rudyvdbrink/CitationDatabase huggingface dataset:
Dense representation of natural odorants in the mouse olfactory bulb.
Nature neuroscience, 2012

In mammals, odorant molecules are thought to activate only a few glomeruli, leading to the hypothesis that odor representation in the olfactory bulb is sparse. However, the studies supporting this model used anesthetized animals or monomolecular odorants at limited concentration ranges. Using optical imaging and two-photon microscopy, we found that natural odorants at their native concentrations could elicit dense representations in the olfactory bulb. Both anesthesia and odorant concentration were found to modulate the representation density of natural odorants.
Bulk loading of calcium indicator dyes to study astrocyte physiology: key limitations and improvements using morphological maps.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011

Calcium signaling has been studied in astrocyte cell bodies using bulk loading of calcium indicator dyes, and astrocytes are known to display intracellular calcium transients. An assumption in recent data on the neuronal impact of somatic astrocyte calcium transients has been that bulk loading reflects signaling in relevant astrocyte compartments such as processes. We assessed bulk loading using Sholl analysis (Sholl, 1953) of astrocytes loaded with common calcium indicator dyes and compared these data with Sholl analysis of astrocyte morphology. In the CA1 region of the hippocampus from rats, we found that bulk loading of calcium indicator dyes only reports on calcium signals within the soma and in the most proximal processes, leaving ∼90% of the area of an astrocyte and its extensive processes unsampled. By using morphological reconstructions as "maps" after the imaging session, we present simple procedures that remedy these shortfalls and permit reliable detection of calcium transients in distal astrocyte processes. The data thus reveal limitations in the interpretation of astrocyte calcium imaging data gathered with bulk loading and provide refinements to minimize these shortcomings.
Gender moderates diurnal cortisol in relation to trauma and PTSD symptoms: A study in Sri Lankan adolescents.
Psychoneuroendocrinology, 2019

Trauma exposure and posttraumatic stress disorder (PTSD) have been linked to aspects of diurnal cortisol secretion in adolescents, but little is known about gender differences in these associations. A school-based sample of Sri Lankan adolescents aged 13-16 years took part in this study 4.5 years after the 2004 tsunami had impacted many of their lives to varying degrees. Saliva samples were obtained 4 times a day for 3 days in 84 participants, who also completed measures of lifetime trauma, current stressors, and posttraumatic stress symptoms (PTSS). We used multilevel regression to estimate effects of trauma exposure and symptoms on cortisol level, diurnal slope, and awakening response (CAR). Results indicated higher cortisol in girls and older adolescents. Although trauma, PTSS, and recent PTSD had non-significant main effects, these three variables interacted with gender, with higher cortisol in girls than in similarly traumatized or symptomatic boys. Co-occurrence of internalizing symptoms and PTSS was also associated with higher cortisol. The 28 adolescents with recent PTSD displayed flatter diurnal slopes, reflecting relatively low morning cortisol. Among the 56 trauma-exposed participants, negative trauma appraisals were associated with higher cortisol. Girls were more likely than boys to display elevated cortisol in relation to re-experiencing and hyperarousal symptoms. In contrast to significant findings for cortisol level and diurnal slope, the CAR showed no association with either trauma or PTSS, irrespective of gender. Findings, viewed in light of normative gender differences in HPA activity during adolescence, can contribute to understanding heightened female vulnerability to posttraumatic stress disorder.
The Complex Interaction of Mitochondrial Genetics and Mitochondrial Pathways in Psychiatric Disease.
Molecular neuropsychiatry, 2018

While accounting for only 2% of the body's weight, the brain utilizes up to 20% of the body's total energy. Not surprisingly, metabolic dysfunction and energy supply-and-demand mismatch have been implicated in a variety of neurological and psychiatric disorders. Mitochondria are responsible for providing the brain with most of its energetic demands, and the brain uses glucose as its exclusive energy source. Exploring the role of mitochondrial dysfunction in the etiology of psychiatric disease is a promising avenue to investigate further. Genetic analysis of mitochondrial activity is a cornerstone in understanding disease pathogenesis related to metabolic dysfunction. In concert with neuroimaging and pathological study, genetics provides an important bridge between biochemical findings and clinical correlates in psychiatric disease. Mitochondrial genetics has several unique aspects to its analysis, and corresponding special considerations. Here, we review the components of mitochondrial genetic analysis - nuclear DNA, mitochon-drial DNA, mitochondrial pathways, pseudogenes, nuclear-mitochondrial mismatch, and microRNAs - that could contribute to an observable clinical phenotype. Throughout, we highlight psychiatric diseases that can arise due to dysfunction in these processes, with a focus on schizophrenia and bipolar disorder.
Olfactory neuroscience: beyond the bulb.
Current biology : CB, 2011

High-resolution tracing of projections from the olfactory bulb to its cortical targets revealed coarse topography and stereotopy in some areas but highly distributed, combinatorial connectivity in others. These results provide a basis for understanding innate and associative olfactory processing and perception.
Shared variance of oculomotor phenotypes in a large sample of healthy young men.
Experimental brain research, 2018

This study used canonical correlation analysis to investigate patterns of shared variance between parameters measured in seven different occulomotor function tasks, namely the visually guided saccade task, the antisaccade task, the closed-loop smooth-pursuit task, the open-loop smooth-pursuit task, and three active visual fixation tasks. These tasks were performed by 2130 young army recruits. Only a small percentage (1-10%) of shared variance existed between sets of parameters for all oculomotor function tasks measured. The most correlated tasks were the visually guided saccade and the antisaccade. The first common factor correlated with speed of performance between these tasks (latency), while the second and third correlated with accuracy of performance. Better performance in active visual fixation tasks correlated with better performance accuracy (lower error rate) and increased speed (lower latency) in the antisaccade and saccade tasks as well as better performance in the closed-loop smooth-pursuit task (increase in gain and decrease in the rate of unwanted saccades during pursuit). Better performance in the closed-loop smooth-pursuit task (increased gain and decreased number of unwanted saccades) also correlated with increased accuracy and increased speed of performing saccades and antisaccades. Finally, the open-loop fixation task had no correlation with all other oculomotor tasks except for a very weak negative correlation with the closed-loop pursuit task where better performance (increased gain) in one correlated with worse performance (decreased gain) in the other. The results of this analysis showed that a small percentage of variance is shared among different oculomotor function tasks. The structure of this shared variance could be used to derive common oculomotor function indices to study their relation to genetic and other sources of inter-subject variation.
Role of estrogen receptor alpha and beta expression and signaling on cognitive function during aging.
Hippocampus, 2012

This review presents evidence for the idea that the expression of estrogen receptor alpha and beta (ERα and ERβ) interacts with the level of estradiol (E2) to influence the etiology of age-related cognitive decline and responsiveness to E2 treatments. There is a nonmonotonic dose response curve for E2 influences on behavior and transcription. Evidence is mounting to indicate that the dose response curve is shifted according to the relative expression of ERα and ERβ. Recent work characterizing age-related changes in the expression of ERα and ERβ in the hippocampus, as well as studies using mutant mice, and viral mediated delivery of estrogen receptors indicate that an age-related shift in ERα/ERβ expression, combined with declining gonadal E2 can impact transcription, cell signaling, neuroprotection, and neuronal growth. Finally, the role of ERα/ERβ on rapid E2 signaling and synaptogenesis as it relates to hippocampal aging is discussed.
The iTreAD project: a study protocol for a randomised controlled clinical trial of online treatment and social networking for binge drinking and depression in young people.
BMC public health, 2015

Depression and binge drinking behaviours are common clinical problems, which cause substantial functional, economic and health impacts. These conditions peak in young adulthood, and commonly co-occur. Comorbid depression and binge drinking are undertreated in young people, who are reluctant to seek help via traditional pathways to care. The iTreAD project (internet Treatment for Alcohol and Depression) aims to provide and evaluate internet-delivered monitoring and treatment programs for young people with depression and binge drinking concerns.
Absence of direct effects on the dopamine D2 receptor by mGluR2/3-selective receptor agonists LY 354,740 and LY 379,268.
Synapse (New York, N.Y.), 2011

We previously reported the absence of high-affinity binding of the group II metabotropic glutamate receptor agonists LY 354,740 and LY 379,268 to the D2L dopamine receptor. A rebuttal to our findings has since been reported (see Introduction section); this study represents our response. Analysis by LCMS of LY 354,740 and LY 379,268 used in this study revealed the correct molecular mass for these compounds. Both LY 354,740 and LY 379,268 exhibited potent agonist activity for mGluR₂ in the ³⁵S-GTPγS assay. Functionally, neither compound displayed antagonist activity in the GTPγS assay with recombinant D₂. At concentrations up to 10 μM, both compounds failed to displace [³H]-raclopride, [³H]-PHNO, or [³H]-domperidone in filter-binding assays under isotonic (120 mM NaCl or N-methyl glucamine) or low-ionic strength (no NaCl or N-methyl glucamine) conditions. Some displacement of [³H]-domperidone (20-40%) was observed at 30 μM of LY 354,740 under low-ionic strength and under isotonic conditions in the absence of NaCl. No displacement of [³H]-domperidone was detected in a two site model at lower (<100 nM) concentrations of either compound. Moreover, no D₂ activity was observed for LY 354,740 or LY 379,268 in the CellKey™ (cellular dielectric spectroscopy) assay. In this communication, we discuss the possible reasons for differences in our study and the previously published work and implications of these studies for mechanisms of antipsychotic action.
P0 protein is required for and can induce formation of schmidt-lantermann incisures in myelin internodes.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2008

Axons in the PNS and CNS are ensheathed by multiple layers of tightly compacted myelin membranes. A series of cytoplasmic channels connect outer and inner margins of PNS, but not CNS, myelin internodes. Membranes of these Schmidt-Lantermann (S-L) incisures contain the myelin-associated glycoprotein (MAG) but not P(0) or proteolipid protein (PLP), the structural proteins of compact PNS (P(0)) and CNS (PLP) myelin. We show here that incisures are present in MAG-null and absent from P(0)-null PNS internodes. To test the possibility that P(0) regulates incisure formation, we replaced PLP with P(0) in CNS myelin. S-L incisures formed in P(0)-CNS myelin internodes. Furthermore, axoplasm ensheathed by 65% of the CNS incisures examined by electron microscopy had focal accumulations of organelles, indicating that these CNS incisures disrupt axonal transport. These data support the hypotheses that P(0) protein is required for and can induce S-L incisures and that P(0)-induced CNS incisures can be detrimental to axonal function.
Abnormal excitability and episodic low-frequency oscillations in the cerebral cortex of the tottering mouse.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2015

The Ca(2+) channelopathies caused by mutations of the CACNA1A gene that encodes the pore-forming subunit of the human Cav2.1 (P/Q-type) voltage-gated Ca(2+) channel include episodic ataxia type 2 (EA2). Although, in EA2 the emphasis has been on cerebellar dysfunction, patients also exhibit episodic, nonmotoric abnormalities involving the cerebral cortex. This study demonstrates episodic, low-frequency oscillations (LFOs) throughout the cerebral cortex of tottering (tg/tg) mice, a widely used model of EA2. Ranging between 0.035 and 0.11 Hz, the LFOs in tg/tg mice can spontaneously develop very high power, referred to as a high-power state. The LFOs in tg/tg mice are mediated in part by neuronal activity as tetrodotoxin decreases the oscillations and cortical neuron discharge contain the same low frequencies. The high-power state involves compensatory mechanisms because acutely decreasing P/Q-type Ca(2+) channel function in either wild-type (WT) or tg/tg mice does not induce the high-power state. In contrast, blocking l-type Ca(2+) channels, known to be upregulated in tg/tg mice, reduces the high-power state. Intriguingly, basal excitatory glutamatergic neurotransmission constrains the high-power state because blocking ionotropic or metabotropic glutamate receptors results in high-power LFOs in tg/tg but not WT mice. The high-power LFOs are decreased markedly by acetazolamide and 4-aminopyridine, the primary treatments for EA2, suggesting disease relevance. Together, these results demonstrate that the high-power LFOs in the tg/tg cerebral cortex represent a highly abnormal excitability state that may underlie noncerebellar symptoms that characterize CACNA1A mutations.
Cryptic asymptomatic parasellar high signal on time-of-flight MR angiography: how to resolve the clinical conundrum.
Neuroradiology, 2020

Hyperintense parasellar signal on time-of-flight MR angiography (TOF-MRA) in asymptomatic patients may be due to a variety of nonpathological causes and mimic parasellar high flow signal in pathological arteriovenous shunts at the cavernous sinus (CSAVS). This creates a clinical conundrum between diagnosing an aggressive yet asymptomatic CSAVS subtype against exposing patients without CSAVS to potential complications of an invasive angiographic evaluation. We reviewed common nonpathological causes of hyperintense parasellar signal and contrast their imaging features against those of pathological CSAVS and proposed a systemic approach to resolve such conundrum.
Mental Fatigue after Mild Traumatic Brain Injury in Relation to Cognitive Tests and Brain Imaging Methods.
International journal of environmental research and public health, 2021

Most people recover within months after a mild traumatic brain injury (TBI) or concussion, but some will suffer from long-term fatigue with a reduced quality of life and the inability to maintain their employment status or education. For many people, mental fatigue is one of the most distressing and long-lasting symptoms following an mTBI. No efficient treatment options can be offered. The best method for measuring fatigue today is with fatigue self-assessment scales, there being no objective clinical tests available for mental fatigue. The aim here is to provide a narrative review and identify fatigue in relation to cognitive tests and brain imaging methods. Suggestions for future research are presented.
Additional Attachment of the Semitendinosus and Gracilis Muscles to the Crural Fascia: A Review and Case Illustration.
Cureus, 2018

The semitendinosus and gracilis muscles insert primarily onto the superior medial aspect of the tibia. These tendons can be harvested for anterior cruciate ligament reconstruction, and knowledge of their accessory attachments is important for the success of such harvesting procedures. Here, we present a case illustration and review of the attachment of these muscles into the crural fascia (deep fascia of the leg), which is often an underappreciated insertion site.
Monitoring Training Load in Handcycling: A Case Study.
Journal of strength and conditioning research, 2017

Zeller, S, Abel, T, and Strueder, HK. Monitoring training load in handcycling: a case study. J Strength Cond Res 31(11): 3094-3100, 2017-The aim of this study was to analyze the training intensity distribution (TID) and the total training load (TTL) for the first time in handcycling of a multiple female Paralympic medalist (lesion level: L2-3 incomplete, ASIA C, classification: WH5). This study focuses on the preparation and the competitive period of the 2015 season. The athlete completed 194 handcycling training sessions in a time of 433:53 hours, covering a total distance of 10.190 km. An average training week consisted of 9:38 ± 4:50 hours of training during 4.3 ± 1.5 training sessions. Training was categorized according to the 3-zone intensity scale (zone 1: below blood lactate levels of 2 mmol·L; zone 2: between 2 mmol·L and 4 mmol·L; and zone 3: above 4 mmol·L). The average TID during the observation was 71.6 ± 14.9% in zone 1, 15.2 ± 8.0% in zone 2, and 13.1 ± 5.5% in zone 3. The analysis of TID throughout the season demonstrates a tendency toward a greater volume in zone 2 than the recommendations in the literature. The mean TTL throughout the season was 804 ± 399 arbitrary units. During the investigation, the performance capacity in the incremental exercise test analog to 4 mmol·L increased by 19% (150-181 W), whereas the peak power output improved by 22% (180-200 W). Currently, no general guideline for the TTL and TID in paraplegic endurance athletes can be given.
Sundowning syndrome in aging and dementia: research in mouse models.
Experimental neurology, 2013

Both normal aging and dementia are associated with altered circadian regulation of physiology and behavior. Elderly individuals and dementia patients commonly experience disrupted sleep-wake cycles, which may lead to psychomotor agitation, confusion, and wandering. These behaviors are disruptive to both patients and caregivers. Sundowning syndrome, which encompasses many of these behaviors, is characterized by a temporal pattern in the severity of symptoms, usually expressed as worse during the late afternoon or evening. Other than antipsychotic medications, off-label medications, and restraint, few treatment options are available. The aim of this paper is to review mouse studies of circadian behavioral disturbances relevant to sundowning, in order to determine potential models for studying the mechanisms of sundowning syndrome. The emergence of a useful mouse model should facilitate the development of novel therapeutic approaches.
Developmental exposure to a serotonin agonist produces subsequent behavioral and neurochemical changes in the adult male prairie vole.
Physiology & behavior, 2012

Autistic spectrum disorders (ASDs) are classified as pervasive developmental disorders characterized by abnormalities in various cognitive and behavioral functions. Although exact underlying causes are still unknown, nearly 30% of autistic patients show elevated blood levels of serotonin (5-HT) and, therefore, various genetic and environmental factors that are known to elevate 5-HT levels may play a role in the development of ASDs. In the present study, we used the socially monogamous male prairie vole (Microtus ochrogaster) as an animal model to examine the effects of perinatal exposure to 5-methoxytryptamine (5-MT), a non-selective serotonin agonist, on subsequent behavioral and neurochemical changes in the brain. 5-MT treated males showed a decrease in affiliation and an increase in anxiety-related behavior, as well as a decrease in the density of 5-HT immunoreactive (ir) fibers in the amygdala and oxytocin-ir and vasopressin-ir cells in the paraventricular nucleus of the hypothalamus, compared to saline treated controls. These data indicate that exposure to 5-HT during early development can induce abnormalities in various neurochemical systems which, in turn, may underlie deficits in social and anxiety-related behaviors. In addition, these data will help to establish the prairie vole model to study the neurobiological underpinnings of complex neuropsychiatric disorders such as ASDs.
Dissecting spatial knowledge from spatial choice by hippocampal NMDA receptor deletion.
Nature neuroscience, 2012

Hippocampal NMDA receptors (NMDARs) and NMDAR-dependent synaptic plasticity are widely considered crucial substrates of long-term spatial memory, although their precise role remains uncertain. Here we show that Grin1(ΔDGCA1) mice, lacking GluN1 and hence NMDARs in all dentate gyrus and dorsal CA1 principal cells, acquired the spatial reference memory water maze task as well as controls, despite impairments on the spatial reference memory radial maze task. When we ran a spatial discrimination water maze task using two visually identical beacons, Grin1(ΔDGCA1) mice were impaired at using spatial information to inhibit selecting the decoy beacon, despite knowing the platform's actual spatial location. This failure could suffice to impair radial maze performance despite spatial memory itself being normal. Thus, these hippocampal NMDARs are not essential for encoding or storing long-term, associative spatial memories. Instead, we demonstrate an important function of the hippocampus in using spatial knowledge to select between alternative responses that arise from competing or overlapping memories.
Quantifying the Test-Retest Reliability of Magnetoencephalography Resting-State Functional Connectivity.
Brain connectivity, 2016

The coordinated activity of the resting-state brain can be evaluated with magnetoencephalography (MEG) for distinct brain rhythms by performing source reconstruction to estimate the activities of target brain regions and employing one of the many existent functional connectivity (FC) algorithms. Although this procedure has been applied in a great amount of studies both with healthy and pathological populations, the reliability of such FC estimates is unknown, and this impairs the use of resting-state MEG FC at the individual level. In this study, the test-retest reliability of MEG resting FC was evaluated by exploring both within- and between-subject variability in FC in 16 healthy subjects who underwent three resting-state MEG scans. FC was computed after beamforming source reconstruction with four popular FC metrics: phase-locking value (PLV), phase lag index (PLI), direct envelope correlation (d-ecor), and envelope correlation with leakage correction (lc-ecor). Then, test-restest reliability and within- and between-subject agreement were evaluated with the intraclass correlation coefficient (ICC) and Kendall's W, respectively. Reliability was found to depend on the FC metric, the frequency band, and the specific link. As a general trend, greater test-retest reliability was found for PLV in theta to gamma, and for lc-ecor and d-ecor in beta. Further inspection of the ICC distribution revealed that volume conduction effects could be contributing to high ICC in PLV and d-ecor. In addition, stronger links were found to be more reliable. Overall, this encourages the further use of resting-state MEG FC for individual-level studies, especially with PLV or envelope correlation metrics.
Muscle MRI of classic infantile pompe patients: Fatty substitution and edema-like changes.
Muscle & nerve, 2017

The aim of this study was to evaluate the muscle MRI pattern of 9 patients (median age: 6.5 ± 2.74 years) affected by classic infantile-onset Pompe disease who were treated with enzyme replacement therapy.