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Neuroscience
Clinical and Molecular Assessment in a Female with Fragile X Syndrome and Tuberous Sclerosis
Feb 24, 2017   Journal Of Genetic Disorders & Genetic Reports
Yrigollen CM, Pacini L, Nobile V, Lozano R, Hagerman RJ, Bagni C, Tassone F
Clinical and Molecular Assessment in a Female with Fragile X Syndrome and Tuberous Sclerosis
Feb 24, 2017
Journal Of Genetic Disorders & Genetic Reports
OBJECTIVE: Fragile X syndrome (FXS) and tuberous sclerosis (TSC) are genetic disorders that result in intellectual disability and an increased prevalence of autism spectrum disorders (ASD). While the clinical presentation of each disorder is distinct, the molecular causes are linked to a disruption in the mTORC1 (mammalian Target of Rapamycin Complex 1) and ERK1/2 (Extracellular signal-Regulated Kinase) signaling pathways. METHODS: We assessed the clinical and molecular characteristics of an individual seen at the UC Davis MIND Institute with a diagnosis of FXS and TSC. Clinical evaluation of physical, behavioral, and cognitive impairments were performed. Additionally, total and phosphorylated proteins along the mTORC1 and ERK1/2 pathways were measured in primary fibroblast cell lines from the proband. RESULTS: In this case the phenotypic effects that result in a human with both FXS and TSC are shown to be severe. Changes in mTORC1 and ERK1/2 signaling proteins and global protein synthesis were not found to be noticeably different between four cohorts (typically developing, CONCLUSION: It has previously been suggested that disruption of the mTORC1 pathway was reciprocal in TSC and FXS double knock-out mouse models so that the regulation of these pathways were more similar to wild-type mice compared to mice harboring a
Irritable Bowel Syndrome and Stress-Related Psychiatric Co-morbidities: Focus on Early Life Stress
Feb 24, 2017   Handbook Of Experimental Pharmacology
O'Mahony SM, Clarke G, Dinan TG, Cryan JF
Irritable Bowel Syndrome and Stress-Related Psychiatric Co-morbidities: Focus on Early Life Stress
Feb 24, 2017
Handbook Of Experimental Pharmacology
Irritable bowel syndrome is a functional gastrointestinal disorder, with stress playing a major role in onset and exacerbation of symptoms such as abdominal pain and altered bowel movements. Stress-related disorders including anxiety and depression often precede the development of irritable bowel syndrome and vice versa. Stressor exposure during early life has the potential to increase an individual's susceptibility to both irritable bowel syndrome and psychiatric disease indicating that there may be a common origin for these disorders. Moreover, adverse early life events significantly impact upon many of the communication pathways within the brain-gut-microbiota axis, which allows bidirectional interaction between the central nervous system and the gastrointestinal tract. This axis is proposed to be perturbed in irritable bowel syndrome and studies now indicate that dysfunction of this axis is also seen in psychiatric disease. Here we review the co-morbidity of irritable bowel syndrome and psychiatric disease with their common origin in mind in relation to the impact of early life stress on the developing brain-gut-microbiota axis. We also discuss the therapeutic potential of targeting this axis in these diseases.
Fine-Tuning Circadian Rhythms: The Importance of
Feb 24, 2017   Frontiers In Neuroscience
Mieda M, Hasegawa E, Kessaris N, Sakurai T
Fine-Tuning Circadian Rhythms: The Importance of
Feb 24, 2017
Frontiers In Neuroscience
Although, the suprachiasmatic nucleus (SCN) of the hypothalamus acts as the central clock in mammals, the circadian expression of clock genes has been demonstrated not only in the SCN, but also in peripheral tissues and brain regions outside the SCN. However, the physiological roles of extra-SCN circadian clocks in the brain remain largely elusive. In response, we generated
Mapping Visual Dominance in Human Sleep
Feb 24, 2017   NeuroImage
McAvoy M, Mitra A, Tagliazucchi E, Laufs H, Raichle ME
Mapping Visual Dominance in Human Sleep
Feb 24, 2017
NeuroImage
Sleep is a universal behavior, essential for humans and animals alike to survive. Its importance to a person's physical and mental health cannot be overstated. Although lateralization of function is well established in the lesion, split-brain and task based neuroimaging literature, and more recently in functional imaging studies of spontaneous fluctuations of the fMRI BOLD signal during wakeful rest, it is unknown if these asymmetries are present during sleep. We investigated hemispheric asymmetries in the global brain signal during non-REM sleep. Here we show that increasing sleep depth is accompanied by an increasing rightward asymmetry of regions in visual cortex including primary bilaterally and in the right hemisphere along the lingual gyrus and middle temporal cortex. In addition, left hemisphere language regions largely maintained their leftward asymmetry during sleep. Right hemisphere attention related regions expressed a more complicated relation with some regions maintaining a rightward asymmetry while this was lost in others. These results suggest that asymmetries in the human brain are state dependent.Copyright © 2017. Published by Elsevier Inc.
Amyloid and Tau PET Demonstrate Region-Specific Associations in Normal Older People
Feb 24, 2017   NeuroImage
Lockhart SN, Schöll M, Baker SL, Ayakta N, Swinnerton KN, Bell RK, Mellinger TJ, Shah VD, O'Neil JP, Janabi M, Jagust WJ
Amyloid and Tau PET Demonstrate Region-Specific Associations in Normal Older People
Feb 24, 2017
NeuroImage
β-amyloid (Aβ) and tau pathology become increasingly prevalent with age, however, the spatial relationship between the two pathologies remains unknown. We examined local (same region) and non-local (different region) associations between these 2 aggregated proteins in 46 normal older adults using [Copyright © 2017. Published by Elsevier Inc.
Optogenetics: Applications in psychiatric research
Feb 24, 2017   Psychiatry And Clinical Neurosciences
Shirai F, Hayashi-Takagi A
Optogenetics: Applications in psychiatric research
Feb 24, 2017
Psychiatry And Clinical Neurosciences
Recently, optogenetic techniques emerged as a method to optically manipulate molecular and cellular events in target cells both in vitro and in vivo. Optogenetics result from the fruitful combination of optics and genetic engineering, maximizing the advantages of each discipline. These advantages are optical control through the manipulation of wavelength and light intensity on the millisecond time scale, and specific gene expression and gene product trafficking with subcellular precision. This kind of fine-tuning cannot be achieved using traditional methods. Therefore, optogenetic techniques have brought a revolution to neuroscience. In this review, we provide a concise summary of the history and recent advances of optogenetics, focusing in particular on applications for psychiatric research.This article is protected by copyright. All rights reserved.
TEMPORARY REMOVAL: Genetic predisposition to advanced biological ageing increases risk for childhood-onset recurrent major depressive disorder in a large UK sample
Feb 24, 2017   Journal Of Affective Disorders
Michalek JE, Kepa A, Vincent J, Frissa S, Goodwin L, Hotopf M, Hatch SL, Breen G, Powell TR
Bipolar disorder risk gene
Feb 24, 2017   Journal Of Psychiatry & Neuroscience : JPN
Shenker JJ, Sengupta SM, Joober R, Malla A, Chakravarty MM, Lepage M
Bipolar disorder risk gene
Feb 24, 2017
Journal Of Psychiatry & Neuroscience : JPN
BACKGROUND: Despite being diagnostically associated uniquely with schizophrenia, negative symptoms are also observed in bipolar disorder (BD). Genome-wide association studies (GWAS) have uncovered a number of shared risk genes between schizophrenia and BD. The objectives of this study were to examine whether previously identified risk genes for BD are associated with negative symptom severity within a first-episode schizophrenia (FES) cohort and to examine whether such genes influence brain morphology. METHODS: Patients experiencing FES were genotyped for 21 previously identified BD risk genes; a series of univariate analyses of covariance examined the association between negative symptom severity, as measured using the Scale for the Assessment of Negative Symptoms (SANS), and genotype. A subset of participants underwent a structural 1.5 T MRI RESULTS: We included 133 patients with FES in our analysis; 61 of them underwent structural MRI. We observed a significant association between negative symptom severity and the BD risk gene LIMITATIONS: Limitations of this study include its modest sample size and lack of a control sample. CONCLUSION: Lacking the
Biomarker-driven phenotyping in Parkinson's disease: A translational missing link in disease-modifying clinical trials
Feb 24, 2017   Movement Disorders : Official Journal Of The Movement Disorder Society
Espay AJ, Schwarzschild MA, Tanner CM, Fernandez HH, Simon DK,   . . . . . .   , Kieburtz K, Woo D, Macklin EA, Standaert DG, Lang AE
Biomarker-driven phenotyping in Parkinson's disease: A translational missing link in disease-modifying clinical trials
Feb 24, 2017
Movement Disorders : Official Journal Of The Movement Disorder Society
Past clinical trials of putative neuroprotective therapies have targeted PD as a single pathogenic disease entity. From an Oslerian clinicopathological perspective, the wide complexity of PD converges into Lewy bodies and justifies a reductionist approach to PD: A single-mechanism therapy can affect most of those sharing the classic pathological hallmark. From a systems-biology perspective, PD is a group of disorders that, while related by sharing the feature of nigral dopamine-neuron degeneration, exhibit unique genetic, biological, and molecular abnormalities, which probably respond differentially to a given therapeutic approach, particularly for strategies aimed at neuroprotection. Under this model, only biomarker-defined, homogenous subtypes of PD are likely to respond optimally to therapies proven to affect the biological processes within each subtype. Therefore, we suggest that precision medicine applied to PD requires a reevaluation of the biomarker-discovery effort. This effort is currently centered on correlating biological measures to clinical features of PD and on identifying factors that predict whether various prodromal states will convert into the classical movement disorder. We suggest, instead, that subtyping of PD requires the reverse view, where abnormal biological signals (i.e., biomarkers), rather than clinical definitions, are used to define disease phenotypes. Successful development of disease-modifying strategies will depend on how relevant the specific biological processes addressed by an intervention are to the pathogenetic mechanisms in the subgroup of targeted patients. This precision-medicine approach will likely yield smaller, but well-defined, subsets of PD amenable to successful neuroprotection. © 2017 International Parkinson and Movement Disorder Society.© 2017 International Parkinson and Movement Disorder Society.
Gait improvement via rhythmic stimulation in Parkinson's disease is linked to rhythmic skills
Feb 24, 2017   Scientific Reports
Bella SD, Benoit CE, Farrugia N, Keller PE, Obrig H, Mainka S, Kotz SA
Gait improvement via rhythmic stimulation in Parkinson's disease is linked to rhythmic skills
Feb 24, 2017
Scientific Reports
Training based on rhythmic auditory stimulation (RAS) can improve gait in patients with idiopathic Parkinson's disease (IPD). Patients typically walk faster and exhibit greater stride length after RAS. However, this effect is highly variable among patients, with some exhibiting little or no response to the intervention. These individual differences may depend on patients' ability to synchronize their movements to a beat. To test this possibility, 14 IPD patients were submitted to RAS for four weeks, in which they walked to music with an embedded metronome. Before and after the training, patients' synchronization was assessed with auditory paced hand tapping and walking to auditory cues. Patients increased gait speed and stride length in non-cued gait after training. However, individual differences were apparent as some patients showed a positive response to RAS and others, either no response, or a negative response. A positive response to RAS was predicted by the synchronization performance in hand tapping and gait tasks. More severe gait impairment, low synchronization variability, and a prompt response to a stimulation change foster a positive response to RAS training. Thus, sensorimotor timing skills underpinning the synchronization of steps to an auditory cue may allow predicting the success of RAS in IPD.
Guiding transcranial brain stimulation by EEG/MEG to interact with ongoing brain activity and associated functions: A position paper
Feb 24, 2017   Clinical Neurophysiology : Official Journal Of The International Federation Of Clinical Neurophysiology
Thut G, Bergmann TO, Fröhlich F, Soekadar SR, Brittain JS, Valero-Cabré A, Sack A, Miniussi C, Antal A, Siebner HR, Ziemann U, Herrmann CS
Guiding transcranial brain stimulation by EEG/MEG to interact with ongoing brain activity and associated functions: A position paper
Feb 24, 2017
Clinical Neurophysiology : Official Journal Of The International Federation Of Clinical Neurophysiology
Non-invasive transcranial brain stimulation (NTBS) techniques have a wide range of applications but also suffer from a number of limitations mainly related to poor specificity of intervention and variable effect size. These limitations motivated recent efforts to focus on the temporal dimension of NTBS with respect to the ongoing brain activity. Temporal patterns of ongoing neuronal activity, in particular brain oscillations and their fluctuations, can be traced with electro- or magnetoencephalography (EEG/MEG), to guide the timing as well as the stimulation settings of NTBS. These novel, online and offline EEG/MEG-guided NTBS-approaches are tailored to specifically interact with the underlying brain activity. Online EEG/MEG has been used to guide the timing of NTBS (i.e., when to stimulate): by taking into account instantaneous phase or power of oscillatory brain activity, NTBS can be aligned to fluctuations in excitability states. Moreover, offline EEG/MEG recordings prior to interventions can inform researchers and clinicians how to stimulate: by frequency-tuning NTBS to the oscillation of interest, intrinsic brain oscillations can be up- or down-regulated. In this paper, we provide an overview of existing approaches and ideas of EEG/MEG-guided interventions, and their promises and caveats. We point out potential future lines of research to address challenges.Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.
General and emotion-specific neural effects of ketamine during emotional memory formation
Feb 24, 2017   NeuroImage
Becker B, Steffens M, Zhao Z, Kendrick KM, Neumann C, Weber B, Schultz J, Mehta MA, Ettinger U, Hurlemann R
General and emotion-specific neural effects of ketamine during emotional memory formation
Feb 24, 2017
NeuroImage
Animal studies suggest that N-methyl-D-aspartate receptor (NMDAR) dependent signalling in limbic and prefrontal regions is critically involved in both cognitive and emotional functions. In humans, ketamine-induced transient, and disorder associated chronic NMDAR hypofunction (i.e. in schizophrenia) has been associated with deficient performance in the domains of memory and higher-order emotional functioning, as well as altered neural activity in the underlying limbic-prefrontal circuits. To model the effects of NMDAR hypofunction on the integration of emotion and cognition the present pharmacological fMRI study applied the NMDAR antagonist ketamine (target plasma level = 100ng/ml) to 21 healthy volunteers in a within-subject placebo-controlled crossover design during encoding of neutral, positive and negative pictures. Our results show that irrespective of emotion, ketamine suppressed parahippocampal and medial prefrontal activity. In contrast, ketamine selectively increased amygdala and orbitofrontal activity during successful encoding of negative stimuli. On the network level ketamine generally increased medial prefrontal-parahippocampal coupling while specifically decreasing amygdala-orbitofrontal interplay during encoding of negative stimuli. On the behavioural level, ketamine produced generally decreased memory performance and abolished the emotional enhancement of memory after a wash-out period of 5 days. The present findings suggest that ketamine produces general as well as valence-specific effects during emotional memory formation. The pattern partly overlaps with alterations previously observed in patients with schizophrenia.Copyright © 2017. Published by Elsevier Inc.
Functional connectomics from a "big data" perspective
Feb 24, 2017   NeuroImage
Xia M, He Y
Functional connectomics from a "big data" perspective
Feb 24, 2017
NeuroImage
In the last decade, explosive growth regarding functional connectome studies has been observed. Accumulating knowledge has significantly contributed to our understanding of the brain's functional network architectures in health and disease. With the development of innovative neuroimaging techniques, the establishment of large brain datasets and the increasing accumulation of published findings, functional connectomic research has begun to move into the era of "big data", which generates unprecedented opportunities for discovery in brain science and simultaneously encounters various challenging issues, such as data acquisition, management and analyses. Big data on the functional connectome exhibits several critical features: high spatial and/or temporal precision, large sample sizes, long-term recording of brain activity, multidimensional biological variables (e.g., imaging, genetic, demographic, cognitive and clinic) and/or vast quantities of existing findings. We review studies regarding functional connectomics from a big data perspective, with a focus on recent methodological advances in state-of-the-art image acquisition (e.g., multiband imaging), analysis approaches and statistical strategies (e.g., graph theoretical analysis, dynamic network analysis, independent component analysis, multivariate pattern analysis and machine learning), as well as reliability and reproducibility validations. We highlight the novel findings in the application of functional connectomic big data to the exploration of the biological mechanisms of cognitive functions, normal development and aging and of neurological and psychiatric disorders. We advocate the urgent need to expand efforts directed at the methodological challenges and discuss the direction of applications in this field.Copyright © 2017 Elsevier Inc. All rights reserved.
A mouse model of paralytic myelitis caused by enterovirus D68
Feb 23, 2017   PLoS Pathogens
Hixon AM, Yu G, Leser JS, Yagi S, Clarke P, Chiu CY, Tyler KL
A mouse model of paralytic myelitis caused by enterovirus D68
Feb 23, 2017
PLoS Pathogens
In 2014, the United States experienced an epidemic of acute flaccid myelitis (AFM) cases in children coincident with a nationwide outbreak of enterovirus D68 (EV-D68) respiratory disease. Up to half of the 2014 AFM patients had EV-D68 RNA detected by RT-PCR in their respiratory secretions, although EV-D68 was only detected in cerebrospinal fluid (CSF) from one 2014 AFM patient. Given previously described molecular and epidemiologic associations between EV-D68 and AFM, we sought to develop an animal model by screening seven EV-D68 strains for the ability to induce neurological disease in neonatal mice. We found that four EV-D68 strains from the 2014 outbreak (out of five tested) produced a paralytic disease in mice resembling human AFM. The remaining 2014 strain, as well as 1962 prototype EV-D68 strains Fermon and Rhyne, did not produce, or rarely produced, paralysis in mice. In-depth examination of the paralysis caused by a representative 2014 strain, MO/14-18947, revealed infectious virus, virion particles, and viral genome in the spinal cords of paralyzed mice. Paralysis was elicited in mice following intramuscular, intracerebral, intraperitoneal, and intranasal infection, in descending frequency, and was associated with infection and loss of motor neurons in the anterior horns of spinal cord segments corresponding to paralyzed limbs. Virus isolated from spinal cords of infected mice transmitted disease when injected into naïve mice, fulfilling Koch's postulates in this model. Finally, we found that EV-D68 immune sera, but not normal mouse sera, protected mice from development of paralysis and death when administered prior to viral challenge. These studies establish an experimental model to study EV-D68-induced myelitis and to better understand disease pathogenesis and develop potential therapies.
Leaky Gate Model: Intensity-Dependent Coding of Pain and Itch in the Spinal Cord
Feb 23, 2017   Neuron
Sun S, Xu Q, Guo C, Guan Y, Liu Q, Dong X
Leaky Gate Model: Intensity-Dependent Coding of Pain and Itch in the Spinal Cord
Feb 23, 2017
Neuron
Coding of itch versus pain has been heatedly debated for decades. However, the current coding theories (labeled line, intensity, and selectivity theory) cannot accommodate all experimental observations. Here we identified a subset of spinal interneurons, labeled by gastrin-releasing peptide (Grp), that receive direct synaptic input from both pain and itch primary sensory neurons. When activated, these GrpCopyright © 2017 Elsevier Inc. All rights reserved.
Transient oxytocin signaling primes the development and function of excitatory hippocampal neurons
Feb 23, 2017   ELife
Ripamonti S, Ambrozkiewicz MC, Guzzi F, Gravati M, Biella G,   . . . . . .   , Nishimori K, Toselli M, Brose N, Parenti M, Rhee J
Transient oxytocin signaling primes the development and function of excitatory hippocampal neurons
Feb 23, 2017
ELife
Beyond its role in parturition and lactation, oxytocin influences higher brain processes that control social behavior of mammals, and perturbed oxytocin signaling has been linked to the pathogenesis of several psychiatric disorders. However, it is still largely unknown how oxytocin exactly regulates neuronal function. We show that early, transient oxytocin exposure
Using hiCLIP to identify RNA duplexes that interact with a specific RNA-binding protein
Feb 23, 2017   Nature Protocols Add nature.com free-link Cancel
Sugimoto Y, Chakrabarti AM, Luscombe NM, Ule J
Using hiCLIP to identify RNA duplexes that interact with a specific RNA-binding protein
Feb 23, 2017
Nature Protocols
The structure of RNA molecules has a critical role in regulating gene expression, largely through influencing their interactions with RNA-binding proteins (RBPs). RNA hybrid and individual-nucleotide resolution UV cross-linking and immunoprecipitation (hiCLIP) is a transcriptome-wide method of monitoring these interactions by identifying RNA duplexes bound by a specific RBP. The hiCLIP protocol consists of the following steps: in vivo cross-linking of RBPs to their bound RNAs; partial RNA digestion and purification of RNA duplexes interacting with the specific RBP using immunoprecipitation; ligation of the two arms of RNA duplexes via a linker; reverse transcription; cDNA library amplification; and finally high-throughput DNA sequencing. Mapping of the sequenced arms to a reference transcriptome identifies the exact locations of duplexes. hiCLIP data can directly identify all types of RNA duplexes bound by RBPs, including those that are challenging to predict computationally, such as intermolecular and long-range intramolecular duplexes. Moreover, the use of an adaptor that links the two arms of the RNA duplex permits hiCLIP to unambiguously identify the duplexes. Here we describe in detail the procedure for a hiCLIP experiment and the subsequent streamlined data analysis with an R package, 'hiclipr' (https://github.com/luslab/hiclipr/). Preparation of the library for high-throughput DNA sequencing takes ∼7 d and the basic bioinformatic pipeline takes 1 d.
Computational approaches to fMRI analysis
Feb 23, 2017   Nature Neuroscience Add nature.com free-link Cancel
Cohen JD, Daw N, Engelhardt B, Hasson U, Li K, Niv Y, Norman KA, Pillow J, Ramadge PJ, Turk-Browne NB, Willke TL
Computational approaches to fMRI analysis
Feb 23, 2017
Nature Neuroscience
Analysis methods in cognitive neuroscience have not always matched the richness of fMRI data. Early methods focused on estimating neural activity within individual voxels or regions, averaged over trials or blocks and modeled separately in each participant. This approach mostly neglected the distributed nature of neural representations over voxels, the continuous dynamics of neural activity during tasks, the statistical benefits of performing joint inference over multiple participants and the value of using predictive models to constrain analysis. Several recent exploratory and theory-driven methods have begun to pursue these opportunities. These methods highlight the importance of computational techniques in fMRI analysis, especially machine learning, algorithmic optimization and parallel computing. Adoption of these techniques is enabling a new generation of experiments and analyses that could transform our understanding of some of the most complex-and distinctly human-signals in the brain: acts of cognition such as thoughts, intentions and memories.
Parkinson Sac Domain Mutation in Synaptojanin 1 Impairs Clathrin Uncoating at Synapses and Triggers Dystrophic Changes in Dopaminergic Axons
Feb 23, 2017   Neuron
Cao M, Wu Y, Ashrafi G, McCartney AJ, Wheeler H, Bushong EA, Boassa D, Ellisman MH, Ryan TA, De Camilli P
Parkinson Sac Domain Mutation in Synaptojanin 1 Impairs Clathrin Uncoating at Synapses and Triggers Dystrophic Changes in Dopaminergic Axons
Feb 23, 2017
Neuron
Synaptojanin 1 (SJ1) is a major presynaptic phosphatase that couples synaptic vesicle endocytosis to the dephosphorylation of PI(4,5)PCopyright © 2017 Elsevier Inc. All rights reserved.
Rapid Integration of Artificial Sensory Feedback during Operant Conditioning of Motor Cortex Neurons
Feb 23, 2017   Neuron
Prsa M, Galiñanes GL, Huber D
Rapid Integration of Artificial Sensory Feedback during Operant Conditioning of Motor Cortex Neurons
Feb 23, 2017
Neuron
Neuronal motor commands, whether generating real or neuroprosthetic movements, are shaped by ongoing sensory feedback from the displacement being produced. Here we asked if cortical stimulation could provide artificial feedback during operant conditioning of cortical neurons. Simultaneous two-photon imaging and real-time optogenetic stimulation were used to train mice to activate a single neuron in motor cortex (M1), while continuous feedback of its activity level was provided by proportionally stimulating somatosensory cortex. This artificial signal was necessary to rapidly learn to increase the conditioned activity, detect correct performance, and maintain the learned behavior. Population imaging in M1 revealed that learning-related activity changes are observed in the conditioned cell only, which highlights the functional potential of individual neurons in the neocortex. Our findings demonstrate the capacity of animals to use an artificially induced cortical channel in a behaviorally relevant way and reveal the remarkable speed and specificity at which this can occur.Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.
Improving data availability for brain image biobanking in healthy subjects: practice-based suggestions from an international multidisciplinary working group
Feb 24, 2017   NeuroImage
BRAINS (Brain Imaging in Normal Subjects) Expert Working Group, Shenkin SD, Pernet C, Nichols TE, Poline JB,   . . . . . .   , Anblagan D, Job DE, Alexander Dickie D, Rodriguez D, Wardlaw JM
Improving data availability for brain image biobanking in healthy subjects: practice-based suggestions from an international multidisciplinary working group
Feb 24, 2017
NeuroImage
Brain imaging is now ubiquitous in clinical practice and research. The case for bringing together large amounts of image data from well-characterised healthy subjects and those with a range of common brain diseases across the life course is now compelling. This report follows a meeting of international experts from multiple disciplines, all interested in brain image biobanking. The meeting included neuroimaging experts (clinical and non-clinical), computer scientists, epidemiologists, clinicians, ethicists, and lawyers involved in creating brain image banks. The meeting followed a structured format to discuss current and emerging brain image banks; applications such as atlases; conceptual and statistical problems (e.g. defining 'normality'); legal, ethical and technological issues (e.g. consents, potential for data linkage, data security, harmonisation, data storage and enabling of research data sharing). We summarise the lessons learned from the experiences of a wide range of individual image banks, and provide practical recommendations to enhance creation, use and reuse of neuroimaging data. Our aim is to maximise the benefit of the image data, provided voluntarily by research participants and funded by many organisations, for human health. Our ultimate vision is of a federated network of brain image biobanks accessible for large studies of brain structure and function.Copyright © 2017. Published by Elsevier Inc.
Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) as a model of small vessel disease: update on clinical, diagnostic, and management aspects
Feb 24, 2017   BMC Medicine
Di Donato I, Bianchi S, De Stefano N, Dichgans M, Dotti MT,   . . . . . .   , Penco S, Rufa A, Sinanović O, Stojanov D, Federico A
Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) as a model of small vessel disease: update on clinical, diagnostic, and management aspects
Feb 24, 2017
BMC Medicine
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common and best known monogenic small vessel disease. Here, we review the clinical, neuroimaging, neuropathological, genetic, and therapeutic aspects based on the most relevant articles published between 1994 and 2016 and on the personal experience of the authors, all directly involved in CADASIL research and care. We conclude with some suggestions that may help in the clinical practice and management of these patients.
Polygenic risk scores for schizophrenia and bipolar disorder associate with addiction
Feb 23, 2017   Addiction Biology
Reginsson GW, Ingason A, Euesden J, Bjornsdottir G, Olafsson S,   . . . . . .   , Steinberg S, Stefansson H, Gudbjartsson DF, Thorgeirsson TE, Stefansson K
Polygenic risk scores for schizophrenia and bipolar disorder associate with addiction
Feb 23, 2017
Addiction Biology
We use polygenic risk scores (PRSs) for schizophrenia (SCZ) and bipolar disorder (BPD) to predict smoking, and addiction to nicotine, alcohol or drugs in individuals not diagnosed with psychotic disorders. Using PRSs for 144 609 subjects, including 10 036 individuals admitted for in-patient addiction treatment and 35 754 smokers, we find that diagnoses of various substance use disorders and smoking associate strongly with PRSs for SCZ (P = 5.3 × 10© 2017 Decode genetics EHF. Addiction Biology published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.
Effects of tDCS on motor learning and memory formation: A consensus and critical position paper
Feb 23, 2017   Clinical Neurophysiology : Official Journal Of The International Federation Of Clinical Neurophysiology
Buch ER, Santarnecchi E, Antal A, Born J, Celnik PA,   . . . . . .   , Sandrini M, Schambra HM, Wassermann EM, Ziemann U, Cohen LG
Effects of tDCS on motor learning and memory formation: A consensus and critical position paper
Feb 23, 2017
Clinical Neurophysiology : Official Journal Of The International Federation Of Clinical Neurophysiology
Motor skills are required for activities of daily living. Transcranial direct current stimulation (tDCS) applied in association with motor skill learning has been investigated as a tool for enhancing training effects in health and disease. Here, we review the published literature investigating whether tDCS can facilitate the acquisition, retention or adaptation of motor skills. Work in multiple laboratories is underway to develop a mechanistic understanding of tDCS effects on different forms of learning and to optimize stimulation protocols. Efforts are required to improve reproducibility and standardization. Overall, reproducibility remains to be fully tested, effect sizes with present techniques vary over a wide range, and the basis of observed inter-individual variability in tDCS effects is incompletely understood. It is recommended that future studies explicitly state in the Methods the exploratory (hypothesis-generating) or hypothesis-driven (confirmatory) nature of the experimental designs. General research practices could be improved with prospective pre-registration of hypothesis-based investigations, more emphasis on the detailed description of methods (including all pertinent details to enable future modeling of induced current and experimental replication), and use of post-publication open data repositories. A checklist is proposed for reporting tDCS investigations in a way that can improve efforts to assess reproducibility.Copyright © 2017. Published by Elsevier B.V.
Building better biomarkers: brain models in translational neuroimaging
Feb 23, 2017   Nature Neuroscience Add nature.com free-link Cancel
Woo CW, Chang LJ, Lindquist MA, Wager TD
Building better biomarkers: brain models in translational neuroimaging
Feb 23, 2017
Nature Neuroscience
Despite its great promise, neuroimaging has yet to substantially impact clinical practice and public health. However, a developing synergy between emerging analysis techniques and data-sharing initiatives has the potential to transform the role of neuroimaging in clinical applications. We review the state of translational neuroimaging and outline an approach to developing brain signatures that can be shared, tested in multiple contexts and applied in clinical settings. The approach rests on three pillars: (i) the use of multivariate pattern-recognition techniques to develop brain signatures for clinical outcomes and relevant mental processes; (ii) assessment and optimization of their diagnostic value; and (iii) a program of broad exploration followed by increasingly rigorous assessment of generalizability across samples, research contexts and populations. Increasingly sophisticated models based on these principles will help to overcome some of the obstacles on the road from basic neuroscience to better health and will ultimately serve both basic and applied goals.

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