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Essential Pathways and Circuits of Autism Pathogenesis

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889199051 Year: Pages: 181 DOI: 10.3389/978-2-88919-905-1 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Neurology --- Genetics
Added to DOAB on : 2016-01-19 14:05:46
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The Centers for Disease Control and Prevention estimate that 1 in 68 children in the United states is afflicted with autism spectrum disorders (ASD), yet at this time, there is no cure for the disease. Autism is characterized by delays in the development of many basic skills, most notably the ability to socialize and adapt to novelty. The condition is typically identified in children around 3 years of age, however the high heritability of autism suggests that the disease process begins at conception. The identification of over 500 ASD risk genes, has enabled the molecular genetic dissection of the pathogenesis of the disease in model organisms such as mice. Despite the genetic heterogeneity of ASD etiology, converging evidence suggests that these disparate genetic lesions may result in the disruption of a limited number of key biochemical pathways or circuits. Classification of patients into groups by pathogenic rather than etiological categories, will likely aid future therapeutic development and clinical trials. In this set of papers, we explore the existing evidence supporting this view. Specifically, we focus on biochemical cascades such as mTOR and ERK signaling, the mRNA network bound by FMRP and UBE3A, dorsal and ventral striatal circuits, cerebellar circuits, hypothalamic projections, as well as prefrontal and anterior cingulate cortical circuits. Special attention will be given to studies that demonstrate the necessity and/or sufficiency of genetic disruptions (e.g. by molecular deletion and/or replacement) in these pathways and circuits for producing characteristic behavioral features of autism. Necessarily these papers will be heavily weighted towards basic mechanisms elucidated in animal models, but may also include investigations in patients.

Frontiers in Brain Based Therapeutic Interventions and Biomarker Research in Child and Adolescent Psychiatry

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889199549 Year: Pages: 107 DOI: 10.3389/978-2-88919-954-9 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General) --- Psychiatry
Added to DOAB on : 2016-01-19 14:05:46
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Developmental neuroscience research is on the cusp of unprecedented advances in the understanding of how variations in brain structure and function within neural circuits confer risk for symptoms of childhood psychiatric disorders. Novel dimensional approaches to illness classification, the availability of non-invasive, diverse and increasingly sophisticated methods to measure brain structure and function in humans in vivo, and advances in genetics, animal model and multimodal research now place brain-based biomarkers within reach in the field of psychiatry. These advances hold great promise for moving neuroscience research into the clinical realm. One exciting new area of translational research in child and adolescent psychiatry, is in the use of a variety of neuroscience research tools to track brain response to clinical intervention. Examples of this include: using longitudinal neuroimaging techniques to track changes in white matter microstructure following a training intervention for children with poor reading skills, or using functional imaging to compare brain activity before and after children with bipolar disorder begin taking psychotropic medication treatment. Brain stimulation is another cutting-edge research area where brain response to therapeutic intervention can be closely tracked with electroencephalography or other brain imaging modalities. Research using neuroscience tools to track brain response to clinical interventions is beginning to yield novel insights into the etiopathogenesis of psychiatric illness, and is providing preliminary feedback around how therapeutic interventions work in the brain to bring about symptom improvement. Using these novel approaches, neuroscience research may soon move into the clinical realm to target early pathophysiology, and tailor treatments to both individuals and specific neurodevelopmental trajectories, in an effort to alter the course of development and mitigate risk for a lifetime of morbidity and ineffective treatments. Excitement and progress in these areas must be tempered with safety and ethical considerations for these vulnerable populations. This research topic focuses on efforts to use neuroscience research tools to identify brain-based biomarkers of therapeutic response in child and adolescent psychiatry.

The Safety and Efficacy of Noninvasive Brain Stimulation in Development and Neurodevelopmental Disorders

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889196999 Year: Pages: 68 DOI: 10.3389/978-2-88919-699-9 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Science (General)
Added to DOAB on : 2016-04-07 11:22:02
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Noninvasive brain stimulation (including Transcranial Magnetic Stimulation (TMS) and Transcranial Current Brain Stimulation (TCS)) can be used both experimentally and therapeutically. In the experimental domain TMS can be applied in single pulses to depolarize a small population of neurons in a targeted brain region. This protocol can be used, for example, to map cortical motor outputs, study central motor conduction time, or evaluate the cortical silent period (a measure of intracortical inhibition) all of which are relevant to neurodevelopment. TMS can also be applied in pairs of pulses (paired pulse stimulation, ppTMS) where two pulses are presented in rapid succession to study intracortical inhibition and facilitation. Trains of repeated TMS (rTMS) pulses can be applied at various stimulation frequencies and patterns to modulate local cortical excitability beyond the duration of the stimulation itself. Depending on the parameters of stimulation the excitability can be either facilitated or suppressed. TCS (including Transcranial Direct Current Stimulation (tDCS), alternating current (tACS), and random noise current stimulation (tRNS) also have the potential to modulate cortical excitability and have also been used to study and modulate cortical activity in healthy and patient populations. The after-effects of rTMS and TCS are thought to be related to changes in efficacy (in either the positive or negative direction) of synaptic connections of the neurons being stimulated, thus these techniques have been used to study and modulate cortical plasticity mechanisms in a number of populations. Recently, researchers have begun to apply these techniques to the study of neurodevelopmental mechanisms as well as the pathophysiology and development of novel treatments for neurodevelopmental disorders. Though there is much promise, caution is warranted given the vulnerability of pediatric and clinical populations and the potential that these techniques have to modify circuit development in a cortex that is in a very dynamic state. This Research Topic hopes to provide an opportunity to share ideas across areas (human and animal researchers, clinicians and basic scientists). We are particularly interested in papers that address issues of choosing a protocol (intensity, frequency, location, coil geometry etc.), populations where noninvasive brain stimulation may have direct impact on diagnostics and treatment, as well as the safety and ethics of applying these techniques in pediatric populations. As many may not be aware of the potential and limitations of noninvasive brain stimulation and its use for research and treatment in this area, this Research Topic promises to have broad appeal. Submissions for all Frontiers article types are encouraged.

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