It has been proposed that accurate motor control relies on Bayesian inference that integrates sensory input with prior contextual knowledge (Bays and Wolpert, 2007; Körding and Wolpert, 2004; Wolpert ...et al., 1995). Recent evidence has suggested that modulations in beta power (∼12–30 Hz) measured over sensorimotor cortices using electroencephalography (EEG) may represent parameters of Bayesian inference. While the well characterised post-movement beta synchronisation has been shown to correlate with prediction error (H. Tan, Jenkinson, & Brown, 2014; Huiling Tan, Wade, & Brown, 2016), recent evidence suggests that beta power may also represent uncertainty measures (Tan et al., 2016; Tzagarakis et al., 2015). The current study aimed to measure the neurophysiological correlates of uncertainty mediating Bayesian updating during a visuomotor adaptation paradigm in healthy human participants. In particular, sensory uncertainty was directly modulated to measure its effect on sensorimotor beta power. Participant's behaviour was modelled using the Hierarchical Gaussian Filter (HGF) in order to extract the latent variables involved in learning actions required by the task and correlate these with the measured EEG. We found that sensorimotor beta power correlated with inverse uncertainty afforded to sensory prediction errors both prior to and following a movement. This suggests that sensorimotor beta oscillations may more readily represent relative uncertainty within the sensorimotor system rather than error. Neurophysiological models describing the generation of beta oscillations offer a potential mechanism by which this neural signature may encode latent uncertainty parameters. This is essential for understanding how the brain controls behaviour.
A number of empirical and theoretical reports link altered interoceptive processing to anxiety. However, the mechanistic understanding of the relationship between the two remains poor. We propose ...that a heightened sensibility for interoceptive signals, combined with a difficulty in attributing these sensations to emotions, increases an individual's vulnerability to anxiety. In order to investigate this, a large sample of general population adults were recruited and completed self-report measures of interoceptive sensibility, trait anxiety and alexithymia. Results confirmed that the positive association between interoceptive sensibility and trait anxiety was partially mediated by alexithymia, such that those most at risk for clinically significant levels of trait anxiety have both significantly higher levels of interoceptive sensibility and alexithymia. A subsequent factor analysis confirmed the independence of the three measures. Altered interoceptive processing in combination with alexithymia, increased the risk for anxiety above and beyond altered interoceptive processing alone. We suggest that a heightened sensibility for interoceptive signals, combined with a difficulty in attributing these sensations to emotions, leaves these sensations vulnerable to catastrophizing interpretation. Interventions that target the attribution of bodily sensations may prove valuable in reducing anxiety.
Sensory attenuation, the top-down filtering or gating of afferent information, has been extensively studied in two fields: physiological and perceptual. Physiological sensory attenuation is ...represented as a decrease in the amplitude of the primary and secondary components of the somatosensory evoked potential (SEP) before and during movement. Perceptual sensory attenuation, described using the analogy of a persons' inability to tickle oneself, is a reduction in the perception of the afferent input of a self-produced tactile sensation due to the central cancellation of the reafferent signal by the efference copy of the motor command to produce the action. The fields investigating these two areas have remained isolated, so the relationship between them is unclear. The current study delivered median nerve stimulation to produce SEPs during a force-matching paradigm (used to quantify perceptual sensory attenuation) in healthy human subjects to determine whether SEP gating correlated with the behavior. Our results revealed that these two forms of attenuation have dissociable neurophysiological correlates and are likely functionally distinct, which has important implications for understanding neurological disorders in which one form of sensory attenuation but not the other is impaired. Time-frequency analyses revealed a negative correlation over sensorimotor cortex between gamma-oscillatory activity and the magnitude of perceptual sensory attenuation. This finding is consistent with the hypothesis that gamma-band power is related to prediction error and that this might underlie perceptual sensory attenuation.
We demonstrate that there are two functionally and mechanistically distinct forms of sensory gating. The literature regarding somatosensory evoked potential (SEP) gating is commonly cited as a potential mechanism underlying perceptual sensory attenuation; however, the formal relationship between physiological and perceptual sensory attenuation has never been tested. Here, we measured SEP gating and perceptual sensory attenuation in a single paradigm and identified their distinct neurophysiological correlates. Perceptual and physiological sensory attenuation has been shown to be impaired in various patient groups, so understanding the differential roles of these phenomena and how they are modulated in a diseased state is very important for aiding our understanding of neurological disorders such as schizophrenia, functional movement disorders, and Parkinson's disease.
•Interoception is the processing and awareness of the physiological state of the body.•The integration of interoceptive and exteroceptive information is important for bodily self-awareness.•The ...ability to attribute mental, emotional and interoceptive states to oneself or another person is an essential aspect of social cognition.•Interoceptive awareness may play a fundamental role in determining how well individuals can make this distinction between self and other.•Interoception may be important for social cognition.
Interoception describes the processing and awareness of bodily signals arising from visceral organs, essential for the organism's homeostatic needs. Beyond homeostasis, the integration of exteroceptive and interoceptive signals is required for the coherence of bodily self-awareness. Here, we suggest that interoception also plays a critical role in social cognition. Relating to others as individuals who are distinct from one's self requires the simultaneous yet distinct co-representation of self and others. We propose that interoceptive awareness appears to stabilise the mental representation of one's self as distinct from others. A more nuanced understanding of the role of interoception in the representation of others in relation to ourselves is vital to determine its importance in social cognition.
•Genetic variants affecting one cortical region often affect other cortical regions.•Standard mass-univariate methods ignore the distributed nature of genetic effects.•Multivariate MOSTest method ...exploits distributed effects boosting genetic discovery.•Considering fine-grained vertex-wise measures improves genetic discovery further.•Obtained increase in discovery does not come at a cost of poorer generalizability.
Brain morphology has been shown to be highly heritable, yet only a small portion of the heritability is explained by the genetic variants discovered so far. Here we extended the Multivariate Omnibus Statistical Test (MOSTest) and applied it to genome-wide association studies (GWAS) of vertex-wise structural magnetic resonance imaging (MRI) cortical measures from N=35,657 participants in the UK Biobank. We identified 695 loci for cortical surface area and 539 for cortical thickness, in total 780 unique genetic loci associated with cortical morphology robustly replicated in 8,060 children of mixed ethnicity from the Adolescent Brain Cognitive Development (ABCD) Study®. This reflects more than 8-fold increase in genetic discovery at no cost to generalizability compared to the commonly used univariate GWAS methods applied to region of interest (ROI) data. Functional follow up including gene-based analyses implicated 10% of all protein-coding genes and pointed towards pathways involved in neurogenesis and cell differentiation. Power analysis indicated that applying the MOSTest to vertex-wise structural MRI data triples the effective sample size compared to conventional univariate GWAS approaches. The large boost in power obtained with the vertex-wise MOSTest together with pronounced replication rates and highlighted biologically meaningful pathways underscores the advantage of multivariate approaches in the context of highly distributed polygenic architecture of the human brain.
•Describes the ABCD study aims and design.•Covers issues surrounding estimation of meaningful associations, including population inferences, effect sizes, and control of covariates.•Outlines best ...practices for reproducible research and reporting of results.•Provides worked examples that illustrate the main points of the paper.
The Adolescent Brain Cognitive Development (ABCD) Study is the largest single-cohort prospective longitudinal study of neurodevelopment and children's health in the United States. A cohort of n = 11,880 children aged 9–10 years (and their parents/guardians) were recruited across 22 sites and are being followed with in-person visits on an annual basis for at least 10 years. The study approximates the US population on several key sociodemographic variables, including sex, race, ethnicity, household income, and parental education. Data collected include assessments of health, mental health, substance use, culture and environment and neurocognition, as well as geocoded exposures, structural and functional magnetic resonance imaging (MRI), and whole-genome genotyping. Here, we describe the ABCD Study aims and design, as well as issues surrounding estimation of meaningful associations using its data, including population inferences, hypothesis testing, power and precision, control of covariates, interpretation of associations, and recommended best practices for reproducible research, analytical procedures and reporting of results.
While low socioeconomic status (SES) introduces risk for developmental outcomes among children, there are an array of proximal processes that determine the ecologies and thus the lived experiences of ...children. This study examined interrelations between 22 proximal measures in the economic, psychosocial, physiological, and perinatal ecologies of children, in association with brain structure and cognitive performance in a diverse sample of 8,158 9-10-year-old children from the Adolescent Brain Cognitive Development (ABCD) study. SES was measured by the income-to-needs ratio (INR), a measure used by federal poverty guidelines. Within the ABCD study, in what is one of the largest and most diverse cohorts of children studied in the United States, we replicate associations of low SES with lower total cortical surface area and worse cognitive performance. Associations between low SES (<200% INR) and measures of development showed the steepest increases with INR, with apparent increases still visible beyond the level of economic disadvantage in the range of 200-400% INR. Notably, we found three latent factors encompassing positive ecologies for children across the areas of economic, psychosocial, physiological, and perinatal well-being in association with better cognitive performance and the higher total cortical surface area beyond the effects of SES. Specifically, latent factors encompassing youth perceived social support and perinatal well-being were positive predictors of developmental measures for all children, regardless of SES. Further, we found a general latent factor that explained relationships between 20 of the proximal measures and encompassed a joint ecology of higher social and economic resources relative to low adversity across psychosocial, physiological, and perinatal domains. The association between the resource-to-adversity latent factor and cognitive performance was moderated by SES, such that for children in higher SES households, cognitive performance progressively increased with these latent factor scores, while for lower SES, cognitive performance increased only among children with the highest latent factor scores. Our findings suggest that both positive ecologies of increased access to resources and lower adversity are mutually critical for promoting better cognitive development in children from low SES households. Our findings inform future studies aiming to examine positive factors that influence healthier development in children.
Spatial and temporal expectations act synergistically to facilitate visual perception. In the current study, we sought to investigate the anticipatory oscillatory markers of combined spatial-temporal ...orienting and to test whether these decline with ageing. We examined anticipatory neural dynamics associated with joint spatial-temporal orienting of attention using magnetoencephalography (MEG) in both younger and older adults. Participants performed a cued covert spatial-temporal orienting task requiring the discrimination of a visual target. Cues indicated both where and when targets would appear. In both age groups, valid spatial-temporal cues significantly enhanced perceptual sensitivity and reduced reaction times. In the MEG data, the main effect of spatial orienting was the lateralised anticipatory modulation of posterior alpha and beta oscillations. In contrast to previous reports, this modulation was not attenuated in older adults; instead it was even more pronounced. The main effect of temporal orienting was a bilateral suppression of posterior alpha and beta oscillations. This effect was restricted to younger adults. Our results also revealed a striking interaction between anticipatory spatial and temporal orienting in the gamma-band (60–75 Hz). When considering both age groups separately, this effect was only clearly evident and only survived statistical evaluation in the older adults. Together, these observations provide several new insights into the neural dynamics supporting separate as well as combined effects of spatial and temporal orienting of attention, and suggest that different neural dynamics associated with attentional orienting appear differentially sensitive to ageing.
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•Both younger and older adults benefit from cued spatial-temporal expectation.•Alpha and beta lateralisation linked to spatial expectation is preserved and even strengthened in older adults.•Temporal expectation modulates decreases in alpha oscillations in younger but not older adults.•Combined spatial-temporal expectation increases contralateral gamma oscillations in older adults.•Different anticipatory neural dynamics may be differentially sensitive to ageing.
Genome-Wide Association studies have typically been limited to univariate analysis in which a single outcome measure is tested against millions of variants. Recent work demonstrates that a ...Multivariate Omnibus Statistic Test (MOSTest) is well powered to discover genomic effects distributed across multiple phenotypes. Applied to cortical brain MRI morphology measures, MOSTest has resulted in a drastic improvement in power to discover loci when compared to established approaches (min-P). One question that arises is how well these discovered loci replicate in independent data. Here we perform 10 times cross validation within 34,973 individuals from UK Biobank for imaging measures of cortical area, thickness and sulcal depth (>1,000 dimensionality for each). By deploying a replication method that aggregates discovered effects distributed across multiple phenotypes, termed PolyVertex Score (MOSTest-PVS), we demonstrate a higher replication yield and comparable replication rate of discovered loci for MOSTest (# replicated loci: 242–496, replication rate: 96–97%) in independent data when compared with the established min-P approach (# replicated loci: 26–55, replication rate: 91–93%). An out-of-sample replication of discovered loci was conducted with a sample of 4,069 individuals from the Adolescent Brain Cognitive Development® (ABCD) study, who are on average 50 years younger than UK Biobank individuals. We observe a higher replication yield and comparable replication rate of MOSTest-PVS compared to min-P. This finding underscores the importance of using well-powered multivariate techniques for both discovery and replication of high dimensional phenotypes in Genome-Wide Association studies.
Findings in adults have shown that crystallized measures of intelligence, which are more culturally sensitive than fluid intelligence measures, have greater heritability; however, these results have ...not been found in children. The present study used data from 8,518 participants between 9 and 11 years old from the Adolescent Brain Cognitive Development (ABCD) Study. We found that polygenic predictors of intelligence test performance (based on genome-wide association meta-analyses of data from 269,867 individuals) and of educational attainment (based on data from 1.1 million individuals) predicted neurocognitive performance. We found that crystallized measures were more strongly associated with both polygenic predictors than were fluid measures. This mirrored heritability differences reported previously in adults and suggests similar associations in children. This may be consistent with a prominent role of gene–environment correlation in cognitive development measured by crystallized intelligence tests. Environmental and experiential mediators may represent malleable targets for improving cognitive outcomes.
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