rudyvdbrink/CitationDatabase huggingface dataset:
Interoception and emotion.
Current opinion in psychology, 2017

Influential theories suggest emotional feeling states arise from physiological changes from within the body. Interoception describes the afferent signalling, central processing, and neural and mental representation of internal bodily signals. Recent progress is made in conceptualizing interoception and its neural underpinnings. These developments are supported by empirical data concerning interoceptive mechanisms and their contribution to emotion. Fresh insights include description of short-term interoceptive effects on neural and mental processes (including fear-specific cardiac effects), the recognition of dissociable psychological dimensions of interoception, and models of interoceptive predictive coding that explain emotions and selfhood (reinforced by structural anatomical models and brain and experimental findings). This growing grasp of interoception is enriching our understanding of emotion and its disorders.
Reduced anterior temporal and hippocampal functional connectivity during face processing discriminates individuals with social anxiety disorder from healthy controls and panic disorder, and increases following treatment.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2014

Group functional magnetic resonance imaging (fMRI) studies suggest that anxiety disorders are associated with anomalous brain activation and functional connectivity (FC). However, brain-based features sensitive enough to discriminate individual subjects with a specific anxiety disorder and that track symptom severity longitudinally, desirable qualities for putative disorder-specific biomarkers, remain to be identified. Blood oxygen level-dependent (BOLD) fMRI during emotional face perceptual tasks and a new, large-scale and condition-dependent FC and machine learning approach were used to identify features (pair-wise correlations) that discriminated patients with social anxiety disorder (SAD, N=16) from controls (N=19). We assessed whether these features discriminated SAD from panic disorder (PD, N=16), and SAD from controls in an independent replication sample that performed a similar task at baseline (N: SAD=15, controls=17) and following 8-weeks paroxetine treatment (N: SAD=12, untreated controls=7). High SAD vs HCs discrimination (area under the ROC curve, AUC, arithmetic mean of sensitivity and specificity) was achieved with two FC features during unattended neutral face perception (AUC=0.88, P<0.05 corrected). These features also discriminated SAD vs PD (AUC=0.82, P=0.0001) and SAD vs HCs in the independent replication sample (FC during unattended angry face perception, AUC=0.71, P=0.01). The most informative FC was left hippocampus-left temporal pole, which was reduced in both SAD samples (replication sample P=0.027), and this FC increased following the treatment (post>pre, t(11)=2.9, P=0.007). In conclusion, SAD is associated with reduced FC between left temporal pole and left hippocampus during face perception, and results suggest promise for emerging FC-based biomarkers for SAD diagnosis and treatment effects.
Evidence for the contribution of NOS1 gene polymorphism (rs3782206) to prefrontal function in schizophrenia patients and healthy controls.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2015

Nitric oxide (NO), a gaseous neurotransmitter, has been implicated in the pathogenesis of schizophrenia. Accordingly, several polymorphisms of the gene that codes for the main NO-producing enzyme, the nitric oxide synthase 1 (NOS1), have been found to convey a risk for schizophrenia. This study examined the role of NOS1 gene polymorphisms in cognitive functions and related neural mechanism. First, with a sample of 580 schizophrenia patients and 720 healthy controls, we found that rs3782206 genotype had main effects on the 1-back task (P=0.005), the 2-back task (P=0.049), the AY condition of the dot-pattern expectancy (DPX) task (P=0.001), and the conflict effect of the attention network (ANT) test (P<0.001 for RT differences and P=0.002 for RT ratio) and interaction effects with diagnosis on the BX condition of the DPX (P=0.009), the AY condition of the DPX (P<0.001), and the Stroop conflict effect (P=0.003 for RT differences and P=0.038 for RT ratio). Simple effect analyses further showed that the schizophrenia risk allele (T) of rs3782206 was associated with poorer performance in five measures for the patients (1-back, P=0.025; BX, P=0.017; AY, P<0.001; ANT conflict effect (RT differences), P=0.005; Stroop conflict effect (RT differences), P=0.019) and three measures for the controls ( for the 2-back task, P=0.042; for the ANT conlict effect (RT differences), P=0.013; for the ANT conflict effect (RT ratios), P=0.028). Then, with a separate sample of 78 healthy controls, we examined the association between rs3782206 and brain activation patterns during the N-back task and the Stroop task. Whole brain analyses found that the risk allele carriers showed reduced activation at the right inferior frontal gyrus (IFG) during both tasks. Finally, we examined functional connectivity seeded from the right IFG to the dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex under three conditions (the N-back task, the Stroop task, and the resting state). Results showed reduced connectivity with the DLPFC for the risk allele carriers mainly in the Stroop task and the resting state. Taken together, results of this study strongly suggested a link between NOS1 gene polymorphism at rs3782206 and cognitive functions and their neural underpinnings at the IFG. These results have important implications for our understanding of the neural mechanism underlying the association between NOS1 gene polymorphism and schizophrenia.
Social Bayes: Using Bayesian Modeling to Study Autistic Trait-Related Differences in Social Cognition.
Biological psychiatry, 2020

The autistic spectrum is characterized by profound impairments of social interaction. The exact subpersonal processes, however, that underlie the observable lack of social reciprocity are still a matter of substantial controversy. Recently, it has been suggested that the autistic spectrum might be characterized by alterations of the brain's inference about the causes of socially relevant sensory signals.
Cerebellar stem cells act as medulloblastoma-initiating cells in a mouse model and a neural stem cell signature characterizes a subset of human medulloblastomas.
Oncogene, 2010

Cells with stem cell properties have been isolated from various areas of the postnatal mammalian brain, most recently from the postnatal mouse cerebellum. We show here that inactivation of the tumor suppressor genes Rb and p53 in these endogenous neural stem cells induced deregulated proliferation and resistance to apoptosis in vitro. Moreover, injection of these cells into mice formed medulloblastomas. Medulloblastomas are the most common malignant brain tumors of childhood, and despite recent advances in treatment they are associated with high morbidity and mortality. They are highly heterogeneous tumors characterized by a diverse genetic make-up and expression profile as well as variable prognosis. Here, we describe a novel ontogenetic pathway of medulloblastoma that significantly contributes to understanding their heterogeneity. Experimental medulloblastomas originating from neural stem cells preferentially expressed stem cell markers Nestin, Sox2 and Sox9, which were not expressed in medulloblastomas originating from granule-cell-restricted progenitors. Furthermore, the expression of these markers identified a subset of human medulloblastomas associated with a poorer clinical outcome.
GABAB receptors in maintenance of neocortical circuit function.
Experimental neurology, 2014

Activation of metabotropic GABAB receptors (GABABRs) enhances tonic GABA current and substantially increases the frequency of spontaneous seizures. Despite the and pro-epileptic consequences of GABABR activation, mice lacking functional GABAB receptors (GABAB1R KO mice) exhibit clonic and rare absence seizures. To examine these mutant mice further, we recorded excitatory and inhibitory synaptic inputs and tonic mutant GABA currents from Layer 2 neocortical pyramidal neurons of GABAB1R WT and KO mice (P30-40). Tonic current was increased while the frequency of synaptic inputs was unchanged in KO mice relative to WT littermates. The neocortical laminar distribution of interneuron subtypes derived from the medial ganglionic eminence (MGE) was also not statistically different in KO mice relative to WT while the number of calretinin-positive, caudal GE-derived cells in Layer 1 was reduced. Transplantation of MGE progenitors obtained from KO mice lacking functional GABAB1R did not increase tonic inhibition in the host brain above that of media-injected controls. Taken together, these results suggest a complex role for GABAB receptors in mediating neocortical circuit function.
Individual Dopaminergic Neurons of Lamprey SNc/VTA Project to Both the Striatum and Optic Tectum but Restrict Co-release of Glutamate to Striatum Only.
Current biology : CB, 2019

Dopaminergic neurons in the substantia nigra (SNc) innervate both striatum and the superior colliculus in mammals, as well as its homolog the optic tectum in lampreys, belonging to the oldest group of living vertebrates [1-3]. In the lamprey, we have previously shown that the same neuron sends axonal branches to both striatum and the optic tectum [3]. Here, we show that most neurons in the lamprey SNc and ventral tegmental area (VTA) (also referred to as the nucleus of the posterior tuberculum) express not only tyrosine hydroxylase (TH), in lamprey a marker of dopaminergic neurons [4], but also the vesicular glutamate transporter (vGluT), suggesting that glutamate is a co-transmitter. Remarkably, the axonal branches that project to striatum elicit both dopaminergic and glutamatergic synaptic effects on striatal neurons, whereas the axonal projections to the optic tectum only evoke dopaminergic effects. Thus, axonal branches from the same neuron can use two transmitters in one branch and only one in the other. Previous studies suggest that, along an individual dopaminergic axon, there can be microdomains of either TH or vGluT [5-8]. In addition, the present results demonstrate that entire axonal branches to one target structure can differ from that of branches to another target, both originating from the same dopamine neuron. This implies that a given dopamine neuron can exert different effects on two different target structures. The combined release of dopamine and glutamate may be appropriate in striatum, whereas the effects exerted on the tectal motor center may be better served with a selective dopaminergic modulation.
ASICs are required for immediate exercise-induced muscle pain and are downregulated in sensory neurons by exercise training.
Journal of applied physiology (Bethesda, Md. : 1985), 2020

Exercise training is an effective therapy for many pain-related conditions, and trained athletes have lower pain perception compared with unconditioned people. Some painful conditions, including strenuous exercise, are associated with elevated levels of protons, metabolites, and inflammatory factors, which may activate receptors and/or ion channels, including acid-sensing ion channels (ASICs), on nociceptive sensory neurons. We hypothesized that ASICs are required for immediate exercise-induced muscle pain (IEIP) and that exercise training diminishes IEIP by modulating ASICs within muscle afferents. We found high-intensity interval training (HIIT) reduced IEIP in C57BL/6 mice and diminished ASIC mRNA levels in lumber dorsal root ganglia, and this downregulation of ASICs correlated with improved exercise capacity. Additionally, we found that
Translational control of myelin basic protein expression by ERK2 MAP kinase regulates timely remyelination in the adult brain.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2015

Successful myelin repair in the adult CNS requires the robust and timely production of myelin proteins to generate new myelin sheaths. The underlying regulatory mechanisms and complex molecular basis of myelin regeneration, however, remain poorly understood. Here, we investigate the role of ERK MAP kinase signaling in this process. Conditional deletion of Erk2 from cells of the oligodendrocyte lineage resulted in delayed remyelination following demyelinating injury to the adult mouse corpus callosum. The delayed repair occurred as a result of a specific deficit in the translation of the major myelin protein, MBP. In the absence of ERK2, activation of the ribosomal protein S6 kinase (p70S6K) and its downstream target, ribosomal protein S6 (S6RP), was impaired at a critical time when premyelinating oligodendrocytes were transitioning to mature cells capable of generating new myelin sheaths. Thus, we have described an important link between the ERK MAP kinase signaling cascade and the translational machinery specifically in remyelinating oligodendrocytes in vivo. These results suggest an important role for ERK2 in the translational control of MBP, a myelin protein that appears critical for ensuring the timely generation of new myelin sheaths following demyelinating injury in the adult CNS.
Social equality in the number of choice options is represented in the ventromedial prefrontal cortex.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014

A distinct aspect of the sense of fairness in humans is that we care not only about equality in material rewards but also about equality in nonmaterial values. One such value is the opportunity to choose freely among many options, often regarded as a fundamental right to economic freedom. In modern developed societies, equal opportunities in work, living, and lifestyle are enforced by antidiscrimination laws. Despite the widespread endorsement of equal opportunity, no studies have explored how people assign value to it. We used functional magnetic resonance imaging to identify the neural substrates for subjective valuation of equality in choice opportunity. Participants performed a two-person choice task in which the number of choices available was varied across trials independently of choice outcomes. By using this procedure, we manipulated the degree of equality in choice opportunity between players and dissociated it from the value of reward outcomes and their equality. We found that activation in the ventromedial prefrontal cortex (vmPFC) tracked the degree to which the number of options between the two players was equal. In contrast, activation in the ventral striatum tracked the number of options available to participants themselves but not the equality between players. Our results demonstrate that the vmPFC, a key brain region previously implicated in the processing of social values, is also involved in valuation of equality in choice opportunity between individuals. These findings may provide valuable insight into the human ability to value equal opportunity, a characteristic long emphasized in politics, economics, and philosophy.
Improved discrimination between normal-tension and primary open-angle glaucoma with advanced vascular examinations - the Leuven Eye Study.
Acta ophthalmologica, 2019

Vascular factors have been suggested to influence the development and progression of glaucoma. They are thought to be especially relevant for normal-tension glaucoma (NTG) patients. We aim to investigate which vascular factors, including advanced vascular examinations, better describe patients with NTG comparing to those with primary open-angle glaucoma (POAG).
Crowned dens syndrome: a neurologist's perspective.
Acta neurologica Belgica, 2019

Crowned dens syndrome is an under-recognized entity that can mimic neurological disease, in particular meningitis or giant-cell arteritis. We present a 48-year-old woman presenting with an inflammatory meningitis-like syndrome with headache and neck stiffness. Lumbar puncture was normal and computed tomography (CT) of the atlantoaxial joint showed abnormal calcifications around the odontoid process, leading to a tentative diagnosis of crowned dens syndrome. In addition, signs of active inflammation in and around the dens were present on cervical MR imaging. Since CDS can mimic meningitis or giant-cell arteritis, neurologists should be aware of this entity. If CDS is suspected, the bone window on the head CT scan can lead to the diagnosis. On the other hand, asymptomatic periodontoid calcifications are common and should not preclude further investigations.
Neural correlates of early cognitive dysfunction in Parkinson's disease.
Annals of clinical and translational neurology, 2019

Dementia is a common and feared aspect of Parkinson's disease but there are no robust predictors of cognitive outcome. Visuoperceptual deficits are linked to risk of dementia in Parkinson's disease but whether they predict cognitive change is not known, and the neural substrates of visuoperceptual dysfunction in Parkinson's have not yet been identified.
Locomotor deficiencies and aberrant development of subtype-specific GABAergic interneurons caused by an unliganded thyroid hormone receptor alpha1.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2008

Thyroid hormone (TH) deficiency during development causes severe and permanent neuronal damage, but the primary insult at the tissue level has remained unsolved. We have defined locomotor deficiencies in mice caused by a mutant thyroid hormone receptor alpha1 (TR alpha1) with potent aporeceptor activity attributable to reduced affinity to TH. This allowed identification of distinct functions that required either maternal supply of TH during early embryonic development or sufficient innate levels of hormone during late fetal development. In both instances, continued exposure to high levels of TH after birth and throughout life was needed. The hormonal dependencies correlated with severely delayed appearance of parvalbumin-immunoreactive GABAergic interneurons and increased numbers of calretinin-immunoreactive cells in the neocortex. This resulted in reduced numbers of fast spiking interneurons and defects in cortical network activity. The identification of locomotor deficiencies caused by insufficient supply of TH during fetal/perinatal development and their correlation with subtype-specific interneurons suggest a previously unknown basis for the neuronal consequences of endemic cretinism and untreated congenital hypothyroidism, and specifies TR alpha1 as the receptor isoform mediating these effects.
The influence of tau, amyloid, alpha-synuclein, TDP-43, and vascular pathology in clinically normal elderly individuals.
Neurobiology of aging, 2019

Many individuals live to older ages without clinical impairment. It is unknown whether brain pathologies in these individuals are associated with subtle clinical deficits. We analyzed the brains of 161 clinically normal (Clinical Dementia Rating score = 0) older individuals enrolled in the Mayo Clinic Patient Registry or Study of Aging. We assessed for the presence and burden of beta-amyloid, tau, alpha-synuclein, TDP-43, and vascular pathology. We investigated whether pathologies were associated with antemortem cognitive and motor function, depression, MRI volumetric measures, or the apolipoprotein E (APOE) ε4 allele. Eighty-six percent had at least 1 pathology, and 63% had mixed pathologies. Tau and vascular pathology were associated with poorer memory scores. Tau was also associated with poorer general cognition scores and smaller amygdala, hippocampi, and entorhinal cortex volumes. Beta-amyloid neuritic plaque burden was associated with greater depression scores. The presence of a greater number of pathologies was associated with APOE e4 carrier status and with poorer memory performance. Some dementia-related pathologies are associated with poorer performance in clinical measures and brain atrophy in the unimpaired elderly.
Silent synapses and the emergence of a postsynaptic mechanism for LTP.
Nature reviews. Neuroscience, 2008

Silent synapses abound in the young brain, representing an early step in the pathway of experience-dependent synaptic development. Discovered amidst the debate over whether long-term potentiation reflects a presynaptic or a postsynaptic modification, silent synapses--which in the hippocampal CA1 subfield are characterized by the presence of NMDA receptors but not AMPA receptors--have stirred some mechanistic controversy of their own. Out of this literature has emerged a model for synapse unsilencing that highlights the central role for postsynaptic AMPA-receptor trafficking in the expression of excitatory synaptic plasticity.
A molecular neuromorphic network device consisting of single-walled carbon nanotubes complexed with polyoxometalate.
Nature communications, 2018

In contrast to AI hardware, neuromorphic hardware is based on neuroscience, wherein constructing both spiking neurons and their dense and complex networks is essential to obtain intelligent abilities. However, the integration density of present neuromorphic devices is much less than that of human brains. In this report, we present molecular neuromorphic devices, composed of a dynamic and extremely dense network of single-walled carbon nanotubes (SWNTs) complexed with polyoxometalate (POM). We show experimentally that the SWNT/POM network generates spontaneous spikes and noise. We propose electron-cascading models of the network consisting of heterogeneous molecular junctions that yields results in good agreement with the experimental results. Rudimentary learning ability of the network is illustrated by introducing reservoir computing, which utilises spiking dynamics and a certain degree of network complexity. These results indicate the possibility that complex functional networks can be constructed using molecular devices, and contribute to the development of neuromorphic devices.
Neuropsychological function at first episode in treatment-resistant psychosis: findings from the ÆSOP-10 study.
Psychological medicine, 2019

Neuropsychological investigations can help untangle the aetiological and phenomenological heterogeneity of schizophrenia but have scarcely been employed in the context of treatment-resistant (TR) schizophrenia. No population-based study has examined neuropsychological function in the first-episode of TR psychosis.
The Distinct Roles of CXCR3 Variants and Their Ligands in the Tumor Microenvironment.
Cells, 2019

First thought to orchestrate exclusively leukocyte trafficking, chemokines are now acknowledged for their multiple roles in the regulation of cell proliferation, differentiation, and survival. Dysregulation of their normal functions contributes to various pathologies, including inflammatory diseases and cancer. The two chemokine receptor 3 variants CXCR3-A and CXCR3-B, together with their cognate chemokines (CXCL11, CXCL10, CXCL9, CXCL4, and CXCL4L1), are involved in the control but also in the development of many tumors. CXCR3-A drives the infiltration of leukocytes to the tumor bed to modulate tumor progression (paracrine axis). Conversely, tumor-driven changes in the expression of the CXCR3 variants and their ligands promote cancer progression (autocrine axis). This review summarizes the anti- and pro-tumoral activities of the CXCR3 variants and their associated chemokines with a focus on the understanding of their distinct biological roles in the tumor microenvironment.