Conscientiousness associated with efficiency of the salience/ventral attention network: Replication in three samples using individualized parcellation.

Conscientiousness, and related constructs impulsivity and self-control, have been related to structural and functional properties of regions in the prefrontal cortex (PFC) and anterior insula. Network-based conceptions of brain function suggest that these regions belong to a single large-scale network, labeled the salience/ventral attention network (SVAN). The current study tested associations between conscientiousness and resting-state functional connectivity in this network using two community samples (N's = 244 and 239) and data from the Human Connectome Project (N = 1000). Individualized parcellation was used to improve functional localization accuracy and facilitate replication. Functional connectivity was measured using an index of network efficiency, a graph theoretical measure quantifying the capacity for parallel information transfer within a network. Efficiency of a set of parcels in the SVAN was significantly associated with conscientiousness in all samples. Findings are consistent with a theory of conscientiousness as a function of variation in neural networks underlying effective prioritization of goals.

Genome-Transcriptome-Functional Connectivity-Cognition Link Differentiates Schizophrenia From Bipolar Disorder.

BACKGROUND AND HYPOTHESIS: Schizophrenia (SZ) and bipolar disorder (BD) share genetic risk factors, yet patients display differential levels of cognitive impairment. We hypothesized a genome-transcriptome-functional connectivity (frontoparietal)-cognition pathway linked to SZ-versus-BD differences, and conducted a multiscale study to delineate this pathway. STUDY DESIGNS: Large genome-wide studies provided single nucleotide polymorphisms (SNPs) conferring more risk for SZ than BD, and we identified their regulated genes, namely SZ-biased SNPs and genes. We then (a) computed the polygenic risk score for SZ (PRSSZ) of SZ-biased SNPs and examined its associations with imaging-based frontoparietal functional connectivity (FC) and cognitive performances; (b) examined the spatial correlation between ex vivo postmortem expressions of SZ-biased genes and in vivo, SZ-related FC disruptions across frontoparietal regions; (c) investigated SZ-versus-BD differences in frontoparietal FC; and (d) assessed the associations of frontoparietal FC with cognitive performances. STUDY RESULTS: PRSSZ of SZ-biased SNPs was significantly associated with frontoparietal FC and working memory test scores. SZ-biased genes' expressions significantly correlated with SZ-versus-BD differences in FC across frontoparietal regions. SZ patients showed more reductions in frontoparietal FC than BD patients compared to controls. Frontoparietal FC was significantly associated with test scores of multiple cognitive domains including working memory, and with the composite scores of all cognitive domains. CONCLUSIONS: Collectively, these multiscale findings support the hypothesis that SZ-biased genetic risk, through transcriptome regulation, is linked to frontoparietal dysconnectivity, which in turn contributes to differential cognitive deficits in SZ-versus BD, suggesting that potential biomarkers for more precise patient stratification and treatment.

Libman-Sacks endocarditis and associated cerebrovascular disease: The role of medical therapy.

BACKGROUND: Libman-Sacks endocarditis in patients with systemic lupus erythematosus (SLE) is commonly complicated with embolic cerebrovascular disease (CVD) or valve dysfunction for which high-risk valve surgery is frequently performed. However, the role of medical therapy alone for Libman-Sacks endocarditis and associated acute CVD remains undefined. OBJECTIVE: To determine in this cross-sectional and longitudinal study if conventional anti-inflammatory and anti-thrombotic therapy may be an effective therapy in SLE patients with Libman-Sacks endocarditis and associated acute CVD. METHODS AND MATERIALS: 17 SLE patients with Libman-Sacks endocarditis detected by two-and-three-dimensional transesophageal echocardiography (TEE) and complicated with acute CVD [stroke/TIA, focal brain injury on MRI, or cognitive dysfunction] were treated with conventional anti-inflammatory and anti-thrombotic therapy for a median of 6 months and then underwent repeat TEE, transcranial Doppler, brain MRI, and neurocognitive testing for re-assessment of Libman-Sacks endocarditis and CVD. RESULTS: Valve vegetations decreased in number, diameter, and area (all p ≤0.01); associated valve regurgitation significantly improved (p = 0.04), and valve thickening did not progress (p = 0.56). In 13 (76%) patients, valve vegetations or valve regurgitation resolved or improved in number and size or by ≥1 degree, respectively, as compared to 4 (24%) patients in whom vegetations or valve regurgitation persisted unchanged or increased in size or by ≥1 degree (p = 0.03). Also, cerebromicroembolism, lobar and global gray and white matter cerebral perfusion, ischemic brain lesion load, and neurocognitive dysfunction resolved or significantly improved (all p ≤0.04). CONCLUSION: These preliminary data suggest that combined conventional anti-inflammatory and antithrombotic therapy may be an effective treatment for Libman-Sacks endocarditis and its associated CVD and may obviate the need for high-risk valve surgery.

Subcortical contributions to higher cognitive function in tumour patients undergoing awake craniotomy.

Primary brain tumours often occur near eloquent regions, affecting language, motor and memory capacity, with awake mapping and tailored resection designed to preserve higher cognitive functioning. The effects of such tumours on subcortical structures, including the thalamus and basal ganglia, have been largely unexplored, in spite of the known importance of such structures to higher cognitive functioning. We sought to explore the effects of volume changes of subcortical structures on cognition, in 62 consecutive patients diagnosed with primary brain tumour and cavernous malformations, referred to our neurosurgical practice. We found right caudate to be highly predictive of intelligence, left pallidum of total neuropsychological function and right hippocampus of mood. Our study is the largest of its kind in exploring subcortical substrates of higher cognition in consecutive patients with brain tumours. This research supports prior literature, showing subcortical structures to be related to higher cognitive functioning, particularly measures of memory and executive functioning implicated in fronto-subcortical circuits. Furthermore, involvement of right mesial temporal structures in mood, further strengthens the central role of Papez circuit in emotional quality of cognition. Attention to subcortical integrity is likely to be important in discussing postsurgical cognitive outcome with patients and their families.

Differences in brain activity patterns during creative idea generation between eminent and non-eminent thinkers.

An influential model of the neural mechanisms of creative thought suggests that creativity is manifested in the joint contributions of the Default Mode Network (DMN; a set of regions in the medial PFC, lateral and medial parietal cortex, and the medial temporal lobes) and the executive networks within the dorsolateral PFC. Several empirical reports have offered support for this model by showing that complex interactions between these brain systems account for individual differences in creative performance. The present study examined whether the engagement of these regions in idea generation is modulated by one's eminence in a creativity-related field. Twenty (n â€‹= â€‹20) healthy eminent creators from diverse fields of expertise and a 'smart' comparison group of sixteen (n â€‹= â€‹16) age- and education-matched non-eminent thinkers were administered a creative generation task (an adaptation of the Alternative Uses Task) and a control perceptual task, while undergoing functional magnetic resonance imaging (fMRI). The participants' verbal responses were recorded through a noise-canceling microphone and were later coded for fluency and accuracy. Behavioral and fMRI analyses revealed commonalities between groups, but also distinct patterns of activation in default mode and executive brain regions between the eminent and the non-eminent participants during creative thinking. We interpret these findings in the context of the well-documented contributions of these regions in the generation of creative ideas as modulated, in this study, by participants' creative eminence.

Resting state functional connectivity underlying musical creativity.

While the behavior of "being musically creative"- improvising, composing, songwriting, etc.-is undoubtedly a complex and highly variable one, recent neuroscientific investigation has offered significant insight into the neural underpinnings of many of the creative processes contributing to such behavior. A previous study from our research group (Bashwiner et al., 2016), which examined two aspects of brain structure as a function of creative musical experience, found significantly increased cortical surface area or subcortical volume in regions of the default-mode network, a motor planning network, and a "limbic" network. The present study sought to determine how these regions coordinate with one another and with other regions of the brain in a large number of participants (n â€‹= â€‹218) during a task-neutral period, i.e., during the "resting state." Deriving from the previous study's results a set of eleven regions of interest (ROIs), the present study analyzed the resting-state functional connectivity (RSFC) from each of these seed regions as a function of creative musical experience (assessed via our Musical Creativity Questionnaire). Of the eleven ROIs investigated, nine showed significant correlations with a total of 22 clusters throughout the brain, the most significant being located in bilateral cerebellum, right inferior frontal gyrus, midline thalamus (particularly the mediodorsal nucleus), and medial premotor regions. These results support prior reports (by ourselves and others) implicating regions of the default-mode, executive, and motor-planning networks in musical creativity, while additionally-and somewhat unanticipatedly-including a potentially much larger role for the salience network than has been previously reported in studies of musical creativity.

Differences in brain morphometry associated with creative performance in high- and average-creative achievers.

Nearly everyone has the ability for creative thought. Yet, certain individuals create works that propel their fields, challenge paradigms, and advance the world. What are the neurobiological factors that might underlie such prominent creative achievement? In this study, we focus on morphometric differences in brain structure between high creative achievers from diverse fields of expertise and a 'smart' comparison group of age-, intelligence-, and education-matched average creative achievers. Participants underwent a high-resolution structural brain imaging scan and completed a series of intelligence, creative thinking, personality, and creative achievement measures. We examined whether high and average creative achievers could be distinguished based on the relationship between morphometric brain measures (cortical area and thickness) and behavioral measures. Although participants' performance on the behavioral measures did not differ between the two groups aside from creative achievement, the relationship between posterior parietal cortex morphometry and creativity, intelligence, and personality measures depended on group membership. These results suggest that extraordinary creativity may be associated with measurable structural brain differences, especially within parietal cortex.

N-BiC: A Method for Multi-Component and Symptom Biclustering of Structural MRI Data: Application to Schizophrenia.

OBJECTIVE: We propose and develop a novel biclustering (N-BiC) approach for performing N-way biclustering of neuroimaging data. Our approach is applicable to an arbitrary number of features from both imaging and behavioral data (e.g., symptoms). We applied it to structural MRI data from patients with schizophrenia. METHODS: It uses a source-based morphometry approach [i.e., independent component analysis of gray matter segmentation maps] to decompose the data into a set of spatial maps, each of which includes regions that covary among individuals. Then, the loading parameters for components of interest are entered to an exhaustive search, which incorporates a modified depth-first search technique to carry out the biclustering, with the goal of obtaining submatrices where the selected rows (individuals) show homogeneity in their expressions of selected columns (components) and vice versa. RESULTS: Findings demonstrate that multiple biclusters have an evident association with distinct brain networks for the different types of symptoms in schizophrenia. The study identifies two components: inferior temporal gyrus (16) and brainstem (7), which are related to positive (distortion/excess of normal function) and negative (diminution/loss of normal function) symptoms in schizophrenia, respectively. CONCLUSION: N-BiC is a data-driven method of biclustering MRI data that can exhaustively explore relationships/substructures from a dataset without any prior information with a higher degree of robustness than earlier biclustering applications. SIGNIFICANCE: The use of such approaches is important to investigate the underlying biological substrates of mental illness by grouping patients into homogeneous subjects, as the schizophrenia diagnosis is known to be relatively nonspecific and heterogeneous.

Neuroanatomy of creative achievement.

Very few studies have investigated neuroanatomical correlates of "everyday" creative achievement in cohorts of normal subjects. In previous research, we first showed that scores on the Creative Achievement Questionnaire (CAQ) were associated with lower cortical thickness within the left lateral orbitofrontal gyrus (LOFG), and increased thickness of the right angular gyrus (AG) (Jung et al., 2010). Newer studies found the CAQ to be associated with decreased volume of the rostral anterior cingulate cortex (ACC), and that artistic and scientific creativity was associated with increased and decreased volumes within the executive control network and salience network (Shi et al., 2017). We desired to replicate and extend our previous study in a larger cohort (N â€‹= â€‹248), comprised of subjects studying and working in science, technology, engineering, and math (STEM). Subjects were young (Range â€‹= â€‹16-32; Mean age â€‹= â€‹21.8; s.d. â€‹= â€‹3.5) all of whom were administered the CAQ, from which we derived artistic and scientific creativity factors. All subjects underwent structural MRI on a 3 â€‹T scanner from which cortical thickness, area, and volume measures were obtained using FreeSurfer. Our results showed mostly cortical thinning in relation to total, scientific, and artistic creative achievement encompassing many regions involved in the cognitive control network (CCN) and default mode network (DMN).

White matter correlates of creative cognition in a normal cohort.

Creative cognition, as measured through divergent thinking (DT), offers insight into one's ability to generate novel ideas. Relatively little work has been done exploring the relationship between creative idea generation tasks and white matter integrity via fractional anisotropy (FA). Our previous work has shown that higher scores on DT tasks were related to reduced fractional anisotropy (FA) within the left hemisphere anterior thalamic radiation (Jung et al., 2010). However, Takeuchi et al., 2010, found positive correlations with FA and DT tasks in the prefrontal cortex and genu of the corpus callosum. The present study assessed subjects studying or working in science, technology, engineering and mathematics (STEM; N â€‹= â€‹178) for correlations in white matter FA, as related to a measure of DT. Healthy normal subjects aged (16-32 years, mean age â€‹= â€‹22.0 â€‹± â€‹3.8; F â€‹= â€‹89/178). Three idea generation DT measures were scored by three raters (α â€‹= â€‹0.71) using the consensual assessment technique, from which a composite creativity index (CCI) was derived. We found that CCI was inversely related to FA (all p â€‹< â€‹0.05, controlling for age, sex, and full scale intelligence, and corrected for multiple comparisons using family wise error), within the left hemisphere inferior frontal gyrus, inferior fronto-occipital fasciculus, cingulate gyrus, inferior longitudinal fasciculus, and right hemisphere uncinate fasciculus. These results are consistent with our previous findings, implicating lower FA in white matter regions linking broad cortical networks, now established in a much larger sample of normal healthy subjects.

Hemispheric asymmetries in cortical gray matter microstructure identified by neurite orientation dispersion and density imaging.

Histological studies have reported microstructural hemispheric asymmetries in several cortical areas of the human brain, but reliable in vivo assessment methods have been lacking so far. Here, we used neurite orientation dispersion and density imaging (NODDI) to examine microstructural asymmetries in in vivo and determine if findings are in accordance with what has been reported in histological studies. We examined intra-neurite volume fraction (INVF), neurite orientation dispersion (ODI), and isotropic volume fraction (ISO) asymmetries in two independent samples of healthy adults (n = 269 and n = 251). Over both samples, we found greater left-hemispheric INVF in early auditory, inferior parietal and temporal-parietal-occipital areas. In contrast, we found greater right-hemispheric INVF in the fusiform and inferior temporal gyrus, reflecting what has been reported in histological studies. ODI was asymmetric towards the left hemisphere in frontal areas and towards the right hemisphere in early auditory areas. ISO showed less pronounced asymmetries. There were hardly any effects of sex or handedness on microstructural asymmetry as determined by NODDI. Taken together, these findings suggest substantial microstructural asymmetries in gray matter, making NODDI a promising marker for future genetic and behavioral studies on laterality.

Shared Genetic Risk of Schizophrenia and Gray Matter Reduction in 6p22.1.

Genetic factors are known to influence both risk for schizophrenia (SZ) and variation in brain structure. A pressing question is whether the genetic underpinnings of brain phenotype and the disorder overlap. Using multivariate analytic methods and focusing on 1,402 common single-nucleotide polymorphisms (SNPs) mapped from the Psychiatric Genomics Consortium (PGC) 108 regions, in 777 discovery samples, we identified 39 SNPs to be significantly associated with SZ-discriminating gray matter volume (GMV) reduction in inferior parietal and superior temporal regions. The findings were replicated in 609 independent samples. These 39 SNPs in chr6:28308034-28684183 (6p22.1), the most significant SZ-risk region reported by PGC, showed regulatory effects on both DNA methylation and gene expression of postmortem brain tissue and saliva. Furthermore, the regulated methylation site and gene showed significantly different levels of methylation and expression in the prefrontal cortex between cases and controls. In addition, for one regulated methylation site we observed a significant in vivo methylation-GMV association in saliva, suggesting a potential SNP-methylation-GMV pathway. Notably, the risk alleles inferred for GMV reduction from in vivo imaging are all consistent with the risk alleles for SZ inferred from postmortem data. Collectively, we provide evidence for shared genetic risk of SZ and regional GMV reduction in 6p22.1 and demonstrate potential molecular mechanisms that may drive the observed in vivo associations. This study motivates dissecting SZ-risk variants to better understand their associations with focal brain phenotypes and the complex pathophysiology of the illness.

Correlation of neurocognitive function and brain lesion load on magnetic resonance imaging in systemic lupus erythematosus.

Neurocognitive dysfunction and brain injury on magnetic resonance imaging (MRI) are common in patients with systemic lupus erythematosus (SLE) and are associated with increased morbidity and mortality. However, brain MRI is expensive, is restricted by payers, and requires high expertise. Neurocognitive assessment is an easily available, safe, and inexpensive clinical tool that may select patients needing brain MRI. In this cross-sectional and controlled study, 76 SLE patients (69 women, age 37 ± 12 years) and 26 age and gender-matched healthy subjects (22 women, age 34 ± 11 years) underwent assessment of attention, memory, processing speed, executive function, motor function, and global neurocognitive function. All subjects underwent brain MRI with T1-weighted, fluid-attenuated inversion recovery (FLAIR), and diffusion-weighted imaging. Hemispheric and whole brain lesion load in cm3 were determined using semi-automated methods. Neurocognitive z-scores in all clinical domains were significantly lower and whole brain and right and left hemispheres brain lesion load were significantly greater in patients than in controls (all p ≤ 0.02). There was significant correlation between neurocognitive z-scores in all domains and whole brain lesion load: processing speed (r = - 0.46; p < 0.0001), attention (r = - 0.42; p < 0.001), memory (r = - 0.40; p = 0.0004), executive function (r = - 0.25; p = 0.03), motor function (r = - 0.25; p = 0.05), and global neurocognitive function (r = - 0.38; p = 0.006). Similar correlations were found for brain hemisphere lesion loads (all p ≤ 0.05). These correlations were strengthened when adjusted for glucocorticoid therapy and SLE disease activity index. Finally, global neurocognitive z-score and erythrosedimentation rate were the only independent predictors of whole brain lesion load (both p ≤ 0.007). Neurocognitive measures and brain lesion load are worse in SLE patients than in controls. In SLE patients, neurocognitive z-scores correlate negatively with and independently predict brain lesion load. Therefore, neurocognitive testing may be an effective clinical tool to select patients needing brain MRI.

Diffusion markers of dendritic density and arborization in gray matter predict differences in intelligence.

Previous research has demonstrated that individuals with higher intelligence are more likely to have larger gray matter volume in brain areas predominantly located in parieto-frontal regions. These findings were usually interpreted to mean that individuals with more cortical brain volume possess more neurons and thus exhibit more computational capacity during reasoning. In addition, neuroimaging studies have shown that intelligent individuals, despite their larger brains, tend to exhibit lower rates of brain activity during reasoning. However, the microstructural architecture underlying both observations remains unclear. By combining advanced multi-shell diffusion tensor imaging with a culture-fair matrix-reasoning test, we found that higher intelligence in healthy individuals is related to lower values of dendritic density and arborization. These results suggest that the neuronal circuitry associated with higher intelligence is organized in a sparse and efficient manner, fostering more directed information processing and less cortical activity during reasoning.

Structural correlates of Openness and Intellect: Implications for the contribution of personality to creativity.

Openness/Intellect (i.e., openness to experience) is the Big Five personality factor most consistently associated with individual differences in creativity. Recent psychometric evidence has demonstrated that this factor consists of two distinct aspects-Intellect and Openness. Whereas Intellect reflects perceived intelligence and intellectual engagement, Openness reflects engagement with fantasy, perception, and aesthetics. We investigated the extent to which Openness and Intellect are associated with variations in brain structure as measured by cortical thickness, area, and volume (N = 185). Our results demonstrated that Openness was correlated inversely with cortical thickness and volume in left middle frontal gyrus (BA 6), middle temporal gyrus (MTG, BA 21), and superior temporal gyrus (BA 41), and exclusively with cortical thickness in left inferior parietal lobule (BA 40), right inferior frontal gyrus (IFG, BA 45), and MTG (BA 37). When age and sex were statistically controlled for, the inverse correlations between Openness and cortical thickness remained statistically significant for all regions except left MTG, whereas the correlations involving cortical volume remained statistically significant only for left middle frontal gyrus. There was no statistically significant correlation between Openness and cortical area, and no statistically significant correlation between Intellect and cortical thickness, area, or volume. Our results demonstrate that individual differences in Openness are correlated with variation in brain structure-particularly as indexed by cortical thickness. Given the involvement of the above regions in processes related to memory and cognitive control, we discuss the implications of our findings for the possible contribution of personality to creative cognition.

Biclustered Independent Component Analysis for Complex Biomarker and Subtype Identification from Structural Magnetic Resonance Images in Schizophrenia.

Clinical and cognitive symptoms domain-based subtyping in schizophrenia (Sz) has been critiqued due to the lack of neurobiological correlates and heterogeneity in symptom scores. We, therefore, present a novel data-driven framework using biclustered independent component analysis to detect subtypes from the reliable and stable gray matter concentration (GMC) of patients with Sz. The developed methodology consists of the following steps: source-based morphometry (SBM) decomposition, selection and sorting of two component loadings, subtype component reconstruction using group information-guided ICA (GIG-ICA). This framework was applied to the top two group discriminative components namely the insula/superior temporal gyrus/inferior frontal gyrus (I-STG-IFG component) and the superior frontal gyrus/middle frontal gyrus/medial frontal gyrus (SFG-MiFG-MFG component) from our previous SBM study, which showed diagnostic group difference and had the highest effect sizes. The aggregated multisite dataset consisted of 382 patients with Sz regressed of age, gender, and site voxelwise. We observed two subtypes (i.e., two different subsets of subjects) each heavily weighted on these two components, respectively. These subsets of subjects were characterized by significant differences in positive and negative syndrome scale (PANSS) positive clinical symptoms (p = 0.005). We also observed an overlapping subtype weighing heavily on both of these components. The PANSS general clinical symptom of this subtype was trend level correlated with the loading coefficients of the SFG-MiFG-MFG component (r = 0.25; p = 0.07). The reconstructed subtype-specific component using GIG-ICA showed variations in voxel regions, when compared to the group component. We observed deviations from mean GMC along with conjunction of features from two components characterizing each deciphered subtype. These inherent variations in GMC among patients with Sz could possibly indicate the need for personalized treatment and targeted drug development.

Bayesian network-response regression.

MOTIVATION: There is increasing interest in learning how human brain networks vary as a function of a continuous trait, but flexible and efficient procedures to accomplish this goal are limited. We develop a Bayesian semiparametric model, which combines low-rank factorizations and flexible Gaussian process priors to learn changes in the conditional expectation of a network-valued random variable across the values of a continuous predictor, while including subject-specific random effects. RESULTS: The formulation leads to a general framework for inference on changes in brain network structures across human traits, facilitating borrowing of information and coherently characterizing uncertainty. We provide an efficient Gibbs sampler for posterior computation along with simple procedures for inference, prediction and goodness-of-fit assessments. The model is applied to learn how human brain networks vary across individuals with different intelligence scores. Results provide interesting insights on the association between intelligence and brain connectivity, while demonstrating good predictive performance. AVAILABILITY AND IMPLEMENTATION: Source code implemented in R and data are available at https://github.com/wangronglu/BNRR. CONTACT: rl.wang@duke.edu. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Fronto-Parietal gray matter and white matter efficiency differentially predict intelligence in males and females.

While there are minimal sex differences in overall intelligence, males, on average, have larger total brain volume and corresponding regional brain volumes compared to females, measures that are consistently related to intelligence. Limited research has examined which other brain characteristics may differentially contribute to intelligence in females to facilitate equal performance on intelligence measures. Recent reports of sex differences in the neural characteristics of the brain further highlight the need to differentiate how the structural neural characteristics relate to intellectual ability in males and females. The current study utilized a graph network approach in conjunction with structural equation modeling to examine potential sex differences in the relationship between white matter efficiency, fronto-parietal gray matter volume, and general cognitive ability (GCA). Participants were healthy adults (n = 244) who completed a battery of cognitive testing and underwent structural neuroimaging. Results indicated that in males, a latent factor of fronto-parietal gray matter was significantly related to GCA when controlling for total gray matter volume. In females, white matter efficiency and total gray matter volume were significantly related to GCA, with no specificity of the fronto-parietal gray matter factor over and above total gray matter volume. This work highlights that different neural characteristics across males and females may contribute to performance on intelligence measures. Hum Brain Mapp 37:4006-4016, 2016. © 2016 Wiley Periodicals, Inc.