rudyvdbrink/CitationDatabase huggingface dataset:
Challenges for Large-Scale Cortical Interfaces.
Neuron, 2020

This Perspective examines the status of large-scale cortical interfaces through the lens of potential applications to active implants for brain-machine interfaces. Examples of research and development in a still embryonic field are discussed from a neuroengineer's perspective, touching on the design of scalable electrophysiological sensors with the ambition to access thousands of cortical points at near-cellular-level resolution. Important issues include microscale geometry of neural probes, design of implantable ultra-low-power electronics, implementation of high-data-rate wireless telemetry, and compatible device packaging-all requiring advanced solutions along a translational path for chronic human use.
Screening of Parkinsonian subtle fine-motor impairment from touchscreen typing via deep learning.
Scientific reports, 2020

Fine-motor impairment (FMI) is progressively expressed in early Parkinson's Disease (PD) patients and is now known to be evident in the immediate prodromal stage of the condition. The clinical techniques for detecting FMI may not be robust enough and here, we show that the subtle FMI of early PD patients can be effectively estimated from the analysis of natural smartphone touchscreen typing via deep learning networks, trained in stages of initialization and fine-tuning. In a validation dataset of 36,000 typing sessions from 39 subjects (17 healthy/22 PD patients with medically validated UPDRS Part III single-item scores), the proposed approach achieved values of area under the receiver operating characteristic curve (AUC) of 0.89 (95% confidence interval: 0.80-0.96) with sensitivity/specificity: 0.90/0.83. The derived estimations result in statistically significant ([Formula: see text]) correlation of 0.66/0.73/0.58 with the clinical standard UPDRS Part III items 22/23/31, respectively. Further validation analysis on 9 de novo PD patients vs. 17 healthy controls classification resulted in AUC of 0.97 (0.93-1.00) with 0.93/0.90. For 253 remote study participants, with self-reported health status providing 252.000 typing sessions via a touchscreen typing data acquisition mobile app (iPrognosis), the proposed approach predicted 0.79 AUC (0.66-0.91) with 0.76/0.71. Remote and unobtrusive screening of subtle FMI via natural smartphone usage, may assist in consolidating early and accurate diagnosis of PD.
Deciphering the natural history of SCA7 in children.
European journal of neurology, 2020

Childhood-onset autosomal dominant cerebellar ataxia type 7 (SCA7) is a severe disease which leads to premature loss of ambulation and death. Early diagnosis of SCA7 is of major importance for genetic counselling and still relies on specific genetic testing, driven by clinical expertise. However, the precise phenotype and natural history of paediatric SCA7 has not yet been fully described. Our aims were to describe the natural history of SCA7 in a large multicentric series of children of all ages, and to find correlates to variables defining this natural history.
Integrated functional neuronal network analysis of 3D silk-collagen scaffold-based mouse cortical culture.
STAR protocols, 2021

Bioengineered 3D tunable neuronal constructs are a versatile platform for studying neuronal network functions, offering numerous advantages over existing technologies and providing for the discovery of new biological insights. Functional neural networks can be evaluated using calcium imaging and quantitatively described using network science. This protocol includes instructions for fabricating protein-based composite scaffolds, 3D
Statistical computer model analysis of the reciprocal and recurrent inhibitions of the Ia-EPSP in α-motoneurons.
Neural computation, 2013

We simulate the inhibition of Ia-glutamatergic excitatory postsynaptic potential (EPSP) by preceding it with glycinergic recurrent (REN) and reciprocal (REC) inhibitory postsynaptic potentials (IPSPs). The inhibition is evaluated in the presence of voltage-dependent conductances of sodium, delayed rectifier potassium, and slow potassium in five α-motoneurons (MNs). We distribute the channels along the neuronal dendrites using, alternatively, a density function of exponential rise (ER), exponential decay (ED), or a step function (ST). We examine the change in EPSP amplitude, the rate of rise (RR), and the time integral (TI) due to inhibition. The results yield six major conclusions. First, the EPSP peak and the kinetics depending on the time interval are either amplified or depressed by the REC and REN shunting inhibitions. Second, the mean EPSP peak, its TI, and RR inhibition of ST, ER, and ED distributions turn out to be similar for analogous ranges of G. Third, for identical G, the large variations in the parameters' values can be attributed to the sodium conductance step (g(Na_step)) and the active dendritic area. We find that small g(Na_step) on a few dendrites maintains the EPSP peak, its TI, and RR inhibition similar to the passive state, but high g(Na_step) on many dendrites decrease the inhibition and sometimes generates even an excitatory effect. Fourth, the MN's input resistance does not alter the efficacy of EPSP inhibition. Fifth, the REC and REN inhibitions slightly change the EPSP peak and its RR. However, EPSP TI is depressed by the REN inhibition more than the REC inhibition. Finally, only an inhibitory effect shows up during the EPSP TI inhibition, while there are both inhibitory and excitatory impacts on the EPSP peak and its RR.
Sex-specific effects of high-fat diet on cognitive impairment in a mouse model of VCID.
FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2020

Mid-life metabolic disease (ie, obesity, diabetes, and prediabetes) causes vascular dysfunction and is a risk factor for vascular contributions to cognitive impairment and dementia (VCID), particularly in women. Using middle-aged mice, we modeled metabolic disease (obesity/prediabetes) via chronic high-fat (HF) diet and modeled VCID via unilateral common carotid artery occlusion. VCID impaired spatial memory in both sexes, but episodic-like memory in females only. HF diet caused greater weight gain and glucose intolerance in middle-aged females than males. HF diet alone impaired episodic-like memory in both sexes, but spatial memory in females only. Finally, the combination of HF diet and VCID elicited cognitive impairments in all tests, in both sexes. Sex-specific correlations were found between metabolic outcomes and memory. Notably, both visceral fat and the pro-inflammatory cytokine tumor necrosis factor alpha correlated with spatial memory deficits in middle-aged females, but not males. Overall, our data show that HF diet causes greater metabolic impairment and a wider array of cognitive deficits in middle-aged females than males. The combination of HF diet with VCID elicits deficits across multiple cognitive domains in both sexes. Our data are in line with clinical data, which shows that mid-life metabolic disease increases VCID risk, particularly in females.
Lipopolysaccharide activates microglia via neuraminidase 1 desialylation of Toll-like Receptor 4.
Journal of neurochemistry, 2020

Most cell surface receptors are sialylated, i.e. have sialic acid as the terminal residue of their sugar chains, but can be desialylated by sialidases, such as neuraminidase 1 (Neu1). Desialylation by Neu1 can activate immune cells, such as neutrophils, macrophages and monocytes. We investigated the role of Neu1 in activation of microglia using BV-2 cells (a murine microglial cell line) by cytokine ELISAs, enzyme activity assays, antibody/lectin binding and proximity labelling. We found that lipopolysaccharide (LPS) activation caused an increase in Neu1 protein on the cell surface, and an increase in surface sialidase activity that was prevented by Neu1 knockdown. Moreover, LPS induced interleukin 6 (IL-6) and MCP-1 release, which was reduced by Neu1 knockdown and increased by Neu1 over-expression. Neu1 knockdown also prevented the maintenance of IL-6 release by microglia after LPS was removed. Sialidase treatment of the cells was sufficient to induce IL-6 release, prevented by inhibiting toll-like receptor 4 (TLR4). Neu1 was found in close proximity to TLR4 on the surface of cells, and LPS induced desialylation of TLR4 on the cell surface, prevented by Neu1 knockdown. Sialic acid-binding immunoglobulin-like lectin E was found to bind to TLR4 via sialic acid residues and inhibit IL-6 release by BV-2 cells. We conclude that LPS causes Neu1 to translocate to the cell surface, where it desialylates TLR4, releasing inhibitory sialic acid-binding immunoglobulin-like lectin E, enhancing and maintaining inflammatory activation of the microglia. Thus, sialylation is a potent regulator of microglial activation, and Neu1 may be a target to reduce activation of microglia.
Understanding Human Neural Control of Short-term Gait Adaptation to the Split-belt Treadmill.
Neuroscience, 2020

Many studies of split-belt treadmill adaptation have been focused on the biomechanical changes that occur in response to walking on belts at different speeds. This process of adaptation, and the ensuing aftereffects that are present when participants return to typical treadmill walking, have inspired the potential use of the split-belt treadmill as a rehabilitation tool. However, a full systematic review of the current split-belt treadmill literature has not yet been published to consolidate what is known about how the human central nervous system (CNS) controls adaptation to this type of symmetry perturbation. A systematic literature search identified 55 studies that investigated the neural control of human gait adaptation to a split-belt treadmill. Studies of infants and manipulated sensory feedback in healthy adults suggest that the initial gait adjustments to split-belt walking are reliant on proprioceptive feedback to inform central pattern generators to modify lower limb muscle activation patterns appropriately. Simultaneously, this literature suggested that proprioceptive and visual feedback inform supraspinal centres for motor planning and motor output to adapt and store a new and efficient gait pattern to walk on belts at different speeds. However, evidence from participants with brain injury (post-stroke, cerebellar lesions) suggest that injury impedes, but does not completely take away, the ability to adjust and adapt aspects of the gait pattern to split-belts. The model proposed from this review provides the overarching roles of the CNS in the adaptation process, specifically in short-term, and potential sites of focus within the human CNS for future rehabilitation-based work.
Gestational Exposure to Benzodiazepines, 2: The Risk of Congenital Malformations Examined Through the Prism of Compatibility Intervals.
The Journal of clinical psychiatry, 2019

A recent meta-analysis of the major malformation risk after gestational exposure to benzodiazepines identified 8 prospective cohort studies with 5,195 exposed and 2,082,467 unexposed women. Benzodiazepine exposure was not associated with a statistically significant increase in the risk of total malformations (8 studies) or cardiac malformations (4 studies). The malformation risk was not significantly increased after specifically first trimester exposure, either (5 studies). However, there was a significant increase in risk associated with combined first trimester exposure to benzodiazepines and antidepressants (3 studies). The authors of the meta-analysis interpreted their findings based on the conventional P < .05 cutoff for statistical significance. However, when the confidence intervals (CIs) associated with the pooled odds ratios (ORs) were examined, it was evident that almost the entire range of values in the CIs for total malformations and for cardiac malformations was compatible with a population value for the OR that indicated increased risk (OR > 1.00). Importantly, the CI for the first trimester exposure analysis was somewhat better distributed around the null (OR = 1.00), suggesting a lower likelihood of increased risk. All ORs were very low to low in value, indicating a very small increase in the absolute risk. Besides explaining how CIs may be interpreted as compatibility intervals, this article reminds readers that associations identified even in meta-analyses of cohort studies do not indicate a causal effect because confounding by indication can never be ruled out in observational research designs. A reasonable conclusion, therefore, is that gestational exposure to benzodiazepines is a marker of risk for cardiac and total malformations, and, importantly, that first trimester exposure to benzodiazepines may not be associated with much increase in risk, if at all.
Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals.
Nature genetics, 2020

Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to ~1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency ≤ 0.01) variant BP associations (P < 5 × 10
Mechanistic insights into the role of pyroptosis in rheumatoid arthritis.
Current research in translational medicine, 2020

Cell death is ascribed as an essential biological process that is fundamental for the development of an organism along with its survival. The procedure comprises of apoptosis and pyroptosis. Pyroptosis is a programmed procedure for cell death which is inflammatory in nature and this pathway gets activated via human caspase-4, human caspase-11 and human caspase-5. The activation of this process leads to release of pro-inflammatory mediators including cytokines, alarmins, IL-18 and IL-1β. The pro-inflammatory mediators released via interaction of intracellular kinases direct the development of Rheumatoid arthritis. Rheumatoid arthritis is characterized as disorder/disease that is auto-immune and chronic in nature. It involves erosions in marginal bone along with articular cartilage which is responsible for joint destruction. The cytokine along with its complex network is responsible for inflammation. The process of pyroptosis is linked with the destruction of plasma membrane, that releases these mediators and excessive release of these mediators is linked with rheumatoid arthritis.
Association of Immunosuppression and Viral Load With Subcortical Brain Volume in an International Sample of People Living With HIV.
JAMA network open, 2021

Despite more widely accessible combination antiretroviral therapy (cART), HIV-1 infection remains a global public health challenge. Even in treated patients with chronic HIV infection, neurocognitive impairment often persists, affecting quality of life. Identifying the neuroanatomical pathways associated with infection in vivo may delineate the neuropathologic processes underlying these deficits. However, published neuroimaging findings from relatively small, heterogeneous cohorts are inconsistent, limiting the generalizability of the conclusions drawn to date.
Migraine and sleep disorders: a systematic review.
The journal of headache and pain, 2020

Migraine and sleep disorders are common and often burdensome chronic conditions with a high prevalence in the general population, and with considerable socio-economic impact and costs.The existence of a relationship between migraine and sleep disorders has been recognized from centuries by clinicians and epidemiological studies. Nevertheless, the exact nature of this association, the underlying mechanisms and interactions are complex and not completely understood. Recent biochemical and functional imaging studies identified central nervous system structures and neurotransmitters involved in the pathophysiology of migraine and also important for the regulation of normal sleep architecture, suggesting a possible causative role, in the pathogenesis of both disorders, of a dysregulation in these common nervous system pathways.This systematic review summarizes the existing data on migraine and sleep disorders with the aim to evaluate the existence of a causal relationship and to assess the presence of influencing factors. The identification of specific sleep disorders associated with migraine should induce clinicians to systematically assess their presence in migraine patients and to adopt combined treatment strategies.
Enhanced phosphorylation of S6 protein in mouse cortical layer V and subplate neurons.
Neuroreport, 2020

The mammalian neocortex is composed of six major layers of neurons. Each group of neurons in the cortical layers has distinct characteristics based on the expression of specific genes and connectivity patterns of neural circuits. Neuronal subtype transition and regional identity acquisition are established by temporal cues and interaction between several transcription factors during neurogenesis. The impairment of cortical lamination or neural circuits results in a wide range of neurodevelopmental disorders such as autism, schizophrenia, and certain forms of childhood epilepsy. Despite continuous efforts to classify neurons with the aid of genetic and epigenetic analyses, the neuron-specific properties associated with post-transcriptional modification remain unclear. In the present study, the distribution of phosphorylated S6-positive layers across the neocortex was examined using several layer markers. The development of pS6 S235/236 layers in layer V and the subplate was spatiotemporally regulated in the mouse brain. In addition, enhanced phosphorylation of ribosomal protein S6 in Ctip2-positive layer V neurons in vivo was sustained under in-vitro conditions using a culture of primary cortical neurons.
Dopaminergic neuromodulation has no detectable effect on visual-cue induced haemodynamic response function in the visual cortex: A double-blind, placebo-controlled functional magnetic resonance imaging study.
Journal of psychopharmacology (Oxford, England), 2021

The aim of this study was to investigate the effect of acute dopamine agonistic and antagonistic manipulation on the visual-cue induced blood oxygen level-dependent signal response in healthy volunteers. Seventeen healthy volunteers in a double-blind placebo-controlled cross-over design received either a dopamine antagonist, agonist or placebo and underwent functional magnetic resonance imaging. Using classical inference and Bayesian statistics, we found no effect of dopaminergic modulation on properties of visual-cue induced blood oxygen level-dependent signals in the visual cortex, particularly on distinct properties of the haemodynamic response function (amplitude, time-to-peak and width). Dopamine-related effects modulating the neurovascular coupling in the visual cortex might be negligible when measured via functional magnetic resonance imaging.
Motor imagery in children with unilateral cerebral palsy: a case-control study.
Developmental medicine and child neurology, 2020

To evaluate whether children with cerebral palsy (CP) are able to engage in a motor imagery task. Possible associations between motor imagery and functional performance, working memory, age, and intelligence were also investigated.
Hydranencephaly: Clinical Features and Survivorship in a Retrospective Cohort.
World neurosurgery, 2020

Hydranencephaly is a congenital central nervous system disorder characterized by the complete or near-complete absence of the cerebral cortex and basal ganglia. Because of its rarity, data on the clinical features and survivorship remain sparse. We aim to determine the clinical features and survivorship of a cohort of patients with hydranencephaly.
Visual attention patterns during online video-mediated interaction in socially anxious individuals.
Journal of behavior therapy and experimental psychiatry, 2020

These days, a growing number of social interactions occur through video-mediated communication (VMC). However, little is known about how socially anxious individuals use this technology. Here, we examined the visual attention patterns of high and low socially anxious individuals during a live interaction with a study confederate using a typical online VMC setup.
Transient deactivation of dorsal premotor cortex or parietal area 5 impairs feedback control of the limb in macaques.
Current biology : CB, 2021

We can generate goal-directed motor corrections with surprising speed, but their neural basis is poorly understood. Here, we show that temporary cooling of dorsal premotor cortex (PMd) impaired both spatial accuracy and the speed of corrective responses, whereas cooling parietal area 5 (A5) impaired only spatial accuracy. Simulations based on optimal feedback control (OFC) models demonstrated that "deactivation" of the control policy (reduction in feedback gain) and state estimation (reduction in Kalman gain) caused impairments similar to that observed for PMd and A5 cooling, respectively. Furthermore, combined deactivation of both cortical regions led to additive impairments of individual deactivations, whereas reducing the amount of cooling to PMd led to impairments in response speed but not spatial accuracy, both also predicted by OFC models. These results provide causal support that frontoparietal circuits beyond primary somatosensory and motor cortices are involved in generating goal-directed motor corrections.
Reference Ability Neural Network-selective functional connectivity across the lifespan.
Human brain mapping, 2021

Previous studies have demonstrated that four latent variables, or reference abilities (RAs), can account for the majority of age-related changes in cognition: these being episodic memory, fluid reasoning, speed of processing, and vocabulary. In the current study, we focused on RA-selective functional connectivity patterns that vary with both age and behavior. We analyzed fMRI data from 287 community-dwelling adults (20-80 years) on a battery of tests relating to the four RAs (three tests per RA = 12 tests). Functional connectivity values were calculated between a pre-defined set of 264 ROIs (nodes). Across all participants, we (a) identified connections (edges) that correlated with an RA-specific indicator variable and, indexing only these edges; (b) performed linear regression analysis per edge, regressing indicator correlations (Model 1) and connectivity values (Model 2) on Age, Behavioral Performance, and the Interaction term; and (c) took the conjunction of significant edges between models. Results revealed a different subset of edges for each RA whose connectivity strength and domain-selectivity varied with age and behavior. Strikingly, the fluid reasoning RA was particularly vulnerable to the effects of age and displayed the most extensive connectivity and selectivity "footprint" for behavior. These findings indicate that different functional networks are recruited across RA, with fluid reasoning displaying a special status among them.