rudyvdbrink/CitationDatabase huggingface dataset:
Two-photon imaging and the activation of cortical neurons.
Neuroscience, 2013

Based on two-photon calcium imaging, Histed et al. (2009) concluded that electrical microstimulation of cortical tissue in mammals activates a sparse and distributed population of neurons. This work has been cited by many as proof that electrical microstimulation is nonfocal, which means it may lack the precision needed for applications in neuroprosthetics. We affirm that the generation of stimulation-evoked behaviour is based primarily on the orthodromic conduction of signals originating mainly from the deepest layers of cortex, while the work of Histed et al. is effectively limited to investigating the antidromic activation of lateral projection neurons of the superficial cortex. The apparent sparse activation is a consequence of the pattern of axonal projections based on activating a volume of axons while imaging cell bodies transecting a single plane through the cortex. This creates the false impression that the distribution of activated neurons is sparse and nonfocal. We recommend how two-photon calcium imaging, which is superb for the study of individual and groups of neurons, might be more effectively used to ascertain how electrical stimulation affects the brains of mammals. This is a timely topic since investigators are using electrical microstimulation in animals to develop prosthetic devices to restore sensory and motor functions in disabled patients.
Dynamic Contrast-Enhanced MRI in the Study of Brain Tumors. Comparison Between the Extended Tofts-Kety Model and a Phenomenological Universalities (PUN) Algorithm.
Journal of digital imaging, 2015

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a well-established technique for studying blood-brain barrier (BBB) permeability that allows measurements to be made for a wide range of brain pathologies, including multiple sclerosis and brain tumors (BT). This latter application is particularly interesting, because high-grade gliomas are characterized by increased microvascular permeability and a loss of BBB function due to the structural abnormalities of the endothelial layer. In this study, we compared the extended Tofts-Kety (ETK) model and an extended derivate class from phenomenological universalities called EU1 in 30 adult patients with different BT grades. A total of 75 regions of interest were manually drawn on the MRI and subsequently analyzed using the ETK and EU1 algorithms. Significant linear correlations were found among the parameters obtained by these two algorithms. The means of R (2) obtained using ETK and EU1 models for high-grade tumors were 0.81 and 0.91, while those for low-grade tumors were 0.82 and 0.85, respectively; therefore, these two models are equivalent. In conclusion, we can confirm that the application of the EU1 model to the DCE-MRI experimental data might be a useful alternative to pharmacokinetic models in the study of BT, because the analytic results can be generated more quickly and easily than with the ETK model.
Incidence, predictors, and etiology of subsequent ischemic stroke within one year after transient ischemic attack.
International journal of stroke : official journal of the International Stroke Society, 2017

Background Incidence and predictors of ischemic stroke in patients with transient ischemic attack (TIA) have not been fully clarified outside Europe and North America. Aims We undertook the present prospective, multicenter study to clarify the incidence, predictors, and etiology of ischemic stroke within one year of TIA onset in Japan. Methods The study subjects were patients within seven days of TIA onset who were enrolled in a prospective register from 57 hospitals between June 2011 and December 2013. The primary endpoint was occurrence of ischemic stroke. Results Of 1365 consecutive patients, 1245 were followed for one year after TIA onset; 101 (8.1%) experienced ischemic stroke during follow-up. The leading subtype of ischemic stroke was small-vessel occlusion (SVO) followed by large-artery atherosclerosis (LAA) attributable to intracranial artery diseases. When dividing ischemic stroke events between those occurring within the first 90 days after TIA onset and those occurring after the first 90 days, the leading subtype of ischemic stroke within the first 90 days after TIA onset was SVO, followed by LAA attributable to intracranial artery diseases. In comparison, the subtypes most commonly seen beyond the first 90 days after TIA onset were cardioembolic and LAA attributable to intracranial artery disease. The one-year risk of ischemic stroke increased significantly as ABCD
Advances in the computational understanding of mental illness.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2021

Computational psychiatry is a rapidly growing field attempting to translate advances in computational neuroscience and machine learning into improved outcomes for patients suffering from mental illness. It encompasses both data-driven and theory-driven efforts. Here, recent advances in theory-driven work are reviewed. We argue that the brain is a computational organ. As such, an understanding of the illnesses arising from it will require a computational framework. The review divides work up into three theoretical approaches that have deep mathematical connections: dynamical systems, Bayesian inference and reinforcement learning. We discuss both general and specific challenges for the field, and suggest ways forward.
Current therapeutic options for hyponatremia: indications, limitations, and confounding variables.
Pharmacotherapy, 2011

The arginine vasopressin receptor antagonists, also known as the vaptans, are a new class of agents that address some of the unmet medical needs of patients with hyponatremia. Traditional therapies, including diuretics, fluid restriction, and saline infusions, have variable effects, potential toxicities, and concerns with patient adherence. Furthermore, these therapies are not specific to the underlying pathophysiology causing the hyponatremia. The recently approved arginine vasopressin receptor antagonists, however, target the underlying abnormal release of arginine vasopressin that is very likely at the core of the pathophysiology. Management of hyponatremia requires balancing the benefits of therapeutic intervention to restore normal serum sodium concentrations against the potential risks. Additional clinical experience is needed to develop reliable criteria for determining which patients should be treated with these agents. However, the data available indicate that this new class of drugs can favorably affect serum sodium concentration and clinical outcomes in patients with hypervolemic and euvolemic hyponatremia.
Effects of IV iron isomaltoside-1000 treatment on regional brain iron status in an iron-deficient animal.
Neuroscience, 2013

Iron deficiency has been documented to affect human cognitive function and conditions with brain iron compromise such as the restless legs syndrome (RLS). Intravenous (IV) iron treatment is used to reduce iron deficiency but its effects on brain iron are not known. It is not known if IV iron is effective in correcting regional brain iron deficiencies nor if it poses a risk of producing iron overload in some brain regions. Preclinical study of IV iron in the iron-deficient (ID) murine model is needed to evaluate and develop IV iron treatments for brain iron deficiency.
Rural trauma challenges in Alaska.
Critical care nursing clinics of North America, 2012

Rural trauma during winter months in Alaska requires a coordinated highly skilled approach for rescue, recovery, resuscitation, and transport to distant tertiary care centers. Clinicians in this state face travel delays, extreme weather conditions, and unique transport scenarios. Early assessment and resuscitation may focus more on minimizing delays than on the traditional ABCs of emergency medicine. Clinical evaluation and treatment is also impacted by subzero temperatures, hypothermia, and prolonged exposure. Mechanical and equipment malfunctions can complicate decisions and further add to the challenges faced by medical teams who respond and deliver care in the vast wilderness of this state.
Frontal Hemodynamic Response During Step Initiation Under Cognitive Conflict in Older and Young Healthy People.
The journals of gerontology. Series A, Biological sciences and medical sciences, 2021

Gait initiation is a daily challenge even for healthy individuals as it requires the timely coupling between the automatic anticipatory postural adjustment (APA) and the voluntary step according to the context. Modulation of this motor event has been thought to involve higher level brain control, including cognitive inhibitory circuitries. Despite the known participation of the supplementary motor area (SMA) in the modulation of some parameters of APA, the participation of areas controlling inhibition during gait initiation still needs to be investigated. In this study, the hemodynamic responses of the SMA and dorsolateral prefrontal cortex (DLPFC) were assessed using functional near-infrared spectroscopy (fNIRS) during a gait initiation task under cognitive conflict to select the foot to step (congruent [CON] and incongruent [INC] conditions). The older group (OG) showed worse inhibitory control than the young group (YG) along with more impairments in APA parameters. OG also had a lower amplitude of hemodynamic responses in both areas than YG in the INC. The INC increased the correlation between SMA and DLPFC only in the YG. Aging seems to impair the interaction between the hemodynamic responses of SMA and DLPFC, which influences APA performance in gait initiation under cognitive conflict.
T helper 17.1 cells associate with multiple sclerosis disease activity: perspectives for early intervention.
Brain : a journal of neurology, 2018

Interleukin-17-expressing CD4+ T helper 17 (Th17) cells are considered as critical regulators of multiple sclerosis disease activity. However, depending on the species and pro-inflammatory milieu, Th17 cells are functionally heterogeneous, consisting of subpopulations that differentially produce interleukin-17, interferon-gamma and granulocyte macrophage colony-stimulating factor. In the current study, we studied distinct effector phenotypes of human Th17 cells and their correlation with disease activity in multiple sclerosis patients. T helper memory populations single- and double-positive for C-C chemokine receptor 6 (CCR6) and CXC chemokine receptor 3 (CXCR3) were functionally assessed in blood and/or cerebrospinal fluid from a total of 59 patients with clinically isolated syndrome, 35 untreated patients and 24 natalizumab-treated patients with relapsing-remitting multiple sclerosis, and nine patients with end-stage multiple sclerosis. Within the clinically isolated syndrome group, 23 patients had a second attack within 1 year and 26 patients did not experience subsequent attacks during a follow-up of >5 years. Low frequencies of T helper 1 (Th1)-like Th17 (CCR6+CXCR3+), and not Th17 (CCR6+CXCR3-) effector memory populations in blood strongly associated with a rapid diagnosis of clinically definite multiple sclerosis. In cerebrospinal fluid of clinically isolated syndrome and relapsing-remitting multiple sclerosis patients, Th1-like Th17 effector memory cells were abundant and showed increased production of interferon-gamma and granulocyte macrophage colony-stimulating factor compared to paired CCR6+ and CCR6-CD8+ T cell populations and their blood equivalents after short-term culturing. Their local enrichment was confirmed ex vivo using cerebrospinal fluid and brain single-cell suspensions. Across all pro-inflammatory T helper cells analysed in relapsing-remitting multiple sclerosis blood, Th1-like Th17 subpopulation T helper 17.1 (Th17.1; CCR6+CXCR3+CCR4-) expressed the highest very late antigen-4 levels and selectively accumulated in natalizumab-treated patients who remained free of clinical relapses. This was not found in patients who experienced relapses during natalizumab treatment. The enhanced potential of Th17.1 cells to infiltrate the central nervous system was supported by their predominance in cerebrospinal fluid of early multiple sclerosis patients and their preferential transmigration across human brain endothelial layers. These findings reveal a dominant contribution of Th1-like Th17 subpopulations, in particular Th17.1 cells, to clinical disease activity and provide a strong rationale for more specific and earlier use of T cell-targeted therapy in multiple sclerosis.
Cognitive complaints are associated with smaller right medial temporal gray-matter volume in younger postmenopausal women.
Menopause (New York, N.Y.), 2020

Menopause is associated with increasing cognitive complaints and older women are at increased risk of developing Alzheimer disease compared to men. However, there is difficulty in early markers of risk using objective performance measures. We investigated the impact of subjective cognitive complaints on the cortical structure in a sample of younger postmenopausal women.
Tissue clearing and its applications in neuroscience.
Nature reviews. Neuroscience, 2020

State-of-the-art tissue-clearing methods provide subcellular-level optical access to intact tissues from individual organs and even to some entire mammals. When combined with light-sheet microscopy and automated approaches to image analysis, existing tissue-clearing methods can speed up and may reduce the cost of conventional histology by several orders of magnitude. In addition, tissue-clearing chemistry allows whole-organ antibody labelling, which can be applied even to thick human tissues. By combining the most powerful labelling, clearing, imaging and data-analysis tools, scientists are extracting structural and functional cellular and subcellular information on complex mammalian bodies and large human specimens at an accelerated pace. The rapid generation of terabyte-scale imaging data furthermore creates a high demand for efficient computational approaches that tackle challenges in large-scale data analysis and management. In this Review, we discuss how tissue-clearing methods could provide an unbiased, system-level view of mammalian bodies and human specimens and discuss future opportunities for the use of these methods in human neuroscience.
Unconscious conflict of interest: a Jewish perspective.
Journal of medical ethics, 2011

In contemporary medicine, it is not always obvious whether the acceptance of a benefit constitutes a conflict of interest. A particular area of controversy has been the impact of small gifts or other benefits from pharmaceutical companies on physicians' behaviour. Typically, in such cases, the gift is not an explicit reward for cooperation; the physician does not perceive the gift as an attempt to influence his or her judgement; and the reward is relatively minor. Under these circumstances, physicians are generally of the view that acceptance of gifts will not affect their behaviour, notwithstanding findings from social psychology and neuroscience that the impact of gifts is often unconscious, shaping action without a person's awareness. Here, we draw on traditional texts of Jewish law pertaining to the prohibition of taking a gift to illustrate recognition by the ancients of unconscious conflicts of interest, and their approach to dealing with the problem.
The anxiolytic effects of cannabidiol in chronically stressed mice are mediated by the endocannabinoid system: Role of neurogenesis and dendritic remodeling.
Neuropharmacology, 2018

Repeated injections of cannabidiol (CBD), the major non-psychotomimetic compound present in the Cannabis sativa plant, attenuate the anxiogenic effects induced by Chronic Unpredictable Stress (CUS). The specific mechanisms remain to be fully understood but seem to involve adult hippocampal neurogenesis and recruitment of endocannabinoids. Here we investigated for the first time if the behavioral and pro-neurogenic effects of CBD administered concomitant the CUS procedure (14 days) are mediated by CB
Gray Matter Volume in Different Cortical Structures Dissociably Relates to Individual Differences in Capacity and Precision of Visual Working Memory.
Cerebral cortex (New York, N.Y. : 1991), 2020

Visual working memory (VWM) refers to our ability to selectively maintain visual information in a mental representation. While cognitive limits of VWM greatly influence a variety of mental operations, it remains controversial whether the quantity or quality of representations in mind constrains VWM. Here, we examined behavior-to-brain anatomical relations as well as brain activity to brain anatomy associations with a "neural" marker specific to the retention interval of VWM. Our results consistently indicated that individuals who maintained a larger number of items in VWM tended to have a larger gray matter (GM) volume in their left lateral occipital region. In contrast, individuals with a superior ability to retain with high precision tended to have a larger GM volume in their right parietal lobe. These results indicate that individual differences in quantity and quality of VWM may be associated with regional GM volumes in a dissociable manner, indicating willful integration of information in VWM may recruit separable cortical subsystems.
Patient-Specific Stress-Abdominal Pain Interaction in Irritable Bowel Syndrome: An Exploratory Experience Sampling Method Study.
Clinical and translational gastroenterology, 2020

Gastrointestinal symptoms in irritable bowel syndrome (IBS) have been correlated with psychological factors using retrospective symptom assessment. However, real-time symptom assessment might reveal the interplay between abdominal and affective symptoms more reliably in a longitudinal perspective. The aim was to evaluate the association between stress and abdominal pain, using the Experience Sampling Method (ESM) as a real-time, repeated measurement method.
Role of serotonergic 1A receptor dysfunction in depression associated with Parkinson's disease.
Movement disorders : official journal of the Movement Disorder Society, 2012

Depression is frequent in Parkinson's disease, but its pathophysiology remains unclear. Two recent studies have investigated the role of serotonergic system at the presynaptic level. The objective of the present study was to use positron emission tomography and [(18)F]MPPF to investigate the role of postsynaptic serotonergic system dysfunction in the pathophysiology of depression in Parkinson's disease. Four parkinsonian patients with depression and 8 parkinsonian patients without depression were enrolled. Each patient underwent a scan using [(18)F]MPPF, a selective serotonin 1A receptor antagonist. Voxel-by-voxel statistical comparison of [(18)F]MPPF uptake of the 2 groups of parkinsonian patients and with 7 matched normal subjects was made using statistical parametric mapping (P uncorrected < .001). Compared with nondepressed parkinsonian patients, depressed patients exhibited reduced tracer uptake in the left hippocampus, the right insula, the left superior temporal cortex, and the orbitofrontal cortex. Compared with controls, nondepressed parkinsonian patients presented reduced [(18)F]MPPF uptake bilaterally in the inferior frontal cortex as well as in the right ventral striatum and insula. Compared with controls, [(18)F]MPPF uptake was decreased in depressed parkinsonian patients in the left dorsal anterior cingulate and orbitofrontal cortices, in the right hippocampic region, and in the temporal cortex. The present imaging study suggests that abnormalities in serotonin 1A receptor neurotransmission in the limbic system may be involved in the neural mechanisms underlying depression in patients with Parkinson's disease.
Visually validated semi-automatic high-frequency oscillation detection aides the delineation of epileptogenic regions during intra-operative electrocorticography.
Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology, 2018

To test the utility of a novel semi-automated method for detecting, validating, and quantifying high-frequency oscillations (HFOs): ripples (80-200 Hz) and fast ripples (200-600 Hz) in intra-operative electrocorticography (ECoG) recordings.
Design and discovery of a selective small molecule κ opioid antagonist (2-methyl-N-((2'-(pyrrolidin-1-ylsulfonyl)biphenyl-4-yl)methyl)propan-1-amine, PF-4455242).
Journal of medicinal chemistry, 2011

By use of parallel chemistry coupled with physicochemical property design, a series of selective κ opioid antagonists have been discovered. The parallel chemistry strategy utilized key monomer building blocks to rapidly expand the desired SAR space. The potency and selectivity of the in vitro κ antagonism were confirmed in the tail-flick analgesia model. This model was used to build an exposure-response relationship between the κ K(i) and the free brain drug levels. This strategy identified 2-methyl-N-((2'-(pyrrolidin-1-ylsulfonyl)biphenyl-4-yl)methyl)propan-1-amine, PF-4455242, which entered phase 1 clinical testing and has demonstrated target engagement in healthy volunteers.
Drosophila pheromone-sensing neurons expressing the ppk25 ion channel subunit stimulate male courtship and female receptivity.
PLoS genetics, 2014

As in many species, gustatory pheromones regulate the mating behavior of Drosophila. Recently, several ppk genes, encoding ion channel subunits of the DEG/ENaC family, have been implicated in this process, leading to the identification of gustatory neurons that detect specific pheromones. In a subset of taste hairs on the legs of Drosophila, there are two ppk23-expressing, pheromone-sensing neurons with complementary response profiles; one neuron detects female pheromones that stimulate male courtship, the other detects male pheromones that inhibit male-male courtship. In contrast to ppk23, ppk25, is only expressed in a single gustatory neuron per taste hair, and males with impaired ppk25 function court females at reduced rates but do not display abnormal courtship of other males. These findings raised the possibility that ppk25 expression defines a subset of pheromone-sensing neurons. Here we show that ppk25 is expressed and functions in neurons that detect female-specific pheromones and mediates their stimulatory effect on male courtship. Furthermore, the role of ppk25 and ppk25-expressing neurons is not restricted to responses to female-specific pheromones. ppk25 is also required in the same subset of neurons for stimulation of male courtship by young males, males of the Tai2 strain, and by synthetic 7-pentacosene (7-P), a hydrocarbon normally found at low levels in both males and females. Finally, we unexpectedly find that, in females, ppk25 and ppk25-expressing cells regulate receptivity to mating. In the absence of the third antennal segment, which has both olfactory and auditory functions, mutations in ppk25 or silencing of ppk25-expressing neurons block female receptivity to males. Together these results indicate that ppk25 identifies a functionally specialized subset of pheromone-sensing neurons. While ppk25 neurons are required for the responses to multiple pheromones, in both males and females these neurons are specifically involved in stimulating courtship and mating.