rudyvdbrink/CitationDatabase huggingface dataset:
Priorities for Advancing Research on Youth with Autism Spectrum Disorder and Co-occurring Anxiety.
Journal of autism and developmental disorders, 2018

Research on anxiety disorders in youth with autism spectrum disorder (ASD) has burgeoned in the past two decades. Yet, critical gaps exist with respect to measuring and treating anxiety in this population. This study used the nominal group technique to identify the most important research priorities on co-occurring anxiety in ASD. An international group of researchers and clinicians with experience in ASD and anxiety participated in the process. Topics ranked as most important focused on understanding how ASD symptoms affect treatment response, implementing treatments in real world settings, developing methods to disentangle overlapping symptoms between anxiety and ASD, and developing objective measures to assess anxiety. Collectively, these priorities can lead to collaborative studies to accelerate research in the field.
Visual crowding in V1.
Cerebral cortex (New York, N.Y. : 1991), 2014

In peripheral vision, objects in clutter are difficult to identify. The exact cause of this "crowding" effect is unclear. To perceive coherent shapes in clutter, the visual system must integrate certain local features across receptive fields while preventing others from being combined. It is believed that this selective feature integration-segmentation process is impaired in peripheral vision, leading to crowding. We used functional magnetic resonance imaging (fMRI) to investigate the neural origin of crowding. We found that crowding was associated with suppressed fMRI signal as early as V1, regardless of whether attention was directed toward or away from a target stimulus. This suppression in early visual cortex was greatest for stimuli that produced the strongest crowding. In contrast, the pattern of activity was mixed in higher level visual areas, such as the lateral occipital cortex. These results support the view that the deficiency in feature integration and segmentation in peripheral vision is present at the earliest stages of cortical processing.
One Step at a Time: Representational Overlap Between Active Voice, Be-passive, and Get-passive Forms in English.
Journal of cognition, 2018

The active voice and passive voice are complementary sentence forms that are available when describing a transitive event. In English, the latter has two variants: be-passive and get-passive. Numerous attempts have been made in the literature to represent the syntactic and semantic differences between these forms, while maintaining their shared features, yet theoretical accounts still differ. At the same time, empirical studies into structural choice have frequently investigated the use of passive voice versus active voice, while the distinction between get- versus be-passive has not received much attention. Here we investigate the degree of similarity between the three transitive variants (be-passive, get-passive, active voice), providing experimental evidence of their mental representations in relation to each other. We describe three experiments in which participants gave acceptability or naturalness ratings for sentences formed with either be-passive or get-passive, and containing one of several adjunct types. Participants were also free to provide an alternative way to phrase each, enabling us to consider whether there are differences in accessing alternatives. We observed overwhelming preferences for changing get-passives into be-passives, and for changing be-passives into active voice, but none for changing get-passives directly into active voice (despite active voice being the most preferred variant). This preference for changing get-passive into be-passive was observed even when a change into active voice was further facilitated by the availability of a 'ready-made' agent. These patterns of change are consistent with partial representational overlap along two dimensions described by Thompson et al. (2013): Patient Prominence and Patient Importance. Our findings also contribute to discussions of passive structure by revealing the relative closeness of the mental representations of these forms.
Blood-Based Protein Changes in Childhood Are Associated With Increased Risk for Later Psychotic Disorder: Evidence From a Nested Case-Control Study of the ALSPAC Longitudinal Birth Cohort.
Schizophrenia bulletin, 2018

The identification of early biological changes associated with the psychotic disorder (PD) is important as it may provide clues to the underlying pathophysiological mechanisms. We undertook the first proteomic profiling of blood plasma samples of children who later develop a PD. Participants were recruited from the UK Avon Longitudinal Study of Parents and Children (ALSPAC) cohort who also participated in psychiatric assessment interviews at age 18. Protein expression levels at age 11 were compared between individuals who developed PD at age 18 (n = 37) with population-based age-matched controls (n = 38). Sixty out of 181 plasma proteins profiled were found to be differentially expressed (P < .05) in children with an outcome of the PD. Thirty-four of these proteins were found to be differentially expressed following correction for multiple comparisons. Pathway analysis implicated the complement and coagulation cascade. A second, targeted proteomic approach was used to verify these findings in age 11 plasma from subjects who reported psychotic experiences at age 18 (n = 40) in comparison to age-matched controls (n = 66). Our findings indicate that the complement and coagulation system is dysregulated in the blood during childhood before the development of the PD.
Cognitive Behavioral Therapy increases pain-evoked activation of the prefrontal cortex in patients with fibromyalgia.
Pain, 2012

Interventions based on Cognitive Behavioral Therapy (CBT) are widely used to treat chronic pain, but the brain mechanisms responsible for these treatment effects are poorly understood. The aim of this study was to validate the relevance of the cortical control theory in response to an exposure-based form of CBT, Acceptance and Commitment Therapy, in patients with chronic pain. Forty-three female patients diagnosed with fibromyalgia syndrome were enrolled in a randomized, 12-week, waiting-list controlled clinical trial (CBT n=25; controls n=18). CBT was administered in groups of six patients during 12 weekly sessions. Functional magnetic resonance imaging (fMRI) during pressure-evoked pain was assessed before and after treatment or the 12-week period. Self-report questionnaires of depression and anxiety were administered pre- and posttreatment as well as 3 months following end of treatment. Patients treated with CBT reported larger improvement of fibromyalgia on the Patient Global Impression of Change measure, and improved depression and anxiety symptoms, compared to the waiting-list controls. However, there were no effects on clinical pain or pain sensitivity measures. An analysis of fMRI scans revealed that CBT led to increased activations in the ventrolateral prefrontal/lateral orbitofrontal cortex; regions associated with executive cognitive control. We suggest that CBT changes the brain's processing of pain through an altered cerebral loop between pain signals, emotions, and cognitions; leading to increased access to executive regions for reappraisal of pain. Our data thereby support our hypothesis about the activation of a cortical control mechanism in response to CBT treatment in chronic pain.
PyrPeg, a Blood-Brain-Barrier-Penetrating Two-Photon Imaging Probe, Selectively Detects Neuritic Plaques, Not Tau Aggregates.
ACS chemical neuroscience, 2020

Amyloid-β (Aβ) tracers have made a significant contribution to the treatment of Alzheimer's disease (AD) by allowing a definitive diagnosis in living patients. Unfortunately, they also detect tau and other protein aggregates that compromise test accuracy. In AD research, there has been a growing need for
Effects of all-trans-retinoic acid on human SH-SY5Y neuroblastoma as in vitro model in neurotoxicity research.
Neurotoxicology, 2009

Human neuroblastoma SH-SY5Y is a dopaminergic neuronal cell line which has been used as an in vitro model for neurotoxicity experiments. Although the neuroblastoma is usually differentiated by all-trans-retinoic acid (RA), both RA-differentiated and undifferentiated SH-SY5Y cells have been used in neuroscience research. However, the changes in neuronal properties triggered by RA as well as the subsequent responsiveness to neurotoxins have not been comprehensively studied. Therefore, we aim to re-evaluate the differentiation property of RA on this cell line. We hypothesize that modulation of signaling pathways and neuronal properties during RA-mediated differentiation in SH-SY5Y cells can affect their susceptibility to neurotoxins. The differentiation property of RA was confirmed by showing an extensive outgrowth of neurites, increased expressions of neuronal nuclei, neuron specific enolase, synaptophysin and synaptic associated protein-97, and decreased expression of inhibitor of differentiation-1. While undifferentiated SH-SY5Y cells were susceptible to 6-OHDA and MPP+, RA-differentiation conferred SH-SY5Y cells higher tolerance, potentially by up-regulating survival signaling, including Akt pathway as inhibition of Akt removed RA-induced neuroprotection against 6-OHDA. As a result, the real toxicity cannot be revealed in RA-differentiated cells. Therefore, undifferentiated SH-SY5Y is more appropriate for studying neurotoxicity or neuroprotection in experimental Parkinson's disease research.
Pharmacological investigations on potential of peroxisome proliferator-activated receptor-gamma agonists in hyperhomocysteinemia-induced vascular dementia in rats.
Neuroscience, 2011

The present study has been designed to investigate the potential of peroxisome proliferator-activated receptor-gamma ([PPAR]-γ) agonists, pioglitazone, and rosiglitazone in hyperhomocysteinemia-induced vascular dementia of rats. l-methionine was administered for 8 weeks to induce hyperhomocysteinemia and associated vascular dementia. Pioglitazone and rosiglitazone were administered to l-methionine-treated rats for 4 weeks (starting from 5th to 8th weeks of methionine treatment). Donepezil served as a positive control in this study. On 52nd day onward, the animals were exposed to Morris water maze (MWM) for testing learning and memory abilities. Vascular endothelial function, serum nitrite/nitrate levels, brain thiobarbituric acid reactive species (TBARS), brain reduced glutathione (GSH) levels, and brain acetylcholinesterase (AChE) activity were also measured. l-methionine-treated animals have shown impairment of learning, memory, endothelial function, decrease in serum nitrite/nitrate levels, and brain GSH levels along with increase in brain TBARS levels and AChE activity. Pioglitazone, rosiglitazone, and donepezil significantly improved hyperhomocysteinemia-induced impairment of learning, memory, endothelial dysfunction, and changes in various biochemical parameters. It is concluded that pioglitazone and rosiglitazone may be considered as potential pharmacological agents for the management of hyperhomocysteinemia-induced vascular dementia.
Local transgene expression and whole-body transgenesis to model brain diseases in nonhuman primate.
Animal models and experimental medicine, 2019

Animal model is an essential tool in the life sciences research, notably in understanding the pathogenesis of the diseases and for further therapeutic intervention success. Rodents have been the most frequently used animals to model human disease since the establishment of gene manipulation technique. However, they remain inadequate to fully mimic the pathophysiology of human brain disease, partially due to huge differences between rodents and humans in terms of anatomy, brain function, and social behaviors. Nonhuman primates are more suitable in translational perspective. Thus, genetically modified animals have been generated to investigate neurologic and psychiatric disorders. The classical transgenesis technique is not efficient in that model; so, viral vector-mediated transgene delivery and the new genome-editing technologies have been promoted. In this review, we summarize some of the technical progress in the generation of an ad hoc animal model of brain diseases by gene delivery and real transgenic nonhuman primate.
High-fat diet-induced obesity exacerbates kainic acid-induced hippocampal cell death.
BMC neuroscience, 2015

Obesity has deleterious effects on the brain, and metabolic dysfunction may exacerbate the outcomes of seizures and brain injuries. However, it is unclear whether obesity affects excitotoxicity-induced neuronal cell death. The purpose of this study was to investigate the effects of a high-fat diet (HFD) on neuroinflammation and oxidative stress in the hippocampus of kainic acid (KA)-treated mice.
Spiking activity propagation in neuronal networks: reconciling different perspectives on neural coding.
Nature reviews. Neuroscience, 2010

The brain is a highly modular structure. To exploit modularity, it is necessary that spiking activity can propagate from one module to another while preserving the information it carries. Therefore, reliable propagation is one of the key properties of a candidate neural code. Surprisingly, the conditions under which spiking activity can be propagated have received comparatively little attention in the experimental literature. By contrast, several computational studies in the last decade have addressed this issue. Using feedforward networks (FFNs) as a generic network model, they have identified two dynamical activity modes that support the propagation of either asynchronous (rate code) or synchronous (temporal code) spiking. Here, we review the dichotomy of asynchronous and synchronous propagation in FFNs, propose their integration into a single extended conceptual framework and suggest experimental strategies to test our hypothesis.
Genome-wide analysis of the nucleus accumbens identifies DNA methylation signals differentiating low/binge from heavy alcohol drinking.
Alcohol (Fayetteville, N.Y.), 2017

Alcohol-use disorders encompass a range of drinking levels and behaviors, including low, binge, and heavy drinking. In this regard, investigating the neural state of individuals who chronically self-administer lower doses of alcohol may provide insight into mechanisms that prevent the escalation of alcohol use. DNA methylation is one of the epigenetic mechanisms that stabilizes adaptations in gene expression and has been associated with alcohol use. Thus, we investigated DNA methylation, gene expression, and the predicted neural effects in the nucleus accumbens core (NAcc) of male rhesus macaques categorized as "low" or "binge" drinkers, compared to "alcohol-naïve" and "heavy" drinkers based on drinking patterns during a 12-month alcohol self-administration protocol. Using genome-wide CpG-rich region enrichment and bisulfite sequencing, the methylation levels of 2.6 million CpGs were compared between alcohol-naïve (AN), low/binge (L/BD), and heavy/very heavy (H/VHD) drinking subjects (n = 24). Through regional clustering analysis, we identified nine significant differential methylation regions (DMRs) that specifically distinguished ANs and L/BDs, and then compared those DMRs among H/VHDs. The DMRs mapped to genes encoding ion channels, receptors, cell adhesion molecules, and cAMP, NF-κβ and Wnt signaling pathway proteins. Two of the DMRs, linked to PDE10A and PKD2L2, were also differentially methylated in H/VHDs, suggesting an alcohol-dose independent effect. However, two other DMRs, linked to the CCBE1 and FZD5 genes, had L/BD methylation levels that significantly differed from both ANs and H/VHDs. The remaining five DMRs also differentiated L/BDs and ANs. However, H/VHDs methylation levels were not distinguishable from either of the two groups. Functional validation of two DMRs, linked to FZD5 and PDE10A, support their role in regulating gene expression and exon usage, respectively. In summary, the findings demonstrate that L/BD is associated with unique DNA methylation signatures in the primate NAcc, and that the methylation signatures identify synaptic genes that may play a role in preventing the escalation of alcohol use.
Feedback-related negativity reflects omission of monetary gains: Evidence from ERP gambling study.
Neuroscience letters, 2018

Feedback processing is an important aspect of learning. In the human brain, feedback processing is often examined by measuring an event-related potential, the feedback-related negativity component. Typically, the feedback-related negativity component is investigated by directly comparing gain with loss feedback randomized across trials; however, this method does not control for confounds associated with unexpected feedback. For this study we used a blocked design gambling task to investigate the sensitivity of feedback-related negativity to positive and negative feedback separately for gains and losses. While there appeared to be no significant feedback-related negativity in the loss domain, results revealed an enlarged feedback-related negativity during the omission of gains compared to the reception of gains. These findings further support the reward positivity hypothesis which declares that the feedback-related negativity is associated with the processing of outcomes in the context of gains as opposed to losses, irrespective of unexpectedness.
Dispensed prescriptions for quetiapine and other second-generation antipsychotics in Canada from 2005 to 2012: a descriptive study.
CMAJ open, 2014

The use of antipsychotic drugs, particularly quetiapine, has increased at an unprecedented rate in the last decade, primarily in relation to nonpsychotic indications. This increased use is concerning because of the high rates of metabolic and extrapyramidal side effects and inadequate monitoring of these complications. The purpose of this study was to measure the use of quetiapine and other second-generation antipsychotics by primary care physicians and psychiatrists and the most common diagnoses associated with quetiapine recommendations.
Cerebrospinal fluid metabolomics identifies a key role of isocitrate dehydrogenase in bipolar disorder: evidence in support of mitochondrial dysfunction hypothesis.
Molecular psychiatry, 2016

Although evidence for mitochondrial dysfunction in the pathogenesis of bipolar disorder (BD) has been reported, the precise biological basis remains unknown, hampering the search for novel biomarkers. In this study, we performed metabolomics of cerebrospinal fluid (CSF) from male BD patients (n=54) and age-matched male healthy controls (n=40). Subsequently, post-mortem brain analyses, genetic analyses, metabolomics of CSF samples from rats treated with lithium or valproic acid were also performed. After multivariate logistic regression, isocitric acid (isocitrate) levels were significantly higher in the CSF from BD patients than healthy controls. Furthermore, gene expression of two subtypes (IDH3A and IDH3B) of isocitrate dehydrogenase (IDH) in the dorsolateral prefrontal cortex from BD patients was significantly lower than that of controls, although the expression of other genes including, aconitase (ACO1, ACO2), IDH1, IDH2 and IDH3G, were not altered. Moreover, protein expression of IDH3A in the cerebellum from BD patients was higher than that of controls. Genetic analyses showed that IDH genes (IDH1, IDH2, IDH3A, IDH3B) and ACO genes (ACO1, ACO2) were not associated with BD. Chronic (4 weeks) treatment with lithium or valproic acid in rats did not alter CSF levels of isocitrate, and mRNA levels of Idh3a, Idh3b, Aco1 and Aco2 genes in the rat brain. These findings suggest that abnormality in the metabolism of isocitrate by IDH3A in the mitochondria plays a key role in the pathogenesis of BD, supporting the mitochondrial dysfunction hypothesis of BD. Therefore, IDH3 in the citric acid cycle could potentially be a novel therapeutic target for BD.
Abnormal tau phosphorylation in primary progressive multiple sclerosis.
Acta neuropathologica, 2010

Although neurodegeneration is the pathological substrate of progression in multiple sclerosis (MS), the underlying mechanisms remain unresolved. Abnormal phosphorylation of tau, implicated in the aetiopathogenesis of a number of classic neurodegenerative disorders, has also recently been described in secondary progressive MS (SPMS). In contrast to SPMS, primary progressive MS (PPMS) represents a significant subset of patients with accumulating neurological disability from onset. The neuropathological relationship between SPMS and PPMS is unknown. Against this background, we investigated tau phosphorylation status in five cases of PPMS using immunohistochemical and biochemical methods. We report widespread abnormal tau hyperphosphorylation of the classic tau phospho-epitopes occurring in multiple cell types but with a clear immunohistochemical glial bias. In addition, biochemical analysis revealed abnormally phosphorylated insoluble tau in all cases. These findings establish a platform for further study of the role of insoluble tau formation, including determining the relevance of glial tau pathology, in the neurodegenerative phase of MS.
Dysfunctional Limbic Circuitry Underlying Freezing of Gait in Parkinson's Disease.
Neuroscience, 2018

Freezing of gait (FOG) is a poorly understood symptom affecting many patients with Parkinson's disease (PD). Despite growing evidence of a behavioral link between anxiety, attention and FOG in PD, no research to date has investigated the neural mechanisms that might explain this relationship. The present study therefore examined resting-state MRI functional connectivity between the amygdala, striatum and frontoparietal attentional control network in PD patients with (freezers: n = 19) and without FOG (non-freezers: n = 21) in the dopaminergic 'off' state. Functional connectivity was subsequently correlated with an objective measure of FOG severity and a subjective scale of affective disorder within each group. Connectivity between the right amygdala and right putamen was significantly increased in freezers compared to non-freezers (p < 0.01). Furthermore, freezers showed increased anti-coupling between the frontoparietal network and left amygdala (p = 0.011), but reduced anti-coupling between this network and the right putamen (p = 0.027) as compared to non-freezers. Key functional connections between the amygdala, putamen and frontoparietal network were significantly associated with FOG severity and a fear of falling. This study provides the first evidence that dysfunctional fronto-striato-limbic processes may underpin the link between anxiety and FOG in PD. It is proposed that freezers have heightened striato-limbic load and reduced top-down attentional control at rest, which when further challenged by the parallel processing demands of walking may precipitate FOG.
The Rab5-Rab11 Endosomal Pathway is Required for BDNF-Induced CREB Transcriptional Regulation in Hippocampal Neurons.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2020

Brain-derived neurotrophic factor (BDNF) is a key regulator of the morphology and connectivity of central neurons. We have previously shown that BDNF/TrkB signaling regulates the activity and mobility of the GTPases Rab5 and Rab11, which in turn determine the postendocytic sorting of signaling TrkB receptors. Moreover, decreased Rab5 or Rab11 activity inhibits BDNF-induced dendritic branching. Whether Rab5 or Rab11 activity is important for local events only or for regulating nuclear signaling and gene expression is unknown. Here, we investigated, in rat hippocampal neuronal cultures derived from embryos of unknown sex, whether BDNF-induced signaling cascades are altered when early and recycling endosomes are disrupted by the expression of dominant-negative mutants of Rab5 and Rab11. The activity of both Rab5 and Rab11 was required for sustained activity of Erk1/2 and nuclear CREB phosphorylation, and increased transcription of a BDNF-dependent program of gene expression containing CRE binding sites, which includes activity-regulated genes such as