rudyvdbrink/CitationDatabase huggingface dataset:
Moment-to-Moment BOLD Signal Variability Reflects Regional Changes in Neural Flexibility across the Lifespan.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2017

Variability of neuronal responses is thought to underlie flexible and optimal brain function. Because previous work investigating BOLD signal variability has been conducted within task-based fMRI contexts on adults and older individuals, very little is currently known regarding regional changes in spontaneous BOLD signal variability in the human brain across the lifespan. The current study used resting-state fMRI data from a large sample of male and female human participants covering a wide age range (6-85 years) across two different fMRI acquisition parameters (TR = 0.645 and 1.4 s). Variability in brain regions including a key node of the salience network (anterior insula) increased linearly across the lifespan across datasets. In contrast, variability in most other large-scale networks decreased linearly over the lifespan. These results demonstrate unique lifespan trajectories of BOLD variability related to specific regions of the brain and add to a growing literature demonstrating the importance of identifying normative trajectories of functional brain maturation.
Candidate mechanisms underlying the association between sleep-wake disruptions and Alzheimer's disease.
Sleep medicine reviews, 2017

During wakefulness, extracellular levels of metabolites in the brain increase. These include amyloid beta (Aβ), which contributes to the pathogenesis of Alzheimer's disease (AD). Counterbalancing their accumulation in the brain, sleep facilitates the removal of these metabolites from the extracellular space by convective flow of the interstitial fluid from the para-arterial to the para-venous space. However, when the sleep-wake cycle is disrupted (characterized by increased brain levels of the wake-promoting neuropeptide orexin and increased neural activity), the central nervous system (CNS) clearance of extracellular metabolites is diminished. Disruptions to the sleep-wake cycle have furthermore been linked to increased neuronal oxidative stress and impaired blood-brain barrier function - conditions that have also been proposed to play a role in the development and progression of AD. Notably, recent human and transgenic animal studies have demonstrated that AD-related pathophysiological processes that occur long before the clinical onset of AD, such as Aβ deposition in the brain, disrupt sleep and circadian rhythms. Collectively, as proposed in this review, these findings suggest the existence of a mechanistic interplay between AD pathogenesis and disrupted sleep-wake cycles, which is able to accelerate the development and progression of this disease.
Transient upregulation of translational efficiency in prodromal and early symptomatic Tg2576 mice contributes to Aβ pathology.
Neurobiology of disease, 2020

TG2576 mice show highest levels of the full length mutant Swedish Human Amyloid Precursor Protein (APPKM670/671LN) during prodromal and early sympotomatic stages. Interestingly, this occurs in association with the unbalanced expression of two of its RNA Binding proteins (RBPs) opposite regulators, the Fragile-X Mental Retardation Protein (FMRP) and the heteronuclear Ribonucleoprotein C (hnRNP C). Whether an augmentation in overall translational efficiency also contributes to the elevation of APP levels at those early developmental stages is currently unknown. We investigated this possibility by performing a longitudinal polyribosome profiling analysis of APP mRNA and protein in total hippocampal extracts from Tg2576 mice. Results showed that protein polysomal signals were exclusively detected in pre-symptomatic (1 months) and early symptomatic (3 months) mutant mice. Differently, hAPP mRNA polysomal signals were detected at any age, but a peak of expression was found when mice were 3-month old. Consistent with an early but transient rise of translational efficiency, the phosphorylated form of the initial translation factor eIF2α (p-eIF2α) was reduced at pre-symptomatic and early symptomatic stages, whereas it was increased at the fully symptomatic stage. Pharmacological downregulation of overall translation in early symptomatic mutants was then found to reduce hippocampal levels of full length APP, Aβspecies, BACE1 and Caspase-3, to rescue predominant LTD at hippocampal synapses, to revert dendritic spine loss and memory alterations, and to reinstate memory-induced c-fosactivation. Altogether, our findings demonstrate that overall translation is upregulated in prodromal and early symptomatic Tg2576 mice, and that restoring proper translational control at the onset of AD-like symptoms blocks the emergence of the AD-like phenotype.
Depression and Catechol-O-methyltransferase (COMT) genetic variants are associated with pain in Parkinson's disease.
Scientific reports, 2017

Pain is a distressing symptom of Parkinson disease (PD). We aim to determine whether the genetic variants of chronic pain-related genes contribute to pain in PD patients. We included 418 PD patients and evaluated pain severity on King's PD pain scale. We genotyped rs6267, rs6269, rs4633, rs4818 and rs4680 of COMT, rs6746030 of SCN9A, and rs1799971 of OPRM1. In total, 193 participants (46.2%) experienced pain. Compared to pain-free PD patients, PD patients with pain had an earlier age of onset, longer disease duration, and higher depression and motor severity (P < 0.01). The frequencies of COMT rs4680 "A" allele were higher in PD patients with pain than those without pain (46.1% vs. 31.1%, P < 0.01). Pain severity was significantly associated with disease duration (P = 0.02), and COMT rs6267 T allele (P < 0.01). We stratified PD by status of depression and the association between COMT rs6267 "GT" genotype and pain severity remained significant (P < 0.01). Furthermore, pain severity was significantly higher in participants having COMT rs4680 "GG" and "GA" genpotypes than those having "AA" genotype (P = 0.04). We concluded that depression and COMT rs4680 "GG" and "GA" genotypes and COMT rs6267 "GT" genotype contribute to pain in PD patients.
Artificial intelligence neuropathologist for glioma classification using deep learning on hematoxylin and eosin stained slide images and molecular markers.
Neuro-oncology, 2021

Pathological diagnosis of glioma subtypes is essential for treatment planning and prognosis. Standard histological diagnosis of glioma is based on postoperative hematoxylin and eosin stained slides by neuropathologists. With advancing artificial intelligence (AI), the aim of this study was to determine whether deep learning can be applied to glioma classification.
Demand elasticity predicts addiction endophenotypes and the therapeutic efficacy of an orexin/hypocretin-1 receptor antagonist in rats.
The European journal of neuroscience, 2019

Behavioral economics is a powerful, translational approach for measuring drug demand in both humans and animals. Here, we asked if demand for cocaine in rats with limited drug experience could be used to identify individuals most at risk of expressing an addiction phenotype following either long- or intermittent access self-administration schedules, both of which model the transition to uncontrolled drug-seeking. Because the orexin-1 receptor antagonist SB-334867 (SB) is particularly effective at reducing drug-seeking in highly motivated individuals, we also asked whether demand measured after prolonged drug experience could predict SB efficacy. Demand elasticity (α) measured immediately following acquisition of cocaine self-administration ('baseline α') was positively correlated with α assessed after 2w of long- or intermittent access. Baseline α also predicted the magnitude of compulsive responding for cocaine, drug-seeking in initial abstinence and cued reinstatement following long-, intermittent- or standard short access. When demand was measured after these differential access conditions, α predicted the same addiction endophenotypes predicted by baseline α, as well as primed reinstatement and the emergence of negative emotional mood behavior following abstinence. α also predicted the efficacy of SB, such that high demand rats showed greater reductions in motivation for cocaine following SB compared to low demand rats. Together, these findings indicate that α might serve as a behavioral biomarker to predict individuals most likely to progress from controlled to uncontrolled drug use, and to identify individuals most likely to benefit from orexin-based therapies for the treatment of addiction.
Effect of Aspirin on Disability-free Survival in the Healthy Elderly.
The New England journal of medicine, 2018

Information on the use of aspirin to increase healthy independent life span in older persons is limited. Whether 5 years of daily low-dose aspirin therapy would extend disability-free life in healthy seniors is unclear.
Inhibition of monoacylglycerol lipase prevents chronic traumatic encephalopathy-like neuropathology in a mouse model of repetitive mild closed head injury.
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 2015

Emerging evidence suggests that the risk of developing chronic traumatic encephalopathy (CTE), a progressive neurodegenerative disease, is significantly increased in military personnel and contact sports players who have been exposed to repetitive trauma brain injury (TBI). Unfortunately there are no effective medications currently available for prevention and treatment of CTE. Here we demonstrate that inhibition of monoacylglycerol lipase (MAGL), the key enzyme that metabolizes the endocannabinoid 2-arachidonoylglycerol (2-AG) in the brain, significantly reduced CTE-like neuropathologic changes in a mouse model of repetitive mild closed head injury (rmCHI). Inhibition of 2-AG metabolism promoted neurologic recovery following rmCHI and reduced proinflammatory cytokines, astroglial reactivity, expression of amyloid precursor protein and the enzymes that make Aβ, as well as formation of Aβ. Importantly, neurodegeneration, TDP-43 protein aggregation, and tau phosphorylation, which are the neuropathologic hallmarks of CTE, were significantly suppressed by MAGL inactivation. Furthermore, alterations in expression of glutamate receptor subunits and impairments in basal synaptic transmission, long-term synaptic plasticity, and spatial learning and memory were recovered by inhibition of 2-AG metabolism in animals exposed to rmCHI. Our results suggest that MAGL inhibition, which boosts 2-AG and reduces 2-AG metabolites prostaglandins in the brain, may lead to a new therapy for CTE.
Real and imagined sensory feedback have comparable effects on action anticipation.
Cortex; a journal devoted to the study of the nervous system and behavior, 2020

The forward model monitors the success of sensory feedback to an action and links it to an efference copy originating in the motor system. The Readiness Potential (RP) of the electroencephalogram has been denoted as a neural signature of the efference copy. An open question is whether imagined sensory feedback works similarly to real sensory feedback. We investigated the RP to audible and imagined sounds in a button-press paradigm and assessed the role of sound complexity (vocal vs. non-vocal sound). Sensory feedback (both audible and imagined) in response to a voluntary action modulated the RP amplitude time-locked to the button press. The RP amplitude increase was larger for actions with expected sensory feedback (audible and imagined) than those without sensory feedback, and associated with N1 suppression for audible sounds. Further, the early RP phase was increased when actions elicited an imagined vocal (self-voice) compared to non-vocal sound. Our results support the notion that sensory feedback is anticipated before voluntary actions. This is the case for both audible and imagined sensory feedback and confirms a role of overt and covert feedback in the forward model.
High-frequency ultrasonic vocalizations in rats in response to tickling: the effects of restraint stress.
Behavioural brain research, 2012

We tested the hypotheses that (a) the propensity to emit high-frequency (∼50 kHz) ultrasonic vocalizations in response to manual "tickling" by an experimenter, may serve as a behavioral marker of positive affect in rats and, (b) that tickling may reduce the severity of stress. Group-housed adult rats were subjected to the 15-s tickling procedure daily, and their ultrasonic vocalization response was measured over a period of two weeks, until it has stabilized. The animals were then subjected to the restraint stress lasting for one week. The experimental groups were exposed to stress 1 h before or 1 h after tickling and the controls were tickled without stressing. Rats that were stressed 1 h before tickling demonstrated a decreased number of the high-frequency calls as compared with the non-stressed controls. Stressing 23 h before tickling reduced the call response less effectively. The propensity to emit high-frequency calls has normalized 7 and 12 days following the end of stressing. In addition, stressed groups showed a diminution of sucrose preference, which in the case of rats stressed 23 h before tickling persisted even for 12 days following the end of restraint. The present data suggest that repeated stress may decrease the propensity to produce high-frequency vocalizations, and that this measure may serve as a biomarker of the depressive state of animals.
False-positive acetylcholine receptor antibody results in patients without myasthenia gravis.
Journal of neuroimmunology, 2019

Acetylcholine receptor antibodies are very specific for myasthenia. During a large prospective cohort study of myasthenia, we encountered five patients, positive for acetylcholine receptor (AChR) antibodies by radioimmunoprecipitation assay (RIA), whose clinical course revealed diagnoses other than myasthenia. Two patients had transiently raised AChR antibodies associated with Guillain-Barré syndrome. Antibodies to clustered AChRs, in a live cell-based assay, were negative in all five patients, suggesting that results from the RIAs were false-positives. It is possible that the AChR antibodies detected by RIA in these cases were non-pathogenic, and directed to intracellular epitopes of the AChR.
A functional classification of medial frontal negativity ERPs: Theta oscillations and single subject effects.
Psychophysiology, 2016

Theta oscillations in the EEG have been linked to several ERPs that are elicited during performance-monitoring tasks, including the error-related negativity (ERN), no-go N2, and the feedback-related negativity (FRN). We used a novel paradigm to isolate independent components (ICs) in single subjects' (n = 27) EEG accounting for a medial frontal negativity (MFN) to response cue stimuli that signal a potential change in future response demands. Medial frontal projecting ICs that were sensitive to these response cues also described the ERNs, no-go N2s, and, to a lesser extent, the FRNs, that were elicited in letter flanker, go/no-go, and time-estimation tasks, respectively. In addition, percentile bootstrap tests using trimmed means indicated that the medial frontal ICs show an increase in theta activity during the ERN, no-go N2, and FRN across tasks and within individuals. Our results provide an important validation of previous studies by showing that increases in medial frontal theta to cognitively challenging events in multiple paradigms is a reliable effect within individuals and can be elicited by basic stimulus cues that signal the potential need to adjust response control. Thus, medial frontal theta reflects a neural response common to all MFN paradigms and characterizes the general process of controlling attention without the need to induce error commission, inhibited responses, or to present negative feedback.
Meta-analysis of changes in the levels of catecholamines and blood pressure with continuous positive airway pressure therapy in obstructive sleep apnea.
Journal of clinical hypertension (Greenwich, Conn.), 2021

Stress from obstructive sleep apnea (OSA) stimulates catecholamine release consequently exacerbating hypertension. However, different studies have shown a conflicting impact of continuous positive airway pressure (CPAP) treatment in patients with OSA on catecholamine levels and blood pressure. We aimed to examine changes to catecholamine levels and blood pressure in response to CPAP treatment. We conducted a meta-analysis of data published up to May 2020. The quality of the studies was evaluated using standard tools for assessing the risk of bias. Meta-analysis was conducted using RevMan (v5.3) and expressed in standardized mean difference (SMD) for catecholamines and mean difference (MD) for systolic (SBP) and diastolic blood pressure (DBP). A total of 38 studies met our search criteria; they consisted of 14 randomized control trials (RCT) totaling 576 participants and 24 prospective cohort studies (PCS) of 547 participants. Mean age ranged between 41 and 62 year and body mass index between 27.2 and 35.1 kg/m
Target-cell-specific Short-term Plasticity Reduces the Excitatory Drive onto CA1 Interneurons Relative to Pyramidal Cells During Physiologically-derived Spike Trains.
Neuroscience, 2018

Short-term plasticity enables synaptic strength to be dynamically regulated by input timing. Excitatory synapses arising from the same axon can have profoundly different presynaptic forms of short-term plasticity onto inhibitory and excitatory neurons. We previously showed that Schaffer collateral synapses onto most hippocampal CA1 stratum radiatum interneurons have less paired-pulse facilitation than synapses onto CA1 pyramidal cells, but little difference in steady-state short-term depression. However, less is known about how synapses onto interneurons respond to temporally complex patterns that occur in vivo. Here we compared Schaffer collateral synapses onto stratum radiatum interneurons and pyramidal cells in acute hippocampal slices in response to physiologically-derived spike trains. We find that synapses onto interneurons have less short-term facilitation than synapses onto pyramidal cells, and a subset expresses only short-term depression. Mathematical modeling predicts this target cell-specific short-term plasticity occurs through differences in initial release probability. All three groups have more short-term facilitation during physiologically-derived train stimulation than during constant-frequency stimulation at the same frequency, indicating that variability in stimulus timing is important. These target-cell specific differences in short-term plasticity reduce the strength of excitatory input onto interneurons relative to pyramidal cells, and of depression interneurons relative to facilitation interneurons, during high frequency portions of the train. This occurs to a similar extent at 25 °C and at 33 °C, and is even greater at physiological extracellular calcium. Target-cell specific differences in short-term plasticity enable synapses to have different temporal filtering characteristics, which may help to dynamically regulate the balance of inhibition and excitation in CA1.
The Effects of Chronic Stress on Brain Myelination in Humans and in Various Rodent Models.
Neuroscience, 2020

The myelination of axons, which is performed in brain tissues by specialized glial cells (oligodendrocytes) is crucial for correct formation of the complicated neural circuitry necessary for normal cognition, sensation, and motor function. Myelin-related anomalies are seen in many neurodegenerative diseases and in psychiatric disorders, including major depressive disorder and post-traumatic stress disorder. Chronic stress involving chronic stress early in life is believed to be a major etiological factor of neuropsychiatric disorders. Although molecular and cellular mechanisms underlying stress-induced psychopathologies are actively investigated, there is still little data about the role that is played in the development of these pathologies by myelin and oligodendrocyte impairments caused by chronic stress. In this article, after brief review of published data on myelin abnormalities in stress-related psychiatric disorders, we focus on recent cellular and molecular discoveries in various rodent models including models of chronic unpredictable stress, social isolation stress, chronic social defeat stress, and chronic immobilization stress. We also attempt to compile and analyze currently scarce data on myelin-related impairments resulting from early postnatal stress.
Tbr2 is required to generate a neural circuit mediating the pupillary light reflex.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014

There are ∼20 types of retinal ganglion cells (RGCs) in mice, each of which has distinct molecular, morphological, and physiological characteristics. Each RGC type sends axon projections to specific brain areas that execute light-dependent behaviors. Here, we show that the T-box transcription factor Tbr2 is required for the development of several RGC types that participate in non-image-forming circuits. These types are molecularly distinct, project to non-image-forming targets, and include intrinsically photosensitive RGCs. Tbr2 mutant mice have reduced retinal projections to non-image-forming nuclei and an attenuated pupillary light reflex. These data demonstrate that Tbr2 acts to execute RGC type choice and/or survival in a set of RGCs that mediates light-induced subconscious behaviors.
Neurons in the Macaque Dorsal Premotor Cortex Respond to Execution and Observation of Actions.
Cerebral cortex (New York, N.Y. : 1991), 2019

We identified neurons in dorsal premotor cortex (PMd) of the macaque brain that respond during execution and observation of reaching-to-grasp actions, thus fulfilling the mirror neuron (MirN) criterion. During observation, the percentage of grip-selective MirNs in PMd and area F5 were comparable, and the selectivity indices in the two areas were similar. During execution, F5-MirNs were more selective than PMd-MirNs for grip, which was reflected in the higher selectivity indices in F5 than in PMd. PMd displayed grip-related information earlier than F5 during both conditions. In both areas, the number of neurons exhibiting congruent visual and motor selectivity did not differ from that expected by chance. However, both the PMd and F5 neuronal ensembles provided observation-execution matching, suggesting that the congruency may be achieved in a distributed fashion across the selective elements of the population. Furthermore, representational similarity analysis revealed that grip encoding in PMd and F5 is alike during both observation and execution. Our study provides direct evidence of mirror activity in PMd during observation of forelimb movements, and suggests that PMd is a node of the MirN circuit.