rudyvdbrink/CitationDatabase huggingface dataset:
Different orientation tuning of near- and far-surround suppression in macaque primary visual cortex mirrors their tuning in human perception.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013

In primary visual cortex (V1), neuronal responses to stimuli inside the receptive field (RF) are usually suppressed by stimuli in the RF surround. This suppression is orientation specific. Similarly, in human vision surround stimuli can suppress perceived contrast of a central stimulus in an orientation-dependent manner. The surround consists of two regions likely generated by different circuits: a near-surround generated predominantly by geniculocortical and intra-V1 horizontal connections, and a far-surround generated exclusively by interareal feedback. Using stimuli confined to the near- or far-surround of V1 neurons, and similar stimuli in human psychophysics, we find that near-surround suppression is more sharply orientation tuned than far-surround suppression in both macaque V1 and human perception. These results point to a similarity between surround suppression in macaque V1 and human vision, and suggest that feedback circuits are less orientation biased than horizontal circuits. We find the sharpest tuning of near-surround suppression in V1 layers (3, 4B, 4Cα) with patterned and orientation-specific horizontal connections. Sharpest tuning of far-surround suppression occurs in layer 4B, suggesting greater orientation specificity of feedback to this layer. Different orientation tuning of near- and far-surround suppression may reflect a statistical bias in natural images, whereby nearby edges have higher probability than distant edges of being co-oriented and belonging to the same contour. Surround suppression would, thus, increase the coding efficiency of frequently co-occurring contours and the saliency of less frequent ones. Such saliency increase can help detect small orientation differences in nearby edges (for contour completion), but large orientation differences in distant edges (for directing saccades/attention).
Sustained Release of Poorly Water-Soluble Drug from Hydrophilic Polymeric Film Sandwiched Between Hydrophobic Layers.
AAPS PharmSciTech, 2018

This proof-of-concept study explores the feasibility of using a drug-loaded hydrophilic polymeric layer sandwiched between two hydrophobic layers for improving film drug load while achieving sustained release of poorly water-soluble drug. Such films having total thickness in range ~ 146-250 μm were prepared by slurry-based casting using hydrophilic hydroxypropyl methylcellulose (HPMC) as matrix layer containing fenofibrate (FNB) as the model drug, encased between two very thin rate-limiting layers of 10 μm each of hydrophobic poly-ɛ-caprolactone (PCL). Film precursor slurry consisted of HPMC with plasticizer and water along with micronized FNB powders, which were dry-coated with hydrophilic silica. Characterization techniques demonstrated the presence of homogeneously dispersed crystalline FNB in films. The films are very thin and hence two-dimensional; hence, average drug load per unit area in range ~ 5 to ~ 9 mg/cm
Chronic Insomnia in Patients With Parkinson Disease: Which Associated Factors Are Relevant?
Journal of geriatric psychiatry and neurology, 2020

Insomnia complaints are frequent in Parkinson disease (PD), affecting up to 55% of patients. Factors related to insomnia in PD are multifactorial and may be associated with the degenerative process of the disease, comorbidities related to aging, and medication use. The aim of this study is to determine the factors associated with the presence of chronic insomnia in patients with PD.
Variations in Dysbindin-1 are associated with cognitive response to antipsychotic drug treatment.
Nature communications, 2018

Antipsychotics are the most widely used medications for the treatment of schizophrenia spectrum disorders. While such drugs generally ameliorate positive symptoms, clinical responses are highly variable in terms of negative symptoms and cognitive impairments. However, predictors of individual responses have been elusive. Here, we report a pharmacogenetic interaction related to a core cognitive dysfunction in patients with schizophrenia. We show that genetic variations reducing dysbindin-1 expression can identify individuals whose executive functions respond better to antipsychotic drugs, both in humans and in mice. Multilevel ex vivo and in vivo analyses in postmortem human brains and genetically modified mice demonstrate that such interaction between antipsychotics and dysbindin-1 is mediated by an imbalance between the short and long isoforms of dopamine D2 receptors, leading to enhanced presynaptic D2 function within the prefrontal cortex. These findings reveal one of the pharmacodynamic mechanisms underlying individual cognitive response to treatment in patients with schizophrenia, suggesting a potential approach for improving the use of antipsychotic drugs.
Applying openEHR's Guideline Definition Language to the SITS international stroke treatment registry: a European retrospective observational study.
BMC medical informatics and decision making, 2017

Interoperability standards intend to standardise health information, clinical practice guidelines intend to standardise care procedures, and patient data registries are vital for monitoring quality of care and for clinical research. This study combines all three: it uses interoperability specifications to model guideline knowledge and applies the result to registry data.
Serines 13 and 16 are critical determinants of full-length human mutant huntingtin induced disease pathogenesis in HD mice.
Neuron, 2009

The N-terminal 17 amino acids of huntingtin (NT17) can be phosphorylated on serines 13 and 16; however, the significance of these modifications in Huntington's disease pathogenesis remains unknown. In this study, we developed BAC transgenic mice expressing full-length mutant huntingtin (fl-mhtt) with serines 13 and 16 mutated to either aspartate (phosphomimetic or SD) or alanine (phosphoresistant or SA). Both mutant proteins preserve the essential function of huntingtin in rescuing knockout mouse phenotypes. However, fl-mhtt-induced disease pathogenesis, including motor and psychiatric-like behavioral deficits, mhtt aggregation, and selective neurodegeneration are abolished in SD but preserved in SA mice. Moreover, modification of these serines in expanded repeat huntingtin peptides modulates aggregation and amyloid fibril formation in vitro. Together, our findings demonstrate that serines 13 and 16 are critical determinants of fl-mhtt-induced disease pathogenesis in vivo, supporting the targeting of huntingtin NT17 domain and its modifications in HD therapy.
Alphaviruses: Semliki forest virus and Sindbis virus vectors for gene transfer into neurons.
Current protocols in neuroscience, 2011

Alphaviral vectors based on Semliki Forest virus and Sindbis virus infect many host cell types, causing rapid and high-level transgene expression. In the CNS, Semliki Forest virus and Sindbis virus exhibit an outstanding preference for neurons rather than glial cells, compared to other viruses. Generation of high-titer virus stocks is rapid (less than two days) and typically requires biosafety level 1 or 2 containment. Wild-type vectors are cytotoxic, permitting short-term transgene expression. However, mutant vectors with decreased cytotoxicity, to prolong host cell survival, have been developed. They also increase transgene expression and cellular co-infection, permitting heteromeric protein expression in individual cells. In addition, mutants with temperature-dependent control of transgene expression and altered host cell preference to target interneurons and astrocytes rather than principal neurons are available. Other alphavirus vectors based on Venezuelan equine encephalitis and Eastern equine encephalitis virus replicons have been engineered, too. Alphavirus vectors have been successfully used not only in neuroscience, but also for other applications including drug discovery, structural biology, vaccine development, and cancer therapy.
The core sequence of PIF competes for insulin/amyloid β in insulin degrading enzyme: potential treatment for Alzheimer's disease.
Oncotarget, 2018

The central pathological feature of Alzheimer's disease (AD) is the sequential proteolytic processing of amyloid precursor protein (APP) to amyloid-β peptides (Aβ) agglomeration. The clearance of Aβ may be induced by the large zinc-binding protease insulin degrading enzyme (IDE). IDE is the common link between AD and Type II diabetes as insulin is an IDE target as well. Not surprisingly, the search for safe and effective drugs modulating IDE is ongoing. A new pregnancy derived peptide, PreImplantation Factor (PIF), inhibits neuro-inflammation and crosses the blood-brain-barrier. Importantly, we report that the (R
Astroglial connexin immunoreactivity is specifically altered at β-amyloid plaques in β-amyloid precursor protein/presenilin1 mice.
Neuroscience, 2010

Activation of astrocytes surrounding amyloid plaques is a hallmark of Alzheimer disease (AD) with consequences yet poorly understood. Astrocytes are characterized by a high level of intercellular communication mediated by two gap-junction forming proteins, connexin-43 and connexin-30. As astroglial connexins (Cxs) are involved in neuronal dysfunctions and death, we have analyzed their expression pattern in two murine models of AD, that is two different β-amyloid precursor protein (APP)/presenilin1(PS1) mice, using western blot and immunohistochemistry analyzed in confocal microscopy. In young mice at 2 months, before the emergence of β-amyloid (Aβ) deposits, the distribution of both Cxs was similar to that of control mice. In older animals≥4 months, local modifications in connexin immunostaining pattern were observed in the microenvironment of dense core Aβ plaques. In a majority of plaques, an elevated immunoreactivity was detected for both Cxs contributing to the overall increase in connexin expression detected in 18 month old APP/PS1 mice. Activated microglial cells did not contribute to the elevated connexin immunoreactivity that was concentrated in astroglial processes infiltrating the plaques. In a small proportion of plaques (≤15%) a depletion of immunoreactive connexin puncta was also found. As astroglial Cxs participate in neuroglial interactions, their remodeling may contribute to neuronal alterations observed at the periplaque area.
Two-photon imaging of calcium in virally transfected striate cortical neurons of behaving monkey.
PloS one, 2010

Two-photon scanning microscopy has advanced our understanding of neural signaling in non-mammalian species and mammals. Various developments are needed to perform two-photon scanning microscopy over prolonged periods in non-human primates performing a behavioral task. In striate cortex in two macaque monkeys, cortical neurons were transfected with a genetically encoded fluorescent calcium sensor, memTNXL, using AAV1 as a viral vector. By constructing an extremely rigid and stable apparatus holding both the two-photon scanning microscope and the monkey's head, single neurons were imaged at high magnification for prolonged periods with minimal motion artifacts for up to ten months. Structural images of single neurons were obtained at high magnification. Changes in calcium during visual stimulation were measured as the monkeys performed a fixation task. Overall, functional responses and orientation tuning curves were obtained in 18.8% of the 234 labeled and imaged neurons. This demonstrated that the two-photon scanning microscopy can be successfully obtained in behaving primates.
Verbal memory after temporal lobe epilepsy surgery in children: Do only mesial structures matter?
Epilepsia, 2017

Previous findings have been mixed regarding verbal memory outcome after left temporal lobectomy in children, and there are few studies comparing verbal memory change after lateral versus mesial temporal lobe resections. We compared verbal memory outcome associated with sparing or including the mesial structures in children who underwent left or right temporal lobe resection. We also investigated predictors of postsurgical verbal memory change.
Spatial precision of population activity in primate area MT.
Journal of neurophysiology, 2015

The middle temporal (MT) area is a cortical area integral to the "where" pathway of primate visual processing, signaling the movement and position of objects in the visual world. The receptive field of a single MT neuron is sensitive to the direction of object motion but is too large to signal precise spatial position. Here, we asked if the activity of MT neurons could be combined to support the high spatial precision required in the where pathway. With the use of multielectrode arrays, we recorded simultaneously neural activity at 24-65 sites in area MT of anesthetized marmoset monkeys. We found that although individual receptive fields span more than 5° of the visual field, the combined population response can support fine spatial discriminations (<0.2°). This is because receptive fields at neighboring sites overlapped substantially, and changes in spatial position are therefore projected onto neural activity in a large ensemble of neurons. This fine spatial discrimination is supported primarily by neurons with receptive fields flanking the target locations. Population performance is degraded (by 13-22%) when correlations in neural activity are ignored, further reflecting the contribution of population neural interactions. Our results show that population signals can provide high spatial precision despite large receptive fields, allowing area MT to represent both the motion and the position of objects in the visual world.
Inhibition of L-Type Ca
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2017

Loss of dopaminergic (DA) neurons leads to Parkinson's disease; however, the mechanism(s) for the vulnerability of DA neurons is(are) not fully understood. We demonstrate that TRPC1 regulates the L-type Ca
Tracing goes viral: Viruses that introduce expression of fluorescent proteins in chemically-specific neurons.
Journal of neuroscience methods, 2021

Over the last century, there has been great progress in understanding how the brain works. In particular, the last two decades have been crucial in gaining more awareness over the complex functioning of neurotransmitter systems. The use of viral vectors in neuroscience has been pivotal for such development. Exploiting the properties of viral particles, modifying them according to the research needs, and making them target chemically-specific neurons, techniques such as optogenetics and chemogenetics have been developed, which could lead to a giant step toward gene therapy for brain disorders. In this review, we aim to provide an overview of some of the most widely used viral techniques in neuroscience. We will discuss advantages and disadvantages of these methods. In particular, attention is dedicated to the pivotal role played by the introduction of adeno-associated virus and the retrograde tracer canine-associated-2 Cre virus in order to achieve optimal visualization, and interrogation, of chemically-specific neuronal populations and their projections.
Calibrated FMRI.
NeuroImage, 2012

Functional magnetic resonance imaging with blood oxygenation level-dependent (BOLD) contrast has had a tremendous influence on human neuroscience in the last twenty years, providing a non-invasive means of mapping human brain function with often exquisite sensitivity and detail. However the BOLD method remains a largely qualitative approach. While the same can be said of anatomic MRI techniques, whose clinical and research impact has not been diminished in the slightest by the lack of a quantitative interpretation of their image intensity, the quantitative expression of BOLD responses as a percent of the baseline T2*- weighted signal has been viewed as necessary since the earliest days of fMRI. Calibrated MRI attempts to dissociate changes in oxygen metabolism from changes in blood flow and volume, the latter three quantities contributing jointly to determine the physiologically ambiguous percent BOLD change. This dissociation is typically performed using a "calibration" procedure in which subjects inhale a gas mixture containing small amounts of carbon dioxide or enriched oxygen to produce changes in blood flow and BOLD signal which can be measured under well-defined hemodynamic conditions. The outcome is a calibration parameter M which can then be substituted into an expression providing the fractional change in oxygen metabolism given changes in blood flow and BOLD signal during a task. The latest generation of calibrated MRI methods goes beyond fractional changes to provide absolute quantification of resting-state oxygen consumption in micromolar units, in addition to absolute measures of evoked metabolic response. This review discusses the history, challenges, and advances in calibrated MRI, from the personal perspective of the author.
TYPE 2 DIABETES IN PATIENTS WITH MAJOR DEPRESSIVE DISORDER: A META-ANALYSIS OF PREVALENCE ESTIMATES AND PREDICTORS.
Depression and anxiety, 2015

Patients with depression may be at increased risk of type 2 diabetes mellitus (T2DM), which is a risk factor for cardiovascular diseases and premature mortality. We aimed to clarify the prevalence and predictors of T2DM in patients with major depressive disorder (MDD) and where possible compare the prevalence of T2DM in those with MDD versus general population controls.
Delayed administration of a PTEN inhibitor BPV improves functional recovery after experimental stroke.
Neuroscience, 2013

Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) inhibitors administered prior to or immediately after experimental stroke confer acute neuroprotection. However, it remains unclear if delayed treatment with a PTEN inhibitor improves long-term functional recovery after stroke. We addressed the issue in this study. Adult male mice were subjected to 1h of middle cerebral artery occlusion (MCAO) followed by treatment with a well-established PTEN inhibitor BPV or saline daily for 14 days, starting at 24h after MCAO. Functional recovery was assessed with behavioral tests and acute infarct volumes were analyzed histologically. Delayed BPV treatment did not reduce infarction during the acute phase, but significantly improved long-term functional recovery after MCAO. Since PTEN is a critical intrinsic inhibitory factor in axonal regeneration, we further examined BPV effects on axonal densities following MCAO using bielschowsky silver staining and immunohistochemistry with antibodies against myelin basic protein. Delayed BPV treatment significantly increased axon densities in the ischemic brain at 14 days after MCAO. Moreover, PTEN expression persistently remained high in the ischemic brain over 14 days after MCAO, and BPV treatment increased post-ischemic activation of Akt and mTOR in the ischemic brain. Akt and mTOR activation are the well-established cascades downstream to PTEN inhibition and have been shown to contribute to post-injury axonal regrowth in response to PTEN inhibition. Consistently, in an in vitro neuronal ischemia model, BPV enhanced axonal outgrowth of primary cortical neurons after oxygen-glucose deprivation and the enhancing effects were abolished by Akt/mTOR inhibition. In conclusion, delayed BPV treatment improved functional recovery from experimental stroke possibly via enhancing axonal growth and Akt/mTOR activation contributed to BPV-enhanced post-stroke axon growth.
Altered volume and hemispheric asymmetry of the superficial cortical layers in the schizophrenia planum temporale.
The European journal of neuroscience, 2009

In vivo structural MRI studies in schizophrenia auditory cerebral cortex have reported smaller volumes and, less consistently, have reported altered hemispheric asymmetry of volumes. We used autopsy brains from 19 schizophrenia and 18 nonpsychiatric male subjects to measure the volume asymmetry of the planum temporal (PT). We then used the most recently autopsied 11 schizophrenia and 10 nonpsychiatric brains to measure the widths and fractional volumes of the upper (I-III) and lower (IV-VI) layers. Measurements of whole PT gray matter volumes did not show significant changes in schizophrenia. Nevertheless, laminar volume measurements revealed that the upper layers of the PT comprise a smaller fraction of the total cortex in schizophrenia than in nonpsychiatric brains. Subdivision of the PT showed that this change was especially prominent caudally, beyond Heschl's gyrus, whereas similar but less pronounced changes were found in the rostral PT and Heschl's gyrus. Complementary measures of laminar widths showed that the altered fractional volume in the caudal left PT was due mainly to approximately 8% thinner upper layers. However, the caudal right PT had a different profile, with thicker lower layers and comparatively unchanged upper layers. Thus, in the present study, laminar measurements provided a more sensitive method for detecting changes than measurement of whole PT volumes. Besides findings in schizophrenia, our cortical width measurements revealed normal hemispheric asymmetries consistent with previous reports. In schizophrenia, the thinner upper layers of the caudal PT suggest disrupted corticocortical processing, possibly affecting the multisensory integration and phonetic processing of this region.
Remote assessment of disease and relapse in major depressive disorder (RADAR-MDD): a multi-centre prospective cohort study protocol.
BMC psychiatry, 2019

There is a growing body of literature highlighting the role that wearable and mobile remote measurement technology (RMT) can play in measuring symptoms of major depressive disorder (MDD). Outcomes assessment typically relies on self-report, which can be biased by dysfunctional perceptions and current symptom severity. Predictors of depressive relapse include disrupted sleep, reduced sociability, physical activity, changes in mood, prosody and cognitive function, which are all amenable to measurement via RMT. This study aims to: 1) determine the usability, feasibility and acceptability of RMT; 2) improve and refine clinical outcome measurement using RMT to identify current clinical state; 3) determine whether RMT can provide information predictive of depressive relapse and other critical outcomes.