rudyvdbrink/CitationDatabase huggingface dataset:
Partial integration of the components of value in anterior cingulate cortex.
Behavioral neuroscience, 2020

Evaluation often involves integrating multiple determinants of value, such as the different possible outcomes in risky choice. A brain region can be placed either before or after a presumed evaluation stage by measuring how responses of its neurons depend on multiple determinants of value. A brain region could also, in principle, show partial integration, which would indicate that it occupies a middle position between (preevaluative) nonintegration and (postevaluative) full integration. Existing mathematical techniques cannot distinguish full from partial integration and therefore risk misidentifying regional function. Here we use a new Bayesian regression-based approach to analyze responses of neurons in dorsal anterior cingulate cortex (dACC) to risky offers. We find that dACC neurons only partially integrate across outcome dimensions, indicating that dACC cannot be assigned to either a pre- or postevaluative position. Neurons in dACC also show putative signatures of value comparison, thereby demonstrating that comparison does not require complete evaluation before proceeding. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
Compound heterozygosity for an expanded (GAA) and a (GAAGGA) repeat at FXN locus: from a diagnostic pitfall to potential clues to the pathogenesis of Friedreich ataxia.
Neurogenetics, 2020

Friedreich's ataxia (FRDA) is usually due to a homozygous GAA expansion in intron 1 of the frataxin (FXN) gene. Rarely, uncommon molecular rearrangements at the FXN locus can cause pitfalls in the molecular diagnosis of FRDA. Here we describe a family whose proband was affected by late-onset Friedreich's ataxia (LOFA); long-range PCR (LR-PCR) documented two small expanded GAA alleles both in the proband and in her unaffected younger sister, who therefore received a diagnosis of pre-symptomatic LOFA. Later studies, however, revealed that the proband's unaffected sister, as well as their healthy mother, were both carriers of an expanded GAA allele and an uncommon (GAAGGA)
Aberrant activity in an intact residual muscle is associated with phantom limb pain in above-knee amputees.
Journal of neurophysiology, 2021

Many individuals who undergo limb amputation experience persistent phantom limb pain (PLP), but the underlying mechanisms of PLP are unknown. The traditional hypothesis was that PLP resulted from maladaptive plasticity in sensorimotor cortex that degrades the neural representation of the missing limb. However, a recent study of individuals with upper limb amputations has shown that PLP is correlated with aberrant electromyographic (EMG) activity in residual muscles, posited to reflect a retargeting of efferent projections from a preserved representation of a missing limb. Here, we assessed EMG activity in a residual thigh muscle (vastus lateralis, VL) in patients with transfemoral amputations during cyclical movements of a phantom foot. VL activity on the amputated side was compared to that recorded on patients' intact side while they moved both the phantom and intact feet synchronously. VL activity in the patient group was also compared to a sample of control participants with no amputation. We show that phantom foot movement is associated with greater VL activity in the amputated leg than that seen in the intact leg as well as that exhibited by controls. The magnitude of residual VL activity was also positively related to ratings of PLP. These results show that phantom limb movement is associated with aberrant activity in a residual muscle after lower-limb amputation and provide evidence of a positive relationship between this activity and phantom limb pain.
What a relief! A role for dopamine in positive (but not negative) valence.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2018

We have long known that dopamine encodes the predictive relationship between cues and rewards. But what about relief learning? In this issue of Neuropsychopharmacology, Mayer et al. show that the same circuits encoding rewarding events also encode relief from aversive events. And this appears to be in a manner distinct from encoding of the aversive event itself. So does dopamine only contribute to learning about positive events? And are these events encoded in the same way regardless of how that positive experience came about? Not quite. Turns out, the devil is in the details.
Spatial Transcriptomics and In Situ Sequencing to Study Alzheimer's Disease.
Cell, 2020

Although complex inflammatory-like alterations are observed around the amyloid plaques of Alzheimer's disease (AD), little is known about the molecular changes and cellular interactions that characterize this response. We investigate here, in an AD mouse model, the transcriptional changes occurring in tissue domains in a 100-μm diameter around amyloid plaques using spatial transcriptomics. We demonstrate early alterations in a gene co-expression network enriched for myelin and oligodendrocyte genes (OLIGs), whereas a multicellular gene co-expression network of plaque-induced genes (PIGs) involving the complement system, oxidative stress, lysosomes, and inflammation is prominent in the later phase of the disease. We confirm the majority of the observed alterations at the cellular level using in situ sequencing on mouse and human brain sections. Genome-wide spatial transcriptomics analysis provides an unprecedented approach to untangle the dysregulated cellular network in the vicinity of pathogenic hallmarks of AD and other brain diseases.
An investigation into the minimum number of tissue groups required for 7T in-silico parallel transmit electromagnetic safety simulations in the human head.
Magnetic resonance in medicine, 2021

Safety limits for the permitted specific absorption rate (SAR) place restrictions on pulse sequence design, especially at ultrahigh fields (≥ 7 tesla). Due to intersubject variability, the SAR is usually conservatively estimated based on standard human models that include an applied safety margin to ensure safe operation. One approach to reducing the restrictions is to create more accurate subject-specific models from their segmented MR images. This study uses electromagnetic simulations to investigate the minimum number of tissue groups required to accurately determine SAR in the human head.
Titrating the Smell of Fear: Initial Evidence for Dose-Invariant Behavioral, Physiological, and Neural Responses.
Psychological science, 2021

It is well accepted that emotional intensity scales with stimulus strength. Here, we used physiological and neuroimaging techniques to ask whether human body odor-which can convey salient social information-also induces dose-dependent effects on behavior, physiology, and neural responses. To test this, we first collected sweat from 36 males classified as low-, medium-, and high-fear responders. Next, in a double-blind within-subjects functional-MRI design, 31 women were exposed to three doses of fear-associated human chemosignals and neutral sweat while viewing face morphs varying between expressions of fear and disgust. Behaviorally, we found that all doses of fear-sweat volatiles biased participants toward perceiving fear in ambiguous morphs, a dose-invariant effect generally repeated across physiological and neural measures. Bayesian dose-response analysis indicated moderate evidence for the null hypothesis (except for the left amygdala), tentatively suggesting that the human olfactory system engages an all-or-none mechanism for tagging fear above a minimal threshold.
Determinants of primate neurogenesis and the deployment of top-down generative networks in the cortical hierarchy.
Current opinion in neurobiology, 2021

What I cannot create I do not understand - Richard Feynman 1978 Because primate cortical development exhibits numerous specific features, the mouse is an imperfect model for human cortical development. Expansion of supragranular neurons is an evolutionary feature characterizing the primate cortex. Increased production of supragranular neurons is supported by a germinal zone innovation of the primate cortex: the Outer SubVentricular Zone, which along with supragranular neurons constitute privileged targets of primate brain-specific gene evolution. The resulting cell-type diversity of human supragranular neurons link cell and molecular evolutionary changes in progenitors with the emergence of distinctive architectural features in the primate cortex. We propose that these changes are required for the expansion of the primate cortical hierarchy deploying top-down generative networks with potentially important consequences for the neurobiology of human psychiatric disorders.
Award for Distinguished Scientific Early Career Contributions to Psychology: David S. Yeager.
The American psychologist, 2020

The Early Career Awards, given for the first time in 1974, recognize the large number of excellent early career psychologists. Recipients of this award may not have held a doctoral degree for more than nine years. For purposes of this award, psychology has been divided into 10 areas: animal learning and behavior, comparative; developmental; health; cognition/human learning; psychopathology; behavioral and cognitive neuroscience; perception/motor performance; social; applied research; and individual differences. Five areas are considered each year, with areas rotated in two-year cycles. The areas considered in 2020 were animal learning and behavior, comparative; developmental; health; cognition/ human learning; and psychopathology. Each year, panels are selected for the areas under consideration, and these panels recommend nominees to the Committee on Scientific Awards. The 2020 recipients of the APA Scientific Contribution Awards were recognized by the 2019 Board of Scientific Affairs and selected by the 2019 Committee on Scientific Awards. For outstanding contributions to understanding adolescent development and enhancing adolescents' well-being. Based on analyses of adolescents' motivations, environments, and behaviors, David S. Yeager has designed and demonstrated the effectiveness of brief interventions for changing trajectories of aggression, depression, stress, and achievement, often on a large scale. His work, which draws from multiple areas of psychology, demonstrates deep theoretical, methodological, and statistical sophistication. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
A systematic review of tools used to assess body image, masculinity and self-esteem in men with prostate cancer.
Psycho-oncology, 2020

Masculinity, body image and self-esteem are important interlinked factors affecting prostate cancer (PCa) patients' quality of life. The aim of this systematic review was to identify and evaluate all tools measuring these domains in men with PCa.
Prefrontal cortex and reversion of atropine-induced disruption of the degraded contingency effect by antipsychotic agents and N-desmethylclozapine in rats.
The international journal of neuropsychopharmacology, 2010

Interactive context processing is a cognitive ability that is altered in psychotic states, including schizophrenia. This deficit has been linked to prefrontal cortical dysfunction in humans. The degraded contingency effect (DCE) is a simple form of interactive context processing by which contextual information interferes with a target conditioned stimulus for control over conditioned responding. We have previously shown that the DCE was disrupted by the muscarinic receptor antagonist atropine and that this disruption was specifically restored by cholinergic drugs displaying an antipsychotic-like profile, such as physostigmine or xanomeline. The DCE was selectively associated with an increase in Fos immunoreactivity in the medial prefrontal cortex (mPFC), an increase that was not observed in the presence of atropine. Here, we set out to test the actions of typical, atypical and potential antipsychotics on atropine-induced disruption of the DCE and the related mPFC Fos-immunoreactivity profile. Low doses of haloperidol, olanzapine, clozapine and N-desmethylclozapine reversed atropine-induced disruption of the DCE, but with different dose-dependent curves (linear shapes for haloperidol and N-desmethylclozapine, inverted U shapes for olanzapine and clozapine). The level of Fos within the mPFC paralleled the pharmacological profile of the different drugs. Compared to contingent control groups, an increased level of Fos immunoreactivity within the mPFC was observed only with doses that reversed atropine-induced disruption of the DCE. These results suggest that the deficit of interactive context processing, which is a hallmark of psychotic states, might originate from a mere deficit of fundamental associative processes. This deficit might result from a cholinergic blockade of the PFC.
SARS-CoV-2 Virus and Human Leukocyte Antigen (HLA) Class II: Investigation in silico of Binding Affinities for COVID-19 Protection and Vaccine Development.
Journal of immunological sciences, 2020

SARS-CoV-2 causes COVID-19, urgently requiring the development of effective vaccine(s). Much of current efforts focus on the SARS-CoV-2 spike-glycoprotein by identifying highly antigenic epitopes as good vaccine candidates. However, high antigenicity is not sufficient, since the activation of relevant T cells depends on the presence of the complex of the antigen with a suitably matching Human Leukocyte Antigen (HLA) Class II molecule, not the antigen alone: in the absence of such a match, even a highly antigenic epitope in vitro will not elicit antibody formation in vivo. Here we assessed systematically in silico the binding affinity of epitopes of the spike-glycoprotein to 66 common HLA-Class-II alleles (frequency ≥ 0.01). We used a sliding epitope window of 22-amino-acid-width to scan the entire protein and determined the binding affinity of each subsequence to each HLA allele. DPB1 had highest binding affinities, followed by DRB1 and DQB1. Higher binding affinities were concentrated in the initial part of the glycoprotein (S1-S460), with a peak at S223-S238. This region would be well suited for effective vaccine development by ensuring high probability for successful matching of the vaccine antigen from that region to a HLA Class II molecule for CD4
Long-term effectiveness of natalizumab on MRI outcomes and no evidence of disease activity in relapsing-remitting multiple sclerosis patients treated in a Czech Republic real-world setting: A longitudinal, retrospective study.
Multiple sclerosis and related disorders, 2020

Magnetic resonance imaging (MRI) data from multiple sclerosis (MS) patients treated in real-world settings are important for understanding disease-modifying therapy effects, including no evidence of disease activity (NEDA) assessment. This longitudinal, retrospective, single-cohort analysis assessed MRI and clinical disease outcomes in patients with relapsing-remitting MS treated with natalizumab for up to 5 years in Prague, the Czech Republic.
Individual factors that influence task performance on a straight ladder in older people.
Experimental gerontology, 2020

Older adults have the highest incidence of domestic ladder falls, but little investigation has been given to this important injury issue. There is therefore a need to understand the influence of individual factors like physical and cognitive ability and psychological status on safe and effective ladder use in this population. This study investigated associations between vision, lower and upper limb sensation, upper limb control, strength, balance, cognitive function and psychological status with task completion time and number of ladder moves taken in a simulated roof gutter clearing task on a straight ladder in 97 older adults. Several measures from upper limb control, strength, balance, processing speed, executive function and psychological domains were significantly associated with the two ladder task performance measures. Upper limb bimanual coordination, knee extension strength, coordinated leaning balance, and self-reported risk-taking were identified as independent and significant predictors of task completion time in a multiple regression model, predicting 56% of the variability in ladder task completion time. Upper limb bimanual coordination and proprioception, simple reaction time and coordinated leaning balance were independent and significant predictors of the number of ladder moves in a separate multiple regression model, predicting 38% of the variability in ladder moves taken. These findings help identify individuals at greater ladder fall risk and can guide ladder fall interventions, such as strength and balance training, ladder design and targeted safety instructions.
Experimental Study on Blue Light Interaction with Human Keloid-Derived Fibroblasts.
Biomedicines, 2020

Keloids are an exuberant response to wound healing, characterized by an exaggerated synthesis of collagen, probably due to the increase of fibroblasts activity and to the reduction of their apoptosis rate: currently no standard treatments or pharmacological therapies are able to prevent keloid recurrence. To reach this goal, in recent years some physical treatments have been proposed, and among them the PhotoBioModulation therapy (PBM). This work analyses the effects of a blue LED light irradiation (410-430 nm, 0.69 W/cm
Phase 1 study to access safety, tolerability, pharmacokinetics, and pharmacodynamics of kynurenine in healthy volunteers.
Pharmacology research & perspectives, 2021

The kynurenine pathway (KP) is the main path for tryptophan metabolism, and it represents a multitude of potential sites for drug discovery in neuroscience, including pain, stroke, and epilepsy. L-kynurenine (LKYN), the first active metabolite in the pathway, emerges to be a prodrug targeting glutamate receptors. The safety, tolerability, pharmacokinetics, and pharmacodynamics of LKYN in humans have not been previously investigated. In an open-label, single ascending dose study, six participants received an intravenous infusion of 50, 100, and 150 µg/kg LKYN and new six participants received an intravenous infusion of 0.3, 0.5, 1, and 5 mg/kg LKYN. To compare the pharmacological effects between species, we investigated in vivo the vascular effects of LKYN in rats. In humans, LKYN was safe and well-tolerated at all dose levels examined. After infusion, LKYN plasma concentration increased significantly over time 3.23 ± 1.12 µg/mL (after 50 µg/kg), 4.04 ± 1.1 µg/mL (after 100 µg/kg), and 5.25 ± 1.01 µg/mL (after 150 µg/kg) (p ≤ 0.001). We observed no vascular changes after infusion compared with baseline. In rats, LKYN had no effect on HR and MAP and caused no dilation of dural and pial arteries. This first-in-human study of LKYN showed that LKYN was safe and well-tolerated after intravenous infusion up to 5 mg/kg over 20 minutes. The lack of change in LKYN metabolites in plasma suggests a relatively slow metabolism of LKYN and no or little feed-back effect of LKYN on its synthesis. The therapeutic potential of LKYN in stroke and epilepsy should be explored in future studies in humans.
Revisiting promising preclinical intracerebral hemorrhage studies to highlight repurposable drugs for translation.
International journal of stroke : official journal of the International Stroke Society, 2021

Intracerebral hemorrhage is a devastating global health burden with limited treatment options and is responsible for 49% of 6.5 million annual stroke-related deaths comparable to ischemic stroke. Despite the impact of intracerebral hemorrhage, there are currently no effective treatments and so weaknesses in the translational pipeline must be addressed. There have been many preclinical studies in intracerebral hemorrhage models with positive outcomes for potential therapies
Monocyte distribution width as a biomarker of sepsis in the intensive care unit: A pilot study.
Annals of clinical biochemistry, 2021

Monocyte distribution width has been recently proposed as a sepsis biomarker in the emergency department. The aim of this study was to assess the role of monocyte distribution width as a diagnostic biomarker of sepsis in the intensive care unit.
Stem cells, evolutionary aspects and pathology of the adrenal medulla: A new developmental paradigm.
Molecular and cellular endocrinology, 2020

The mammalian adrenal gland is composed of two main components; the catecholaminergic neural crest-derived medulla, found in the center of the gland, and the mesoderm-derived cortex producing steroidogenic hormones. The medulla is composed of neuroendocrine chromaffin cells with oxygen-sensing properties and is dependent on tissue interactions with the overlying cortex, both during development and in adulthood. Other relevant organs include the Zuckerkandl organ containing extra-adrenal chromaffin cells, and carotid oxygen-sensing bodies containing glomus cells. Chromaffin and glomus cells reveal a number of important similarities and are derived from the multipotent nerve-associated descendants of the neural crest, or Schwann cell precursors. Abnormalities in complex developmental processes during differentiation of nerve-associated and other progenitors into chromaffin and oxygen-sensing populations may result in different subtypes of paraganglioma, neuroblastoma and pheochromocytoma. Here, we summarize recent findings explaining the development of chromaffin and oxygen-sensing cells, as well as the potential mechanisms driving neuroendocrine tumor initiation.
A unique experiment in neurological surgery: intracerebral injection of antitoxin for tetanus.
Journal of neurosurgery, 2010

The discipline of neurological surgery was considered primarily "hopeless" and, at best, experimental in the late 19th century. Harvey Cushing's efforts during his initial uncharted voyage through the surgery of the human cranium were rudimentary and exploratory. A direct review of his available patient records from early in his career provides the opportunity to look back at Cushing as a physician-scientist, uncovering work that demonstrates that he was at the forefront of neurosurgical intervention in avenues that have been largely overlooked. The authors present Cushing's notes pertaining to a case of tetanus. This case represents the intersection of neurosurgery and tetanus treatment in Dr. Cushing's intracerebral injection of antitoxin to treat generalized tetanus.
Cortical connectivity of the nucleus basalis of Meynert in Parkinson's disease and Lewy body dementias.
Brain : a journal of neurology, 2021

Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB) are related conditions that are associated with cholinergic system dysfunction. Dysfunction of the nucleus basalis of Meynert (NBM), a basal forebrain structure that provides the dominant source of cortical cholinergic innervation, has been implicated in the pathogenesis of both PDD and DLB. Here we leverage the temporal resolution of magnetoencephalography with the spatial resolution of MRI tractography to explore the intersection of functional and structural connectivity of the NBM in a unique cohort of PDD and DLB patients undergoing deep brain stimulation of this structure. We observe that NBM-cortical structural and functional connectivity correlate within spatially and spectrally segregated networks including: (i) a beta band network to supplementary motor area, where activity in this region was found to drive activity in the NBM; (ii) a delta/theta band network to medial temporal lobe structures encompassing the parahippocampal gyrus; and (iii) a delta/theta band network to visual areas including lingual gyrus. These findings reveal functional networks of the NBM that are likely to subserve important roles in motor control, memory and visual function, respectively. Furthermore, they motivate future studies aimed at disentangling network contribution to disease phenotype.