rudyvdbrink/CitationDatabase huggingface dataset:
Stable maintenance of multiple representational formats in human visual short-term memory.
Proceedings of the National Academy of Sciences of the United States of America, 2020

Visual short-term memory (VSTM) enables humans to form a stable and coherent representation of the external world. However, the nature and temporal dynamics of the neural representations in VSTM that support this stability are barely understood. Here we combined human intracranial electroencephalography (iEEG) recordings with analyses using deep neural networks and semantic models to probe the representational format and temporal dynamics of information in VSTM. We found clear evidence that VSTM maintenance occurred in two distinct representational formats which originated from different encoding periods. The first format derived from an early encoding period (250 to 770 ms) corresponded to higher-order visual representations. The second format originated from a late encoding period (1,000 to 1,980 ms) and contained abstract semantic representations. These representational formats were overall stable during maintenance, with no consistent transformation across time. Nevertheless, maintenance of both representational formats showed substantial arrhythmic fluctuations, i.e., waxing and waning in irregular intervals. The increases of the maintained representational formats were specific to the phases of hippocampal low-frequency activity. Our results demonstrate that human VSTM simultaneously maintains representations at different levels of processing, from higher-order visual information to abstract semantic representations, which are stably maintained via coupling to hippocampal low-frequency activity.
Human Alzheimer's disease gene expression signatures and immune profile in APP mouse models: a discrete transcriptomic view of Aβ plaque pathology.
Journal of neuroinflammation, 2018

Alzheimer's disease (AD) is a chronic neurodegenerative disease with pathological hallmarks including the formation of extracellular aggregates of amyloid-beta (Aβ) known as plaques and intracellular tau tangles. Coincident with the formation of Aβ plaques is recruitment and activation of glial cells to the plaque forming a plaque niche. In addition to histological data showing the formation of the niche, AD genetic studies have added to the growing appreciation of how dysfunctional glia pathways drive neuropathology, with emphasis on microglia pathways. Genomic approaches enable comparisons of human disease profiles between different mouse models informing on their utility to evaluate secondary changes to triggers such as Aβ deposition.
A new model for simultaneous dimensionality reduction and time-varying functional connectivity estimation.
PLoS computational biology, 2021

An important question in neuroscience is whether or not we can interpret spontaneous variations in the pattern of correlation between brain areas, which we refer to as functional connectivity or FC, as an index of dynamic neuronal communication in fMRI. That is, can we measure time-varying FC reliably? And, if so, can FC reflect information transfer between brain regions at relatively fast-time scales? Answering these questions in practice requires dealing with the statistical challenge of having high-dimensional data and a comparatively lower number of time points or volumes. A common strategy is to use PCA to reduce the dimensionality of the data, and then apply some model, such as the hidden Markov model (HMM) or a mixture model of Gaussian distributions, to find a set of distinct FC patterns or states. The distinct spatial properties of these FC states together with the time-resolved switching between them offer a flexible description of time-varying FC. In this work, I show that in this context PCA can suffer from systematic biases and loss of sensitivity for the purposes of finding time-varying FC. To get around these issues, I propose a novel variety of the HMM, named HMM-PCA, where the states are themselves PCA decompositions. Since PCA is based on the data covariance, the state-specific PCA decompositions reflect distinct patterns of FC. I show, theoretically and empirically, that fusing dimensionality reduction and time-varying FC estimation in one single step can avoid these problems and outperform alternative approaches, facilitating the quantification of transient communication in the brain.
Parameterizing neural power spectra into periodic and aperiodic components.
Nature neuroscience, 2020

Electrophysiological signals exhibit both periodic and aperiodic properties. Periodic oscillations have been linked to numerous physiological, cognitive, behavioral and disease states. Emerging evidence demonstrates that the aperiodic component has putative physiological interpretations and that it dynamically changes with age, task demands and cognitive states. Electrophysiological neural activity is typically analyzed using canonically defined frequency bands, without consideration of the aperiodic (1/f-like) component. We show that standard analytic approaches can conflate periodic parameters (center frequency, power, bandwidth) with aperiodic ones (offset, exponent), compromising physiological interpretations. To overcome these limitations, we introduce an algorithm to parameterize neural power spectra as a combination of an aperiodic component and putative periodic oscillatory peaks. This algorithm requires no a priori specification of frequency bands. We validate this algorithm on simulated data, and demonstrate how it can be used in applications ranging from analyzing age-related changes in working memory to large-scale data exploration and analysis.
Exploring the modulation of hypoxia-inducible factor (HIF)-1α by volatile anesthetics as a possible mechanism underlying volatile anesthetic-induced CNS injury.
Neurochemical research, 2014

This review summarizes recent research on the potential cognitive and behavioural abnormalities induced by exposure to volatile anesthetics and suggests a role of hypoxia-inducible factor (HIF)-1α in mediating these events. Volatile anesthetics are widely utilized in clinical and research settings, yet the long-term safety of exposure to these agents is under debate. Findings from various animal models suggest volatile anesthetics induce widespread apoptosis in the central nervous system (CNS) that correlates with lasting deficits in learning and memory. Longitudinal analysis of clinical data highlight an increased risk of developmental disorders later in life when children are exposed to volatile anesthetics, particularly when exposures occur over multiple sessions. However, the mechanisms underlying these events have yet to be established. Considering the extensive use of volatile anesthetics, it is crucial that these events are better understood. The possible role of HIF-1α in volatile anesthetic-induced CNS abnormalities will be suggested and areas requiring urgent attention will be outlined.
Cultural differences in sensitivity to the relationship between objects and contexts: evidence from P3.
Neuroreport, 2014

Cross-cultural differences in Easterners and Westerners have been observed in different cognitive domains. Differential sensitivity to the relationship between objects and contexts might be an underlying cognitive mechanism for these differences. Twenty-one Chinese and 22 Germans participated in a three-stimulus event-related potential oddball task. They were instructed to monitor geometrical forms filled in black (targets) that were presented among a series of blank geometrical forms (standards). Novel stimuli were colored images of common objects. Robust novelty P3 and target P3 over the entire scalp were observed in both groups. As compared with the German group, Chinese participants showed larger amplitudes of novelty P3 and target P3 over frontal regions and earlier peak latency for target P3. This indicates a higher sensitivity to the relationship between contexts and objects in the Chinese as compared with the German group, which might be an underlying mechanism for cross-cultural differences reported in many cognitive domains.
Moderate Prenatal Alcohol Exposure Impairs Visual-Spatial Discrimination in a Sex-Specific Manner: Effects of Testing Order and Difficulty on Learning Performance.
Alcoholism, clinical and experimental research, 2020

Exposure to high levels of alcohol during development leads to alterations in neurogenesis and deficits in hippocampal-dependent learning. Evidence suggests that even more moderate alcohol consumption during pregnancy can have negative impacts on the cognitive function of offspring. Methods for assessing impairments differ greatly across species, complicating translation of preclinical findings into potential therapeutics. We have demonstrated the utility of a touchscreen operant measure for assessing hippocampal function in mice.
Psychological mechanisms and functions of 5-HT and SSRIs in potential therapeutic change: Lessons from the serotonergic modulation of action selection, learning, affect, and social cognition.
Neuroscience and biobehavioral reviews, 2020

Uncertainty regarding which psychological mechanisms are fundamental in mediating SSRI treatment outcomes and wide-ranging variability in their efficacy has raised more questions than it has solved. Since subjective mood states are an abstract scientific construct, only available through self-report in humans, and likely involving input from multiple top-down and bottom-up signals, it has been difficult to model at what level SSRIs interact with this process. Converging translational evidence indicates a role for serotonin in modulating context-dependent parameters of action selection, affect, and social cognition; and concurrently supporting learning mechanisms, which promote adaptability and behavioural flexibility. We examine the theoretical basis, ecological validity, and interaction of these constructs and how they may or may not exert a clinical benefit. Specifically, we bridge crucial gaps between disparate lines of research, particularly findings from animal models and human clinical trials, which often seem to present irreconcilable differences. In determining how SSRIs exert their effects, our approach examines the endogenous functions of 5-HT neurons, how 5-HT manipulations affect behaviour in different contexts, and how their therapeutic effects may be exerted in humans - which may illuminate issues of translational models, hierarchical mechanisms, idiographic variables, and social cognition.
Making oneself predictable in linguistic interactions.
Acta psychologica, 2020

While language production is a highly demanding task, conversational partners are known to coordinate their turns with striking precision. Among the mechanisms that allow them to do so is listeners' ability to predict what the speaker will say, and thus to prepare their response in advance. But do speakers also play a role in facilitating coordination? We hypothesized that speakers contribute by using coordination smoothers - in particular by making their turns easier to predict. To test this, we asked participants to type definitions for common English words, either on their own (n = 26 individuals) or interacting with a partner (n = 18 pairs), and we measured the timing with which they produced the definitions. In a post-test, additional participants (n = 55) attempted to predict the final word of these definitions and rated them for quality. We found that interacting speakers initiated their turns with less variable delays than solo individuals. In contrast, our post-test measures suggested that jointly produced definitions were in fact of lower predictability and quality than those produced by individuals, but the analysis revealed these findings were likely confounded by task difficulty. We propose that the reduction in temporal variability observed for interacting speakers may facilitate prediction and thus act as a coordination smoother in linguistic interactions.
Low-spatial-frequency priming potentiates the high-level mechanisms of contextual influence.
Vision research, 2020

The context sensitivity of visual size perception can be enhanced by prior exposure to low-spatial-frequency (LSF) relative to high-spatial-frequency information. Whether LSF priming affects low- or high-level mechanisms of contextual influence remains to be clarified. By using the Ebbinghaus illusion, which is a classic example of context-dependent size perception, we reduced the lightness contrast of surrounding inducers relative to the background and the shape similarity of the central target and surrounding inducers to diminish or eliminate low-level contour interaction and high-level size contrast, respectively. The results showed that LSF-related enhancement of context influence was unaffected by a change to the surround elements' contrast but not by a change to the shape similarity between the target and surround. The findings provide evidence that LSF priming primarily affects high-level rather than low-level mechanisms of contextual influence, possibly by weakening the suppressive function of feedback connections from higher visual regions to the early visual cortex.
DNA extraction from fresh and frozen plasma: an alternative for real-time PCR genotyping in pharmacogenetics.
Molecular biology reports, 2020

Genomic DNA, extracted from whole blood samples, is a key element for all genotyping workflows. When stored serum or plasma is the only source of DNA available, the main problem to overcome is the low quantity and poor quality of the DNA obtained, irrespective of the isolation procedure applied. The prevalence of artifacts, such as unbalanced amplification of alleles at specific sites (allelic dropout), is typically associated with PCR amplification of low quality/quantity DNA template, which is known to promote genotyping errors. The aim of this study was to determine whether the quality of genomic DNA from plasma samples may affect genotyping results. The ABCB1 c.3435C>T polymorphism was determined with two different real-time PCR assays, LightSNiP and TaqMan assays. We observed higher signal fluorescence values with DNA isolated from whole blood samples than with those from fresh and frozen plasma samples, due to reduced DNA concentration in the second ones. Despite the signal strength, a 100% concordance of genotyping data was however obtained in both assay types, regardless of the method of extraction. Our results show that, regardless of the lower DNA yield, extraction from plasma samples can still represent a valid alternative for real-time PCR genotyping application.
Reactivation during sleep with incomplete reminder cues rather than complete ones stabilizes long-term memory in humans.
Communications biology, 2020

Reactivation by reminder cues labilizes memories during wakefulness, requiring reconsolidation to persist. In contrast, during sleep, cued reactivation seems to directly stabilize memories. In reconsolidation, incomplete reminders are more effective in reactivating memories than complete reminders by inducing a mismatch, i.e. a discrepancy between expected and actual events. Whether mismatch is likewise detected during sleep is unclear. Here we test whether cued reactivation during sleep is more effective for mismatch-inducing incomplete than complete reminders. We first establish that only incomplete but not complete reminders labilize memories during wakefulness. When complete or incomplete reminders are presented during 40-min sleep, both reminders are equally effective in stabilizing memories. However, when extending the retention interval for another 7 hours (following 40-min sleep), only incomplete but not complete reminders stabilize memories, regardless of the extension containing wakefulness or sleep. We propose that, during sleep, only incomplete reminders initiate long-term memory stabilization via mismatch detection.
The Florey turns 50.
Clinical and experimental pharmacology & physiology, 2014

The origins of the Howard Florey Laboratories of Experimental Physiology, Department of Physiology, The University of Melbourne, are tied to the ground-breaking clinical work of Derek A Denton in 1947 and to the investigations of the initial scientific team into the control of salt and water balance in health and disease over the period 1947-1963 were Professor RD Wright, Drs JR Goding, IR McDonald, John P Coghlan, E Marelyn Wintour and John R Blair-West. An Act of Parliament in 1971 by the Victorian State Government formally established the Institute named after Howard Florey, the Australian Nobel Prize winner who isolated penicillin. The Howard Florey Laboratories/Institute quickly became an international leader in the scientific areas of the physiological control of body fluids and electrolyte balance, especially sodium regulation and the regulation of the secretion of aldosterone, the adrenal salt-retaining hormone; the micro measurement of hormones, in particular steroids and peptides; instinctive ingestive behaviour; fetal fluid regulation; hybridization histochemistry, and the hormone relaxin. Subsequently, the senior staff included, inter alia, Bruce Scoggins, Richard Weisinger, John McDougall, Brian Oldfield, Michael McKinley, Robin McAllen, Hugh Niall, Geoff Tregear and Felix Beck. During the 1990s, an explosion occurred in neuroscience and, in 1997, the Board made the strategic decision to change the focus of the Institute to brain disorders. From 1997 to 2007, Fred Mendelsohn steered the Florey to become one of Australia's premier brain research institutes and, under the current director (the eminent clinician and neuroscientist Geoffrey Donnan), this reputation has been further enhanced.
The impact of HPV-specific infection in women diagnosed with atypical glandular cells: Results from the HPV-AGC study.
Pathology, research and practice, 2020

To evaluate the impact of various HPV types on the risk of developing lesions of the uterus (either uterine cervix and endometrium) in women diagnosed with "atypical glandular cells" (AGC) at Pap smear.
A new mouse tool for studying dopaminergic neurons.
Journal of neuroscience methods, 2021

Dopaminergic neurons play important roles in brain function and studying dopaminergic system has been a major field of neuroscience research. Genetically modified mice have greatly advanced research of dopaminergic neurons. However, it has been shown that dopaminergic neurons contain several subtypes expressing distinct genetic markers, and it is challenging to study genetically different subtypes of dopaminergic neurons using current mouse lines. Here, we report a newly developed Dat-ires-flp line, in which flippase gene is knocked in after the stop codon of Slc6a3 (dopamine transporter, DAT) gene. We validated this line to show that flp is specifically expressed in dopaminergic neurons, and by breeding with Cre-expressing line (i.e. Vglut2-cre) we can study a specific subpopulation of dopaminergic neurons. We expect this line will be widely used to study different subtypes of dopaminergic neurons in diverse contexts.
Lesional expression of EMAPII in macrophages/microglia following cerebral ischemia in rats.
The International journal of neuroscience, 2011

Cerebral ischemia triggers acute inflammation, which exacerbates primary brain damage. Characterization of cytokine expression to the early damaged tissue might aid in further understanding of lesion development and contribute to definition of molecular targets for selective immunotherapy. Endothelial monocyte-activating polypeptide II (EMAPII) is a proinflammatory, antiangiogenic cytokine whose expression following cerebral ischemia remained unknown. Therefore, we studied the spatiotemporal expression of EMAPII in early brain lesions after cerebral ischemia-reperfusion injury.
Internal States Influence the Representation and Modulation of Food Intake by Subthalamic Neurons.
Neuroscience bulletin, 2020

Deep brain stimulation of the subthalamic nucleus (STN) is an effective therapy for motor deficits in Parkinson's disease (PD), but commonly causes weight gain in late-phase PD patients probably by increasing feeding motivation. It is unclear how STN neurons represent and modulate feeding behavior in different internal states. In the present study, we found that feeding caused a robust activation of STN neurons in mice (GCaMP6 signal increased by 48.4% ± 7.2%, n = 9, P = 0.0003), and the extent varied with the size, valence, and palatability of food, but not with the repetition of feeding. Interestingly, energy deprivation increased the spontaneous firing rate (8.5 ± 1.5 Hz, n = 17, versus 4.7 ± 0.7 Hz, n = 18, P = 0.03) and the depolarization-induced spikes in STN neurons, as well as enhanced the STN responses to feeding. Optogenetic experiments revealed that stimulation and inhibition of STN neurons respectively reduced (by 11% ± 6%, n = 6, P = 0.02) and enhanced (by 36% ± 15%, n = 7, P = 0.03) food intake only in the dark phase. In conclusion, our results support the hypothesis that STN neurons are activated by feeding behavior, depending on energy homeostatic status and the palatability of food, and modulation of these neurons is sufficient to regulate food intake.
Neurofunctional abnormalities in antisocial spectrum: A meta-analysis of fMRI studies on Five distinct neurocognitive research domains.
Neuroscience and biobehavioral reviews, 2020

Past functional magnetic resonance imaging on antisocial subjects have shown important inconsistencies and methodological problems (e.g. heterogeneity in fMRI tasks domain, small sample sizes, analyses on regions-of-interest). We aimed to conduct a meta-analysis of whole-brain fMRI studies on antisocial individuals based on distinct neurocognitive domains. A voxel-based meta-analysis via permutation of subject images (SDM-PSI) was performed on studies using fMRI tasks in the domains of acute threat response, cognitive control, social cognition, punishment and reward processing. Overall, 83 studies were retrieved. Using a liberal statistical threshold, several key regions were identified in the meta-analysis, principally during acute threat response, social cognition and cognitive control tasks. Additionally, we observed that the right amygdala was negatively associated with both callous-unemotional traits and severity of antisocial behaviors, in meta-analyses on region-of-interest and on dimensional studies, respectively. The findings show that the most prominent functional brain deficits arise during acute threat response, social cognitions and cognitive control neurocognitive domains. These results provide substantial insights for our understanding of aberrant neural processing across specific contexts.
Brain insulin signaling and cerebrovascular disease in human postmortem brain.
Acta neuropathologica communications, 2021

Insulin is an important hormone for brain function, and alterations in insulin metabolism may be associated with neuropathology. We examined associations of molecular markers of brain insulin signaling with cerebrovascular disease. Participants were enrolled in the Religious Orders Study (ROS), an ongoing epidemiologic community-based, clinical-pathologic study of aging from across the United States. Using cross-sectional analyses, we studied a subset of ROS: 150 persons with or without diabetes, matched 1:1 by sex on age-at-death and education. We used ELISA, immunohistochemistry, and ex vivo stimulation with insulin, to document insulin signaling in postmortem midfrontal gyrus cortex tissue. Postmortem neuropathologic data identified cerebrovascular disease including brain infarcts, classified by number (as none for the reference; one; and more than one), size (gross and microscopic infarcts), and brain region/location (cortical and subcortical). Cerebral vessel pathologies were assessed, including severity of atherosclerosis, arteriolosclerosis, and amyloid angiopathy. In separate regression analyses, greater AKT1 phosphorylation at T