rudyvdbrink/CitationDatabase huggingface dataset:
Someone's lurking in the dark: The role of state anxiety on attention deployment to threat-related stimuli.
Biological psychology, 2017

Anxious states can alter attention, impairing goal-directed processing in favor of bottom-up capture. However, it is still unclear whether anxiety-related biases already influence the earliest stage of information processing, especially for unattended threat-related stimuli. Here we tested, using EEG, if the amplitude of the first component of the Visual Evoked Potentials (C1) to simple visual stimuli (either neutral or threat-related) varied depending on anxiety level and task demands. Results showed that anxiety altered goal-directed processing, reducing P300 amplitude to target stimuli, while it increased the C1 to irrelevant stimuli, regardless of their emotional content. Moreover, enhanced load at fixation reduced the amplitude of this component to neutral stimuli, but this early filtering effect was abolished by state anxiety. These results shed light on the time-course of attentional biases in anxiety, confirming that this transient state can enhance bottom-up capture as early as in V1, at the expense of goal-directed processing.
Human pluripotent stem cells as tools for neurodegenerative and neurodevelopmental disease modeling and drug discovery.
Expert opinion on drug discovery, 2015

Although intensive efforts have been made, effective treatments for neurodegenerative and neurodevelopmental diseases have not been yet discovered. Possible reasons for this include the lack of appropriate disease models of human neurons and a limited understanding of the etiological and neurobiological mechanisms. Recent advances in pluripotent stem cell (PSC) research have now opened the path to the generation of induced pluripotent stem cells (iPSCs) starting from somatic cells, thus offering an unlimited source of patient-specific disease-relevant neuronal cells.
Dissociation between line bisection and mental-number-line bisection in healthy adults.
Neuropsychologia, 2015

Healthy adults bisect visual horizontal lines slightly to the left of their true center. This bias has been termed "pseudoneglect" and is considered to reflect right hemisphere dominance in the orienting of spatial attention. A previous investigation reported a positive correlation between pseudoneglect and a corresponding negative bias towards numbers lower than the true midpoint, i.e. supposedly to the left of the midpoint, during the mental bisection of number intervals that were defined by two visual arabic digits presented one to the left and one to the right of a horizontal line (Longo and Lourenco, 2007, Neuropsychologia, 45, 7, 1400-1407). Here, studying a sample of 60 healthy participants we verified whether this correlation still holds when the endpoints of number intervals are defined verbally, i.e. with no visual-spatial cues suggesting their left-to-right arrangement. Participants bisected horizontal lines (2 cm, 10 cm and 20 cm), short number intervals (3-, 5-, 7- and 9-unit) and large number intervals (16-, 24-, 32-, 40-, 48-, 56-, and 64-unit). Pseudoneglect was observed both in line and number interval bisection, confirming the results of Longo and Lourenco (2007). Nonetheless, the study of correlations between bisection biases averaged across different line and number intervals lengths and between all possible pairings of line and number interval lengths revealed no significant or systematic pattern. During line bisection pseudoneglect increased as a function of line length while with short number intervals pseudoneglect decreased and turned into an opposite positive bias as a function of interval length. With large number intervals no linear relationship was present between bisection bias and interval length and, as in Longo and Lourenco (2007), the higher was the starting point of the number interval the larger was pseudoneglect. These results show that verbally defined number intervals are not mentally inspected with the same mechanisms that are engaged by the bisection of horizontal visual lines. This suggests that number intervals are not inherently arranged along the mental equivalent of a left-to-right oriented horizontal line. This spatial representation seems rather adopted when, as in the case of the SNARC task, "left" vs. "right" codes must be used for the selection of responses associated with numbers or when, as in the case of Longo and Lourenco (2007), the numerical material to be processed is arranged in left-to-right order.
Doxorubicin and cyclophosphamide induce cognitive dysfunction and activate the ERK and AKT signaling pathways.
Behavioural brain research, 2015

Chemotherapy is associated with long-term cognitive deficits in breast cancer survivors. Studies suggest that these impairments result in the loss of cognitive reserve and/or induce a premature aging of the brain. This study has been aimed to determine the potential underlying mechanisms that induce cognitive impairments by chemotherapeutic agents commonly used in breast cancer. Intact and ovariectomized (OVX) female rats were treated intravenously with either saline or a combination of cyclophosphamide (40 mg/kg) and doxorubicin (4 mg/kg). All subjects were tested for anxiety, locomotor activity, working, visual and spatial memory consecutively. Although anxiety and visual memory were not affected, chemotherapy significantly decreased locomotor activity and impaired working and spatial memory in female rats, independent of their hormonal status. The cognitive deficits observed are hippocampal dependent. Therefore, as a first step to identity the potential signaling pathways involved in this cognitive dysfunction, the protein levels of extracellular signal-regulated kinase 1/2 (Erk1/2), Akt (neuroprotectant) BDNF and (structural protein) PSD95 in hippocampal lysates were measured. Erk1/2 and Akt pathways are known to modulate synaptic plasticity, neuronal survival, aging and cancer. We found an increased activation of Erk1/2 and Akt as well as an increase in the protein levels of PSD95 in OVX female rodents. However, OVX females had a higher overall BDNF level, independent of chemotherapy. These studies provide additional evidence that commonly used chemotherapeutic agents affect cognitive function and impact synaptic plasticity/aging molecules which may be part of the underlying biology explaining cognitive change and can be potential therapeutic targets.
In idiopathic cervical dystonia movement direction is inaccurate when reaching in unusual workspaces.
Parkinsonism & related disorders, 2011

When reaching movements are performed in an unusual area of work, normal subjects produce a rightward directional error. This has been considered to be caused by an impaired representation of limb configuration, which hampers the actual movement vector. Motor programming has been found to be impaired in dystonia. To understand how patients affected by idiopathic cervical dystonia (CD) perform reaching movements in an unusual area of work, we investigated 10 CD patients and 10 age-matched controls. Reaching movements on a digitized tablet were recorded both with the right arm aligned to the midline (central position) and shifted to the right (lateral position), but hidden from view. While differences in the main kinematic parameters were not affected by the position both in patients and controls, the directional error was significantly increased in dystonic patients for the lateral position. We hypothesise that an impaired integration of proprioceptive information with the motor output and egocentric spatial perception could be responsible for a greater error in spatial representation of hand location and consequently to an increased directional error in dystonic patients.
Upper- and lower-limb amputees show reduced levels of eeriness for images of prosthetic hands.
Psychonomic bulletin & review, 2019

The "uncanny phenomenon" describes the feeling of unease associated with seeing an image that is close to appearing human. Prosthetic hands in particular are well known to induce this effect. Little is known, however, about this phenomenon from the viewpoint of prosthesis users. We studied perceptions of eeriness and human-likeness for images of different types of mechanical, cosmetic, and anatomic hands in upper-limb prosthesis users (n=9), lower-limb prosthesis users (n=10), prosthetists (n=16), control participants with no prosthetic training (n=20), and control participants who were trained to use a myoelectric prosthetic hand simulator (n=23). Both the upper- and lower-limb prosthesis user groups showed a reduced uncanny phenomenon (i.e., significantly lower levels of eeriness) for cosmetic prosthetic hands compared to the other groups, with no concomitant reduction in how these stimuli were rated in terms of human-likeness. However, a similar effect was found neither for prosthetists with prolonged visual experience of prosthetic hands nor for the group with short-term training with the simulator. These findings in the prosthesis users therefore seem likely to be related to limb absence or prolonged experience with prostheses.
Distentangling the systems contributing to changes in learning during adolescence.
Developmental cognitive neuroscience, 2020

Multiple neurocognitive systems contribute simultaneously to learning. For example, dopamine and basal ganglia (BG) systems are thought to support reinforcement learning (RL) by incrementally updating the value of choices, while the prefrontal cortex (PFC) contributes different computations, such as actively maintaining precise information in working memory (WM). It is commonly thought that WM and PFC show more protracted development than RL and BG systems, yet their contributions are rarely assessed in tandem. Here, we used a simple learning task to test how RL and WM contribute to changes in learning across adolescence. We tested 187 subjects ages 8 to 17 and 53 adults (25-30). Participants learned stimulus-action associations from feedback; the learning load was varied to be within or exceed WM capacity. Participants age 8-12 learned slower than participants age 13-17, and were more sensitive to load. We used computational modeling to estimate subjects' use of WM and RL processes. Surprisingly, we found more protracted changes in RL than WM during development. RL learning rate increased with age until age 18 and WM parameters showed more subtle, gender- and puberty-dependent changes early in adolescence. These results can inform education and intervention strategies based on the developmental science of learning.
Moment-to-moment brain signal variability: a next frontier in human brain mapping?
Neuroscience and biobehavioral reviews, 2013

Neuroscientists have long observed that brain activity is naturally variable from moment-to-moment, but neuroimaging research has largely ignored the potential importance of this phenomenon. An emerging research focus on within-person brain signal variability is providing novel insights, and offering highly predictive, complementary, and even orthogonal views of brain function in relation to human lifespan development, cognitive performance, and various clinical conditions. As a result, brain signal variability is evolving as a bona fide signal of interest, and should no longer be dismissed as meaningless noise when mapping the human brain.
Dendritic integration in pyramidal neurons during network activity and disease.
Brain research bulletin, 2014

Neurons have intricate dendritic morphologies which come in an array of shapes and sizes. Not only do they give neurons their unique appearance, but dendrites also endow neurons with the ability to receive and transform synaptic inputs. We now have a wealth of information about the functioning of dendrites which suggests that the integration of synaptic inputs is highly dependent on both dendritic properties and neuronal input patterns. It has been shown that dendrites can perform non-linear processing, actively transforming synaptic input into Na(+) spikes, Ca(2+) plateau spikes and NMDA spikes. These membrane non-linearities can have a large impact on the neuronal output and have been shown to be regulated by numerous factors including synaptic inhibition. Many neuropathological diseases involve changes in how dendrites receive and package synaptic input by altering dendritic spine characteristics, ion channel expression and the inhibitory control of dendrites. This review focuses on the role of dendrites in integrating and transforming input and what goes wrong in the case of neuropathological diseases.
Treating Heel Pain in Adults: A Randomized Controlled Trial of Hard vs Modified Soft Custom Orthotics and Heel Pads.
Archives of physical medicine and rehabilitation, 2021

This study compared the effectiveness of soft vs hard orthotics in treating heel pain and plantar fasciitis in adults. It also compared the level of function after orthotic use, cost, and number of visits for orthotics and explored whether age was a factor in orthotic effectiveness.
Human in vitro systems for examining synaptic function and plasticity in the brain.
Journal of neurophysiology, 2020

The human brain shows remarkable complexity in its cellular makeup and function, which are distinct from nonhuman species, signifying the need for human-based research platforms for the study of human cellular neurophysiology and neuropathology. However, the use of adult human brain tissue for research purposes is hampered by technical, methodological, and accessibility challenges. One of the major problems is the limited number of in vitro systems that, in contrast, are readily available from rodent brain tissue. With recent advances in the optimization of protocols for adult human brain preparations, there is a significant opportunity for neuroscientists to validate their findings in human-based systems. This review addresses the methodological aspects, advantages, and disadvantages of human neuron in vitro systems, focusing on the unique properties of human neurons and synapses in neocortical microcircuits. These in vitro models provide the incomparable advantage of being a direct representation of the neurons that have formed part of the human brain until the point of recording, which cannot be replicated by animal models nor human stem-cell systems. Important distinct cellular mechanisms are observed in human neurons that may underlie the higher order cognitive abilities of the human brain. The use of human brain tissue in neuroscience research also raises important ethical, diversity, and control tissue limitations that need to be considered. Undoubtedly however, these human neuron systems provide critical information to increase the potential of translation of treatments from the laboratory to the clinic in a way animal models are failing to provide.
Facile Impedimetric Analysis of Neuronal Exosome Markers in Parkinson's Disease Diagnostics.
Analytical chemistry, 2020

The egress of α-synuclein in neuronally derived exosomes predates the clinical presentation of Parkinson's disease (PD), offering a means of developing a predictive or prognostic test. Here, we report the reagentless impedimetric assay of two internal exosome markers (α-synuclein and syntenin-1) from neuronal exosomes. Exosomes were efficiently extracted from patient sera using anti-L1CAM conjugated zwitterionic polymer-modified magnetic beads prior to lysis and analyzed by electrochemical impedance spectroscopy. The quantification of α-synuclein level across 40 clinical samples resolved statistically significant differences between PD patients and healthy controls (HC).
Synaptic abnormalities in the infralimbic cortex of a model of congenital depression.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013

Multiple lines of evidence suggest that disturbances in excitatory transmission contribute to depression. Whether these defects involve the number, size, or composition of glutamatergic contacts is unclear. This study used recently introduced procedures for fluorescence deconvolution tomography in a well-studied rat model of congenital depression to characterize excitatory synapses in layer I of infralimbic cortex, a region involved in mood disorders, and of primary somatosensory cortex. Three groups were studied: (1) rats bred for learned helplessness (cLH); (2) rats resistant to learned helplessness (cNLH); and (3) control Sprague Dawley rats. In fields within infralimbic cortex, cLH rats had the same numerical density of synapses, immunolabeled for either the postsynaptic density (PSD) marker PSD95 or the presynaptic protein synaptophysin, as controls. However, PSD95 immunolabeling intensities were substantially lower in cLH rats, as were numerical densities of synapse-sized clusters of the AMPA receptor subunit GluA1. Similar but less pronounced differences (comparable numerical densities but reduced immunolabeling intensity for PSD95) were found in the somatosensory cortex. In contrast, non-helpless rats had 25% more PSDs than either cLH or control rats without any increase in synaptophysin-labeled terminal frequency. Compared with controls, both cLH and cNLH rats had fewer GABAergic contacts. These results indicate that congenital tendencies that increase or decrease depression-like behavior differentially affect excitatory synapses.
Inhibiting cyclin-dependent kinase 5 in the nucleus accumbens enhances the expression of amphetamine-induced locomotor conditioning.
Behavioural brain research, 2014

When psychostimulant drugs like amphetamine are administered repeatedly in the presence of a contextual stimulus complex, long-lasting associations form between the unconditioned effects of the drug and the contextual stimuli. Here we assessed the role played by the proline-directed serine/threonine kinase cyclin-dependent kinase 5 (Cdk5) in the nucleus accumbens (NAcc) on the expression of the conditioned locomotion normally observed when rats are returned to a context previously paired with amphetamine. Infusing the Cdk5 inhibitor roscovitine (40nmol/0.5μl/side) into the NAcc 30-min before the test for conditioning significantly enhanced the conditioned locomotor response observed in rats previously administered amphetamine in the test environment. This effect was specific to the expression of a conditioned response as inhibiting Cdk5 produced no effect in control rats previously administered saline or previously administered amphetamine elsewhere. As inhibiting Cdk5 during exposure to amphetamine has been found to block the accrual of locomotor conditioning, the present results suggest distinct roles for NAcc Cdk5 in the induction and expression of excitatory conditioning by amphetamine.
Shared and unique neural mechanisms underlying pediatric trichotillomania and obsessive compulsive disorder.
Psychiatry research, 2021

Little is known about the neural underpinnings of pediatric trichotillomania (TTM). We examined error-related negativity (ERN)-amplitude and theta-EEG power differences among youth with TTM, OCD, and healthy controls (HC).
Assessment of a Risk Index for Suicide Attempts Among US Army Soldiers With Suicide Ideation: Analysis of Data From the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS).
JAMA network open, 2019

The Department of Veterans Affairs recently began requiring annual suicide ideation (SI) screening of all patients and additional structured questions for patients reporting SI. Related changes are under consideration at the Department of Defense. These changes will presumably lead to higher SI detection, which will require hiring additional clinical staff and/or developing a clinical decision support system to focus in-depth suicide risk assessments on patients considered high risk.
VEGF shows its attractive side at the midline.
Neuron, 2011

Vascular endothelial growth factor (VEGF) family members are best known for their powerful mitotic and angiogenic activities toward endothelial cells. Two independent studies in this issue of Neuron now provide compelling evidence that VEGF-A secreted at the CNS midline functions as an attractant for developing axons of spinal commissural neurons and contralaterally projecting retinal ganglion cells.
High-performance capillary electrophoresis for determining HIV-1 Tat protein in neurons.
PloS one, 2011

The HIV-1 protein, Tat has been implicated in AIDS pathogenesis however, the amount of circulating Tat is believed to be very low and its quantification has been difficult. We performed the quantification of Tat released from infected cells and taken up by neurons using high performance capillary electrophoresis. This is the first report to successfully measure the amount of Tat in neurons and places Tat as a key player involved in HIV-associated neurocognitive disorders.
Scale-free properties of the functional magnetic resonance imaging signal during rest and task.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011

It has been shown recently that a significant portion of brain electrical field potentials consists of scale-free dynamics. These scale-free brain dynamics contain complex spatiotemporal structures and are modulated by task performance. Here we show that the fMRI signal recorded from the human brain is also scale free; its power-law exponent differentiates between brain networks and correlates with fMRI signal variance and brain glucose metabolism. Importantly, in parallel to brain electrical field potentials, the variance and power-law exponent of the fMRI signal decrease during task activation, suggesting that the signal contains more long-range memory during rest and conversely is more efficient at online information processing during task. Remarkably, similar changes also occurred in task-deactivated brain regions, revealing the presence of an optimal dynamic range in the fMRI signal. The scale-free properties of the fMRI signal and brain electrical field potentials bespeak their respective stationarity and nonstationarity. This suggests that neurovascular coupling mechanism is likely to contain a transformation from nonstationarity to stationarity. In summary, our results demonstrate the functional relevance of scale-free properties of the fMRI signal and impose constraints on future models of neurovascular coupling.
Agonist-induced restoration of hippocampal neurogenesis and cognitive improvement in a model of cholinergic denervation.
Neuropharmacology, 2010

Loss of basal forebrain cholinergic innervation of the hippocampus and severe neuronal loss within the hippocampal CA1 region are early hallmarks of Alzheimer's disease, and are strongly correlated with cognitive status. Various therapeutic approaches involve attempts to enhance neurotransmission or to provide some level of neuroprotection for remaining cells. An alternative approach may involve the generation of new cells to replace those lost in AD. Indeed, a simple shift in the balance between cell generation and cell loss may slow disease progression and possibly even reverse existing cognitive deficits. One potential neurogenic regulator might be acetylcholine, itself, which has been shown to play a critical role in hippocampal development. Here, we report the effects of various cholinergic compounds on indices of hippocampal neurogenesis, demonstrating a significant induction following pharmacological activation of muscarinic M1 receptors, located on hippocampal progenitors in the adult brain. This is the first report that a small-molecule agonist may induce neurogenesis in the hippocampal CA1 region. Furthermore, such treatment reversed deficits in markers of neurogenesis and spatial working memory triggered by cholinergic denervation in a rodent model. This study suggests the use of small molecule, receptor agonists may represent a novel means to trigger the restoration of specific neuronal populations lost to a variety of neurodegenerative disorders, such as Parkinson's, Alzheimer's, Huntington's and Amyotrophic Lateral Sclerosis.