ResearchPad - Developmental Neuroscience https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Misophonia: Phenomenology, comorbidity and demographics in a large sample]]> https://www.researchpad.co/product?articleinfo=N4224db8b-e824-4eb2-b1dc-d3c3ccfee32c

Objective

Analyze a large sample with detailed clinical data of misophonia subjects in order to determine the psychiatric, somatic and psychological nature of the condition.

Methods

This observational study of 779 subjects with suspected misophonia was conducted from January 2013 to May 2017 at the outpatient-clinic of the Amsterdam University Medical Centers, location AMC, the Netherlands. We examined DSM-IV diagnoses, results of somatic examination (general screening and hearing tests), and 17 psychological questionnaires (e.g., SCL-90-R, WHOQoL).

Results

The diagnosis of misophonia was confirmed in 575 of 779 referred subjects (74%). In the sample of misophonia subjects (mean age, 34.17 [SD = 12.22] years; 399 women [69%]), 148 (26%) subjects had comorbid traits of obsessive-compulsive personality disorder, 58 (10%) mood disorders, 31 (5%) attention-deficit (hyperactivity) disorder, and 14 (3%) autism spectrum conditions. Two percent reported tinnitus and 1% hyperacusis. In a random subgroup of 109 subjects we performed audiometry, and found unilateral hearing loss in 3 of them (3%). Clinical neurological examination and additional blood test showed no abnormalities. Psychological tests revealed perfectionism (97% CPQ>25) and neuroticism (stanine 7 NEO-PI-R). Quality of life was heavily impaired and associated with misophonia severity (rs (184) = -.34 p = < .001, p = < .001).

Limitations

This was a single site study, leading to possible selection–and confirmation bias, since AMC-criteria were used.

Conclusions

This study with 575 subjects is the largest misophonia sample ever described. Based on these results we propose a set of revised criteria useful to diagnose misophonia as a psychiatric disorder.

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<![CDATA[Social re-orientation and brain development: An expanded and updated view]]> https://www.researchpad.co/product?articleinfo=Ned891d80-d904-4901-a305-83a0fe0cc6fc

Highlights

  • We expand our adolescent re-orientation model to include other developmental periods.

  • We review neuroimaging literature on social information processing.

  • We combine human and animal based approaches to social behavior.

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<![CDATA[The dual systems model: Review, reappraisal, and reaffirmation]]> https://www.researchpad.co/product?articleinfo=Nd9d7997f-e8be-49f0-af38-adb730c99c8b

Highlights

  • Evidence related to the dual systems model of adolescent risk taking is reviewed.

  • The review encompasses both the psychological and neuroimaging literatures.

  • Recent findings (since 2008) generally support the dual systems model.

  • Recommendations are made for future research directions.

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<![CDATA[Developing developmental cognitive neuroscience: From agenda setting to hypothesis testing]]> https://www.researchpad.co/product?articleinfo=Nb2719aad-255f-4e35-8c0b-7efa7ce45044 ]]> <![CDATA[Beyond simple models of adolescence to an integrated circuit-based account: A commentary]]> https://www.researchpad.co/product?articleinfo=N1ca63c6a-8b21-4244-aee3-fe5a05e0bbec ]]> <![CDATA[The developmental neuroscience of adolescence: Revisiting, refining, and extending seminal models]]> https://www.researchpad.co/product?articleinfo=Nae9367c3-4e37-4bf7-a6d9-d2f7a406db06 ]]> <![CDATA[The importance of sexual and romantic development in understanding the developmental neuroscience of adolescence]]> https://www.researchpad.co/product?articleinfo=N94f95d8c-1ca1-4014-98ea-f4a28caaca5e ]]> <![CDATA[Effects of ketamine on voltage-gated sodium channels in the barrel cortex and the ventral posteromedial nucleus slices of rats]]> https://www.researchpad.co/product?articleinfo=N33919e34-532b-4436-9da0-077de6a1c876

Supplemental Digital Content is available in the text.

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<![CDATA[Brain expansion promoted by polycomb-mediated anterior enhancement of a neural stem cell proliferation program]]> https://www.researchpad.co/product?articleinfo=5c7ee7d4d5eed0c4848f4f0c

During central nervous system (CNS) development, genetic programs establish neural stem cells and drive both stem and daughter cell proliferation. However, the prominent anterior expansion of the CNS implies anterior–posterior (A–P) modulation of these programs. In Drosophila, a set of neural stem cell factors acts along the entire A–P axis to establish neural stem cells. Brain expansion results from enhanced stem and daughter cell proliferation, promoted by a Polycomb Group (PcG)->Homeobox (Hox) homeotic network. But how does PcG->Hox modulate neural-stem-cell–factor activity along the A–P axis? We find that the PcG->Hox network creates an A–P expression gradient of neural stem cell factors, thereby driving a gradient of proliferation. PcG mutants can be rescued by misexpression of the neural stem cell factors or by mutation of one single Hox gene. Hence, brain expansion results from anterior enhancement of core neural-stem-cell–factor expression, mediated by PcG repression of brain Hox expression.

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<![CDATA[Antipruritic effects of electroacupuncture on morphine-induced pruritus model mice through the TLR2/4-MyD88-NF-κB pathway]]> https://www.researchpad.co/product?articleinfo=5c973e4ed5eed0c48496b471

Pruritus is one of the common side effects of intrathecal or epidural injection of opioids. The aim of this study was to test the antipruritic effect of acupuncture and its possible mechanism. We used electroacupuncture (EA), toll-like receptor (TLR)2/4 antagonist sparstolonin B (SsnB), and TLR2/4 agonist peptidoglycan (PGN) to precondition female wild-type BALB/c mice, and then prepared a morphine-induced pruritus model. The mRNA and protein expression levels of TLR2, TLR4, MyD88, and NF-κB were detected by RT-PCR and western blotting. The contents of interleukin (IL)-1, IL-6, IL-12, IL-10, and tumor necrosis factor-α in serum were measured by ELISA assays. Flow cytometry was performed to analyze the ratio of M1-phenotype to M2-phenotype macrophages. Our results showed that EA preconditioning improved pruritus; reduced the expressions of TLR2, TLR4, MyD88, and NF-κB both at the mRNA and protein levels (P<0.05); reduced the expression of proinflammatory cytokines IL-1, IL-6, IL-12, and tumor necrosis factor-α; and increased the expression of anti-inflammatory cytokine IL-10 (P<0.05). EA promoted M2-phenotype macrophage differentiation. Moreover, these results showed no significant difference between the SsnB group and the EA+SsnB group (P>0.05), but showed a significant difference between the PGN group and the EA+PGN group (P<0.05). Therefore, we propose that EA may be involved in the remission of pruritus in morphine-induced pruritus model mice through the TLR2/4-MyD88-NF-κB pathway. EA is a potential therapeutic treatment for pruritus.

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<![CDATA[Leonurine promotes neurite outgrowth and neurotrophic activity by modulating the GR/SGK1 signaling pathway in cultured PC12 cells]]> https://www.researchpad.co/product?articleinfo=5c973acdd5eed0c484966137

Depression is a common psychiatric disorder that affects almost 10% of children and adolescents worldwide. Numerous synthetic chemical antidepressants used to treat depression have adverse side effects. Therefore, new therapeutic approaches for depression treatment are urgently needed. Leonurus cardiaca has recently been shown to be effective for the treatment of nervous system diseases such as depression, but its mechanism is not clear. In this study, we aimed to reveal the mechanism underlying leonurine’s antidepressant activity. Leonurine was used to treat corticosterone-induced PC12 cells to examine its effect on neurite outgrowth and neurotrophic factors after treatment with the inhibitor of glucocorticoid receptor (GR) and serum-inducible and glucocorticoid-inducible kinase 1 (SGK1). Methyl thiazolyl tetrazolium assays were used to evaluate the viability of cells. High content analysis was used to detect cell area, total neurite length, maximum neurite length, and expression of GR, SGK1, brain-derived neurotrophic factor (BDNF), neurotrophic factor-3 (NT-3), and B-cell lymphoma-2 (BCL-2). The results showed that leonurine increased cell viability in a concentration-dependent manner, with the maximal prosurvival effect at 60 μM. Leonurine increased cell area, total neurite length, and maximum neurite length of corticosterone-induced PC12 cells, increased the expression of GR, BDNF, NT-3, and BCL-2, and decreased the expression of SGK1. After treatment with GR inhibitor RU486, the expressions of GR, BDNF, NT-3, and BCL-2 were significantly decreased and SGK1 was increased. In contrast, treatment with GSK650394 had the opposite effect of RU486. Our data indicate that leonurine promotes neurite outgrowth and neurotrophic activity in cultured PC12 cells, and its potential mechanism may involve the GR/SGK1 signaling pathway.

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<![CDATA[Endothelin receptor Aa regulates proliferation and differentiation of Erb-dependent pigment progenitors in zebrafish]]> https://www.researchpad.co/product?articleinfo=5c803c68d5eed0c484ad88f6

Skin pigment patterns are important, being under strong selection for multiple roles including camouflage and UV protection. Pigment cells underlying these patterns form from adult pigment stem cells (APSCs). In zebrafish, APSCs derive from embryonic neural crest cells, but sit dormant until activated to produce pigment cells during metamorphosis. The APSCs are set-aside in an ErbB signaling dependent manner, but the mechanism maintaining quiescence until metamorphosis remains unknown. Mutants for a pigment pattern gene, parade, exhibit ectopic pigment cells localised to the ventral trunk, but also supernumerary cells restricted to the Ventral Stripe. Contrary to expectations, these melanocytes and iridophores are discrete cells, but closely apposed. We show that parade encodes Endothelin receptor Aa, expressed in the blood vessels, most prominently in the medial blood vessels, consistent with the ventral trunk phenotype. We provide evidence that neuronal fates are not affected in parade mutants, arguing against transdifferentiation of sympathetic neurons to pigment cells. We show that inhibition of BMP signaling prevents specification of sympathetic neurons, indicating conservation of this molecular mechanism with chick and mouse. However, inhibition of sympathetic neuron differentiation does not enhance the parade phenotype. Instead, we pinpoint ventral trunk-restricted proliferation of neural crest cells as an early feature of the parade phenotype. Importantly, using a chemical genetic screen for rescue of the ectopic pigment cell phenotype of parade mutants (whilst leaving the embryonic pattern untouched), we identify ErbB inhibitors as a key hit. The time-window of sensitivity to these inhibitors mirrors precisely the window defined previously as crucial for the setting aside of APSCs in the embryo, strongly implicating adult pigment stem cells as the source of the ectopic pigment cells. We propose that a novel population of APSCs exists in association with medial blood vessels, and that their quiescence is dependent upon Endothelin-dependent factors expressed by the blood vessels.

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<![CDATA[Disrupted reinforcement learning during post-error slowing in ADHD]]> https://www.researchpad.co/product?articleinfo=5c76fe43d5eed0c484e5b7bb

ADHD is associated with altered dopamine regulated reinforcement learning on prediction errors. Despite evidence of categorically altered error processing in ADHD, neuroimaging advances have largely investigated models of normal reinforcement learning in greater detail. Further, although reinforcement leaning critically relies on ventral striatum exerting error magnitude related thresholding influences on substantia nigra (SN) and dorsal striatum, these thresholding influences have never been identified with neuroimaging. To identify such thresholding influences, we propose that error magnitude related activities must first be separated from opposite activities in overlapping neural regions during error detection. Here we separate error detection from magnitude related adjustment (post-error slowing) during inhibition errors in the stop signal task in typically developing (TD) and ADHD adolescents using fMRI. In TD, we predicted that: 1) deactivation of dorsal striatum on error detection interrupts ongoing processing, and should be proportional to right frontoparietal response phase activity that has been observed in the SST; 2) deactivation of ventral striatum on post-error slowing exerts thresholding influences on, and should be proportional to activity in dorsal striatum. In ADHD, we predicted that ventral striatum would instead correlate with heightened amygdala responses to errors. We found deactivation of dorsal striatum on error detection correlated with response-phase activity in both groups. In TD, post-error slowing deactivation of ventral striatum correlated with activation of dorsal striatum. In ADHD, ventral striatum correlated with heightened amygdala activity. Further, heightened activities in locus coeruleus (norepinephrine), raphe nucleus (serotonin) and medial septal nuclei (acetylcholine), which all compete for control of DA, and are altered in ADHD, exhibited altered correlations with SN. All correlations in TD were replicated in healthy adults. Results in TD are consistent with dopamine regulated reinforcement learning on post-error slowing. In ADHD, results are consistent with heightened activities in the amygdala and non-dopaminergic neurotransmitter nuclei preventing reinforcement learning.

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<![CDATA[Increased arterial pressure in mice with overexpression of the ADHD candidate gene calcyon in forebrain]]> https://www.researchpad.co/product?articleinfo=5c6c7585d5eed0c4843cfe50

The link between blood pressure (BP) and cerebral function is well established. However, it is not clear whether a common mechanism could underlie the relationship between elevated BP and cognitive deficits. The expression of calcyon, a gene abundant in catecholaminergic and hypothalamic nuclei along with other forebrain regions, is increased in the brain of the spontaneously hypertensive rat (SHR) which is a widely accepted animal model of essential hypertension and attention deficit hyperactivity disorder (ADHD). Previous studies demonstrated that mice with up-regulation of calcyon in forebrain (CalOE) exhibit deficits in working memory. To date, there is no evidence directly connecting calcyon to BP regulation. Here, we investigated whether forebrain up-regulation of calcyon alters BP using radiotelemetry. We found that CalOE mice exhibited higher mean arterial pressure (MAP) compared to tTA controls. Plasma norepinephrine levels were significantly higher in CalOE mice compared to tTA controls. Silencing the transgene with doxycycline normalized BP in CalOE mice, whereas challenging the mice with 4% high salt diet for 12 days exacerbated the MAP differences between CalOE and tTA mice. High salt diet challenge also increased proteinuria and urinary thiobarbituric acid reactive substances (TBARs) in tTA and CalOE; and the increases were more prominent in CalOE mice. Taken together, our data suggest that upregulation of calcyon in forebrain could increase BP via alterations in noradrenergic transmission and increased oxidative stress during high salt challenge. Overall, this study reveals that calcyon could be a novel neural regulator of BP raising the possibility that it could play a role in the development of vascular abnormalities.

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<![CDATA[Patterns of multimorbidity and polypharmacy in young and adult population: Systematic associations among chronic diseases and drugs using factor analysis]]> https://www.researchpad.co/product?articleinfo=5c648d0cd5eed0c484c81e2d

Objectives

The objective was to identify the systematic associations among chronic diseases and drugs in the form of patterns and to describe and clinically interpret the constituted patterns with a focus on exploring the existence of potential drug-drug and drug-disease interactions and prescribing cascades.

Methods

This observational, cross-sectional study used the demographic and clinical information from electronic medical databases and the pharmacy billing records of all users of the public health system of the Spanish region of Aragon in 2015. An exploratory factor analysis was conducted based on the tetra-choric correlations among the diagnoses of chronic diseases and the dispensed drugs in 887,572 patients aged ≤65 years. The analysis was stratified by age and sex. To name the constituted patterns, assess their clinical nature, and identify potential interactions among diseases and drugs, the associations found in each pattern were independently reviewed by two pharmacists and two doctors and tested against the literature and the information reported in the technical medicinal forms.

Results

Six multimorbidity-polypharmacy patterns were found in this large-scale population study, named as respiratory, mental health, cardiometabolic, endocrinological, osteometabolic, and mechanical-pain. The nature of the patterns in terms of diseases and drugs differed by sex and age and became more complex as age advanced.

Conclusions

The six clinically sound multimorbidity-polypharmacy patterns described in this non-elderly population confirmed the existence of systematic associations among chronic diseases and medications, and revealed some unexpected associations suggesting the prescribing cascade phenomenon as a potential underlying factor. These findings may help to broaden the focus and orient the early identification of potential interactions when caring for multimorbid patients at high risk of adverse health outcomes due to polypharmacy.

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<![CDATA[Top-down inputs drive neuronal network rewiring and context-enhanced sensory processing in olfaction]]> https://www.researchpad.co/product?articleinfo=5c50c46bd5eed0c4845e873d

Much of the computational power of the mammalian brain arises from its extensive top-down projections. To enable neuron-specific information processing these projections have to be precisely targeted. How such a specific connectivity emerges and what functions it supports is still poorly understood. We addressed these questions in silico in the context of the profound structural plasticity of the olfactory system. At the core of this plasticity are the granule cells of the olfactory bulb, which integrate bottom-up sensory inputs and top-down inputs delivered by vast top-down projections from cortical and other brain areas. We developed a biophysically supported computational model for the rewiring of the top-down projections and the intra-bulbar network via adult neurogenesis. The model captures various previous physiological and behavioral observations and makes specific predictions for the cortico-bulbar network connectivity that is learned by odor exposure and environmental contexts. Specifically, it predicts that—after learning—the granule-cell receptive fields with respect to sensory and with respect to cortical inputs are highly correlated. This enables cortical cells that respond to a learned odor to enact disynaptic inhibitory control specifically of bulbar principal cells that respond to that odor. For this the reciprocal nature of the granule cell synapses with the principal cells is essential. Functionally, the model predicts context-enhanced stimulus discrimination in cluttered environments (‘olfactory cocktail parties’) and the ability of the system to adapt to its tasks by rapidly switching between different odor-processing modes. These predictions are experimentally testable. At the same time they provide guidance for future experiments aimed at unraveling the cortico-bulbar connectivity.

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<![CDATA[Online comprehension across different semantic categories in preschool children with autism spectrum disorder]]> https://www.researchpad.co/product?articleinfo=5c6b2693d5eed0c484289cd9

Background

Word comprehension across semantic categories is a key area of language development. Using online automated eye-tracking technology to reduce response demands during a word comprehension test may be advantageous in children with autism spectrum disorder (ASD).

Objectives

To measure online accuracy of word recognition across eleven semantic categories in preschool children with ASD and in typically developing (TD) children matched for gender and developmental age.

Methods

Using eye-tracker methodology we measured the relative number of fixations on a target image as compared to a foil of the same category shown simultaneously on screen. This online accuracy measure was considered a measure of word understanding. We tested the relationship between online accuracy and offline word recognition and the effects of clinical variables on online accuracy. Twenty-four children with ASD and 21 TD control children underwent the eye-tracking task.

Results

On average, children with ASD were significantly less accurate at fixating on the target image than the TD children. After multiple comparison correction, no significant differences were found across the eleven semantic categories of the experiment between preschool children with ASD and younger TD children matched for developmental age. The ASD group showed higher intragroup variability consistent with greater variation in vocabulary growth rates. Direct effects of non-verbal cognitive levels, vocabulary levels and gesture productions on online word recognition in both groups support a dimensional view of language abilities in ASD.

Conclusions

Online measures of word comprehension across different semantic categories show higher interindividual variability in children with ASD and may be useful for objectively monitor gains on targeted language interventions.

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<![CDATA[Coordinated electrical activity in the olfactory bulb gates the oscillatory entrainment of entorhinal networks in neonatal mice]]> https://www.researchpad.co/product?articleinfo=5c5ca2dbd5eed0c48441ebcc

Although the developmental principles of sensory and cognitive processing have been extensively investigated, their synergy has been largely neglected. During early life, most sensory systems are still largely immature. As a notable exception, the olfactory system is functional at birth, controlling mother–offspring interactions and neonatal survival. Here, we elucidate the structural and functional principles underlying the communication between olfactory bulb (OB) and lateral entorhinal cortex (LEC)—the gatekeeper of limbic circuitry—during neonatal development. Combining optogenetics, pharmacology, and electrophysiology in vivo with axonal tracing, we show that mitral cell–dependent discontinuous theta bursts in OB drive network oscillations and time the firing in LEC of anesthetized mice via axonal projections confined to upper cortical layers. Acute pharmacological silencing of OB activity diminishes entorhinal oscillations, whereas odor exposure boosts OB–entorhinal coupling at fast frequencies. Chronic impairment of olfactory sensory neurons disrupts OB–entorhinal activity. Thus, OB activity shapes the maturation of entorhinal circuits.

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<![CDATA[Evaluation of a template for countering misinformation—Real-world Autism treatment myth debunking]]> https://www.researchpad.co/product?articleinfo=5c5b5287d5eed0c4842bcab4

Misinformation poses significant challenges to evidence-based practice. In the public health domain specifically, treatment misinformation can lead to opportunity costs or direct harm. Alas, attempts to debunk misinformation have proven sub-optimal, and have even been shown to “backfire”, including increasing misperceptions. Thus, optimized debunking strategies have been developed to more effectively combat misinformation. The aim of this study was to test these strategies in a real-world setting, targeting misinformation about autism interventions. In the context of professional development training, we randomly assigned participants to an “optimized-debunking” or a “treatment-as-usual” training condition and compared support for non-empirically-supported treatments before, after, and six weeks following completion of online training. Results demonstrated greater benefits of optimized debunking immediately after training; thus, the implemented strategies can serve as a general and flexible debunking template. However, the effect was not sustained at follow-up, highlighting the need for further research into strategies for sustained change.

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<![CDATA[Melanotan-II reverses autistic features in a maternal immune activation mouse model of autism]]> https://www.researchpad.co/product?articleinfo=5c40f77dd5eed0c48438626a

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by impaired social interactions, difficulty with communication, and repetitive behavior patterns. In humans affected by ASD, there is a male pre-disposition towards the condition with a male to female ratio of 4:1. In part due to the complex etiology of ASD including genetic and environmental interplay, there are currently no available medical therapies to improve the social deficits of ASD. Studies in rodent models and humans have shown promising therapeutic effects of oxytocin in modulating social adaptation. One pharmacological approach to stimulating oxytocinergic activity is the melanocortin receptor 4 agonist Melanotan-II (MT-II). Notably the effects of oxytocin on environmental rodent autism models has not been investigated to date. We used a maternal immune activation (MIA) mouse model of autism to assess the therapeutic potential of MT-II on autism-like features in adult male mice. The male MIA mice exhibited autism-like features including impaired social behavioral metrics, diminished vocal communication, and increased repetitive behaviors. Continuous administration of MT-II to male MIA mice over a seven-day course resulted in rescue of social behavioral metrics. Normal background C57 male mice treated with MT-II showed no significant alteration in social behavioral metrics. Additionally, there was no change in anxiety-like or repetitive behaviors following MT-II treatment of normal C57 mice, though there was significant weight loss following subacute treatment. These data demonstrate MT-II as an effective agent for improving autism-like behavioral deficits in the adult male MIA mouse model of autism.

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