rudyvdbrink/CitationDatabase huggingface dataset:
The over-pruning hypothesis of autism.
Developmental science, 2016

This article outlines the over-pruning hypothesis of autism. The hypothesis originates in a neurocomputational model of the regressive sub-type (Thomas, Knowland & Karmiloff-Smith, 2011a, 2011b). Here we develop a more general version of the over-pruning hypothesis to address heterogeneity in the timing of manifestation of ASD, including new computer simulations which reconcile the different observed developmental trajectories (early onset, late onset, regression) via a single underlying atypical mechanism; and which show how unaffected siblings of individuals with ASD may differ from controls either by inheriting a milder version of the pathological mechanism or by co-inheriting the risk factors without the pathological mechanism. The proposed atypical mechanism involves overly aggressive synaptic pruning in infancy and early childhood, an exaggeration of a normal phase of brain development. We show how the hypothesis generates novel predictions that differ from existing theories of ASD including that (1) the first few months of development in ASD will be indistinguishable from typical, and (2) the earliest atypicalities in ASD will be sensory and motor rather than social. Both predictions gain cautious support from emerging longitudinal studies of infants at-risk of ASD. We review evidence consistent with the over-pruning hypothesis, its relation to other current theories (including C. Frith's under-pruning proposal; C. Frith, 2003, 2004), as well as inconsistent data and current limitations. The hypothesis situates causal accounts of ASD within a framework of protective and risk factors (Newschaffer et al., 2012); clarifies different versions of the broader autism phenotype (i.e. the implication of observed similarities between individuals with autism and their family members); and integrates data from multiple disciplines, including behavioural studies, neuroscience studies, genetics, and intervention studies.
3D patterned stem cell differentiation using thermo-responsive methylcellulose hydrogel molds.
Scientific reports, 2016

Tissue-specific patterned stem cell differentiation serves as the basis for the development, remodeling, and regeneration of the multicellular structure of the native tissues. We herein proposed a cytocompatible 3D casting process to recapitulate this patterned stem cell differentiation for reconstructing multicellular tissues in vitro. We first reconstituted the 2D culture conditions for stem cell fate control within 3D hydrogel by incorporating the sets of the diffusible signal molecules delivered through drug-releasing microparticles. Then, utilizing thermo-responsivity of methylcellulose (MC), we developed a cytocompatible casting process to mold these hydrogels into specific 3D configurations, generating the targeted spatial gradients of diffusible signal molecules. The liquid phase of the MC solution was viscous enough to adopt the shapes of 3D impression patterns, while the gelated MC served as a reliable mold for patterning the hydrogel prepolymers. When these patterned hydrogels were integrated together, the stem cells in each hydrogel distinctly differentiated toward individually defined fates, resulting in the formation of the multicellular tissue structure bearing the very structural integrity and characteristics as seen in vascularized bones and osteochondral tissues.
Exposure to DMSO during infancy alters neurochemistry, social interactions, and brain morphology in long-evans rats.
Brain and behavior, 2021

Dimethyl sulfoxide (DMSO) is a widely used solvent to dissolve hydrophobic substances for clinical uses and experimental in vivo purposes. While usually regarded safe, our prior studies suggest changes to behavior following DMSO exposure. We therefore evaluated the effects of a five-day, short-term exposure to DMSO on postnatal infant rats (P6-10).
Increased hippocampal neurogenesis and p21 expression in depression: dependent on antidepressants, sex, age, and antipsychotic exposure.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2013

The mammalian hippocampus continues to generate new neurons throughout life. The function of adult-generated neurons remains controversial, but adult neurogenesis in the hippocampus is related to depression. Studies show that neurogenesis in the hippocampus is regulated by antidepressants in both humans and rodents, but no studies have examined the effects of age, sex, or antipsychotic exposure on the relationship between depression, antidepressant exposure, and hippocampal neurogenesis in humans. Hippocampal sections were obtained from the Stanley Medical Research Institute and were immunohistochemically labeled for the immature neuron marker doublecortin and the cell cycle arrest marker p21. We compared the number of cells in the granule cell layer and subgranular zone that expressed these proteins in brains from control subjects (n=12), patients with major depressive disorder (MDD) without psychotic symptoms (n=12), and patients with MDD and psychotic symptoms (n=12). We show here that the density of doublecortin/NeuN expression was increased in MDD patients compared with controls and MDD patients with psychosis, with the effect greater in women. Further, we show that older depressed patients without psychosis had higher levels of p21/NeuN expression and that depressed individuals prescribed antidepressants had higher levels of p21/NeuN expression, but only in older women. We show for the first time that changes in neurogenesis due to prescribed antidepressants or depression are dependent on age, sex, and the presence of antipsychotics or psychotic symptoms.
tTARGIT AAVs mediate the sensitive and flexible manipulation of intersectional neuronal populations in mice.
eLife, 2021

While Cre-dependent viral systems permit the manipulation of many neuron types, some cell populations cannot be targeted by a single DNA recombinase. Although the combined use of Flp and Cre recombinases can overcome this limitation, insufficient recombinase activity can reduce the efficacy of existing Cre+Flp-dependent viral systems. We developed a sensitive dual recombinase-activated viral approach: tTA-driven Recombinase-Guided Intersectional Targeting (tTARGIT) adeno-associated viruses (AAVs). tTARGIT AAVs utilize a Flp-dependent tetracycline transactivator (tTA) 'Driver' AAV and a tetracycline response element-driven, Cre-dependent 'Payload' AAV to express the transgene of interest. We employed this system in
Probabilistic Representation in Human Visual Cortex Reflects Uncertainty in Serial Decisions.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2019

How does the brain represent the reliability of its sensory evidence? Here, we test whether sensory uncertainty is encoded in cortical population activity as the width of a probability distribution, a hypothesis that lies at the heart of Bayesian models of neural coding. We probe the neural representation of uncertainty by capitalizing on a well-known behavioral bias called serial dependence. Human observers of either sex reported the orientation of stimuli presented in sequence, while activity in visual cortex was measured with fMRI. We decoded probability distributions from population-level activity and found that serial dependence effects in behavior are consistent with a statistically advantageous sensory integration strategy, in which uncertain sensory information is given less weight. More fundamentally, our results suggest that probability distributions decoded from human visual cortex reflect the sensory uncertainty that observers rely on in their decisions, providing critical evidence for Bayesian theories of perception.
The impact of nonverbal ability on prevalence and clinical presentation of language disorder: evidence from a population study.
Journal of child psychology and psychiatry, and allied disciplines, 2016

Diagnosis of 'specific' language impairment traditionally required nonverbal IQ to be within normal limits, often resulting in restricted access to clinical services for children with lower NVIQ. Changes to DSM-5 criteria for language disorder removed this NVIQ requirement. This study sought to delineate the impact of varying NVIQ criteria on prevalence, clinical presentation and functional impact of language disorder in the first UK population study of language impairment at school entry.
The Bidirectional Relationship between Diabetes and Depression: A Literature Review.
Korean journal of family medicine, 2018

Diabetes is a major public health problem worldwide. Depression is a serious mental condition that decreases mental and physical functioning and reduces the quality of life. Several lines of evidence suggest a bidirectional relationship between diabetes and depression: diabetes patients are twice as likely to experience depression than nondiabetic individuals. In contrast, depression increases the risk of diabetes and interferes with its daily self-management. Diabetes patients with depression have poor glycemic control, reduced quality of life, and an increased risk of diabetes complications, consequently having an increased mortality rate. Conflicting evidence exists on the potential role of factors that may account for or modulate the relationship between diabetes and depression. Therefore, this review aims to highlight the most notable body of literature that dissects the various facets of the bidirectional relationship between diabetes and depression. A focused discussion of the proposed mechanisms underlying this relationship is also provided. We systematically reviewed the relevant literature in the PubMed database, using the keywords "Diabetes AND Depression". After exclusion of duplicate and irrelevant material, literature eligible for inclusion in this review was based on meta-analysis studies, clinical trials with large sample sizes (n≥1,000), randomized clinical trials, and comprehensive national and cross-country clinical studies. The evidence we present in this review supports the pressing need for long, outcome-oriented, randomized clinical trials to determine whether the identification and treatment of patients with these comorbid conditions will improve their medical outcomes and quality of life.
Cross-Cultural Effects of Cannabis Use Disorder: Evidence to Support a Cultural Neuroscience Approach.
Current addiction reports, 2017

Cannabis use disorders (CUDs) are prevalent worldwide. Current epidemiological studies underscore differences in behaviors that contribute to cannabis use across cultures that can be leveraged towards prevention and treatment of CUDs. This review proposes a framework for understanding the effects of cross-cultural differences on psychological, neural, and genomic processes underlying CUDs that has the potential to inform global policies and impact global public health.
Emotional and behavioural problems in Swedish preschool children rated by preschool teachers with the Strengths and Difficulties Questionnaire (SDQ).
BMC pediatrics, 2017

There is a high risk that young children who show early signs of mental health problems develop symptoms in the same or overlapping areas some years later. The Strengths and Difficulties Questionnaire (SDQ) is widely used to screen externalizing and internalizing problems early in life. In Sweden 80-90% of all children aged 1-5 years go to preschool and preschool is thus an appropriate context for finding early signs of mental health problems among children.
Multi-component health promotion and disease prevention for community-dwelling frail elderly persons: a systematic review.
European journal of ageing, 2009

The objective was to investigate definitions of frailty used in studies of multi-component health promotion and disease-preventive (HPDP) intervention programmes for community-dwelling frail elderly persons and to review the content, organisation and effects of HPDP interventions. A systematic review of 19 articles was made, and the International Classification of Functioning, Disability and Health (ICF) was used as a structural framework for the analysis. The result shows that a consensus was reached on including various aspects of impairments in body functions and structures as an integral part of the frailty concept, with the exception of one subgroup: mental/cognitive functions. Additionally, opinions varied quite consistently regarding aspects of activity limitations and participation restrictions, personal and environmental factors. Ten of the 14 HPDP programmes covered various intervention elements referring to all four ICF components. Eleven programmes involved registered personnel only, while a more divergent pattern was seen in the remaining organisational aspects of the interventions: length of interventions and location plus age segments, participatory approach and contextual information, as well as the theoretical foundation of the interventions. Measures of body functions and structures were significantly improved in 5 out of 17 (29%) targeted aspects. For activity and participation, 12 out of 32 (38%) targeted aspects were positively changed, while the score for environmental factors was 7 out of 22 (32%), and for personal factors 8 out of 22 (36%). Our review suggests that further research is needed to explore and disentangle the complex interrelationships between various interventions and outcomes.
The impact of cognitive training in substance use disorder: the effect of working memory training on impulse control in methamphetamine users.
Psychopharmacology, 2017

Impulsivity is a vulnerability trait for poor self-regulation in substance use disorder (SUD). Working memory (WM) training improves impulsivity and self-regulation in psychiatric disorders. Here we test WM training in methamphetamine use disorder (MUD).
Dissociable source-monitoring impairments in obsessive-compulsive disorder and schizophrenia.
European psychiatry : the journal of the Association of European Psychiatrists, 2020

Based on the observed clinical overlap between obsessive-compulsive disorder (OCD) and schizophrenia (SCZ), both conditions may share, at least in part, common cognitive underpinnings. Among the cognitive deficits that could be involved, it has been hypothesized that patients share a failure in their abilities to monitor their own thoughts (source monitoring), leading to confusion between what they actually did or perceived and what they imagined. Although little is known regarding source-monitoring performances in patients with OCD, numerous studies in patients with SCZ have observed a relationship between delusions and/or hallucinations and deficits in both internal source- and reality-monitoring abilities.
Plasticity of recurrent l2/3 inhibition and gamma oscillations by whisker experience.
Neuron, 2013

Local recurrent networks in neocortex are critical nodes for sensory processing, but their regulation by experience is much less understood than for long-distance (translaminar or cross-columnar) projections. We studied local L2/3 recurrent networks in rat somatosensory cortex during deprivation-induced whisker map plasticity, by expressing channelrhodopsin-2 (ChR2) in L2/3 pyramidal cells and measuring light-evoked synaptic currents in ex vivo S1 slices. In columns with intact whiskers, brief light impulses evoked recurrent excitation and supralinear inhibition. Deprived columns showed modestly reduced excitation and profoundly reduced inhibition, providing a circuit locus for disinhibition of whisker-evoked responses observed in L2/3 in vivo. Slower light ramps elicited sustained gamma frequency oscillations, which were nearly abolished in deprived columns. Reduction in gamma power was also observed in spontaneous LFP oscillations in L2/3 of deprived columns in vivo. Thus, L2/3 recurrent networks are a powerful site for homeostatic modulation of excitation-inhibition balance and regulation of gamma oscillations.
An In Vitro Study of Aromatic Stacking of Drug Molecules.
Journal of the American Society for Mass Spectrometry, 2019

In this paper, drug-drug chemical interactions between two different aromatic compounds were studied by mass spectrometry. Specifically, we examined non-covalent complexes (NCX) between paclitaxel, a chemotherapeutic compound, and medications widely used in palliative care for depression, psychosis, and anxiety. It is unknown whether psychotropic medications directly interact with paclitaxel. Here, we use a simple and rapid electrospray ionization mass spectrometry in vitro assay, which has been predictive in the case of neuropeptides, to measure the relative strength of non-covalent interactions. This chemical interaction is most likely due to the overlap of aromatic rings of π-orbitals between paclitaxel and five commonly used medications: diazepam, clonozepam, sertraline, fluoxetine, and haloperidol. Molecular modeling illustrates that differences in the stability of the NCXs are likely due to the distance between the aromatic rings present in both the paclitaxel and antidepressant medications. Graphical Abstract.
Neuroimaging perspectives on fetal motor behavior.
Neuroscience and biobehavioral reviews, 2018

We are entering a new era of understanding human development with the ability to perform studies at the earliest time points possible. There is a substantial body of evidence to support the concept that early motor behaviour originates from supraspinal motor centres, reflects neurological integrity, and that altered patterns of behaviour precede clinical manifestation of disease. Cine Magnetic Resonance Imaging (cineMRI) has established its value as a novel method to visualise motor behaviour in the human fetus, building on the wealth of knowledge gleaned from ultrasound based studies. This paper presents a state of the art review incorporating findings from human and preclinical models, the insights from which, we propose, can proceed a reconceptualisation of fetal motor behaviour using advanced imaging techniques. Foremost is the need to better understand the role of the intrauterine environment, and its inherent unique set of stimuli that activate sensorimotor pathways and shape early brain development. Finally, an improved model of early motor development, combined with multimodal imaging, will provide a novel source of in utero biomarkers predictive of neurodevelopmental disorders.
Responsiveness of stem-like human glioma cells to all-trans retinoic acid and requirement of retinoic acid receptor isotypes α, β and γ.
Neuroscience, 2014

Retinoic acid (RA) is required for development and homeostasis of the normal mammalian brain and may play a role in the initiation and progression of malignant brain tumors, such as the glioblastoma multiforme (GBM) and the gliosarcoma (Gsarc). The subpopulation of stem-like glioma cells (SLGCs) was shown to resist standard glioma radio-/chemotherapy and to propagate tumor regrowth. We used phenotypically distinct, self-renewing SLGC lines from six human GBMs, two Gsarcs, and two subcloned SLGC derivatives in order to investigate their responsiveness to all-trans retinoic acid (atRA) and to identify the RA-receptor (RAR) isotypes involved. In general, atRA exerted a pro-proliferative and pro-survival effect on SLGCs, though the efficacy was distinct. By means of RAR isotype-selective retinoids we disclosed that these effects were mediated by RARα and RARγ, except for one SLGC line, in which the pro-proliferative signal was induced by the RARβ-selective retinoid. Only one GBM-derived cell line (T1338) and a subpopulation of another (T1389) displayed neural differentiation in response to atRA. Differentiation of T1338 was induced by RARα and RARγ isotype-selective retinoids, associated with down-regulation of Sox2, and the failure to induce orthotopic tumors in the brains of SCID mice. The differential responsiveness of the SLGC lines appeared unrelated to the expression of RARβ, as (i) atRA augmented RAR isotype mRNA expression and particularly rarβ mRNA in all SLGC lines, (ii) rarβ promoter hypomethylation in the SLGC lines was not related to differentiation and (iii) the induction of T1338 differentiation was by RARα- and RARγ-selective ligands.
Early deprivation, atypical brain development, and internalizing symptoms in late childhood.
Neuroscience, 2017

Children exposed to extreme early-life neglect such as in institutional rearing are at heightened risk for developing depression and anxiety disorders, and internalizing problems more broadly. These outcomes are believed to be due to alterations in the development of neural circuitry that supports emotion regulation. The specific neurodevelopmental changes that contribute to these difficulties are largely unknown. This study examined whether microstructural alterations in white matter pathways predicted long-term risk for internalizing problems in institutionally reared children. Data from 69 children were drawn from the Bucharest Early Intervention Project, a randomized clinical trial of foster care for institutionally reared children. White matter was assessed using diffusion tensor imaging (DTI) when children were between 8 and 10years of age. Internalizing symptoms were assessed at the time of the MRI scan, and once children reached 12-14years of age. Results indicated that neglect-associated alterations in the external capsule and corpus callosum partially explained links between institutional rearing status and internalizing symptoms in middle childhood and early adolescence. Findings shed light on neural mechanisms contributing to increased risk for emotional difficulties among children reared in adverse conditions and have implications for prevention and intervention.
Brain monoamine oxidase A activity predicts trait aggression.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2008

The genetic deletion of monoamine oxidase A (MAO A), an enzyme that breaks down the monoamine neurotransmitters norepinephrine, serotonin, and dopamine, produces aggressive phenotypes across species. Therefore, a common polymorphism in the MAO A gene (MAOA, Mendelian Inheritance in Men database number 309850, referred to as high or low based on transcription in non-neuronal cells) has been investigated in a number of externalizing behavioral and clinical phenotypes. These studies provide evidence linking the low MAOA genotype and violent behavior but only through interaction with severe environmental stressors during childhood. Here, we hypothesized that in healthy adult males the gene product of MAO A in the brain, rather than the gene per se, would be associated with regulating the concentration of brain amines involved in trait aggression. Brain MAO A activity was measured in vivo in healthy nonsmoking men with positron emission tomography using a radioligand specific for MAO A (clorgyline labeled with carbon 11). Trait aggression was measured with the multidimensional personality questionnaire (MPQ). Here we report for the first time that brain MAO A correlates inversely with the MPQ trait measure of aggression (but not with other personality traits) such that the lower the MAO A activity in cortical and subcortical brain regions, the higher the self-reported aggression (in both MAOA genotype groups) contributing to more than one-third of the variability. Because trait aggression is a measure used to predict antisocial behavior, these results underscore the relevance of MAO A as a neurochemical substrate of aberrant aggression.