rudyvdbrink/CitationDatabase huggingface dataset:
Exploring spatiotemporal network transitions in task functional MRI.
Human brain mapping, 2015

A critical question for cognitive neuroscience regards how transitions between cognitive states emerge from the dynamic activity of functional brain networks. Here we combine a simple data reorganization with spatial independent component analysis (ICA), enabling a spatiotemporal ICA (stICA) which captures the consistent evolution of networks during the onset and offset of a task. The technique was applied to functional magnetic resonance imaging (MRI) (FMRI) datasets involving alternating between rest and task, and to simple synthetic data. Starting and finishing time-points of periods of interest (anchors) were defined at task block onsets and offsets. For each subject, the 10 volumes following each anchor were extracted and concatenated spatially, producing a single 3D sample. Samples for all anchors and subjects were concatenated along the fourth dimension. This 4D dataset was decomposed using ICA into spatiotemporal components. One component exhibited the transition with task onset from a default mode network (DMN) becoming less active to a frontoparietal control network becoming more active. We observed other changes with relevance to understanding network dynamics, for example, the DMN showed a changing spatial distribution, shifting to an anterior/superior pattern of deactivation during task from a posterior/inferior pattern during rest. By anchoring analyses to periods associated with the onsets and offsets of task, our approach reveals novel aspects of the dynamics of network activity accompanying these transitions. Importantly, these findings were observed without specifying a priori either the spatial networks or the task time courses.
Retinal Ganglion Cells With a Glaucoma OPTN(E50K) Mutation Exhibit Neurodegenerative Phenotypes when Derived from Three-Dimensional Retinal Organoids.
Stem cell reports, 2020

Retinal ganglion cells (RGCs) serve as the connection between the eye and the brain, with this connection disrupted in glaucoma. Numerous cellular mechanisms have been associated with glaucomatous neurodegeneration, and useful cellular models of glaucoma allow for the precise analysis of degenerative phenotypes. Human pluripotent stem cells (hPSCs) serve as powerful tools for studying human disease, particularly cellular mechanisms underlying neurodegeneration. Thus, efforts focused upon hPSCs with an E50K mutation in the Optineurin (OPTN) gene, a leading cause of inherited forms of glaucoma. CRISPR/Cas9 gene editing introduced the OPTN(E50K) mutation into existing lines of hPSCs, as well as generating isogenic controls from patient-derived lines. RGCs differentiated from OPTN(E50K) hPSCs exhibited numerous neurodegenerative deficits, including neurite retraction, autophagy dysfunction, apoptosis, and increased excitability. These results demonstrate the utility of OPTN(E50K) RGCs as an in vitro model of neurodegeneration, with the opportunity to develop novel therapeutic approaches for glaucoma.
Effect of head and jaw position on respiratory-related motion of the genioglossus.
Journal of applied physiology (Bethesda, Md. : 1985), 2016

Head and jaw position influence upper airway patency and electromyographic (EMG) activity of the main upper airway dilator muscle, the genioglossus. However, it is not known whether changes in genioglossus EMG activity translate into altered muscle movement during respiration. The aim of this study was to determine the influence of head and jaw position on dilatory motion of the genioglossus in healthy adult men during quiet breathing by measuring the displacement of the posterior tongue in six positions--neutral, head extension, head rotation, head flexion, mouth opening, and mandibular advancement. Respiratory-related motion of the genioglossus was imaged with spatial modulation of magnetization (SPAMM) in 12 awake male participants. Tissue displacement was quantified with harmonic phase (HARP) analysis. The genioglossus moved anteriorly beginning immediately before or during inspiration, and there was greater movement in the oropharynx than in the velopharynx in all positions. Anterior displacements of the oropharyngeal tongue varied between neutral head position (0.81 ± 0.41 mm), head flexion (0.62 ± 0.45 mm), extension (0.39 ± 0.19 mm), axial rotation (0.39 ± 0.2 mm), mouth open (1.24 ± 0.72 mm), and mandibular advancement (1.08 ± 0.65 mm). Anteroposterior displacement increased in the mouth-open position and decreased in the rotated position relative to cross-sectional area (CSA) (P = 0.002 and 0.02, respectively), but CSA did not independently predict anteroposterior movement overall (P = 0.057). The findings of this study suggest that head position influences airway dilation during inspiration and may contribute to variation in airway patency in different head positions.
Alpha-synuclein and Parkinson's disease: a proteomic view.
Expert review of proteomics, 2008

In this review, we report how proteomic methodologies have been used to investigate cellular and animal models of Parkinson's disease (PD), with a special focus on alpha-synuclein. PD is a complex, multifactorial neurodegenerative disease affecting approximately 2% of the population over 65 years of age, pathologically characterized by alpha-synuclein intraneuronal inclusions. Etiopathogenetic mechanisms of PD are not fully understood, although a number of factors contributing to the selective degeneration of substantia nigra neurons have been identified. Therefore, cellular and animal models of the disease have been developed to investigate single factors contributing to disease pathogenesis; for example, alpha-synuclein aggregation and altered dopamine homeostasis. Proteomic studies on cellular and animal models have not only confirmed existing theories on PD pathogenesis (mitochondrial impairment, oxidative stress, failure of the ubiquitine-proteasome system), but also allowed the discovery of new important common features of presymptomatic (or premotor) stages of PD, such as dysregulation of cytoskeletal proteins that could be involved at the origin of the disorder.
Food pleasantness affects visual selective attention.
Quarterly journal of experimental psychology (2006), 2011

Fundamental to adaptive behaviour is the ability to select environmental objects that best satisfy current needs and preferences. Here we investigated whether temporary changes in food preference influence visual selective attention. To this end, we exploited the fact that when a food is eaten to satiety its motivational value and perceived pleasantness decrease relative to other foods not eaten in the meal, an effect termed sensory-specific satiety. A total of 26 hungry participants were fed until sated with one of two palatable foods. Before and after selective satiation, participants rated the pleasantness of the two foods and then viewed the same as stimuli on a computer screen while attention was assessed by a visual probe task. Results showed that the attentional bias for the food eaten decreased markedly from pre- to postsatiety, along with the subjective pleasantness for that food. By contrast, subjective pleasantness and attentional bias for the food not eaten did not show any such decrease. These findings suggest that the allocation of visual selective attention is flexibly and rapidly adjusted to reflect temporary shift in relative preference for different foods.
Cognitive effects of long-term dydrogesterone treatment used alone or with estrogen on rat menopausal models of different ages.
Neuroscience, 2015

Menopause can cause cognitive decline. Hormone Replacement Therapy (HRT) is the most effective treatment for the climacteric symptoms. However, its cognitive effect has not been well clarified, especially for the progestin component. The study investigated the effects of dydrogesterone (DG) on spatial learning and memory of the ovariectomized (OVX) rat models and the impact of aging on its cognitive effects. Eighty female Sprague-Dawley rats were included in the experiment. They belonged to two cohorts, the adult (7 months) and the aged (18 months). Each cohort was divided into five groups: Sham, OVX, OVX+E2 (OVX+17β-estrogen), OVX+E2/DG and OVX+DG. The replacement therapy lasted for 20 weeks. Two classical behavioral tests were performed: open field test (OFT) and the Morris water maze (MWM). The breast morphology and uterine weight were obtained to assess the safety and complication of dydrogesterone. In MWM, the OVX group displayed prolonged latency and less target quadrant time than the other groups. Across 5 days' testing, all the adult groups receiving hormone therapy, except the OVX+DG group, performed better than the OVX group (P<0.001); but there was no significant difference among the aged groups. The uterus weight/body weight ratio of OVX+E2/DG group was lower than the sham and OVX+E2 group. The mammary glands of OVX+E2/DG group displayed normal structure or mild hyperplasia. The results suggested that DG-alone treatment had no significant benefit for the OVX rats of both adult and aged groups on the behavioral tests. DG combined with E2 could ameliorate cognition in adult rats with uterus protection and without breast harm. The cognitive-improve effects were more remarkable for the adult rats than the aged ones. The findings support the potential clinical application of dydrogesterone combined with estrogen in preventing cognitive decline, especially for the early iatrogenic menopausal women.
Clinical correlates in children with autism spectrum disorder and CNVs: Systematic investigation in a clinical setting.
International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience, 2020

Autism spectrum disorder (ASD) is associated with various molecular mechanisms including copy number variants (CNVs). We investigated possible associations between CNVs and ASD clinical correlates. We evaluated pertinent physical characteristics and phenotypic measures such as cognitive level, severity of ASD symptoms and comorbid conditions in ASD patients consecutively recruited over the study period. Children with causative (C-CNVs), non-causative (NC-CNVs) and without CNVs (W-CNVs) were compared. Out of 109 patients, 31 imbalances (16 duplications and 15 deletions) were detected in 25 subjects. Seven (6.4%) had C-CNVs and 18 (16.5%) had NC-CNVs. Paired post hoc comparisons with Bonferroni adjustment showed that dysmorphisms and microcephaly were significantly more frequent in the C-CNVs group. Patients with C-CNVs had more severe autistic core symptoms, while comorbid internalizing behavioral symptoms were more represented among participants with NC-CNVs. No significant differences were observed for distribution of macrocephaly, intellectual disability, epilepsy, isolated electroencephalogram abnormalities and studied neuroimaging characteristics among groups. Recurrent and rare C-CNVs highlighting genes relevant to neurodevelopment had a statistically higher occurrence in children with more severe ASD symptoms and further developmental abnormalities. This study documents the importance of measuring the physical and neurobehavioural correlates of ASD phenotypes to unravel the underlying molecular mechanisms in patient subgroups.
Identification of Erbin interlinking MuSK and ErbB2 and its impact on acetylcholine receptor aggregation at the neuromuscular junction.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2010

Erbin, a binding partner of ErbB2, was identified as the first member of the LAP family of proteins. Erbin was shown at postsynaptic membranes of the neuromuscular junction (NMJ) or in cultured C2C12 myotubes (1) to be concentrated, (2) to regulate the Ras-Raf-Mek pathway, and (3) to inhibit TGF-beta signaling. In the CNS, Erbin interacts with PSD-95. Furthermore, agrin-MuSK signaling initiates formation of AChR aggregates at the postsynaptic membrane. In search of proteins interacting with MuSK, we identified Erbin as a MuSK binding protein. We verified the interaction of MuSK with Erbin, or both concomitantly with ErbB2 by coimmunoprecipitation, and we mapped the interacting epitopes between Erbin and MuSK. We demonstrated elevated mRNA levels of Erbin at synaptic nuclei and colocalized Erbin and MuSK at postsynaptic membranes. We identified several Erbin isoforms at the NMJ, all of which contained the MuSK binding domain. By knocking down Erbin, we observed agrin-dependent AChR aggregates on murine primary skeletal myotubes and C2C12 cells, and in the absence of agrin, microclusters, both of significantly lower density. Complementary, AChR-epsilon-reporter expression was reduced in myotubes overexpressing Erbin. We show that myotubes also express other LAP protein family members, namely Scribble and Lano, and that both affect physical dimensions of agrin-dependent AChR aggregates and density of microclusters formed in the absence of agrin. Moreover, MuSK-Erbin-ErbB2 signaling influences TGF-beta signaling. Our data define the requirement of Erbin on the cross talk between agrin and neuregulin signaling pathways at the NMJ.
Environmental enrichment as a therapeutic avenue for anxiety in aged Wistar rats: Effect on cat odor exposition and GABAergic interneurons.
Neuroscience, 2016

The use of more ethological animal models to study the neurobiology of anxiety has increased in recent years. We assessed the effect of an environmental enrichment (EE) protocol (24h/day over a period of two months) on anxiety-related behaviors when aged Wistar rats (21months old) were confronted with cat odor stimuli. Owing to the relationship between GABAergic interneurons and the anxiety-related neuronal network, we examined changes in the expression of Parvalbumin (PV) and 67kDa form of glutamic acid decarboxylase (GAD-67) immunoreactive cells in different brain regions involved in stress response. Behavioral results revealed that enriched rats traveled further and made more grooming behaviors during the habituation session. In the cat odor session, they traveled longer distances and they showed more active interaction with the odor stimuli and less time in freezing behavior. Zone analysis revealed that the enriched group spent more time in the intermediate zone according to the proximity of the predator odor. Regarding the neurobiological data, the EE increased the expression of PV-positive cells in some medial prefrontal regions (cingulate (Cg) and prelimbic (PL) cortices), whereas the GAD-67 expression in the basolateral amygdala was reduced in the enriched group. Our results suggest that EE is able to reduce anxiety-like behaviors in aged animals even when ethologically relevant stimuli are used. Moreover, GABAergic interneurons could be involved in mediating this resilient behavior.
Tumor treating fields: a novel treatment modality and its use in brain tumors.
Neuro-oncology, 2016

Tumor treating fields (TTFields) are low-intensity electric fields alternating at an intermediate frequency (200kHz), which have been demonstrated to block cell division and interfere with organelle assembly. This novel treatment modality has shown promise in a variety of tumor types. It has been evaluated in randomized phase 3 trials in glioblastoma (GBM) and demonstrated to prolong progression-free survival (PFS) and overall survival (OS) when administered together with standard maintenance temozolomide (TMZ) chemotherapy in patients with newly diagnosed GBM. TTFields are continuously delivered by 4 transducer arrays consisting each of 9 insulated electrodes that are placed on the patient's shaved scalp and connected to a portable device. Here we summarize the preclinical data and mechanism of action, the available clinical data, and further outlook of this treatment modality in brain tumors and other cancer indications.
Emotion regulation before and after transcranial magnetic stimulation in obsessive compulsive disorder.
Psychological medicine, 2015

Impaired emotion regulation may underlie exaggerated emotional reactivity in patients with obsessive compulsive disorder (OCD), yet instructed emotion regulation has never been studied in the disorder.
Short-term monocular deprivation alters early components of visual evoked potentials.
The Journal of physiology, 2015

Short-term monocular deprivation in adult humans produces a perceptual boost of the deprived eye reflecting homeostatic plasticity. Visual evoked potentials (VEPs) to transient stimuli change after 150 min of monocular deprivation in adult humans. The amplitude of the C1 component of the VEP at a latency of about 100 ms increases for the deprived eye and decreases for the non-deprived eye after deprivation, the two effects being highly negatively correlated. Similarly, the evoked alpha rhythm increases after deprivation for the deprived eye and decreases for the non-deprived eye. The data demonstrate that primary visual cortex excitability is altered by a short period of monocular deprivation, reflecting homeostatic plasticity.
Neurite outgrowth in normal and injured primary sensory neurons reveals different regulation by nerve growth factor (NGF) and artemin.
Molecular and cellular neurosciences, 2015

Neurotrophic factors have been intensively studied as potential therapeutic agents for promoting neural regeneration and functional recovery after nerve injury. Artemin is a member of the glial cell line-derived neurotrophic factor (GDNF) family of ligands (GFLs) that forms a signalling complex with GFRα3 and the tyrosine kinase Ret. Systemic administration of artemin in rodents is reported to facilitate regeneration of primary sensory neurons following axotomy, improve recovery of sensory function, and reduce sensory hypersensitivity that is a cause of pain. However, the biological mechanisms that underlie these effects are mostly unknown. This study has investigated the biological significance of the colocalisation of GFRα3 with TrkA (neurotrophin receptor for nerve growth factor [NGF]) in the peptidergic type of unmyelinated (C-fibre) sensory neurons in rat dorsal root ganglia (DRG). In vitro neurite outgrowth assays were used to study the effects of artemin and NGF by comparing DRG neurons that were previously uninjured, or were axotomised in vivo by transecting a visceral or somatic peripheral nerve. We found that artemin could facilitate neurite initiation but in comparison to NGF had low efficacy for facilitating neurite elongation and branching. This low efficacy was not increased when a preconditioning in vivo nerve injury was used to induce a pro-regenerative state. Neurite initiation was unaffected by artemin when PI3 kinase and Src family kinase signalling were blocked, but NGF had a reduced effect.
Animals with a schizophrenia-like phenotype are differentially sensitive to the motivational effects of cannabinoid agonists in conditioned place preference.
Behavioural brain research, 2014

Cannabis is the most consumed illicit drug worldwide, but among patients with a diagnosis of schizophrenia, this consumption is higher suggesting that they are differentially sensitive to cannabis. We chose to study this problematic using a neurodevelopmental model of schizophrenia: neonatal ventral hippocampus lesions (NVHL). In a first study, we compared the locomotor response to novelty, a mild stress and two doses of amphetamine (0.75 and 1.5 mg/kg) in sham and NVHL rats at post-natal day 35 (PD35) or 56 (PD56). In a second study, we investigated the valence of the motivational effect of Delta-9-tetrahydrocannabinnol (THC, 0.5 mg/kg, i.p.) and the cannabinoid receptor agonist, WIN55,212-2 (WIN, 1 mg/kg, i.p.), using the conditioned place preference paradigm; we used a biased procedure that comprised 12 days of testing with 3 paired-conditioning. The effects of this dose of WIN were also measured on locomotor activity. Results confirmed that the adult NVHL animals displayed a stronger locomotor response to the two doses of amphetamine, but not to novelty and a mild stress. In adult NVHL, but not sham animals, WIN stimulated locomotor activity and produced a conditioned place aversion. At the dose tested, THC tended to produce an aversion in adult sham but not NVHL animals. Taken together these findings show that adult animals with a schizophrenia-like phenotype are differentially sensitive to the motivational effect of cannabinoids.
Quaking Regulates Neurofascin 155 Expression for Myelin and Axoglial Junction Maintenance.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2016

RNA binding proteins required for the maintenance of myelin and axoglial junctions are unknown. Herein, we report that deletion of the Quaking (QKI) RNA binding proteins in oligodendrocytes (OLs) using Olig2-Cre results in mice displaying rapid tremors at postnatal day 10, followed by death at postnatal week 3. Extensive CNS hypomyelination was observed as a result of OL differentiation defects during development. The QKI proteins were also required for adult myelin maintenance, because their ablation using PLP-CreERT resulted in hindlimb paralysis with immobility at ∼30 d after 4-hydroxytamoxifen injection. Moreover, deterioration of axoglial junctions of the spinal cord was observed and is consistent with a loss of Neurofascin 155 (Nfasc155) isoform that we confirmed as an alternative splice target of the QKI proteins. Our findings define roles for the QKI RNA binding proteins in myelin development and maintenance, as well as in the generation of Nfasc155 to maintain healthy axoglial junctions.
EEG Frontal Alpha Asymmetry and Dream Affect: Alpha Oscillations over the Right Frontal Cortex during REM Sleep and Presleep Wakefulness Predict Anger in REM Sleep Dreams.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2019

Affective experiences are central not only to our waking life but also to rapid eye movement (REM) sleep dreams. Despite our increasing understanding of the neural correlates of dreaming, we know little about the neural correlates of dream affect. Frontal alpha asymmetry (FAA) is considered a marker of affective states and traits as well as affect regulation in the waking state. Here, we explored whether FAA during REM sleep and during evening resting wakefulness is related to affective experiences in REM sleep dreams. EEG recordings were obtained from 17 human participants (7 men) who spent 2 nights in the sleep laboratory. Participants were awakened 5 min after the onset of every REM stage after which they provided a dream report and rated their dream affect. Two-minute preawakening EEG segments were analyzed. Additionally, 8 min of evening presleep and morning postsleep EEG were recorded during resting wakefulness. Mean spectral power in the alpha band (8-13 Hz) and corresponding FAA were calculated over the frontal (F4-F3) sites. Results showed that FAA during REM sleep, and during evening resting wakefulness, predicted ratings of dream anger. This suggests that individuals with greater alpha power in the right frontal hemisphere may be less able to regulate (i.e., inhibit) strong affective states, such as anger, in dreams. Additionally, FAA was positively correlated across wakefulness and REM sleep. Together, these findings imply that FAA may serve as a neural correlate of affect regulation not only in the waking but also in the dreaming state.
Safety and Outcomes of Different Surgical Techniques for Cubital Tunnel Decompression: A Systematic Review and Network Meta-analysis.
JAMA network open, 2020

Cubital tunnel syndrome is the second most common compressive neuropathy, affecting 6% of the population. Numerous different operations are performed globally to treat it; however, prior conventional (pairwise) meta-analyses have been unable to determine which procedure is associated with the best outcomes and fewest complications.