"Non-Eloquent" brain regions predict neuropsychological outcome in tumor patients undergoing awake craniotomy.

Supratotal resection of primary brain tumors is being advocated especially when involving "non-eloquent" tissue. However, there is extensive neuropsychological data implicating functions critical to higher cognition in areas considered "non-eloquent" by most surgeons. The goal of the study was to determine pre-surgical brain regions that would be predictive of cognitive outcome at 4-6 months post-surgery. Cortical reconstruction and volumetric segmentation were performed with the FreeSurfer-v6.0 image analysis suite. Linear regression models were used to regress cortical volumes from both hemispheres, against the total cognitive z-score to determine the relationship between brain structure and broad cognitive functioning while controlling for age, sex, and total segmented brain volume. We identified 62 consecutive patients who underwent planned awake resections of primary (n = 55, 88%) and metastatic at the University of New Mexico Hospital between 2015 and 2019. Of those, 42 (23 males, 25 left hemispheric lesions) had complete pre and post-op neuropsychological data available and were included in this study. Overall, total neuropsychological functioning was somewhat worse (p = 0.09) at post-operative neuropsychological outcome (Mean = -.20) than at baseline (Mean = .00). Patients with radiation following resection (n = 32) performed marginally worse (p = .036). We found that several discrete brain volumes obtained pre-surgery predicted neuropsychological outcome post-resection. For the total sample, these volumes included: left fusiform, right lateral orbital frontal, right post central, and right paracentral regions. Regardless of lesion lateralization, volumes within the right frontal lobe, and specifically right orbitofrontal cortex, predicted neuropsychological difference scores. The current study highlights the gaps in our current understanding of brain eloquence. We hypothesize that the volume of tissue within the right lateral orbital frontal lobe represents important cognitive reserve capacity in patients undergoing tumor surgery. Our data also cautions the neurosurgeon when considering supratotal resections of tumors that do not extend into areas considered "non-eloquent" by current standards.

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.

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.

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.

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.

Multimodal data revealed different neurobiological correlates of intelligence between males and females.

Intelligence is a socially and scientifically interesting topic because of its prominence in human behavior, yet there is little clarity on how the neuroimaging and neurobiological correlates of intelligence differ between males and females, with most investigations limited to using either mass-univariate techniques or a single neuroimaging modality. Here we employed connectome-based predictive modeling (CPM) to predict the intelligence quotient (IQ) scores for 166 males and 160 females separately, using resting-state functional connectivity, grey matter cortical thickness or both. The identified multimodal, IQ-predictive imaging features were then compared between genders. CPM showed high out-of-sample prediction accuracy (r > 0.34), and integrating both functional and structural features further improved prediction accuracy by capturing complementary information (r = 0.45). Male IQ demonstrated higher correlations with cortical thickness in the left inferior parietal lobule, and with functional connectivity in left parahippocampus and default mode network, regions previously implicated in spatial cognition and logical thinking. In contrast, female IQ was more correlated with cortical thickness in the right inferior parietal lobule, and with functional connectivity in putamen and cerebellar networks, regions previously implicated in verbal learning and item memory. Results suggest that the intelligence generation of males and females may rely on opposite cerebral lateralized key brain regions and distinct functional networks consistent with their respective superiority in cognitive domains. Promisingly, understanding the neural basis of gender differences underlying intelligence may potentially lead to optimized personal cognitive developmental programs and facilitate advancements in unbiased educational test design.

Gender Differences in Connectome-based Predictions of Individualized Intelligence Quotient and Sub-domain Scores.

Scores on intelligence tests are strongly predictive of various important life outcomes. However, the gender discrepancy on intelligence quotient (IQ) prediction using brain imaging variables has not been studied. To this aim, we predicted individual IQ scores for males and females separately using whole-brain functional connectivity (FC). Robust predictions of intellectual capabilities were achieved across three independent data sets (680 subjects) and two intelligence measurements (IQ and fluid intelligence) using the same model within each gender. Interestingly, we found that intelligence of males and females were underpinned by different neurobiological correlates, which are consistent with their respective superiority in cognitive domains (visuospatial vs verbal ability). In addition, the identified FC patterns are uniquely predictive on IQ and its sub-domain scores only within the same gender but neither for the opposite gender nor on the IQ-irrelevant measures such as temperament traits. Moreover, females exhibit significantly higher IQ predictability than males in the discovery cohort. This findings facilitate our understanding of the biological basis of intelligence by demonstrating that intelligence is underpinned by a variety of complex neural mechanisms that engage an interacting network of regions-particularly prefrontal-parietal and basal ganglia-whereas the network pattern differs between genders.

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.

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).

Real-time presurgical resting-state fMRI in patients with brain tumors: Quality control and comparison with task-fMRI and intraoperative mapping.

Resting-state functional magnetic resonance imaging (rsfMRI) is a promising task-free functional imaging approach, which may complement or replace task-based fMRI (tfMRI) in patients who have difficulties performing required tasks. However, rsfMRI is highly sensitive to head movement and physiological noise, and validation relative to tfMRI and intraoperative electrocortical mapping is still necessary. In this study, we investigate (a) the feasibility of real-time rsfMRI for presurgical mapping of eloquent networks with monitoring of data quality in patients with brain tumors and (b) rsfMRI localization of eloquent cortex compared with tfMRI and intraoperative electrocortical stimulation (ECS) in retrospective analysis. Five brain tumor patients were studied with rsfMRI and tfMRI on a clinical 3T scanner using MultiBand(8)-echo planar imaging (EPI) with repetition time: 400 ms. Moving-averaged sliding-window correlation analysis with regression of motion parameters and signals from white matter and cerebrospinal fluid was used to map sensorimotor and language resting-state networks. Data quality monitoring enabled rapid optimization of scan protocols, early identification of task noncompliance, and head movement-related false-positive connectivity to determine scan continuation or repetition. Sensorimotor and language resting-state networks were identifiable within 1 min of scan time. The Euclidean distance between ECS and rsfMRI connectivity and task-activation in motor cortex, Broca's, and Wernicke's areas was 5-10 mm, with the exception of discordant rsfMRI and ECS localization of Wernicke's area in one patient due to possible cortical reorganization and/or altered neurovascular coupling. This study demonstrates the potential of real-time high-speed rsfMRI for presurgical mapping of eloquent cortex with real-time data quality control, and clinically acceptable concordance of rsfMRI with tfMRI and ECS localization.

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.