rudyvdbrink/CitationDatabase huggingface dataset:
Cortico-limbic-striatal contribution after response and reversal learning: a metabolic mapping study.
Brain research, 2011

Learning of arbitrary stimulus-response associations is an adaptive behavior essential for species survival in an ever-changing environment. Particular subdivisions of the striatum have been shown to be critical for both motor-response learning and reversal learning. However, recent evidence suggests that different cortical and subcortical brain regions may be involved in response learning, a kind of learning more complex than previously thought. In fact, many brain regions subserving response learning seem to be also related to reversal learning, traditionally ascribed to the prefrontal cortex. The present study examined the role of different subdivisions of the rat prefrontal cortex, striatum, amygdala and the ventral tegmental area on both response and reversal learning evaluated in the water T-maze. Increased neuronal metabolic activity, as measured by cytochrome oxidase (CO) histochemistry, was found in most brain regions after training rats in a response learning task as compared to yoked controls. Reversal learning was associated with a return to baseline CO activity levels except for the orbitofrontal cortex and the ventral tegmental area. Analysis of functional connectivity among brain regions showed significant correlations in CO activity between particular cortical and striatal subdivisions in the reversal learning group. These findings suggest that the interaction of specific frontal and subcortical regions is required for reversal but not for response learning. However, our findings support the involvement of a cortico-limbic-striatal circuit in both types of learning.
Neuronal hyperactivity accelerates depletion of neural stem cells and impairs hippocampal neurogenesis.
Cell stem cell, 2015

Adult hippocampal neurogenesis is believed to maintain a range of cognitive functions, many of which decline with age. We recently reported that radial neural stem cells (rNSCs) in the hippocampus undergo activation-dependent conversion into astrocytes, a mechanism that over time contributes to a reduction in the rNSC population. Here, we injected low and high levels of kainic acid (KA) in the dentate gyrus to assess whether neuronal hyperexcitation, a hallmark of epileptic disorders, could accelerate this conversion. At low levels of KA, generating epileptiform activity without seizures, we indeed found increased rNSC activation and conversion into astrocytes. At high levels, generating sustained epileptic seizures, however, we find that rNSCs divide symmetrically and that both mother and daughter cells convert into reactive astrocytes. Our results demonstrate that a threshold response for neuronal hyperexcitation provokes a dramatic shift in rNSC function, which impairs adult hippocampal neurogenesis in the long term.
Early-onset and robust amyloid pathology in a new homozygous mouse model of Alzheimer's disease.
PloS one, 2009

Transgenic mice expressing mutated amyloid precursor protein (APP) and presenilin (PS)-1 or -2 have been successfully used to model cerebral beta-amyloidosis, one of the characteristic hallmarks of Alzheimer's disease (AD) pathology. However, the use of many transgenic lines is limited by premature death, low breeding efficiencies and late onset and high inter-animal variability of the pathology, creating a need for improved animal models. Here we describe the detailed characterization of a new homozygous double-transgenic mouse line that addresses most of these issues.
Dynamic behavioural changes in the Spontaneously Hyperactive Rat: 3. Control by reinforcer rate changes and predictability.
Behavioural brain research, 2009

Variable intervals are widely believed to produce steady rates of responding. However, based on the calming effect of unpredictability in attention deficit hyperactivity disorder (ADHD) we hypothesised that an animal model of this disorder, the Spontaneously Hyperactive (or Hypertensive) Rat, would become less active following particularly variable sequences of interval-lengths in a variable interval schedule. From a large dataset of holepokes and tray-reports by rats in a variable interval reinforcement schedule, we extracted numerous short sequences of intervals on the basis of the first, second, and third derivatives of reinforcement timing (i.e. rate, acceleration, and jerk) in recent intervals. Sets of selected intervals were compared with one another to elucidate the effect of these different derivatives on behaviour in the current interval. Results show that SHR are more active after richer recent reinforcement; after decelerating reinforcers; and after predictable reinforcers. The hypothesis is supported. In conclusion, SHR behaviour largely complies with the Extended Temporal Difference model which in turn has been previously validated against published data in ADHD. The Extended TD model therefore is able to account for two species' behaviour in a wide range of experimental paradigms. SHR are similar in several respects to group averages of children with ADHD, except that SHR have reduced variability and perform actions faster than controls. Hyperactivity in the SHR is very dependent on momentary environmentally determined states, which is an important area for future investigation of ADHD.
Topography of the human acoustic radiation as revealed by ex vivo fibers micro-dissection and in vivo diffusion-based tractography.
Brain structure & function, 2018

The acoustic radiation is a compact bundle of fibers conveying auditory information from the medial geniculate nucleus of the thalamus to the auditory cortex. Topographical knowledge of this bundle in primates is scarce and in vivo diffusion-based tractography reconstructions in humans remains challenging, especially with the most widely used MRI acquisition protocols. Therefore, the AR represents a notable anatomical omission in the neurobiological investigation of acoustic and linguistic functional mechanisms in humans. In this study, we combine blunt micro-dissections and advanced diffusion tractography methods to provide novel insights into the topographical anatomy of this bundle in humans. Evidences from ex vivo blunt micro-dissection in three human (two right) hemispheres are compared to the 3D profile of this bundle as reconstructed by tractography techniques in four healthy adult data sets provided by the Human Connectome Project. Both techniques show the unique trajectory of the AR, a transversal course from the midline to the lateral convexity of the posterior temporal lobe. Blunt dissections demonstrated three portions of this bundle that we defined as the genu, stem, and fan, revealing the intimate relationships that each of these components has with neighboring association and projection pathways. Probabilistic tractography and ultra-high b values provided results comparable to blunt micro-dissections and highlighted the main limitations in tracking the AR. This is, to our knowledge, the first ex vivo/in vivo integrated study providing novel and reliable information about the precise anatomy of the AR, which will be important for future investigations in the neuroscientific, clinical, and surgical field.
Transthyretin-related familial amyloidotic polyneuropathy: description of a cohort of patients with Leu64 mutation and late onset.
Journal of the peripheral nervous system : JPNS, 2012

Transthyretin-related familial amyloidotic polyneuropathy (TTR-FAP) usually presents itself as a progressive sensorimotor polyneuropathy with severe autonomic dysfunction and cardiomyopathy. Eighteen patients carrying the Leu64 mutation underwent a series of regular follow-ups, including: neurological examination, electroneurography, electromyography, electrocardiography and echocardiography, blood analysis, a questionnaire on autonomic symptoms, cardiovascular autonomic tests and a 99mTc-DPD examination study. A late onset of a slowly progressive disease which reached its terminal stage after about 10  years was observed. The onset was mainly a length-dependent sensory neuropathy, although a focal onset with carpal tunnel syndrome was detected in three patients. At the onset of the disease, autonomic dysfunction was present in a small number of patients, but, within a few years, this had manifested in all members of the sample group. The only extra-neurological manifestations were cardiac related. It is reasonable to consider Southern Italy as an endemic focus of TTR-FAP. An underestimation of disease prevalence could be caused by a late onset of FAP, which can manifest in patients up to their late 70s. Follow-up of asymptomatic individuals may permit the early detection of symptoms and signs, allowing a detailed record of the natural history of the disease from the beginning and facilitating prompt treatment.
Emotional task management: neural correlates of switching between affective and non-affective task-sets.
Social cognitive and affective neuroscience, 2015

Although task-switching has been investigated extensively, its interaction with emotionally salient task content remains unclear. Prioritized processing of affective stimulus content may enhance accessibility of affective task-sets and generate increased interference when switching between affective and non-affective task-sets. Previous research has demonstrated that more dominant task-sets experience greater switch costs, as they necessitate active inhibition during performance of less entrenched tasks. Extending this logic to the affective domain, the present experiment examined (a) whether affective task-sets are more dominant than non-affective ones, and (b) what neural mechanisms regulate affective task-sets, so that weaker, non-affective task-sets can be executed. While undergoing functional magnetic resonance imaging, participants categorized face stimuli according to either their gender (non-affective task) or their emotional expression (affective task). Behavioral results were consistent with the affective task dominance hypothesis: participants were slower to switch to the affective task, and cross-task interference was strongest when participants tried to switch from the affective to the non-affective task. These behavioral costs of controlling the affective task-set were mirrored in the activation of a right-lateralized frontostriatal network previously implicated in task-set updating and response inhibition. Connectivity between amygdala and right ventrolateral prefrontal cortex was especially pronounced during cross-task interference from affective features.
Astrocytes control synaptic strength by two distinct v-SNARE-dependent release pathways.
Nature neuroscience, 2017

Communication between glia cells and neurons is crucial for brain functions, but the molecular mechanisms and functional consequences of gliotransmission remain enigmatic. Here we report that astrocytes express synaptobrevin II and cellubrevin as functionally non-overlapping vesicular SNARE proteins on glutamatergic vesicles and neuropeptide Y-containing large dense-core vesicles, respectively. Using individual null-mutants for Vamp2 (synaptobrevin II) and Vamp3 (cellubrevin), as well as the corresponding compound null-mutant for genes encoding both v-SNARE proteins, we delineate previously unrecognized individual v-SNARE dependencies of astrocytic release processes and their functional impact on neuronal signaling. Specifically, we show that astroglial cellubrevin-dependent neuropeptide Y secretion diminishes synaptic signaling, while synaptobrevin II-dependent glutamate release from astrocytes enhances synaptic signaling. Our experiments thereby uncover the molecular mechanisms of two distinct v-SNARE-dependent astrocytic release pathways that oppositely control synaptic strength at presynaptic sites, elucidating new avenues of communication between astrocytes and neurons.
Modification and validation of a performance-based functional capacity instrument for individuals with schizophrenia.
Psychiatry research, 2019

Functional impairments are common in schizophrenia patients, but few performance-based instruments are available to evaluate their functional capacity, especially those that are culturally adapted for use in China. This study aimed to modify the items of the original Beijing Performance-based Functional Ecological Test (BJ-PERFECT) due to limited tasks in a particular scenario and examine the psychometric properties of the newly modified BJ-PERFECT in schizophrenia patients. Participants of the study comprised 105 schizophrenia patients and 45 healthy controls (HCs). All of them were administered the modified BJ-PERFECT, the University of California, San Diego, Performance-based Skill Assessment-Brief version (UPSA-B) and the Global Assessment of Functioning (GAF). The modified BJ-PERFECT retained seven original items and added 4 new items. The validity of the modified BJ-PERFECT was supported by its significant correlation with the UPSA-B but not the GAF and by the significant difference on the instrument's scores between the schizophrenia patients and HCs. The internal consistency reliability was found to be good. Level of education was found to have a significant relationship with functional capacity. The modified BJ-PERFECT was found to be psychometrically valid to assess functional capacity in schizophrenia patients.
Immunocytochemical Evidence for Golgi Vesicle Involvement in Milk Fat Globule Secretion.
The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society, 2015

The exact mechanism of secretion of the milk fat globule (MFG) from the mammary secretory cell is still controversial. We have previously suggested close involvement of Golgi vesicles in this process. This paper provides direct immunocytochemical evidence that butyrophilin is present in the Golgi stack and vesicles in ovine and caprine mammary glands. We suggest that it is the butyrophilin in the Golgi vesicle membrane that forms the specific association with the adipophilin on the lipid surface in the cytoplasm. Exocytosis of the associated Golgi vesicle will then initiate the process of MFG secretion. Further exocytosis of associated Golgi vesicles will continue and complete the process. Areas of the plasmalemma that have butyrophilin delivered by previous non-lipid associated Golgi exocytoses may also contribute to the process of forming the milk fat globule membrane (MFGM).
Simvastatin Treatment in Traumatic Brain Injury: Operation Brain Trauma Therapy.
Journal of neurotrauma, 2016

Simvastatin, the fourth drug selected for testing by Operation Brain Trauma Therapy (OBTT), is a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor used clinically to reduce serum cholesterol. In addition, simvastatin has demonstrated potent antineuroinflammatory and brain edema reducing effects and has shown promise in promoting functional recovery in pre-clinical models of traumatic brain injury (TBI). The purpose of this study was to assess the potential neuroprotective effects of oral administration of simvastatin on neurobehavioral, biomarker, and histopathological outcome measures compared across three pre-clinical TBI animal models. Adult male Sprague-Dawley rats were exposed to either moderate fluid percussion injury (FPI), controlled cortical impact injury (CCI), or penetrating ballistic-like brain injury (PBBI). Simvastatin (1 or 5 mg/kg) was delivered via oral gavage at 3 h post-injury and continued once daily out to 14 days post-injury. Results indicated an intermediate beneficial effect of simvastatin on motor performance on the gridwalk (FPI), balance beam (CCI), and rotarod tasks (PBBI). No significant therapeutic benefit was detected, however, on cognitive outcome across the OBTT TBI models. In fact, Morris water maze (MWM) performance was actually worsened by treatment in the FPI model and scored full negative points for low dose in the MWM latency and swim distance to locate the hidden platform. A detrimental effect on cortical tissue loss was also seen in the FPI model, and there were no benefits on histology across the other models. Simvastatin also produced negative effects on circulating glial fibrillary acidic protein biomarker outcomes that were evident in the FPI and PBBI models. Overall, the current findings do not support the beneficial effects of simvastatin administration over 2 weeks post-TBI using the oral route of administration and, as such, it will not be further pursued by OBTT.
Reward system and temporal pole contributions to affective evaluation during a first person shooter video game.
BMC neuroscience, 2011

Violent content in video games evokes many concerns but there is little research concerning its rewarding aspects. It was demonstrated that playing a video game leads to striatal dopamine release. It is unclear, however, which aspects of the game cause this reward system activation and if violent content contributes to it. We combined functional Magnetic Resonance Imaging (fMRI) with individual affect measures to address the neuronal correlates of violence in a video game.
Mitochondrial genome copy number measured by DNA sequencing in human blood is strongly associated with metabolic traits via cell-type composition differences.
Human genomics, 2021

Mitochondrial genome copy number (MT-CN) varies among humans and across tissues and is highly heritable, but its causes and consequences are not well understood. When measured by bulk DNA sequencing in blood, MT-CN may reflect a combination of the number of mitochondria per cell and cell-type composition. Here, we studied MT-CN variation in blood-derived DNA from 19184 Finnish individuals using a combination of genome (N = 4163) and exome sequencing (N = 19034) data as well as imputed genotypes (N = 17718).
StimDuino: an Arduino-based electrophysiological stimulus isolator.
Journal of neuroscience methods, 2015

Electrical stimulus isolator is a widely used device in electrophysiology. The timing of the stimulus application is usually automated and controlled by the external device or acquisition software; however, the intensity of the stimulus is adjusted manually. Inaccuracy, lack of reproducibility and no automation of the experimental protocol are disadvantages of the manual adjustment. To overcome these shortcomings, we developed StimDuino, an inexpensive Arduino-controlled stimulus isolator allowing highly accurate, reproducible automated setting of the stimulation current.
Attenuating GABA(A) receptor signaling in dopamine neurons selectively enhances reward learning and alters risk preference in mice.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011

Phasic dopamine (DA) transmission encodes the value of reward-predictive stimuli and influences both learning and decision-making. Altered DA signaling is associated with psychiatric conditions characterized by risky choices such as pathological gambling. These observations highlight the importance of understanding how DA neuron activity is modulated. While excitatory drive onto DA neurons is critical for generating phasic DA responses, emerging evidence suggests that inhibitory signaling also modulates these responses. To address the functional importance of inhibitory signaling in DA neurons, we generated mice lacking the β3 subunit of the GABA(A) receptor specifically in DA neurons (β3-KO mice) and examined their behavior in tasks that assessed appetitive learning, aversive learning, and risk preference. DA neurons in midbrain slices from β3-KO mice exhibited attenuated GABA-evoked IPSCs. Furthermore, electrical stimulation of excitatory afferents to DA neurons elicited more DA release in the nucleus accumbens of β3-KO mice as measured by fast-scan cyclic voltammetry. β3-KO mice were more active than controls when given morphine, which correlated with potential compensatory upregulation of GABAergic tone onto DA neurons. β3-KO mice learned faster in two food-reinforced learning paradigms, but extinguished their learned behavior normally. Enhanced learning was specific for appetitive tasks, as aversive learning was unaffected in β3-KO mice. Finally, we found that β3-KO mice had enhanced risk preference in a probabilistic selection task that required mice to choose between a small certain reward and a larger uncertain reward. Collectively, these findings identify a selective role for GABA(A) signaling in DA neurons in appetitive learning and decision-making.
Effects of Voice Therapy: A Comparison Between Individual and Group Therapy.
Journal of voice : official journal of the Voice Foundation, 2018

The primary aim of this clinical evaluation project is to study the effect of voice therapy given in the speech-language pathology clinic, as individual and group therapy, as well as finding out some of the reasons for not attending the recommended therapy.
Damage to the left ventral, arcuate fasciculus and superior longitudinal fasciculus-related pathways induces deficits in object naming, phonological language function and writing, respectively.
The International journal of neuroscience, 2013

The anatomic localization of brain functions can be characterized via diffusion tensor imaging in patients with brain tumors and neurological symptoms. The goal of the present study was to evaluate the function of the ventral, arcuate fasciculus (AF) and the superior longitudinal fasciculus (SLF)-related language pathways using these techniques by analyzing 9 patients treated in our hospital between 2007 and 2011. In cases 1-3, the left ventral pathways, namely, the inferior longitudinal fasciculus, uncinate fasciculus or inferior fronto-occipital fasciculus, were mainly damaged, and the common dysfunction experienced by these patients was a deficit in object naming. In cases 4-6, the left SLF was mainly damaged, and the common deficit was dysgraphia. In cases 7-9, the left AF was mainly damaged, and almost all language functions related to phonology were abnormal. These results suggest that the left ventral, AF and SLF-related pathways are closely related to visual, auditory and hand-related language function, respectively.
Homeostatic signaling and the stabilization of neural function.
Neuron, 2013

The brain is astonishing in its complexity and capacity for change. This has fascinated scientists for more than a century, filling the pages of this journal for the past 25 years. But a paradigm shift is underway. It seems likely that the plasticity that drives our ability to learn and remember can only be meaningful in the context of otherwise stable, reproducible, and predictable baseline neural function. Without the existence of potent mechanisms that stabilize neural function, our capacity to learn and remember would be lost in the chaos of daily experiential change. This underscores two great mysteries in neuroscience. How are the functional properties of individual neurons and neural circuits stably maintained throughout life? And, in the face of potent stabilizing mechanisms, how can neural circuitry be modified during neural development, learning, and memory? Answers are emerging in the rapidly developing field of homeostatic plasticity.
Intraoperative MRI for transphenoidal procedures: short-term outcome for 100 consecutive cases.
Clinical neurology and neurosurgery, 2011

The majority of pituitary lesions are benign and can be cured with complete surgical resection. However, the transsphenoidal technique (the most common approach for pathology in this region) is limited by poor visualization and anatomical constraints. This can lead to incomplete tumor resection and thus increased recurrence rates. The use of iMRI during these procedures offers the advantage of radiographic confirmation during the procedure and may improve extent of resection. We reviewed our experience with this technology in 100 consecutive cases and compared the outcomes to published results.