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Psychology
The role of attention in human motor resonance
May 16, 2017   PloS One
Puglisi G, Leonetti A, Landau A, Fornia L, Cerri G, Borroni P
The role of attention in human motor resonance
May 16, 2017
PloS One
Observation of others' actions evokes in primary motor cortex and spinal circuits of observers a subliminal motor resonance response, which reflects the motor program encoding observed actions. We investigated the role of attention in human motor resonance with four experimental conditions, explored in different subject groups: in the first explicit condition, subjects were asked to observe a rhythmic hand flexion-extension movement performed live in front of them. In two other conditions subjects had to monitor the activity of a LED light mounted on the oscillating hand. The hand was clearly visible but it was not the focus of subjects' attention: in the semi-implicit condition hand movement was relevant to task completion, while in the implicit condition it was irrelevant. In a fourth, baseline, condition subjects observed the rhythmic oscillation of a metal platform. Motor resonance was measured with the H-reflex technique as the excitability modulation of cortico-spinal motorneurons driving a hand flexor muscle. As expected, a normal resonant response developed in the explicit condition, and no resonant response in the baseline condition. Resonant responses also developed in both semi-implicit and implicit conditions and, surprisingly, were not different from each other, indicating that viewing an action is, per se, a powerful stimulus for the action observation network, even when it is not the primary focus of subjects' attention and even when irrelevant to the task. However, the amplitude of these responses was much reduced compared to the explicit condition, and the phase-lock between the time courses of observed movement and resonant motor program was lost. In conclusion, different parameters of the response were differently affected by subtraction of attentional resources with respect to the explicit condition: time course and muscle selection were preserved while the activation of motor circuits resulted in much reduced amplitude and lost its kinematic specificity.
Fronto-temporal interactions are functionally relevant for semantic control in language processing
May 15, 2017   PloS One
Wawrzyniak M, Hoffstaedter F, Klingbeil J, Stockert A, Wrede K, Hartwigsen G, Eickhoff SB, Classen J, Saur D
Fronto-temporal interactions are functionally relevant for semantic control in language processing
May 15, 2017
PloS One
Semantic cognition, i.e. processing of meaning is based on semantic representations and their controlled retrieval. Semantic control has been shown to be implemented in a network that consists of left inferior frontal (IFG), and anterior and posterior middle temporal gyri (a/pMTG). We aimed to disrupt semantic control processes with continuous theta burst stimulation (cTBS) over left IFG and pMTG and to study whether behavioral effects are moderated by induced alterations in resting-state functional connectivity. To this end, we applied real cTBS over left IFG and left pMTG as well as sham stimulation on 20 healthy participants in a within-subject design. Stimulation was followed by resting-state functional magnetic resonance imaging and a semantic priming paradigm. Resting-state functional connectivity of regions of interest in left IFG, pMTG and aMTG revealed highly interconnected left-lateralized fronto-temporal networks representing the semantic system. We did not find any significant direct modulation of either task performance or resting-state functional connectivity by effective cTBS. However, after sham cTBS, functional connectivity between IFG and pMTG correlated with task performance under high semantic control demands in the semantic priming paradigm. These findings provide evidence for the functional relevance of interactions between IFG and pMTG for semantic control processes. This interaction was functionally less relevant after cTBS over aIFG which might be interpretable in terms of an indirect disruptive effect of cTBS.
Judging time-to-passage of looming sounds: Evidence for the use of distance-based information
May 22, 2017   PloS One
Silva RM, Lamas J, Silva CC, Coello Y, Mouta S, Santos JA
Judging time-to-passage of looming sounds: Evidence for the use of distance-based information
May 22, 2017
PloS One
Perceptual judgments are an essential mechanism for our everyday interaction with other moving agents or events. For instance, estimation of the time remaining before an object contacts or passes us is essential to act upon or to avoid that object. Previous studies have demonstrated that participants use different cues to estimate the time to contact or the time to passage of approaching visual stimuli. Despite the considerable number of studies on the judgment of approaching auditory stimuli, not much is known about the cues that guide listeners' performance in an auditory Time-to-Passage (TTP) task. The present study evaluates how accurately participants judge approaching white-noise stimuli in a TTP task that included variable occlusion periods (portion of the presentation time where the stimulus is not audible). Results showed that participants were able to accurately estimate TTP and their performance, in general, was weakly affected by occlusion periods. Moreover, we looked into the psychoacoustic variables provided by the stimuli and analysed how binaural cues related with the performance obtained in the psychophysical task. The binaural temporal difference seems to be the psychoacoustic cue guiding participants' performance for lower amounts of occlusion, while the binaural loudness difference seems to be the cue guiding performance for higher amounts of occlusion. These results allowed us to explain the perceptual strategies used by participants in a TTP task (maintaining accuracy by shifting the informative cue for TTP estimation), and to demonstrate that the psychoacoustic cue guiding listeners' performance changes according to the occlusion period.
Untangling a Cholinergic Pathway from Wakefulness to Memory
May 18, 2017   Neuron
Gais S, Schönauer M
Untangling a Cholinergic Pathway from Wakefulness to Memory
May 18, 2017
Neuron
Acetylcholine is a major modulator of learning and memory, and its availability varies across the sleep-wake cycle. In this issue of Neuron, Papouin et al. (2017) describe a D-serine-dependent pathway involving astroglia by which the transmitter tunes the hippocampus toward memory encoding during wakefulness. Copyright © 2017. Published by Elsevier Inc.
Computing the Social Brain Connectome Across Systems and States
May 18, 2017   Cerebral Cortex (New York, N.Y. : 1991)
Alcalá-López D, Smallwood J, Jefferies E, Van Overwalle F, Vogeley K, Mars RB, Turetsky BI, Laird AR, Fox PT, Eickhoff SB, Bzdok D
Computing the Social Brain Connectome Across Systems and States
May 18, 2017
Cerebral Cortex (New York, N.Y. : 1991)
Social skills probably emerge from the interaction between different neural processing levels. However, social neuroscience is fragmented into highly specialized, rarely cross-referenced topics. The present study attempts a systematic reconciliation by deriving a social brain definition from neural activity meta-analyses on social-cognitive capacities. The social brain was characterized by meta-analytic connectivity modeling evaluating coactivation in task-focused brain states and physiological fluctuations evaluating correlations in task-free brain states. Network clustering proposed a functional segregation into (1) lower sensory, (2) limbic, (3) intermediate, and (4) high associative neural circuits that together mediate various social phenomena. Functional profiling suggested that no brain region or network is exclusively devoted to social processes. Finally, nodes of the putative mirror-neuron system were coherently cross-connected during tasks and more tightly coupled to embodied simulation systems rather than abstract emulation systems. These first steps may help reintegrate the specialized research agendas in the social and affective sciences. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
Multiple modality biomarker prediction of cognitive impairment in prospectively followed de novo Parkinson disease
May 18, 2017   PloS One
Caspell-Garcia C, Simuni T, Tosun-Turgut D, Wu IW, Zhang Y,   . . . . . .   , Hawkins KA, Litvan I, Richard I, Weintraub D, Parkinson’s Progression Markers Initiative (PPMI)
Multiple modality biomarker prediction of cognitive impairment in prospectively followed de novo Parkinson disease
May 18, 2017
PloS One
To assess the neurobiological substrate of initial cognitive decline in Parkinson's disease (PD) to inform patient management, clinical trial design, and development of treatments. We longitudinally assessed, up to 3 years, 423 newly diagnosed patients with idiopathic PD, untreated at baseline, from 33 international movement disorder centers. Study outcomes were four determinations of cognitive impairment or decline, and biomarker predictors were baseline dopamine transporter (DAT) single photon emission computed tomography (SPECT) scan, structural magnetic resonance imaging (MRI; volume and thickness), diffusion tensor imaging (mean diffusivity and fractional anisotropy), cerebrospinal fluid (CSF; amyloid beta [Aβ], tau and alpha synuclein), and 11 single nucleotide polymorphisms (SNPs) previously associated with PD cognition. Additionally, longitudinal structural MRI and DAT scan data were included. Univariate analyses were run initially, with false discovery rate = 0.2, to select biomarker variables for inclusion in multivariable longitudinal mixed-effect models. By year 3, cognitive impairment was diagnosed in 15-38% participants depending on the criteria applied. Biomarkers, some longitudinal, predicting cognitive impairment in multivariable models were: (1) dopamine deficiency (decreased caudate and putamen DAT availability); (2) diffuse, cortical decreased brain volume or thickness (frontal, temporal, parietal, and occipital lobe regions); (3) co-morbid Alzheimer's disease Aβ amyloid pathology (lower CSF Aβ 1-42); and (4) genes (COMT val/val and BDNF val/val genotypes). Cognitive impairment in PD increases in frequency 50-200% in the first several years of disease, and is independently predicted by biomarker changes related to nigrostriatal or cortical dopaminergic deficits, global atrophy due to possible widespread effects of neurodegenerative disease, co-morbid Alzheimer's disease plaque pathology, and genetic factors.
"Do it-yourself": Home blood pressure as a predictor of traditional and everyday cognition in older adults
May 18, 2017   PloS One
Yeung SE, Loken Thornton W
"Do it-yourself": Home blood pressure as a predictor of traditional and everyday cognition in older adults
May 18, 2017
PloS One
Hypertension guidelines recommend home blood pressure (HBP) monitoring in adjunct to office blood pressure (OBP) for its greater reproducibility and prognostic utility in the prevention of cardiovascular outcomes, especially stroke. To date, the relationship between HBP and cognitive function remains unexplored. We examined HBP as a cognitive predictor in a multi-ethnic group of community-dwelling adults aged 60 and over (N = 133) using neuropsychological measures and analyzed the data using multiple regression analyses. We also employed "everyday cognition" measures that have been found to have higher prognostic utility for real-world functioning than traditional cognitive tasks. Good to perfect HBP monitoring compliance over seven days was achieved by 88.7% of the participants with superior reliability (ICC≥.96) to office readings. Higher home systolic BP and pulse pressure predicted worse processing speed, executive function, and everyday cognitive function, whereas lower home diastolic BP predicted worse everyday cognition. Office readings were similarly associated with everyday cognitive function but with no other cognitive measures. Our findings are the first to validate HBP as a predictor of neuropsychological function in older adults beyond cognitive screening. Differential relationships among blood pressure variables and specific cognitive domains were observed. With proper standardization and training, we demonstrated that HBP can be obtained in a multi-ethnic community-dwelling older adult cohort. Our findings emphasize the importance of employing blood pressure and cognitive measures that are adequately sensitive to detect vascular-related cognitive impairment in a relatively healthy population. Implications regarding proper HBP measurement for hypertension management, cognitive health, and everyday function are discussed.
Hick-Hyman Law is Mediated by the Cognitive Control Network in the Brain
May 22, 2017   Cerebral Cortex (New York, N.Y. : 1991)
Wu T, Dufford AJ, Egan LJ, Mackie MA, Chen C, Yuan C, Chen C, Li X, Liu X, Hof PR, Fan J
Hick-Hyman Law is Mediated by the Cognitive Control Network in the Brain
May 22, 2017
Cerebral Cortex (New York, N.Y. : 1991)
The Hick-Hyman law describes a linear increase in reaction time (RT) as a function of the information entropy of response selection, which is computed as the binary logarithm of the number of response alternatives. While numerous behavioral studies have provided evidence for the Hick-Hyman law, its neural underpinnings have rarely been examined and are still unclear. In this functional magnetic resonance imaging study, by utilizing a choice reaction time task to manipulate the entropy of response selection, we examined brain activity mediating the input and the output, as well as the connectivity between corresponding regions in human participants. Beyond confirming the Hick-Hyman law in RT performance, we found that activation of the cognitive control network (CCN) increased and activation of the default mode network (DMN) decreased, both as a function of entropy. However, only the CCN, but not the DMN, was involved in mediating the relationship between entropy and RT. The CCN was involved in both stages of uncertainty representation and response generation, while the DMN was mainly involved at the stage of uncertainty representation. These findings indicate that the CCN serves as a core entity underlying the Hick-Hyman law by coordinating uncertainty representation and response generation in the brain. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
View-Independent Working Memory Representations of Artificial Shapes in Prefrontal and Posterior Regions of the Human Brain
May 15, 2017   Cerebral Cortex (New York, N.Y. : 1991)
Christophel TB, Allefeld C, Endisch C, Haynes JD
View-Independent Working Memory Representations of Artificial Shapes in Prefrontal and Posterior Regions of the Human Brain
May 15, 2017
Cerebral Cortex (New York, N.Y. : 1991)
Traditional views of visual working memory postulate that memorized contents are stored in dorsolateral prefrontal cortex using an adaptive and flexible code. In contrast, recent studies proposed that contents are maintained by posterior brain areas using codes akin to perceptual representations. An important question is whether this reflects a difference in the level of abstraction between posterior and prefrontal representations. Here, we investigated whether neural representations of visual working memory contents are view-independent, as indicated by rotation-invariance. Using functional magnetic resonance imaging and multivariate pattern analyses, we show that when subjects memorize complex shapes, both posterior and frontal brain regions maintain the memorized contents using a rotation-invariant code. Importantly, we found the representations in frontal cortex to be localized to the frontal eye fields rather than dorsolateral prefrontal cortices. Thus, our results give evidence for the view-independent storage of complex shapes in distributed representations across posterior and frontal brain regions. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
Empathic nonverbal behavior increases ratings of both warmth and competence in a medical context
May 15, 2017   PloS One
Kraft-Todd GT, Reinero DA, Kelley JM, Heberlein AS, Baer L, Riess H
Empathic nonverbal behavior increases ratings of both warmth and competence in a medical context
May 15, 2017
PloS One
In medicine, it is critical that clinicians demonstrate both empathy (perceived as warmth) and competence. Perceptions of these qualities are often intuitive and are based on nonverbal behavior. Emphasizing both warmth and competence may prove problematic, however, because there is evidence that they are inversely related in other settings. We hypothesize that perceptions of physician competence will instead be positively correlated with perceptions of physician warmth and empathy, potentially due to changing conceptions of the physician's role. We test this hypothesis in an analog medical context using a large online sample, manipulating physician nonverbal behaviors suggested to communicate empathy (e.g. eye contact) and competence (the physician's white coat). Participants rated physicians displaying empathic nonverbal behavior as more empathic, warm, and more competent than physicians displaying unempathic nonverbal behavior, adjusting for mood. We found no warmth/competence tradeoff and, additionally, no significant effects of the white coat. Further, compared with male participants, female participants perceived physicians displaying unempathic nonverbal behavior as less empathic. Given the significant consequences of clinician empathy, it is important for clinicians to learn how nonverbal behavior contributes to perceptions of warmth, and use it as another tool to improve their patients' emotional and physical health.
Genome-wide association meta-analysis of 78,308 individuals identifies new loci and genes influencing human intelligence
May 22, 2017   Nature Genetics Add nature.com free-link Cancel
Sniekers S, Stringer S, Watanabe K, Jansen PR, Coleman JRI,   . . . . . .   , Plomin R, Rietveld CA, Tiemeier H, van Duijn CM, Posthuma D
Genome-wide association meta-analysis of 78,308 individuals identifies new loci and genes influencing human intelligence
May 22, 2017
Nature Genetics
Intelligence is associated with important economic and health-related life outcomes. Despite intelligence having substantial heritability (0.54) and a confirmed polygenic nature, initial genetic studies were mostly underpowered. Here we report a meta-analysis for intelligence of 78,308 individuals. We identify 336 associated SNPs (METAL P < 5 × 10-8) in 18 genomic loci, of which 15 are new. Around half of the SNPs are located inside a gene, implicating 22 genes, of which 11 are new findings. Gene-based analyses identified an additional 30 genes (MAGMA P < 2.73 × 10-6), of which all but one had not been implicated previously. We show that the identified genes are predominantly expressed in brain tissue, and pathway analysis indicates the involvement of genes regulating cell development (MAGMA competitive P = 3.5 × 10-6). Despite the well-known difference in twin-based heratiblity for intelligence in childhood (0.45) and adulthood (0.80), we show substantial genetic correlation (rg = 0.89, LD score regression P = 5.4 × 10-29). These findings provide new insight into the genetic architecture of intelligence.
Brain activation of semantic category-based grouping in multiple identity tracking task
May 15, 2017   PloS One
Wei L, Zhang X, Lyu C, Hu S, Li Z
Brain activation of semantic category-based grouping in multiple identity tracking task
May 15, 2017
PloS One
Using Multiple Identity Tracking task and the functional magnetic resonance imaging (fMRI) technology, the present study aimed to isolate and visualize the functional anatomy of neural systems involved in the semantic category-based grouping process. Three experiment conditions were selected and compared: the category-based targets grouping (TG) condition, the targets-distractors grouping (TDG) condition and the homogenous condition. In the TG condition, observers could utilize the categorical distinction between targets and distractors, to construct a uniform presentation of targets, that is, to form a group of the targets to facilitate tracking. In the TDG condition, half the targets and half the distractors belonged to the same category. Observers had to inhibit the grouping of targets and distractors in one category to complete tracking. In the homogenous condition, where targets and distractors consisted of the same objects, no grouping could be formed. The "TG-Homogenous" contrast (p
Gender differences in the transmission of risk for antisocial behavior problems across generations
May 15, 2017   PloS One
Li P, Becker JB, Heitzeg MM, McClellan ML, Reed BG, Zucker RA
Gender differences in the transmission of risk for antisocial behavior problems across generations
May 15, 2017
PloS One
Previous studies have shown that children of alcohol use disorder (AUD) parents are more likely to develop alcohol problems as well as antisocial and other behavior problems. The purpose of this study was to examine gender discordance in the effect of early maternal and paternal influences on antisocial behaviors of boys and girls, as well as the environmental factors that moderate the parental effects. Specifically, we examined the effects of childhood and adulthood antisocial behavior of the parents on offspring antisocial behavior as young adults. We also examined whether mothers' and fathers' drinking problems when offspring were young children (6-8 years) affected offspring antisocial behavior as young adults (18-21 years). We evaluated 655 children from 339 families in the Michigan Longitudinal Study (MLS), a prospective study of AUD and non-AUD families. Path models were constructed in order to test for the parental contributions to offspring outcomes. We found that both mothers' and fathers' antisocial behavior contributed to the children's young adult antisocial behavior. Only mothers' drinking problems while their children were little had a significant effect on their sons' later drinking, but not on their daughters'. These different parental effects suggest that maternal and paternal influences may be mediated by different mechanisms.
Effect on healthcare utilization and costs of spinal manual therapy for acute low back pain in routine care: A propensity score matched cohort study
May 15, 2017   PloS One
Walker J, Mertens UK, Schmidt CO, Chenot JF
Effect on healthcare utilization and costs of spinal manual therapy for acute low back pain in routine care: A propensity score matched cohort study
May 15, 2017
PloS One
Spinal manual therapy (SMT) is a popular treatment option for low back pain (LBP). The aim of our analysis was to evaluate the effects of manual therapy delivered by general practitioners and ambulatory orthopedic surgeons in routine care on follow up consultations, sick leave, health service utilization and costs for acute LBP compared to matched patients not receiving manual therapy. This is a propensity score matched cohort study based on health claims data. We identified a total of 113.652 adult patients with acute LBP and no coded red flags of whom 21.021 (18%) received SMT by physicians. In the final analysis 17.965 patients in each group could be matched. Balance on patients' coded characteristics, comorbidity and prior health service utilization was achieved. The provision of SMT for acute LBP had no relevant impact on follow up visits and days of sick leave for LBP in the index billing period and the following year. SMT was associated with a higher proportion of imaging studies for LBP (30.6% vs. 23%, SMD: 0.164 [95% CI 0.143-0.185]). SMT did not lead to meaningful savings by replacing other health services for LBP. SMT for acute non-specific LBP in routine care was not clinically meaningful effective to reduce sick leave and reconsultation rates compared to no SMT and did not lead to meaningful savings by replacing other health services from the perspective of health insurance. This does not imply that SMT is ineffective but might reflect a problem with selection of suitable patients and the quality and quantity of SMT in routine care. National Manual Medicine societies should state clearly that imaging is not routinely needed prior to SMT in patients with low suspicion of presence of red flags and monitor the quality of provided services.
Global Tactile Coding in Rat Barrel Cortex in the Absence of Local Cues
May 12, 2017   Cerebral Cortex (New York, N.Y. : 1991)
Gerdjikov TV, Bergner CG, Schwarz C
Global Tactile Coding in Rat Barrel Cortex in the Absence of Local Cues
May 12, 2017
Cerebral Cortex (New York, N.Y. : 1991)
Although whisker-related perception is based predominantly on local, near-instantaneous coding, global, intensive coding, which integrates the vibrotactile signal over time, has also been shown to play a role given appropriate behavioral conditions. Here, we study global coding in isolation by studying head-fixed rats that identified pulsatile stimuli differing in pulse frequency but not in pulse waveforms, thus abolishing perception based on local coding. We quantified time locking and spike counts as likely variables underpinning the 2 coding schemes. Both neurometric variables contained substantial stimulus information, carried even by spikes of single barrel cortex neurons. To elucidate which type of information is actually used by the rats, we systematically compared psychometric with neurometric sensitivity based on the 2 coding schemes. Neurometric performance was calculated by using a population-encoding model incorporating the properties of our recorded neuron sample. We found that sensitivity calculated from spike counts sampled over long periods (>1 s) matched the performance of rats better than the one carried by spikes time-locked to the stimulus. We conclude that spike counts are more relevant to tactile perception when instantaneous kinematic parameters are not available. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
From CNTNAP2 to Early Expressive Language in Infancy: The Mediation Role of Rapid Auditory Processing
May 12, 2017   Cerebral Cortex (New York, N.Y. : 1991)
Riva V, Cantiani C, Benasich AA, Molteni M, Piazza C, Giorda R, Dionne G, Marino C
From CNTNAP2 to Early Expressive Language in Infancy: The Mediation Role of Rapid Auditory Processing
May 12, 2017
Cerebral Cortex (New York, N.Y. : 1991)
Although it is clear that early language acquisition can be a target of CNTNAP2, the pathway between gene and language is still largely unknown. This research focused on the mediation role of rapid auditory processing (RAP). We tested RAP at 6 months of age by the use of event-related potentials, as a mediator between common variants of the CNTNAP2 gene (rs7794745 and rs2710102) and 20-month-old language outcome in a prospective longitudinal study of 96 Italian infants. The mediation model examines the hypothesis that language outcome is explained by a sequence of effects involving RAP and CNTNAP2. The ability to discriminate spectrotemporally complex auditory frequency changes at 6 months of age mediates the contribution of rs2710102 to expressive vocabulary at 20 months. The indirect effect revealed that rs2710102 C/C was associated with lower P3 amplitude in the right hemisphere, which, in turn, predicted poorer expressive vocabulary at 20 months of age. These findings add to a growing body of literature implicating RAP as a viable marker in genetic studies of language development. The results demonstrate a potential developmental cascade of effects, whereby CNTNAP2 drives RAP functioning that, in turn, contributes to early expressive outcome. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
When do traumatic experiences alter risk-taking behavior? A machine learning analysis of reports from refugees
May 12, 2017   PloS One
Augsburger M, Elbert T
When do traumatic experiences alter risk-taking behavior? A machine learning analysis of reports from refugees
May 12, 2017
PloS One
Exposure to traumatic stressors and subsequent trauma-related mental changes may alter a person's risk-taking behavior. It is unclear whether this relationship depends on the specific types of traumatic experiences. Moreover, the association has never been tested in displaced individuals with substantial levels of traumatic experiences. The present study assessed risk-taking behavior in 56 displaced individuals by means of the balloon analogue risk task (BART). Exposure to traumatic events, symptoms of posttraumatic stress disorder and depression were assessed by means of semi-structured interviews. Using a novel statistical approach (stochastic gradient boosting machines), we analyzed predictors of risk-taking behavior. Exposure to organized violence was associated with less risk-taking, as indicated by fewer adjusted pumps in the BART, as was the reported experience of physical abuse and neglect, emotional abuse, and peer violence in childhood. However, civil traumatic stressors, as well as other events during childhood were associated with lower risk taking. This suggests that the association between global risk-taking behavior and exposure to traumatic stress depends on the particular type of the stressors that have been experienced.
Investigating the causal effect of smoking on hay fever and asthma: a Mendelian randomization meta-analysis in the CARTA consortium
May 23, 2017   Scientific Reports
Skaaby T, Taylor AE, Jacobsen RK, Paternoster L, Thuesen BH,   . . . . . .   , Romundstad PR, Skorpen F, Kaprio J, R Munafò M, Linneberg A
Investigating the causal effect of smoking on hay fever and asthma: a Mendelian randomization meta-analysis in the CARTA consortium
May 23, 2017
Scientific Reports
Observational studies on smoking and risk of hay fever and asthma have shown inconsistent results. However, observational studies may be biased by confounding and reverse causation. Mendelian randomization uses genetic variants as markers of exposures to examine causal effects. We examined the causal effect of smoking on hay fever and asthma by using the smoking-associated single nucleotide polymorphism (SNP) rs16969968/rs1051730. We included 231,020 participants from 22 population-based studies. Observational analyses showed that current vs never smokers had lower risk of hay fever (odds ratio (OR) = 0·68, 95% confidence interval (CI): 0·61, 0·76; P 
The etiology of autistic traits in preschoolers: a population-based twin study
May 19, 2017   Journal Of Child Psychology And Psychiatry, And Allied Disciplines
de Zeeuw EL, van Beijsterveldt CEM, Hoekstra RA, Bartels M, Boomsma DI
The etiology of autistic traits in preschoolers: a population-based twin study
May 19, 2017
Journal Of Child Psychology And Psychiatry, And Allied Disciplines
Autism Spectrum Disorders (ASD) are highly heritable, but the exact etiological mechanisms underlying the condition are still unclear. Using a multiple rater twin design in a large sample of general population preschool twins, this study aimed to (a) estimate the contribution of genetic and environmental factors to autistic traits, controlling for the possible effects of rater bias, (b) to explore possible sex differences in etiology and (c) to investigate the discordance in autistic traits in monozygotic and same-sex dizygotic twin pairs. The Netherlands Twin Register collected maternal and paternal ratings on autistic traits from a general population of 38,798 three-year-old twins. Autistic traits were assessed with the DSM-oriented Pervasive Developmental Problems scale of the Child Behavior Check List for preschoolers (1½-5 years). Mother and fathers showed high agreement in their assessment of autistic traits (r = .60-.66). Differences between children in autistic traits were largely accounted for by genetic effects (boys: 78% and girls: 83%). Environmental effects that are unique to a child also played a modest role. Environmental effects shared by children growing up in the same family were negligible, once rater bias was controlled for. While the prevalence for clinical ASD is higher in boys than in girls, this study did not find evidence for striking differences in the etiology of autistic traits across the sexes. Even though the heritability was high, 29% of MZ twin pairs were discordant for high autistic traits (clinical range vs. normal development), suggesting that despite high genetic risk, environmental factors might lead to resilience, unaffected status in the context of genetic risk, in some children. It is important to focus future research on risk factors that might interplay with a genetic disposition for ASD, but also on protective factors that make a difference in the lives of children at genetic risk. © 2017 Association for Child and Adolescent Mental Health.
Multiple Transient Signals in Human Visual Cortex Associated with an Elementary Decision
May 12, 2017   The Journal Of Neuroscience : The Official Journal Of The Society For Neuroscience
Meindertsma T, Kloosterman NA, Nolte G, Engel AK, Donner TH
Multiple Transient Signals in Human Visual Cortex Associated with an Elementary Decision
May 12, 2017
The Journal Of Neuroscience : The Official Journal Of The Society For Neuroscience
The cerebral cortex continuously undergoes changes in its state, which manifest in transient modulations of the cortical power spectrum. Cortical state changes occur also at full wakefulness, during rapid cognitive acts, such as perceptual decisions. Previous studies found a global modulation of beta-band (12-30 Hz) activity in human and monkey visual cortex during an elementary visual decision: reporting the appearance or disappearance of salient visual targets surrounded by a distractor. The previous studies did neither disentangle the motor action associated with behavioral report, nor other secondary processes, such as arousal, from perceptual decision processing per se. Here, we used magnetoencephalography (MEG) in humans to pinpoint the factors underlying the beta-band modulation. We found that disappearances of a salient target were associated with beta-band suppression and target reappearances with beta-band enhancement. This was true for both overt behavioral reports (immediate button presses) and silent counting of the perceptual events. This finding indicates that the beta-band modulation was unrelated to the execution of the motor act associated with behavioral report of the perceptual decision. Further, neither changes in pupil-linked arousal, fixational eye movements, or gamma-band responses were necessary for the beta-band modulation. Taken together, our results suggest that the beta-band modulation was a top-down signal associated with the process of converting graded perceptual signals into a categorical format underlying flexible behavior. This signal may have been fed back from brain regions involved in decision processing to visual cortex, thus enforcing a 'decision-consistent' cortical state.SIGNIFICANCE STATEMENTElementary visual decisions are associated with a rapid state change in visual cortex, indexed by a modulation of neural activity in the beta-frequency range. Such decisions are also followed by other events that might affect the state of visual cortex, including the motor command associated with the report of the decision, an increase in pupil-linked arousal, fixational eye movements, and fluctuations in bottom-up sensory processing. Here, we ruled out the necessity of these events for the beta-band modulation visual cortex. We propose that the modulation reflects a decision-related state change, which is induced by the conversion of graded perceptual signals into a categorical format underlying behavior. The resulting decision signal may be fed back to visual cortex. Copyright © 2017 Meindertsma et al.
Contrasting the role of xCT and GLT-1 upregulation in the ability of ceftriaxone to attenuate the cue-induced reinstatement of cocaine-seeking and normalize AMPA receptor subunit expression
May 12, 2017   The Journal Of Neuroscience : The Official Journal Of The Society For Neuroscience
Lacrosse AL, O'Donovan SM, Sepulveda-Orengo MT, McCullumsmith RE, Reissner KJ, Schwendt M, Knackstedt LA
Contrasting the role of xCT and GLT-1 upregulation in the ability of ceftriaxone to attenuate the cue-induced reinstatement of cocaine-seeking and normalize AMPA receptor subunit expression
May 12, 2017
The Journal Of Neuroscience : The Official Journal Of The Society For Neuroscience
Chronic treatment with ceftriaxone attenuates reinstatement of cocaine-seeking while increasing the function of the glutamate transporter GLT-1 and system xC- (Sxc) in the nucleus accumbens core (NAc). Sxc contributes the majority of non-synaptic extracellular glutamate in the NAc, while GLT-1 is responsible for the majority of glutamate uptake. Here we used antisense to decrease the expression of GLT-1 and xCT (catalytic subunit of Sxc), in order to determine the relative importance of both proteins in mediating ceftriaxone's ability to prevent cue-induced reinstatement of cocaine-seeking and normalize glutamatergic proteins in the NAc of rats. Intra-NAc xCT knockdown prevented ceftriaxone from attenuating reinstatement and from upregulating GLT-1, and resulted in increased surface expression of AMPA receptor subunits GluA1 and GluA2. Intra-NAc GLT-1 knockdown also prevented ceftriaxone from attenuating reinstatement and from upregulating xCT expression, without affecting GluA1 and GluA2 expression. In the absence of cocaine or ceftriaxone treatment, xCT knockdown in the NAc increased expression of both GluA1 and GluA2 without affecting GLT-1 expression while GLT-1 knockdown had no effect. PCR and immunoprecipitation of GLT-1 revealed that ceftriaxone does not upregulate GLT-1 and xCT through a transcriptional mechanism and their co-regulation by ceftriaxone is not mediated by physical interaction. These data support important and distinct roles for xCT and GLT-1 in the actions of ceftriaxone and add to a body of literature finding evidence for co-regulation of these transporters. Our results also point to xCT expression and subsequent basal glutamate levels as a key mediator of AMPA receptor expression in the NAc.SIGNIFICANCE STATEMENTCeftriaxone attenuates the reinstatement of cocaine-, alcohol- and heroin-seeking. The mechanism of action of this behavioral effect has been attributed to GLT-1 and xCT/system xc- upregulation in the nucleus accumbens core. Here we used an antisense strategy to knock down GLT-1 or xCT in the nucleus accumbens core and examined the behavioral and molecular consequences. While upregulation of both xCT and GLT-1 are essential to the ability of ceftriaxone to attenuate cue-induced reinstatement of cocaine-seeking, each protein uniquely affects the expression of other glutamate receptor and transporter proteins. We also report that reducing basal glutamate levels through manipulation of xCT expression increases surface expression of AMPA receptor subunits, providing insight to the mechanism by which cocaine alters AMPA surface expression. Copyright © 2017 the authors.
Voluntary Control of Epileptiform Spike-Wave Discharges in Awake Rats
May 19, 2017   The Journal Of Neuroscience : The Official Journal Of The Society For Neuroscience
Taylor JA, Rodgers KM, Bercum FM, Booth CJ, Dudek FE, Barth DS
Voluntary Control of Epileptiform Spike-Wave Discharges in Awake Rats
May 19, 2017
The Journal Of Neuroscience : The Official Journal Of The Society For Neuroscience
Genetically inherited absence epilepsy in humans is typically characterized by brief (seconds) spontaneous seizures, which involve spike-wave discharges (SWDs) in the EEG and interruption of consciousness and ongoing behavior. Genetic (inbred) models of this disorder in rats have been used to examine mechanisms, comorbidities and anti-absence drugs. SWDs have also been proposed as models of complex partial seizures (CPSs) following traumatic brain injury (post-traumatic epilepsy; PTE). However, the ictal characteristics of these rat models, including SWDs and associated immobility, are also prevalent in healthy outbred laboratory rats. We therefore hypothesized that SWDs are not always associated with classically defined absence seizures or CPSs.To test this hypothesis, we used operant conditioning in male rats to determine if outbred strains, Sprague Dawley and Long Evans, and/or the inbred WAG/Rij strain (a rat model of heritable human absence epilepsy) could exercise voluntary control over these epileptiform events. We discovered that both inbred and outbred rats could shorten the duration of SWDs to obtain a reward.These results indicate that SWD/immobility in rats may not reflect the obvious cognitive/behavioral-interruption classically associated with absence seizures or CPSs in humans. One interpretation of these results is that human absence seizures and perhaps CPSs could permit a far greater degree of cognitive capacity than often assumed and might be brought under voluntary control in some cases. However, these results also suggest that SWD/immobility may be non-epileptic in healthy outbred rats and reflect instead voluntary rodent behavior unrelated to genetic manipulation or to brain trauma.SIGNIFICANCE STATEMENTOur evidence that inbred and outbred rats learn to control the duration of SWDs suggests a voluntary behavior with maintenance of consciousness. If SWDs model mild absence seizures and/or CPSs in humans, it suggests an opportunity for operant control complementing or in some cases replacing medication. Their equal occurrence in outbred rats also implies a major potential confound for behavioral neuroscience experiments, at least in adult rats where SWDs are prevalent. Alternatively, the presence and voluntary control of SWDs in healthy outbred rats could indicate these phenomena do not always model heritable absence epilepsy or PTE in humans, and may instead reflect typical rodent behavior. Copyright © 2017 the authors.
Optogenetic inhibition of ventral pallidum neurons impairs context-driven salt-seeking
May 12, 2017   The Journal Of Neuroscience : The Official Journal Of The Society For Neuroscience
Chang SE, Smedley EB, Stansfield KJ, Stott JJ, Smith KS
Optogenetic inhibition of ventral pallidum neurons impairs context-driven salt-seeking
May 12, 2017
The Journal Of Neuroscience : The Official Journal Of The Society For Neuroscience
Salt appetite, in which animals can immediately seek out salt when under a novel state of sodium deprivation, is a classic example of how homeostatic systems interface with learned associations to produce an on-the-fly updating of motivated behavior. Neural activity in the ventral pallidum (VP) has been shown to encode changes in the value of salt under such conditions, both the value of salt itself (Tindell et al., 2006) and the motivational value of its predictive cues (Tindell et al., 2009; Robinson & Berridge, 2013). However, it is not known whether the VP is necessary for salt appetite in terms of seeking out salt or consuming salt following sodium depletion. Here, we used a conditioned place preference procedure to investigate the effects of optogenetically inhibiting the VP on context-driven salt-seeking and the consumption of salt following deprivation. Male rats learned to associate one context with sucrose and another context with less-desirable salt. Following sodium depletion, and in the absence of either sucrose or salt, we found that inhibiting the VP selectively reduced the elevation in time spent in the salt-paired context. VP inhibition had minimal effects on the consumption of salt once it was made available. To our knowledge, this is the first evidence that the VP or any brain region is necessary for the ability to use contextual cues to guide context-driven salt-seeking. These results highlight a dissociation between deficit-driven reward-seeking and reward consumption to replenish those deficits, with the former process being particularly sensitive to on-line VP activity.SIGNIFICANCE STATEMENTSalt appetite, in which rats will immediately seek out a once undesirable highly-concentrated salt solution after being depleted of bodily sodium despite never having tasted salt as a positive reward, is a phenomenon showing how animals can update their motivational goals without any new learning or conditioning. This salt-seeking behavior is also observed when presented with salt-paired cues. The neural circuitry necessary for context-driven salt-seeking behavior is unknown. We used a novel conditioned place procedure to show that optogenetic inhibition of the ventral pallidum (VP), a region known for processing reward, impairs context-driven salt-seeking and has minimal effects on the consumption of salt itself following sodium depletion. These results highlight the importance of the VP in context-driven reward-seeking behavior. Copyright © 2017 the authors.
MicroRNAs 146a/b-5 and 425-3p and 24-3p are markers of antidepressant response and regulate MAPK/Wnt-system genes
May 22, 2017   Nature Communications
Lopez JP, Fiori LM, Cruceanu C, Lin R, Labonte B,   . . . . . .   , Mechawar N, Nestler EJ, Uher R, Kennedy SH, Turecki G
MicroRNAs 146a/b-5 and 425-3p and 24-3p are markers of antidepressant response and regulate MAPK/Wnt-system genes
May 22, 2017
Nature Communications
Antidepressants (ADs) are the most common treatment for major depressive disorder (MDD). However, only ∼30% of patients experience adequate response after a single AD trial, and this variability remains poorly understood. Here, we investigated microRNAs (miRNAs) as biomarkers of AD response using small RNA-sequencing in paired samples from MDD patients enrolled in a large, randomized placebo-controlled trial of duloxetine collected before and 8 weeks after treatment. Our results revealed differential expression of miR-146a-5p, miR-146b-5p, miR-425-3p and miR-24-3p according to treatment response. These results were replicated in two independent clinical trials of MDD, a well-characterized animal model of depression, and post-mortem human brains. Furthermore, using a combination of bioinformatics, mRNA studies and functional in vitro experiments, we showed significant dysregulation of genes involved in MAPK/Wnt signalling pathways. Together, our results indicate that these miRNAs are consistent markers of treatment response and regulators of the MAPK/Wnt systems.
Mir-132/212 is required for maturation of binocular matching of orientation preference and depth perception
May 23, 2017   Nature Communications
Mazziotti R, Baroncelli L, Ceglia N, Chelini G, Sala GD, Magnan C, Napoli D, Putignano E, Silingardi D, Tola J, Tognini P, Arthur JSC, Baldi P, Pizzorusso T
Mir-132/212 is required for maturation of binocular matching of orientation preference and depth perception
May 23, 2017
Nature Communications
MicroRNAs (miRNAs) are known to mediate post-transcriptional gene regulation, but their role in postnatal brain development is still poorly explored. We show that the expression of many miRNAs is dramatically regulated during functional maturation of the mouse visual cortex with miR-132/212 family being one of the top upregulated miRNAs. Age-downregulated transcripts are significantly enriched in miR-132/miR-212 putative targets and in genes upregulated in miR-132/212 null mice. At a functional level, miR-132/212 deletion affects development of receptive fields of cortical neurons determining a specific impairment of binocular matching of orientation preference, but leaving orientation and direction selectivity unaltered. This deficit is associated with reduced depth perception in the visual cliff test. Deletion of miR-132/212 from forebrain excitatory neurons replicates the binocular matching deficits. Thus, miR-132/212 family shapes the age-dependent transcriptome of the visual cortex during a specific developmental window resulting in maturation of binocular cortical cells and depth perception.

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