rudyvdbrink/CitationDatabase huggingface dataset:
An empirical assessment of appearance descriptors applied to MRI for automated diagnosis of TLE and MCI.
Computers in biology and medicine, 2020

Differential diagnosis of mild cognitive impairment MCI and temporal lobe epilepsy TLE is a debated issue, specifically because these conditions may coincide in the elderly population. We evaluate automated differential diagnosis based on characteristics derived from structural brain MRI of different brain regions.
Astroglial FMRP modulates synaptic signaling and behavior phenotypes in FXS mouse model.
Glia, 2021

Fragile X syndrome (FXS) is one of the most common inherited intellectual disability (ID) disorders, in which the loss of FMRP protein induces a range of cellular signaling changes primarily through excess protein synthesis. Although neuron-centered molecular and cellular events underlying FXS have been characterized, how different CNS cell types are involved in typical FXS synaptic signaling changes and behavioral phenotypes is largely unknown. Recent evidence suggests that selective loss of astroglial FMRP is able to dysregulate glutamate uptake, increase spine density, and impair motor-skill learning. Here we investigated the effect of astroglial FMRP on synaptic signaling and FXS-related behavioral and learning phenotypes in astroglial Fmr1 cKO and cON mice in which FMRP expression is selectively diminished or restored in astroglia. We found that selective loss of astroglial FMRP contributes to cortical hyperexcitability by enhancing NMDAR-mediated evoked but not spontaneous miniEPSCs and elongating cortical UP state duration. Selective loss of astroglial FMRP is also sufficient to increase locomotor hyperactivity, significantly diminish social novelty preference, and induce memory acquisition and extinction deficits in astroglial Fmr1 cKO mice. Importantly, re-expression of astroglial FMRP is able to significantly rescue the hyperactivity (evoked NMDAR response, UP state duration, and open field test) and social novelty preference in astroglial Fmr1 cON mice. These results demonstrate a profound role of astroglial FMRP in the evoked synaptic signaling, spontaneously occurring cortical UP states, and FXS-related behavioral and learning phenotypes and provide important new insights in the cell type consideration for the FMRP reactivation strategy.
The Feasibility, Tolerability, and Safety of Administering a Very High Alcohol Dose to Drinkers with Alcohol Use Disorder.
Alcoholism, clinical and experimental research, 2020

There remains a paucity of research quantifying alcohol's effects in drinkers with alcohol use disorder (AUD), particularly responses to very high alcohol doses (≥0.8 g/kg). As drinkers with AUD frequently engage in very heavy drinking (8 to 10 drinks/occasion), doses of ≤0.8 g/kg may lack ecological validity. The present study examined the feasibility, tolerability, and safety of administering a very high alcohol dose (1.2 g/kg) to non-treatment-seeking AUD participants.
Dynamic Functional Connectivity between order and randomness and its evolution across the human adult lifespan.
NeuroImage, 2020

Functional Connectivity (FC) during resting-state or task conditions is not static but inherently dynamic. Yet, there is no consensus on whether fluctuations in FC may resemble isolated transitions between discrete FC states rather than continuous changes. This quarrel hampers advancing the study of dynamic FC. This is unfortunate as the structure of fluctuations in FC can certainly provide more information about developmental changes, aging, and progression of pathologies. We merge the two perspectives and consider dynamic FC as an ongoing network reconfiguration, including a stochastic exploration of the space of possible steady FC states. The statistical properties of this random walk deviate both from a purely "order-driven" dynamics, in which the mean FC is preserved, and from a purely "randomness-driven" scenario, in which fluctuations of FC remain uncorrelated over time. Instead, dynamic FC has a complex structure endowed with long-range sequential correlations that give rise to transient slowing and acceleration epochs in the continuous flow of reconfiguration. Our analysis for fMRI data in healthy elderly revealed that dynamic FC tends to slow down and becomes less complex as well as more random with increasing age. These effects appear to be strongly associated with age-related changes in behavioural and cognitive performance.
Endocannabinoid metabolism and transport as targets to regulate intraocular pressure.
Experimental eye research, 2020

Cannabinoids are part of an endogenous signaling system found throughout the body, including the eye. Hepler and Frank showed in the early 1970s that plant cannabinoids can lower intraocular pressure (IOP), an effect since shown to occur via cannabinoid CB1 and GPR18 receptors. Endocannabinoids are synthesized and metabolized enzymatically. Enzymes implicated in endocannabinoids breakdown include monoacylglycerol lipase (MAGL) and fatty acid amide hydrolase (FAAH), but also ABHD12, NAAA, and COX-2. Inhibition of MAGL activity raises levels of the endocannabinoid 2-arachidonoyl glycerol and substantially lowers IOP. Blocking other cannabinoid metabolizing enzymes or cannabinoid transporters may similarly contribute to lowering IOP and so serve as therapeutic targets for treating glaucoma. We have tested blockers for several cannabinoid-metabolizing enzymes and transporters (FABP5 and membrane reuptake) for their ability to alter ocular pressure in a murine model of IOP. Of FAAH, ABHD12, NAAA, and COX2, only FAAH was seen to play a role in regulation of IOP. Only the FAAH blocker URB597 lowered IOP, but in a temporally, diurnally, and sex-specific manner. We also tested two blockers of cannabinoid transport (SBFI-26 and WOBE437), finding that each lowered IOP in a CB1-dependent manner. Though we see a modest, limited role for FAAH, our results suggest that MAGL is the primary cannabinoid-metabolizing enzyme in regulating ocular pressure, thus pointing towards a role of 2-arachidonoyl glycerol. Interestingly, inhibition of cannabinoid transport mechanisms independent of hydrolysis may prove to be an alternative strategy to lower ocular pressure.
How do spatial representations enhance cognitive numerical processing?
Cognitive processing, 2012

Several philosophical theories attempt to explain how actions performed in the world enhance cognitive processing: internalism, active externalism, and cognitive integration. The aim of this paper is to examine whether the use of spatial representations in arithmetic can shed light on this debate. Relying on philosophical analysis, on a discussion of empirical work in the cognitive neuroscience of number, and on a historical case study, I will show that spatial representations of number indicate an integration between internal and external cognitive processes.
Depression history as a moderator of relations between cortisol and shame responses to social-evaluative threat in young adults.
Biological psychology, 2015

Changes in cortisol and shame are commonly elicited by psychosocial stressors involving social-evaluative threat. According to social self preservation theory, this coordinated psychobiological response is adaptive. Individuals with a history of depression, however, may exhibit diminished cortisol reactivity to acute stressors, which could interfere with coordinated cortisol and shame responses. The present study examined temporal relations between cortisol and shame responses to a psychosocial stress task in young adults who varied in their history of depression (56 remitted-depressed, 46 never-depressed). Lagged effects multilevel models revealed that depression history moderated relations between cortisol levels and shame ratings 25-55min later. The pattern of these interactions was similar: whereas higher cortisol levels predicted increases in shame in never-depressed individuals, cortisol levels were unrelated to shame responses in remitted-depressed individuals. Findings suggest a dissociation between cortisol and shame responses to stress in individuals with a history of depression.
Don't count your chickens before they're hatched: elaborative encoding in REM dreaming in face of the physiology of sleep stages.
The Behavioral and brain sciences, 2013

Llewellyn suggests that episodic memories undergo "elaborative encoding" during rapid eye movement (REM) dreams, generating novel associations between recent and remote memories that are then instantiated during non-REM (NREM) sleep. This hypothesis conflicts with our knowledge of the physiology of NREM and then REM sleep stages and their ordered succession. Moreover, associations during sleep might also involve the extraction of hidden patterns rather than de novo associations.
Human PNPLA3-I148M variant increases hepatic retention of polyunsaturated fatty acids.
JCI insight, 2019

The common patatin-like phospholipase domain-containing protein 3 (PNPLA3) variant I148M predisposes to nonalcoholic liver disease but not its metabolic sequelae. We compared the handling of labeled polyunsaturated fatty acids (PUFAs) and saturated fatty acids (SFA) in vivo in humans and in cells harboring different PNPLA3 genotypes. In 148M homozygous individuals, triglycerides (TGs) in very low-density lipoproteins (VLDL) were depleted of PUFAs both under fasting and postprandial conditions compared with 148I homozygotes, and the PUFA/SFA ratio in VLDL-TGs was lower relative to the chylomicron precursor pool. In human PNPLA3-148M and PNPLA3-KO cells, PUFA but not SFA incorporation into TGs was increased at the expense of phosphatidylcholines, and under lipolytic conditions, PUFA-containing diacylglycerols (DAGs) accumulated compared with PNPLA3-148I cells. Polyunsaturated TGs were increased, while phosphatidylcholines (PCs) were decreased in the human liver in 148M homozygous individuals as compared with 148I homozygotes. We conclude that human PNPLA3-I148M is a loss-of-function allele that remodels liver TGs in a polyunsaturated direction by impairing hydrolysis/transacylation of PUFAs from DAGs to feed phosphatidylcholine synthesis.
Effect of nitric oxide on spinal evoked potentials and survival rate in rats with decompression sickness.
Journal of applied physiology (Bethesda, Md. : 1985), 2015

Nitric oxide (NO) releasing agents have, in experimental settings, been shown to decrease intravascular nitrogen bubble formation and to increase the survival rate during decompression sickness (DCS) from diving. The effect has been ascribed to a possible removal of preexisting micronuclei or an increased nitrogen washout on decompression through augmented blood flow rate. The present experiments were conducted to investigate whether a short- or long-acting NO donor [glycerol trinitrate (GTN) or isosorbide-5-mononitrate (ISMN), respectively] would offer the same protection against spinal cord DCS evaluated by means of spinal evoked potentials (SEPs). Anesthetized rats were decompressed from a 1-h hyperbaric air dive at 506.6 kPa (40 m of seawater) for 3 min and 17 s, and spinal cord conduction was studied by measurements of SEPs. Histological samples of the spinal cord were analyzed for lesions of DCS. In total, 58 rats were divided into 6 different treatment groups. The first three received either saline (group 1), 300 mg/kg iv ISMN (group 2), or 10 mg/kg ip GTN (group 3) before compression. The last three received either 300 mg/kg iv ISMN (group 4), 1 mg/kg iv GTN (group 5), or 75 μg/kg iv GTN (group 6) during the dive, before decompression. In all groups, decompression caused considerable intravascular bubble formation. The ISMN groups showed no difference compared with the control group, whereas the GTN groups showed a tendency toward faster SEP disappearance and shorter survival times. In conclusion, neither a short- nor long-acting NO donor had any protective effect against fatal DCS by intravenous bubble formation. This effect is most likely due to a fast ascent rate overriding the protective effects of NO, rather than the total inert tissue gas load.
Preclinical models of disease and multimorbidity with focus upon cardiovascular disease and dementia.
Mechanisms of ageing and development, 2020

The use of animal models is fundamental to furthering our understanding of human disease mechanisms, as well as identifying potential therapeutic targets. Diseases of ageing often involve multiple body systems; however, multi-systemic features are not fully recapitulated in the many of the animal models available. Therefore, combining pre-clinical models to better reflect the multimorbidities observed at the clinical level is critical. This review will highlight some of the key pre-clinical experimental models associated with cardiovascular (atherosclerosis, coronary heart disease), cerebrovascular (stroke, vascular dementia), metabolic (obesity, type-2 diabetes mellitus) and neurological (amyotrophic lateral sclerosis, frontotemporal dementia, Parkinson's, epilepsy) diseases, and whether these models encompass known multimorbidities. In addition to this, we discuss established pre-clinical models that combine two or more conditions, within the context of dementia.
Single fiber EMG Fiber density and its relationship to Macro EMG amplitude in reinnervation.
Journal of electromyography and kinesiology : official journal of the International Society of Electrophysiological Kinesiology, 2014

The objective was to elucidate the relation between the Macro EMG parameters fiber density (FD) and Macro amplitude in reinnervation in the purpose to use the FD parameter as a surrogate marker for reinnervation instead of the Macro amplitude. Macro EMG with FD was performed in 278 prior polio patients. The Biceps Brachii and the Tibialis anterior muscles were investigated. FD was more sensitive for detection of signs of reinnervation but showed lesser degree of abnormality than the Macro amplitude. FD and Macro MUP amplitude showed a non-linear relation with a great variation in FD for given Macro amplitude level. The relatively smaller increase in FD compared to Macro amplitude in addition to the non-linear relationship between the FD and the Macro amplitude regarding reinnervation in prior polio can be due to technical reasons and muscle fiber hypertrophy. The FD parameter has a relation to Macro MUP amplitude but cannot alone be used as a quantitative marker of the degree of reinnervation.
Myasthenia gravis and acetylcholine receptor antibodies: a clinico immunological correlative study on South Indian patients.
Annals of Indian Academy of Neurology, 2008

Acquired myasthenia Gravis (MG), a disorder of impaired neuromuscular transmission is recognized as an autoimmune disorder, with a majority of the patients having antibodies against acetylcholine receptor (AChR antibodies) in the serum.
Brain microvascular occlusive disorder in COVID-19: a case report.
Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology, 2020

We describe the case of a COVID-19 patient with severely impaired consciousness after sedation hold, showing magnetic resonance imaging (MRI) findings of (i) acute bilateral supratentorial ischemic lesions involving the fronto-parietal white matter and the corpus callosum and (ii) multiple diffuse susceptibility weighted imaging (SWI) hypointense foci, infra and supratentorial, predominantly bithalamic, suggestive of microhemorrhage or alternatively microthrombi. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) RNA was detected in the cerebrospinal fluid. Our findings suggest the occurrence of vascular damage, predominantly involving microvessels. The underlying mechanisms, which include direct and indirect penetration of the virus to the central nervous system and systemic cardiorespiratory complications, are yet to be elucidated, and a direct correlation with SARS-CoV-2 infection remains uncertain.
Physiological and anatomical development of glycinergic inhibition in the mouse superior paraolivary nucleus following hearing onset.
Journal of neurophysiology, 2020

Neural circuits require balanced synaptic excitation and inhibition to ensure accurate neural computation. Our knowledge about the development and maturation of inhibitory synaptic inputs is less well developed than that concerning excitation. Here we describe the maturation of an inhibitory circuit within the mammalian auditory brainstem where counterintuitively, inhibition drives action potential firing of principal neurons. With the use of combined anatomical tracing and electrophysiological recordings from mice, neurons of the superior paraolivary nucleus (SPN) are shown to receive converging glycinergic input from at least four neurons of the medial nucleus of the trapezoid body (MNTB). These four axons formed 30.71 ± 2.72 (means ± SE) synaptic boutons onto each SPN neuronal soma, generating a total inhibitory conductance of 80 nS. Such strong inhibition drives the underlying postinhibitory rebound firing mechanism, which is a hallmark of SPN physiology. In contrast to inhibitory projections to the medial and lateral superior olives, the inhibitory projection to the SPN does not exhibit experience-dependent synaptic refinement following the onset of hearing. These findings emphasize that the development and function of neural circuits cannot be inferred from one synaptic target to another, even if both originate from the same neuron.
Aβ oligomers promote oligodendrocyte differentiation and maturation via integrin β1 and Fyn kinase signaling.
Cell death & disease, 2019

Alzheimer´s disease (AD) is characterized by a progressive cognitive decline that correlates with the levels of amyloid β-peptide (Aβ) oligomers. Strong evidences connect changes of oligodendrocyte function with the onset of neurodegeneration in AD. However, the mechanisms controlling oligodendrocyte responses to Aβ are still elusive. Here, we tested the role of Aβ in oligodendrocyte differentiation, maturation, and survival in isolated oligodendrocytes and in organotypic cerebellar slices. We found that Aβ peptides specifically induced local translation of 18.5-kDa myelin basic protein (MBP) isoform in distal cell processes concomitant with an increase of process complexity of MBP-expressing oligodendrocytes. Aβ oligomers required integrin β1 receptor, Src-family kinase Fyn and Ca
Mitochondrial disorders of the OXPHOS system.
FEBS letters, 2021

Mitochondrial disorders are among the most frequent inborn errors of metabolism, their primary cause being the dysfunction of the oxidative phosphorylation system (OXPHOS). OXPHOS is composed of the electron transport chain (ETC), formed by four multimeric enzymes and two mobile electron carriers, plus an ATP synthase [also called complex V (cV)]. The ETC performs the redox reactions involved in cellular respiration while generating the proton motive force used by cV to synthesize ATP. OXPHOS biogenesis involves multiple steps, starting from the expression of genes encoded in physically separated genomes, namely the mitochondrial and nuclear DNA, to the coordinated assembly of components and cofactors building each individual complex and eventually the supercomplexes. The genetic cause underlying around half of the diagnosed mitochondrial disease cases is currently known. Many of these cases result from pathogenic variants in genes encoding structural subunits or additional factors directly involved in the assembly of the ETC complexes. Here, we review the historical and most recent findings concerning the clinical phenotypes and the molecular pathological mechanisms underlying this particular group of disorders.
The pathophysiological impact of stress on the dopamine system is dependent on the state of the critical period of vulnerability.
Molecular psychiatry, 2020

Unregulated stress during critical periods of development is proposed to drive deficits consistent with schizophrenia in adults. If accurate, reopening the critical period could make the adult susceptible to pathology. We evaluated the impact of early adolescent and adult stress exposure (combination of daily footshock for 10 days and 3 restraint sessions) on (1) midbrain dopamine (DA) neuron activity, (2) ventral hippocampal (vHipp) pyramidal neuron activity, and (3) the number of parvalbumin (PV) interneurons in the vHipp and their associated perineuronal nets (PNNs). Ventral tegmental area (VTA) DA neuron population activity and vHipp activity was increased 1-2 and 5-6 weeks post-adolescent stress, along with a decrease in the number of PV+, PNN+, PV + /PNN + cells in the vHipp, which are consistent with the MAM model of schizophrenia. In contrast, adult stress decreased VTA DA neuron population activity only at 1-2 weeks post stress, which is consistent with what has been observed in animal models of depression, without impacting vHipp activity and PV/PNN expression. Administration of valproate (VPA), which can re-instate the critical period of plasticity via histone deacetylase (HDAC) inhibition, caused adult stress to produce changes similar to those induced by adolescent stress, presumably by increasing stress vulnerability to early adolescent levels. Our findings indicate that timing of stress is a critical determinant of the pathology produced in the adult: adolescent stress led to circuit deficits that recapitulates schizophrenia, whereas adult stress induced a depression-like hypodopaminergic state. Reopening the critical period in the adult restores vulnerability to stress-induced pathology resembling schizophrenia.
Degeneracy and Redundancy in Active Inference.
Cerebral cortex (New York, N.Y. : 1991), 2020

The notions of degeneracy and redundancy are important constructs in many areas, ranging from genomics through to network science. Degeneracy finds a powerful role in neuroscience, explaining key aspects of distributed processing and structure-function relationships in the brain. For example, degeneracy accounts for the superadditive effect of lesions on functional deficits in terms of a "many-to-one" structure-function mapping. In this paper, we offer a principled account of degeneracy and redundancy, when function is operationalized in terms of active inference, namely, a formulation of perception and action as belief updating under generative models of the world. In brief, "degeneracy" is quantified by the "entropy" of posterior beliefs about the causes of sensations, while "redundancy" is the "complexity" cost incurred by forming those beliefs. From this perspective, degeneracy and redundancy are complementary: Active inference tries to minimize redundancy while maintaining degeneracy. This formulation is substantiated using statistical and mathematical notions of degenerate mappings and statistical efficiency. We then illustrate changes in degeneracy and redundancy during the learning of a word repetition task. Finally, we characterize the effects of lesions-to intrinsic and extrinsic connections-using in silico disconnections. These numerical analyses highlight the fundamental difference between degeneracy and redundancy-and how they score distinct imperatives for perceptual inference and structure learning that are relevant to synthetic and biological intelligence.