Conflict adaptation is a hallmark effect of adaptive cognitive control and refers to the adjustment of control to the level of previously experienced conflict. Conflict monitoring theory assumes that ...the dorsolateral prefrontal cortex (DLPFC) is causally involved in this adjustment. However, to date, evidence in humans is predominantly correlational, and heterogeneous with respect to the lateralization of control in the DLPFC. We used high-definition transcranial direct current stimulation (HD-tDCS), which allows for more focal current delivery than conventional tDCS, to clarify the causal involvement of the DLPFC in conflict adaptation. Specifically, we investigated the regional specificity and lateralization of potential beneficial stimulation effects on conflict adaptation during a visual flanker task. One hundred twenty healthy participants were assigned to four HD-tDCS conditions: left or right DLPFC or left or right primary motor cortex (M1). Each group underwent both active and sham HD-tDCS in crossover, double-blind designs. We obtained a sizeable conflict adaptation effect (measured as the modulation of the flanker effect as a function of previous response conflict) in all groups and conditions. However, this effect was larger under active HD-tDCS than under sham stimulation in both DLPFC groups. In contrast, active stimulation had no effect on conflict adaptation in the M1 groups. In sum, the present results indicate that the DLPFC plays a causal role in adaptive cognitive control, but that the involvement of DLPFC in control is not restricted to the left or right hemisphere. Moreover, our study confirms the potential of HD-tDCS to modulate cognition in a regionally specific manner.
Conflict adaptation is a hallmark effect of adaptive cognitive control. While animal studies have suggested causal involvement of the DLPFC in this phenomenon, such evidence is currently lacking in humans. The present study used high-definition transcranial direct current stimulation (HD-tDCS) to demonstrate that the DLPFC is causally involved in conflict adaptation in humans. Our study confirms a central claim of conflict monitoring theory, which up to now has predominantly relied on correlational studies. Our results further indicate an equal involvement of the left and right DLPFC in adaptive control, whereas stimulation of a control region-the primary motor cortex-had no effect on adaptive control. The study thus confirms the potential of HD-tDCS to modulate cognition in a regionally specific manner.
Abstract
Quantifying the genetic architecture of the cerebral cortex is necessary for understanding disease and changes to the brain across the lifespan. Prior work shows that both surface area (SA) ...and cortical thickness (CT) are heritable. However, we do not yet understand the extent to which region-specific genetic factors (i.e., independent of global effects) play a dominant role in the regional patterning or inter-regional associations across the cortex. Using a population sample of young adult twins (N = 923), we show that the heritability of SA and CT varies widely across regions, generally independent of measurement error. When global effects are controlled for, we detected a complex pattern of genetically mediated clusters of inter-regional associations, which varied between hemispheres. There were generally weak associations between the SA of different regions, except within the occipital lobe, whereas CT was positively correlated within lobar divisions and negatively correlated across lobes, mostly due to genetic covariation. These findings were replicated in an independent sample of twins and siblings (N = 698) from the Human Connectome Project. The different genetic contributions to SA and CT across regions reveal the value of quantifying sources of covariation to appreciate the genetic complexity of cortical structures.
The hippocampus is a brain region critical for learning and memory, and is also implicated in several neuropsychiatric disorders that show sex differences in prevalence, symptom expression, and mean ...age of onset. On average, males have larger hippocampal volumes than females, but findings are inconclusive after adjusting for overall brain size. Although the hippocampus is a heterogenous structure, few studies have focused on sex differences in the hippocampal subfields – with little consensus on whether there are regionally specific sex differences in the hippocampus after adjusting for brain size, or whether it is important to adjust for total hippocampal volume (HPV). Here, using two young adult cohorts from the Queensland Twin IMaging study (QTIM; N = 727) and the Human Connectome Project (HCP; N = 960), we examined differences between males and females in the volumes of 12 hippocampal subfields, extracted using FreeSurfer 6.0. After adjusting the subfield volumes for either HPV or brain size (brain segmentation volume (BSV)) using four controlling methods (allometric, covariate, residual and matching), we estimated the percentage difference of the sex effect (males versus females) and Cohen’s d using hierarchical general linear models. Males had larger volumes compared to females in the parasubiculum (up to 6.04%; Cohen’s d = 0.46) and fimbria (up to 8.75%; d = 0.54) after adjusting for HPV. These sex differences were robust across the two cohorts and multiple controlling methods, though within cohort effect sizes were larger for the matched approach, due to the smaller sub-sample. Additional sex effects were identified in the HCP cohort and combined (QTIM and HCP) sample (hippocampal fissure (up to 6.79%), presubiculum (up to 3.08%), and hippocampal tail (up to −0.23%)). In contrast, no sex differences were detected for the volume of the cornu ammonis (CA)2/3, CA4, Hippocampus-Amygdala Transition Area (HATA), or the granule cell layer of the dentate gyrus (GCDG). These findings show that, independent of differences in HPV, there are regionally specific sex differences in the hippocampus, which may be most prominent in the fimbria and parasubiculum. Further, given sex differences were less consistent across cohorts after controlling for BSV, adjusting for HPV rather than BSV may benefit future studies. This work may help in disentangling sex effects, and provide a better understanding of the implications of sex differences for behaviour and neuropsychiatric disorders.
•Region-specific sex differences were found after adjusting for hippocampal volume.•Males have larger parasubiculum, fimbria, hippocampal fissure, and presubiculum.•Females show larger volumes for the hippocampal tail.•No sex differences were found in the CA2/3, CA4, HATA, or GCDG subfields.
Across spoken languages, there are some words whose acoustic features resemble the meanings of their referents by evoking perceptual imagery, i.e., they are iconic (e.g., in English, "splash" ...imitates the sound of an object hitting water). While these sound symbolic form-meaning relationships are well-studied, relatively little work has explored whether the sensory properties of English words also involve systematic (i.e., statistical) form-meaning mappings. We first test the prediction that surface form properties can predict sensory experience ratings for over 5,000 monosyllabic and disyllabic words (Juhasz & Yap, 2013), confirming they explain a significant proportion of variance. Next, we show that iconicity and sensory form typicality, a statistical measure of how well a word's form aligns with its sensory experience rating, are only weakly related to each other, indicating they are likely to be distinct constructs. To determine whether form typicality influences processing of sensory words, we conducted regression analyses using lexical decision, word recognition, naming and semantic decision tasks from behavioral megastudy data sets. Across the data sets, sensory form typicality was able to predict more variance in performance than sensory experience or iconicity ratings. Further, the effects of typicality were consistently inhibitory in comprehension (i.e., more typical forms were responded to more slowly and less accurately), whereas for production the effect was facilitatory. These findings are the first evidence that systematic form-meaning mappings in English sensory words influence their processing. We discuss how language processing models incorporating Bayesian prediction mechanisms might be able to account for form typicality in the lexicon.
Public Significance Statement
For over a century, language researchers have generally assumed that the relationship between the sound of a word and its meaning is entirely arbitrary. Our study shows there are systematic associations between English words referencing sensory experiences and their sound features beyond previously reported iconic relationships. We also show that these sensory sound-meaning associations influence language comprehension and production.
There is increasing interest in the potential contribution of the gut microbiome to autism spectrum disorder (ASD). However, previous studies have been underpowered and have not been designed to ...address potential confounding factors in a comprehensive way. We performed a large autism stool metagenomics study (n = 247) based on participants from the Australian Autism Biobank and the Queensland Twin Adolescent Brain project. We found negligible direct associations between ASD diagnosis and the gut microbiome. Instead, our data support a model whereby ASD-related restricted interests are associated with less-diverse diet, and in turn reduced microbial taxonomic diversity and looser stool consistency. In contrast to ASD diagnosis, our dataset was well powered to detect microbiome associations with traits such as age, dietary intake, and stool consistency. Overall, microbiome differences in ASD may reflect dietary preferences that relate to diagnostic features, and we caution against claims that the microbiome has a driving role in ASD.
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•Limited autism-microbiome associations from stool metagenomics of n = 247 children•Romboutsia timonensis was the only taxa associated with autism diagnosis•Autistic traits such as restricted interests are associated with less-diverse diet•Less-diverse diet, in turn, is associated with lower microbiome alpha-diversity
Large autism stool metagenomics study finds limited direct autism associations, in contrast to strong relationships with dietary traits, stool consistency, and age, suggestive of a model whereby genetic and phenotypic measures of the autism spectrum promote a less-diverse diet that reduces microbiome diversity.
Adolescence is a risk period for the development of mental illness, as well as a time for pronounced change in sleep behaviour. While prior studies, including several meta-analyses show a ...relationship between sleep and depressive symptoms, there were many inconsistences found in the literature.
To investigate the relationship between subjective sleep and depressive symptoms.
Following PRISMA guidelines, we conducted a literature search that yielded forty-nine recent studies (2014–2020) with adolescent samples aged 9 to 25-year-olds, and more than double the sample size of previous meta-analyses (N = 318,256).
In a series of meta-analyses, we show that while several common categories of subjective sleep are associated with depressive symptoms in adolescents, the strength of this relationship varies. Measures of sleep perception: poor sleep quality (r = 0.41), insomnia (r = 0.37), sleep disturbances (r = 0.36), wake after sleep onset (r = 0.31), and daytime sleepiness (r = 0.30) correlated more strongly with depressive symptoms, than measures of sleep behaviour: sleep latency (r = 0.22), and sleep duration (r = −0.19).
These findings suggest that in studies of depressive symptoms it may be important to assess an adolescent's perception about their sleep, in addition to their sleep/wake behaviours.
•Largest analysis of the relationship between sleep and depression in adolescence.•All sleep measures were associated with depressive symptoms, but not equally.•Stronger associations for sleep perception than sleep/wake behaviour.•When considering adolescent depression, it is vital to also assess sleep quality.
Studies of semantic context effects in spoken word production have typically distinguished between categorical (or taxonomic) and associative relations. However, associates tend to confound semantic ...features or morphological representations, such as whole-part relations and compounds (e.g., BOAT-anchor, BEE-hive). Using a picture-word interference paradigm and functional magnetic resonance imaging (fMRI), we manipulated categorical (COW-rat) and thematic (COW-pasture) TARGET-distractor relations in a balanced design, finding interference and facilitation effects on naming latencies, respectively, as well as differential patterns of brain activation compared with an unrelated distractor condition. While both types of distractor relation activated the middle portion of the left middle temporal gyrus (MTG) consistent with retrieval of conceptual or lexical representations, categorical relations involved additional activation of posterior left MTG, consistent with retrieval of a lexical cohort. Thematic relations involved additional activation of the left angular gyrus. These results converge with recent lesion evidence implicating the left inferior parietal lobe in processing thematic relations and may indicate a potential role for this region during spoken word production.
The human hippocampal formation can be divided into a set of cytoarchitecturally and functionally distinct subregions, involved in different aspects of memory formation. Neuroanatomical disruptions ...within these subregions are associated with several debilitating brain disorders including Alzheimer's disease, major depression, schizophrenia, and bipolar disorder. Multi-center brain imaging consortia, such as the Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) consortium, are interested in studying disease effects on these subregions, and in the genetic factors that affect them. For large-scale studies, automated extraction and subsequent genomic association studies of these hippocampal subregion measures may provide additional insight. Here, we evaluated the test–retest reliability and transplatform reliability (1.5T versus 3T) of the subregion segmentation module in the FreeSurfer software package using three independent cohorts of healthy adults, one young (Queensland Twins Imaging Study, N=39), another elderly (Alzheimer's Disease Neuroimaging Initiative, ADNI-2, N=163) and another mixed cohort of healthy and depressed participants (Max Planck Institute, MPIP, N=598). We also investigated agreement between the most recent version of this algorithm (v6.0) and an older version (v5.3), again using the ADNI-2 and MPIP cohorts in addition to a sample from the Netherlands Study for Depression and Anxiety (NESDA) (N=221). Finally, we estimated the heritability (h2) of the segmented subregion volumes using the full sample of young, healthy QTIM twins (N=728). Test–retest reliability was high for all twelve subregions in the 3T ADNI-2 sample (intraclass correlation coefficient (ICC)=0.70–0.97) and moderate-to-high in the 4T QTIM sample (ICC=0.5–0.89). Transplatform reliability was strong for eleven of the twelve subregions (ICC=0.66–0.96); however, the hippocampal fissure was not consistently reconstructed across 1.5T and 3T field strengths (ICC=0.47–0.57). Between-version agreement was moderate for the hippocampal tail, subiculum and presubiculum (ICC=0.78–0.84; Dice Similarity Coefficient (DSC)=0.55–0.70), and poor for all other subregions (ICC=0.34–0.81; DSC=0.28–0.51). All hippocampal subregion volumes were highly heritable (h2=0.67–0.91). Our findings indicate that eleven of the twelve human hippocampal subregions segmented using FreeSurfer version 6.0 may serve as reliable and informative quantitative phenotypes for future multi-site imaging genetics initiatives such as those of the ENIGMA consortium.
•FreeSurfer v6.0 produced reliable volume estimates for 11 hippocampal subregions.•Agreement between v5.3 and v6.0 was poor for small subregions (e.g. fimbria).•All hippocampal subregion volumes were highly heritable (h2=0.67–0.91).•Hippocampal subregions may be useful quantitative phenotypes for future GWA studies.
Inter-individual variation in facial shape is one of the most noticeable phenotypes in humans, and it is clearly under genetic regulation; however, almost nothing is known about the genetic basis of ...normal human facial morphology. We therefore conducted a genome-wide association study for facial shape phenotypes in multiple discovery and replication cohorts, considering almost ten thousand individuals of European descent from several countries. Phenotyping of facial shape features was based on landmark data obtained from three-dimensional head magnetic resonance images (MRIs) and two-dimensional portrait images. We identified five independent genetic loci associated with different facial phenotypes, suggesting the involvement of five candidate genes--PRDM16, PAX3, TP63, C5orf50, and COL17A1--in the determination of the human face. Three of them have been implicated previously in vertebrate craniofacial development and disease, and the remaining two genes potentially represent novel players in the molecular networks governing facial development. Our finding at PAX3 influencing the position of the nasion replicates a recent GWAS of facial features. In addition to the reported GWA findings, we established links between common DNA variants previously associated with NSCL/P at 2p21, 8q24, 13q31, and 17q22 and normal facial-shape variations based on a candidate gene approach. Overall our study implies that DNA variants in genes essential for craniofacial development contribute with relatively small effect size to the spectrum of normal variation in human facial morphology. This observation has important consequences for future studies aiming to identify more genes involved in the human facial morphology, as well as for potential applications of DNA prediction of facial shape such as in future forensic applications.
One of the grand challenges faced by neuroscience is to delineate the determinants of interindividual variation in the comprehensive structural and functional connection matrices that comprise the ...human connectome. At present, this endeavor appears most tractable at the macroanatomic scale, where intrinsic brain activity exhibits robust patterns of synchrony that recapitulate core functional circuits at the individual level. Here, we use a classical twin study design to examine the heritability of intrinsic functional network properties in 101 twin pairs, including network activity (i.e., variance of a network's specific temporal fluctuations) and internetwork coherence (i.e., correlation between networks' specific temporal fluctuations). Five of 7 networks exhibited significantly heritable (23.3-65.2%) network activity, 6 of the 21 internetwork coherences were significantly heritable (25.6-42.0%), and 11 of the 21 internetwork coherences were significantly influenced by common environmental factors (18.0-47.1%). These results suggest that the source of interindividual variation in functional connectome has a modular architecture: individual modules represented by intrinsic connectivity networks are genetic controlled, while environmental factors influence the interplays between the modules. This work further provides network-specific hypotheses for discovery of the specific genetic and environmental factors influencing functional specialization and integration of the human brain.
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