rudyvdbrink/CitationDatabase huggingface dataset:
Sparse coupled logistic regression to estimate co-activation and modulatory influences of brain regions.
Journal of neural engineering, 2020

Accurate mapping of the functional interactions between remote brain areas with resting-state functional magnetic resonance imaging requires the quantification of their underlying dynamics. In conventional methodological pipelines, a spatial scale of interest is first selected and dynamic analysis then proceeds at this hypothesised level of complexity. If large-scale functional networks or states are studied, more local regional rearrangements are then not described, potentially missing important neurobiological information. Here, we propose a novel mathematical framework that jointly estimates resting-state functional networks and spatially more localised cross-regional modulations. To do so, the changes in activity of each brain region are modelled by a logistic regression including co-activation coefficients (reflective of network assignment, as they highlight simultaneous activations across areas) and causal interplays (denoting finer regional cross-talks, when one region active at time
SUMO E3 ligase PIAS1 is a potential biomarker indicating stress susceptibility.
Psychoneuroendocrinology, 2020

Prior studies suggest that individual differences in stress responses contribute to the pathogenesis of neuropsychiatric disorders. In the present study, we investigated the role of small ubiquitin-like modifier (SUMO) E3 ligase protein inhibitor of activated STAT1 (PIAS1) in mediating stress responses to chronic social defeat stress (CSDS). We found that mRNA and protein levels of PIAS 1 were decreased in the hippocampus of high-susceptibility (HS) mice but not in low-susceptibility (LS) mice after CSDS. Local overexpression of PIAS1 in the hippocampus followed by CSDS exposure promoted stress resilience by attenuating social avoidance and improving anxiety-like behaviors. Viral-mediated gene transfer to generate a conditional knockdown of PIAS1 in the hippocampus promoted social avoidance and stress vulnerability after subthreshold microdefeat. HS mice displayed decreased levels of glucocorticoid receptor (GR) expression, and GR SUMOylation in the hippocampus was associated with stress vulnerability. Furthermore, cytokine/chemokine levels were changed predominantly in the hippocampus of HS mice. These results suggest that hippocampal PIAS1 plays a role in the regulation of stress susceptibility by post-translational modification of GRs.
Neural indices of associative learning in pre-adolescents: An event-related potential study.
Brain and cognition, 2019

This study investigated electroencephalography (EEG) correlates of prediction error during probabilistic learning in pre-adolescents. The detection of prediction errors, the discrepancies between experienced and anticipated outcomes, is thought to be a critical mechanism that drives new learning. Thirty-three typically developing pre-adolescents (mean age = 10.62 years) participated in an associative learning task in which they learned the probabilistic relationships between cues and outcome stimuli in the absence of explicit feedback. We investigated whether three outcome-locked event-related potentials (ERPs) could reflect prediction error processing: the P3, the late positive potential (LPP), and the feedback-related negativity (FRN). All ERP components investigated were sensitive to the magnitude of hypothetical prediction errors that were estimated based on each individual's learning performance. Higher estimated prediction errors generated larger P3 and LPP components, and a more negative FRN. These findings indicate that pre-adolescents are capable of undergoing probabilistic learning in the absence of explicit feedback, much in the same way as adults, and that prediction error processing is physiologically indexed via the FRN, P3 and LPP following outcome stimuli.
Treatment of resistant epilepsy.
Clinical medicine (London, England), 2014

Treatment resistance affects around 20% of people with epilepsy and carries a significant comorbidity. It is important to ensure that the diagnosis of epilepsy is secure and the underlying cause of the epilepsy is investigated thoroughly. Management involves early referral for epilepsy surgery when suitable, optimisation of pharmacological treatment, and consideration of comorbidities such as depression.
Programming Algorithms for Sacral Neuromodulation: Clinical Practice and Evidence-Recommendations for Day-to-Day Practice.
Neuromodulation : journal of the International Neuromodulation Society, 2020

In sacral neuromodulation (SNM), stimulation programming plays a key role to achieve success of the therapy. However to date, little attention has been given to the best ways to set and optimize SNM programming during the test and chronic stimulation phases of the procedure.
Communication from the cerebellum to the neocortex during sleep spindles.
Progress in neurobiology, 2021

Surprisingly little is known about neural activity in the sleeping cerebellum. Using long-term wireless recording, we characterised dynamic cerebro-thalamo-cerebellar interactions during natural sleep in monkeys. Similar sleep cycles were evident in both M1 and cerebellum as cyclical fluctuations in firing rates as well as a reciprocal pattern of slow waves and sleep spindles. Directed connectivity from motor cortex to the cerebellum suggested a neocortical origin of slow waves. Surprisingly however, spindles were associated with a directional influence from the cerebellum to motor cortex, conducted via the thalamus. Furthermore, the relative phase of spindle-band oscillations in the neocortex and cerebellum varied systematically with their changing amplitudes. We used linear dynamical systems analysis to show that this behaviour could only be explained by a system of two coupled oscillators. These observations appear inconsistent with a single spindle generator within the thalamo-cortical system, and suggest instead a cerebellar contribution to neocortical sleep spindles. Since spindles are implicated in the off-line consolidation of procedural learning, we speculate that this may involve communication via cerebello-thalamo-neocortical pathways in sleep.
Acute Nicotine Treatment Alleviates LPS-Induced Impairment of Fear Memory Reconsolidation Through AMPK Activation and CRTC1 Upregulation in Hippocampus.
The international journal of neuropsychopharmacology, 2020

Fear memory is a fundamental capability for animals and humans to survive. Its impairment results in the disability to avoid danger. When memory is reactivated, a reconsolidation process, which can be disrupted by various stimuli, including inflammation, is required to become permanent. Nicotine has been shown to improve cognitive deficits induced by inflammation and other stimuli. Therefore, in the present study, we investigated the effect of nicotine on lipopolysaccharide (LPS)-induced impairment of fear memory reconsolidation and the underlying mechanism.
Adult convulsive status epileptic us: clinical, etiological, and predictors of outcome study from rural population of North India.
The International journal of neuroscience, 2019

To determine the clinical profile, etiologies and predictors of mortality in patients with convulsive status epilepticus (CSE) among rural population of North India in view of limited published data on epidemiology and etiology of status epilepticus (SE) from developing countries.
Brain Tissue Culture of 
Bio-protocol, 2018

In circadian research, it is essential to be able to track a biological rhythm for several days with the minimum perturbation for the organisms or tissues. The use of transgenic mice lines, in which the luciferase reporter is coupled to a molecular clock protein (here PERIOD2), gives us the opportunity to follow the circadian activity in different tissues or even single clock cells for days without manipulation. This method creates sections using a mouse brain matrix, which allows us to obtain several brain samples quickly at a single time point.
Neuronal correlates of strategic cooperation in monkeys.
Nature neuroscience, 2021

We recorded neural activity in male monkeys playing a variant of the game 'chicken' in which they made decisions to cooperate or not cooperate to obtain rewards of different sizes. Neurons in the middle superior temporal sulcus (mSTS)-previously implicated in social perception-signaled strategic information, including payoffs, intentions of the other player, reward outcomes and predictions about the other player. Moreover, a subpopulation of mSTS neurons selectively signaled cooperatively obtained rewards. Neurons in the anterior cingulate gyrus, previously implicated in vicarious reinforcement and empathy, carried less information about strategic variables, especially cooperative reward. Strategic signals were not reducible to perceptual information about the other player or motor contingencies. These findings suggest that the capacity to compute models of other agents has deep roots in the strategic social behavior of primates and that the anterior cingulate gyrus and the mSTS support these computations.
Supervised machine learning for diagnostic classification from large-scale neuroimaging datasets.
Brain imaging and behavior, 2020

There are growing concerns about the generalizability of machine learning classifiers in neuroimaging. In order to evaluate this aspect across relatively large heterogeneous populations, we investigated four disorders: Autism spectrum disorder (N = 988), Attention deficit hyperactivity disorder (N = 930), Post-traumatic stress disorder (N = 87) and Alzheimer's disease (N = 132). We applied 18 different machine learning classifiers (based on diverse principles) wherein the training/validation and the hold-out test data belonged to samples with the same diagnosis but differing in either the age range or the acquisition site. Our results indicate that overfitting can be a huge problem in heterogeneous datasets, especially with fewer samples, leading to inflated measures of accuracy that fail to generalize well to the general clinical population. Further, different classifiers tended to perform well on different datasets. In order to address this, we propose a consensus-classifier by combining the predictive power of all 18 classifiers. The consensus-classifier was less sensitive to unmatched training/validation and holdout test data. Finally, we combined feature importance scores obtained from all classifiers to infer the discriminative ability of connectivity features. The functional connectivity patterns thus identified were robust to the classification algorithm used, age and acquisition site differences, and had diagnostic predictive ability in addition to univariate statistically significant group differences between the groups. A MATLAB toolbox called Machine Learning in NeuroImaging (MALINI), which implements all the 18 different classifiers along with the consensus classifier is available from Lanka et al. (2019) The toolbox can also be found at the following URL: https://github.com/pradlanka/malini .
Enhancing the Activity of Glucocerebrosidase as a Treatment for Parkinson Disease.
CNS drugs, 2020

Mutations in the glucocerebrosidase (GBA1) gene are the most common genetic risk factor for Parkinson disease (PD). Homozygous or compound heterozygous GBA1 mutations cause the lysosomal storage disorder Gaucher disease (GD), characterized by deficient activity of the glucocerebrosidase enzyme (GCase). Both individuals with GD type I and heterozygous carriers of pathogenic variants of GBA1 have an increased risk of developing PD, by approximately ten- to 20-fold compared to non-carriers. GCase activity is also reduced in PD patients without GBA1 mutations, suggesting that the GCase lysosomal pathway might be involved in PD pathogenesis. Available evidence indicates that GCase can affect α-synuclein pathology in different ways. Misfolded GCase proteins are retained in the endoplasmic reticulum, altering the lysosomal trafficking of the enzyme and disrupting protein trafficking. Also, deficient GCase leads to accumulation of substrates that in turn may bind α-synuclein and promote pathological formation of aggregates. Furthermore, α-synuclein itself can lower the enzymatic activity of GCase, indicating that a bidirectional interaction exists between GCase and α-synuclein. Targeted therapies aimed at enhancing GCase activity, augmenting the trafficking of misfolded GCase proteins by small molecule chaperones, or reducing substrate accumulation, have been tested in preclinical and clinical trials. This article reviews the molecular mechanisms linking GCase to α-synuclein and discusses the therapeutic drugs that by targeting the GCase pathway can influence PD progression.
The burden of non-symptomatic cerebral ischemia on MRI and its effect on clinical outcomes in patients with first-ever intracerebral hemorrhage.
The International journal of neuroscience, 2018

To compare the burden of non-symptomatic cerebral ischemia (NSCI) detected on magnetic resonance imaging (MRI) and computed tomography (CT), and assess the association of MRI-NSCI with clinical outcomes among patients with first-ever intracerebral hemorrhage (ICH).
Multidimensional prognostic index in the elderly with hip or neck femur fracture.
Orthopedic reviews, 2012

Hip and neck femur fracture surgery was associated with high post-operative mortality and poor functional results. The decision-making process with regards to the elderly with hip or neck femur fractures was of great importance, requiring consideration of ethical, medico legal and economic factors in addition to the purely medical ones. An important component in the decision-making process was the precise knowledge of the expected mortality. We considered here several articles from 1 January 2002 to 31 August 2010 that identified the possible scoring system to predict mortality in the elderly undergoing hip or neck femur fracture surgery. We found seven studies which included a total of 12,177 patients that were assigned to hip/neck femur fracture surgery. Each study identified the possible scoring system to predict mortality in the elderly undergoing hip/neck femur fracture surgery. By reviewing the literature available, it was shown that there were more multidimensional prognostic indexes in the elderly after hospitalization than multidimensional prognostic indexes with hip or neck femur fracture which could be used as a simple point scoring system at the bedside to predict mortality in the elderly undergoing hip or neck femur fracture surgery. Although, all the prognostic indexes searched worked well for a general population, but they were of limited validity in the specific, relatively homogeneous population of hip/neck femur fracture patients.
Presynaptic congenital myasthenic syndrome due to three novel mutations in SLC5A7 encoding the sodium-dependant high-affinity choline transporter.
Neuromuscular disorders : NMD, 2021

SLC5A7 encodes the presynaptic sodium-dependant high-affinity choline transporter 1 (CHT), which uptakes choline to the presynaptic nerve terminal following the breakdown of acetylcholine by the acetylcholinesterase within the synaptic cleft. We report 5 patients from three consanguineous families with congenital myasthenic syndrome type 20 caused by novel mutations in SLC5A7. The individuals from family 1 and 2 were homozygous for c.320G>A; (p.Arg107His) and c.886G>A (p.Ala296Thr), respectively, and their phenotype was characterised by recurrent apnoeic attacks early after birth and learning and speech difficulties in childhood. Individuals from family 3 were homozygous for c.1240T>A (p.Tyr414Asn) and suffered from more severe central and peripheral manifestations with lack of spontaneous movements and respiratory drive and overall minimal response to external stimuli. All individuals tested showed neurophysiological defects compatible with impaired neuromuscular transmission. Combined treatment with cholinesterase inhibitors and β2-adrenergic agonists was beneficial in patients from family 1 and 2. Affected individuals from family 3 died from complications directly related to their underlying genetic condition. This report provides three novel pathogenic variants in SLC5A7 and highlights the variability in the clinical phenotype, severity and prognosis of this syndrome.
The practice of experimental studies in psychopharmacology: Top 10 tips from one centre's experience.
Human psychopharmacology, 2018

Recent efforts to optimise translation of basic research findings to successful clinical trials have led to a sharper focus on experimental medicine translational studies. This is coupled with a movement towards greater methodological integrity and openness. Although this can be achieved through preregistration and detailed reporting of study methodology, the reality of study application can often be lost.
Alterations of Brain Networks in Alzheimer's Disease and Mild Cognitive Impairment: A Resting State fMRI Study Based on a Population-specific Brain Template.
Neuroscience, 2021

This study aimed to investigate the alterations in brain networks in patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI) based on a population-specific brain template. Previous studies on AD brain networks using graph theory rarely adopted brain templates specific for certain ethnicities. In this study, patients were divided into 3 groups: AD (n = 24), MCI (n = 27), and healthy controls (HCs, n = 33), and all of the subjects are Chinese. Functional brain networks were constructed for each group based on a Chinese brain template using resting-state functional magnetic resonance imaging (rs-fMRI) data; several graph metrics were calculated. Graph metrics with significant differences after false discovery rate (FDR) correction were analyzed with respect to correlations with four neuropsychological test scores: Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Activities of Daily Living (ADL), and Clinical Dementia Rating (CDR), which assessed the subjects' cognitive functions and ability to engage in ADL. Graph metrics including assortativity coefficient, nodal degree centrality, nodal clustering coefficient, nodal efficiency, and nodal local efficiency of the frontal gyrus and cerebellum were significantly altered in AD and MCI compared with HC. Several graph metrics were significantly correlated with cognitive function and the ability to engage in daily activities. The findings suggest that altered graph metrics in the frontal gyrus may reflect brain plasticity, and that patients with MCI may have unique graph metric alterations in the cerebellum. Future graph analysis studies on functional brain networks in AD and MCI based on population-specific brain atlases for particular ethnicities may prove valuable.
Patient-reported impact of Charcot-Marie-Tooth disease: protocol for a real-world digital lifestyle study.
Neurodegenerative disease management, 2021

Charcot-Marie-Tooth disease (CMT) is a rare, chronic, progressive motor and sensory neuropathy affecting the peripheral nervous system. This study will explore the real-world impact of CMT. The trial is a digital study of approximately 2000 people in 6 countries with CMT ≥18 years. Participants will use a smartphone application to check eligibility, provide consent and contribute data. The dataset will include a personal profile, covering demographics, lifestyle, diagnosis and treatment and a selection of validated generic and disease-specific instruments. Participants will provide data for up to 2 years. Data analysis will be conducted upon registration of the 1000th participant and at 12-month intervals from launch. This study is designed to help researchers and clinicians understand the real-world impact of CMT and the unmet needs of patients. ClinicalTrials.gov identifier: NCT03782883.
Aging, Vestibular Function, and Balance: Proceedings of a National Institute on Aging/National Institute on Deafness and Other Communication Disorders Workshop.
The journals of gerontology. Series A, Biological sciences and medical sciences, 2020

Balance impairment and falls are among the most prevalent and morbid conditions affecting older adults. A critical contributor to balance and gait function is the vestibular system; however, there remain substantial knowledge gaps regarding age-related vestibular loss and its contribution to balance impairment and falls in older adults. Given these knowledge gaps, the National Institute on Aging and the National Institute on Deafness and Other Communication Disorders convened a multidisciplinary workshop in April 2019 that brought together experts from a wide array of disciplines, such as vestibular physiology, neuroscience, movement science, rehabilitation, and geriatrics. The goal of the workshop was to identify key knowledge gaps on vestibular function and balance control in older adults and develop a research agenda to make substantial advancements in the field. This article provides a report of the proceedings of this workshop. Three key questions emerged from the workshop, specifically: (i) How does aging impact vestibular function?; (ii) How do we know what is the contribution of age-related vestibular impairment to an older adult's balance problem?; and more broadly, (iii) Can we develop a nosology of balance impairments in older adults that can guide clinical practice? For each of these key questions, the current knowledge is reviewed, and the critical knowledge gaps and research strategies to address them are discussed. This document outlines an ambitious 5- to 10-year research agenda for increasing knowledge related to vestibular impairment and balance control in older adults, with the ultimate goal of linking this knowledge to more effective treatment.
Cynical hostility relates to a lack of habituation of the cardiovascular response to repeated acute stress.
Psychophysiology, 2020

Hostility is associated with increased risk for cardiovascular disease. Heightened cardiovascular reactivity to psychological stress has been proposed as a potential mechanism. Recent work has emphasized a need to measure cardiovascular reactivity across multiple stress exposures to assess potential habituation over time. The aims of the current study were (a) to examine the relationship between each of the three main components of hostility (i.e., emotional, cognitive, and behavioral) and cardiovascular reactivity at two separate stress testing visits and (b) to examine the relationship between hostility components and cardiovascular reactivity habituation. This study utilized previously collected data from the Pittsburgh Cold Study 3. One hundred and ninety-six participants (Mean (SD)[range] age = 29.9 (10.8)[18-55] years, 42.9% female, 67.3% Caucasian) completed 2 separate, identical laboratory sessions, consisting of a 20-min baseline and 15-min stress (Trier Social Stress Test). Heart rate and systolic/diastolic blood pressure were recorded throughout. Reactivity was calculated separately for heart rate, systolic, and diastolic blood pressure (stress-baseline). Participants also completed a modified version of the Cook-Medley Hostility Scale. Results indicated that greater cognitive hostility (i.e., cynicism) was associated with blunted cardiovascular reactivity at Visit 1 and less cardiovascular reactivity habituation between visits, even when controlling for confounding variables. No significant relationships to cardiovascular reactivity or habituation were found for emotional (i.e., hostile affect) or behavioral (i.e., aggressive responding) components. Outcomes for total hostility did not survive adjustment for confounders. These results identify a potential pathway through which hostility, particularly cynicism, contributes to disease risk.