding light on a better understanding of tPBM effects on brain networks.
Auditory and Somatosensory P3 Are Complementary for the Assessment of Patients with Disorders of Consciousness.
Brain sciences, 2020

The evaluation of the level of consciousness in patients with disorders of consciousness (DOC) is primarily based on behavioural assessments. Patients with unresponsive wakefulness syndrome (UWS) do not show any sign of awareness of their environment, while minimally conscious state (MCS) patients show reproducible but fluctuating signs of awareness. Some patients, although with remaining cognitive abilities, are not able to exhibit overt voluntary responses at the bedside and may be misdiagnosed as UWS. Several studies investigated functional neuroimaging and neurophysiology as an additional tool to evaluate the level of consciousness and to detect covert command following in DOC. Most of these studies are based on auditory stimulation, neglecting patients suffering from decreased or absent hearing abilities. In the present study, we aim to assess the response to a P3-based paradigm in 40 patients with DOC and 12 healthy participants using auditory (AEP) and vibrotactile (VTP) stimulation. To this end, an EEG-based brain-computer interface was used at DOC patient's bedside. We compared the significance of the P3 performance (i.e., the interpretation of significance of the evoked P3 response) as obtained by 'direct processing' (i.e., theoretical-based significance threshold) and 'offline processing' (i.e., permutation-based single subject level threshold). We evaluated whether the P3 performances were dependent on clinical variables such as diagnosis (UWS and MCS), aetiology and time since injury. Last we tested the dependency of AEP and VTP performances at the single subject level. Direct processing tends to overestimate P3 performance. We did not find any difference in the presence of a P3 performance according to the level of consciousness (UWS vs. MCS) or the aetiology (traumatic vs. non-traumatic brain injury). The performance achieved at the AEP paradigm was independent from what was achieved at the VTP paradigm, indicating that some patients performed better on the AEP task while others performed better on the VTP task. Our results support the importance of using multimodal approaches in the assessment of DOC patients in order to optimise the evaluation of patient's abilities.
The immunomodulatory effects of endocrine therapy in breast cancer.
Journal of experimental & clinical cancer research : CR, 2021

Endocrine therapies with SERMs (selective estrogen receptor modulators) or SERDs (selective estrogen receptor downregulators) are standard therapies for patients with estrogen receptor (ER)-positive breast cancer. Multiple small molecule inhibitors targeting the PI3K-AKT-mTOR pathway or CDK4/6 have been developed to be used in combination with anti-estrogen drugs to overcome endocrine resistance. In addition to their direct antitumor effects, accumulating evidence has revealed the tumor immune microenvironment (TIM)-modulating effects of these therapeutic strategies, which have not been properly acknowledged previously. The immune microenvironment of breast tumors plays a crucial role in tumor development, metastasis and treatment response to endocrine therapy and immunotherapy. Therefore, in our current work, we comprehensively review the immunomodulatory effect of endocrine therapy and discuss its potential applications in combination with immune checkpoint inhibitors in breast cancer treatment.
Trajectories of depressive symptoms and associated patterns of cognitive decline.
Scientific reports, 2020

The aim was to investigate the pattern and rate of cognitive decline across distinctive trajectories of depressive symptoms in older adults. In this prospective multinational cohort study on 69,066 participants (on average 64 years at baseline, 55% women), assessments of cognitive functions (immediate recall, delayed recall, verbal fluency) and depressive symptoms (EURO-D scale) were conducted at 2-year intervals. The trajectories of depressive symptoms were obtained using latent growth mixture modelling, cognitive decline was assessed using smoothing splines and linear mixed effects models. Four distinct trajectories of depressive symptoms were identified: constantly low (n = 49,660), constantly high (n = 2999), increasing (n = 6828) and decreasing (n = 9579). Individuals with increasing and constantly high depressive symptoms showed linear cognitive decline, while those with constantly low and decreasing depressive symptoms had fluctuating cognition. Participants with increasing depressive symptoms had the fastest decline, while those with decreasing symptoms were spared from decline in cognition. This study suggests that the pattern as well as the rate of cognitive decline co-occurs with specific patterns of changes in depressive symptoms over time. The most pronounced cognitive decline is present in individuals, in whom depressive symptoms increase late in life. Unique mechanisms of cognitive decline may exist for subgroups of the population, and are associated with the trajectory of depressive symptoms.
Machine learning methods for brain network classification: Application to autism diagnosis using cortical morphological networks.
Journal of neuroscience methods, 2020

Autism spectrum disorder (ASD) affects the brain connectivity at different levels. Nonetheless, non-invasively distinguishing such effects using magnetic resonance imaging (MRI) remains very challenging to machine learning diagnostic frameworks due to ASD heterogeneity. So far, existing network neuroscience works mainly focused on functional (derived from functional MRI) and structural (derived from diffusion MRI) brain connectivity, which might not directly capture relational morphological changes between brain regions. Indeed, machine learning (ML) studies for ASD diagnosis using morphological brain networks derived from conventional T1-weighted MRI are very scarce.
An update on the pharmacological management of pain in patients with multiple sclerosis.
Expert opinion on pharmacotherapy, 2020

The prevalence of pain in Multiple Sclerosis (MS) is estimated to be between 29-86% depending on various stages of the disease. According to a recent mechanism-based classification, MS pain syndromes include ongoing extremity pain, trigeminal neuralgia, and Lhermitte's phenomenon, painful tonic spasms and spasticity pain, pain associated with optic neuritis, musculoskeletal pain, migraine, and treatment-induced pain.
David S. Miller: Scientist, Mentor, Friend-a tribute and thank you.
Fluids and barriers of the CNS, 2020

David S. Miller was Acting Scientific Director of the Division of Intramural Research at the National Institute of Environmental Health Sciences, National Institutes of Health, and Head of the Intracellular Regulation Group in the Laboratory of Toxicology and Pharmacology before he retired in 2016. David received his Ph.D. in biochemistry from the University of Maine in 1973. David was a Group Leader at the Michigan Cancer Foundation before joining the NIEHS in 1985. His research covered a wide range from renal excretory transport mechanisms to regulation of transporters at the blood-CSF and blood-brain barriers, from fish, amphibians and birds to mammals. David was an outstanding scientist with irresistible enthusiasm for science and an incredible ability to think outside the box while being an exceptional mentor and friend.
Good news regarding SSRI safety in Danish meta-analysis.
Acta neuropsychiatrica, 2020

In two previous letters on an selective serotonin reuptake inhibitor (SSRI) meta-analysis conducted by the Copenhagen Trial Unit at Copenhagen University Hospital, we have commented on a large number of errors, almost all of which have tilted the results in an anti-drug direction, that unfortunately mar this publication. While the authors have acknowledged many of these mishaps, and may now be expected to submit an extensive errata list to the journal where their paper was once published, we regretfully note that also their latest contribution to this exchange is surprisingly inaccurate. However, its many shortcomings notwithstanding, their meta-analysis does add to the current literature by confirming that SSRIs do not seem to enhance the risk for suicide or death, and also that these drugs seem to enhance the risk of side effects categorised as serious only in the elderly.
NF-κB pathway activation during endothelial-to-mesenchymal transition in a rat model of doxorubicin-induced cardiotoxicity.
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 2020

Doxorubicin is a commonly used anthracycline chemotherapeutic agent; however, its application is limited owing to its cardiotoxicity. Current clinical treatments cannot efficiently or fully prevent doxorubicin-induced toxicity, primarily because its pathogenesis and mechanisms of action remain unknown. In this study, we established a rat model of chronic doxorubicin-induced cardiotoxicity, in which the severity of cardiac fibrosis and hydroxyproline levels increased in a time-dependent manner. Doxorubicin damaged the mitochondria and blood vessels and induced autophagy. Cells undergoing endothelial-to-mesenchymal transition (EndoMT)and those expressing endothelial cell and myofibroblast markers were simultaneously observed in vitro and in rats treated with doxorubicin. The NF-κB pathway was activated during EndoMT, andp65 and p-p65 were strongly expressed in the nucleus of endothelial cells in vitro. Taken together, these results suggest that vascular injury and cardiac fibrosis are characteristic symptoms of doxorubicin-induced cardiotoxicity. The NF-κB pathway-associated EndoMT may influence the pathogenesis of doxorubicin-induced cardiotoxicity, and the constituents of this pathway may be potential therapeutic targets to prevent the development of this condition.
Influence of theta-burst transcranial magnetic stimulation over the dorsolateral prefrontal cortex on emotion processing in healthy volunteers.
Cognitive, affective & behavioral neuroscience, 2020

Repetitive transcranial magnetic stimulation is a potential treatment option for depression, with the newer intermittent theta-burst stimulation (iTBS) protocols providing brief intervention. However, their mechanism of action remains unclear. We investigated the hypothesis that iTBS influences brain circuits involved in emotion processing that are also affected by antidepressants. We predicted that iTBS would lead to changes in performance on emotion-processing tasks. We investigated the effects of intermittent TBS (iTBS) over the left dorsolateral prefrontal cortex (DLPFC) on the processing of emotional information (word recall and categorization, facial emotion recognition, and decision-making) in 28 healthy volunteers by contrasting these effects with those of sham stimulation. Each volunteer received iTBS and sham stimulation in a blinded crossover design and completed the emotion-processing tasks before and after stimulation. Compared to sham stimulation, iTBS increased positive affective processing for word recall, yet had an unexpected effect on facial emotion recognition for happy and sad faces. There was no evidence of an effect on decision-making or word categorization. We found support for our hypothesis that iTBS influences emotion processing, though some changes were not in the expected direction. These findings suggest a possible common mechanism of action between iTBS and antidepressants, and a complex neural circuitry involved in emotion processing that could potentially be tapped into via brain stimulation. Future research should investigate the neural correlates of emotion processing more closely to inform future iTBS protocols.
Circadian rhythm in idiopathic normal pressure hydrocephalus.
Clinical neurology and neurosurgery, 2018

The pathogenesis of idiopathic normal pressure hydrocephalus (iNPH) takes place in structures close to the cerebral ventricular system. Suprachiasmatic nucleus (SCN), situated close to the third ventricle, is involved in circadian rhythm. Diurnal disturbances are well-known in demented patients. The cognitive decline in iNPH is potentially reversible after a shunt operation. Diurnal rhythm has never been studied in iNPH. We hypothesize that there is a disturbance of circadian rhythm in iNPH-patients and the aim was to study any changes of the diurnal rhythm (mesor and circadian period) as well as any changes of the diurnal amplitude and acrophase of the activity in iNPH-patients before and after a shunt operation.