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1.
Neuropsychol Rev ; 2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32189178

RESUMO

The cerebellum facilitates and modulates cognitive functions using forward and inverse internal models to predict and control behavior, respectively. Despite neuroimaging evidence that regions of the cerebellum are active during executive function (EF) tasks in general, little is known about the cerebellum's role in specific EFs and their underlying neural networks. Inhibitory control specifically may be facilitated by cerebellar internal models predicting responses during proactive control (withholding), and controlling responses during reactive control (inhibiting). The stop signal task (SST) is an inhibitory control task often used in neuroimaging studies to measure neural responses to both proactive and reactive control. Thus, in this review, we examine evidence for the cerebellum's role in inhibitory control by reviewing studies of healthy adults that utilized the SST in event-related functional magnetic resonance imaging (fMRI) experiments. Twenty-one studies that demonstrated cerebellar results were eligible for review, including 749 participants, 28 contrasts, and 38 cerebellar clusters. We also performed activation likelihood estimation (ALE) meta-analysis of contrasts derived from reviewed studies. This review illustrates evidence for the cerebellum participating in inhibitory control independent of motor control. Most significant cerebellar clusters were located in the left posterior cerebellum, suggesting that it communicates with the established cortical right-lateralized inhibitory control network. Cerebellar activity was most consistently observed for contrasts that measured proactive control, and ALE analysis confirmed that left Crus I is most likely to be activated in studies of proactive control measuring monitoring and anticipation. Results suggest that the left posterior cerebellum may communicate with right frontal and parietal cortices, using forward models to predict appropriate responses. Reactive control contrasts indicated a possible role for cerebellar regions in enhancing inhibition efficiency through inverse models, but ALE meta-analysis did not confirm this hypothesis. Limitations in the current literature, clinical implications, and directions for future research are discussed.

2.
Am J Psychiatry ; : appiajp201919030225, 2020 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-32212855

RESUMO

OBJECTIVE: Schizophrenia has recently been associated with widespread white matter microstructural abnormalities, but the functional effects of these abnormalities remain unclear. Widespread heterogeneity of results from studies published to date preclude any definitive characterization of the relationship between white matter and cognitive performance in schizophrenia. Given the relevance of deficits in cognitive function to predicting social and functional outcomes in schizophrenia, the authors carried out a meta-analysis of available data through the ENIGMA Consortium, using a common analysis pipeline, to elucidate the relationship between white matter microstructure and a measure of general cognitive performance, IQ, in patients with schizophrenia and healthy participants. METHODS: The meta-analysis included 760 patients with schizophrenia and 957 healthy participants from 11 participating ENIGMA Consortium sites. For each site, principal component analysis was used to calculate both a global fractional anisotropy component (gFA) and a fractional anisotropy component for six long association tracts (LA-gFA) previously associated with cognition. RESULTS: Meta-analyses of regression results indicated that gFA accounted for a significant amount of variation in cognition in the full sample (effect size [Hedges' g]=0.27, CI=0.17-0.36), with similar effects sizes observed for both the patient (effect size=0.20, CI=0.05-0.35) and healthy participant groups (effect size=0.32, CI=0.18-0.45). Comparable patterns of association were also observed between LA-gFA and cognition for the full sample (effect size=0.28, CI=0.18-0.37), the patient group (effect size=0.23, CI=0.09-0.38), and the healthy participant group (effect size=0.31, CI=0.18-0.44). CONCLUSIONS: This study provides robust evidence that cognitive ability is associated with global structural connectivity, with higher fractional anisotropy associated with higher IQ. This association was independent of diagnosis; while schizophrenia patients tended to have lower fractional anisotropy and lower IQ than healthy participants, the comparable size of effect in each group suggested a more general, rather than disease-specific, pattern of association.

3.
NMR Biomed ; : e4294, 2020 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-32207187

RESUMO

The human brain is asymmetrically lateralized for certain functions (such as language processing) to regions in one hemisphere relative to the other. Asymmetries are measured with a laterality index (LI). However, traditional LI measures are limited by a lack of consensus on metrics used for its calculation. To address this limitation, source-based laterality (SBL) leverages an independent component analysis for the identification of laterality-specific alterations, identifying covarying components between hemispheres across subjects. SBL is successfully implemented with simulated data with inherent differences in laterality. SBL is then compared with a voxel-wise analysis utilizing structural data from a sample of patients with schizophrenia and controls without schizophrenia. SBL group comparisons identified three distinct temporal regions and one cerebellar region with significantly altered laterality in patients with schizophrenia relative to controls. Previous work highlights reductions in laterality (ie, reduced left gray matter volume) in patients with schizophrenia compared with controls without schizophrenia. Results from this pilot SBL project are the first, to our knowledge, to identify covarying laterality differences within discrete temporal brain regions. The authors argue SBL provides a unique focus to detect covarying laterality differences in patients with schizophrenia, facilitating the discovery of laterality aspects undetected in previous work.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31944934

RESUMO

OBJECTIVE: Multimodal measurements of the same phenomena provide complementary information and highlight different perspectives, albeit each with their own limitations. A focus on a single modality may lead to incorrect inferences, which is especially important when a studied phenomenon is a disease. In this paper, we introduce a method that takes advantage of multimodal data in addressing the hypotheses of disconnectivity and dysfunction within schizophrenia (SZ). METHODS: We start with estimating and visualizing links within and among extracted multimodal data features using a Gaussian graphical model (GGM). We then propose a modularity-based method that can be applied to the GGM to identify links that are associated with mental illness across a multimodal data set. Through simulation and real data, we show our approach reveals important information about disease-related network disruptions that are missed with a focus on a single modality. We use functional MRI (fMRI), diffusion MRI (dMRI), and structural MRI (sMRI) to compute the fractional amplitude of low frequency fluctuations (fALFF), fractional anisotropy (FA), and gray matter (GM) concentration maps. These three modalities are analyzed using our modularity method. RESULTS: Our results show missing links that are only captured by the cross-modal information that may play an important role in disconnectivity between the components. CONCLUSION: we identified multimodal (fALFF, FA and GM) disconnectivity in the default mode network area in patients with SZ, which would not have been detectable in a single modality. SIGNIFICANCE: The proposed approach provides an important new tool for capturing information that is distributed among multiple imaging modalities.

5.
Psychiatry Res Neuroimaging ; 295: 111006, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31760338

RESUMO

The amygdala factors prominently in neurobiological models of social anxiety (SA), yet amygdala volume findings regarding SA have been inconsistent and largely focused on case-control characterization. One source of discrepant findings could be variability in volumetric techniques. Therefore, we compared amygdala volumes derived via an automated technique (Freesurfer) against a manually corrected approach, also involving Freesurfer. Additionally, we tested whether the relationship between volume and SA symptom severity would differ across volumetric techniques. We pooled participants (n = 76) from archival studies. SA severity was assessed with the Liebowitz Social Anxiety Scale; scores ranged from non-clinical to clinical levels. Freesurfer produced significantly larger amygdalar volumes for participants with poor image quality. Even after excluding such participants, paired sample t-tests showed Freesurfer's boundaries produced significantly larger amygdalar volumes than manually corrected ones, bilaterally. Yet, intra-class correlation coefficients between the two methods were high, which suggests that Freesurfer's over-estimation of amygdala volume was systemic. Regardless of segmentation technique, volumes were not associated with SA symptom severity. Potentially, amygdala sub-regions may yield clearer patterns regarding SA symptoms. Further, our study underscores the importance of image quality for segmentation of the amygdala, and image quality may be particularly valuable when examining anatomical data for subtle inter-individual differences.

6.
Neuroimage ; 207: 116370, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31751666

RESUMO

Although both resting and task-induced functional connectivity (FC) have been used to characterize the human brain and cognitive abilities, the potential of task-induced FCs in individualized prediction for out-of-scanner cognitive traits remains largely unexplored. A recent study Greene et al. (2018) predicted the fluid intelligence scores using FCs derived from rest and multiple task conditions, suggesting that task-induced brain state manipulation improved prediction of individual traits. Here, using a large dataset incorporating fMRI data from rest and 7 distinct task conditions, we replicated the original study by employing a different machine learning approach, and applying the method to predict two reading comprehension-related cognitive measures. Consistent with their findings, we found that task-based machine learning models often outperformed rest-based models. We also observed that combining multi-task fMRI improved prediction performance, yet, integrating the more fMRI conditions can not necessarily ensure better predictions. Compared with rest, the predictive FCs derived from language and working memory tasks were highlighted with more predictive power in predominantly default mode and frontoparietal networks. Moreover, prediction models demonstrated high stability to be generalizable across distinct cognitive states. Together, this replication study highlights the benefit of using task-based FCs to reveal brain-behavior relationships, which may confer more predictive power and promote the detection of individual differences of connectivity patterns underlying relevant cognitive traits, providing strong evidence for the validity and robustness of the original findings.

7.
IEEE Trans Biomed Eng ; 67(1): 110-121, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-30946659

RESUMO

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.

8.
Hum Brain Mapp ; 2019 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-31876339

RESUMO

Exploring brain changes across the human lifespan is becoming an important topic in neuroscience. Though there are multiple studies which investigated the relationship between age and brain imaging, the results are heterogeneous due to small sample sizes and relatively narrow age ranges. Here, based on year-wise estimation of 5,967 subjects from 13 to 72 years old, we aimed to provide a more precise description of adult lifespan variation trajectories of gray matter volume (GMV), structural network correlation (SNC), and functional network connectivity (FNC) using independent component analysis and multivariate linear regression model. Our results revealed the following relationships: (a) GMV linearly declined with age in most regions, while parahippocampus showed an inverted U-shape quadratic relationship with age; SNC presented a U-shape quadratic relationship with age within cerebellum, and inverted U-shape relationship primarily in the default mode network (DMN) and frontoparietal (FP) related correlation. (b) FNC tended to linearly decrease within resting-state networks (RSNs), especially in the visual network and DMN. Early increase was revealed between RSNs, primarily in FP and DMN, which experienced a decrease at older ages. U-shape relationship was also revealed to compensate for the cognition deficit in attention and subcortical related connectivity at late years. (c) The link between middle occipital gyrus and insula, as well as precuneus and cerebellum, exhibited similar changing trends between SNC and FNC across the adult lifespan. Collectively, these results highlight the benefit of lifespan study and provide a precise description of age-related regional variation and SNC/FNC changes based on a large dataset.

9.
Brain Struct Funct ; 224(9): 3031-3044, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31701266

RESUMO

In this paper, we review and discuss brain imaging studies which have used the source-based morphometry (SBM) approach over the past decade. SBM is a data-driven linear multivariate approach for decomposing structural brain imaging data into commonly covarying imaging components and subject-specific loading parameters. It is a well-established technique which has predominantly been used to study neuroanatomic differences between healthy controls and patients with neuropsychiatric diseases. We start by discussing the advantages of this technique over univariate analysis for imaging studies, followed by a discussion of results from recent studies which have successfully applied this methodology. We also present recent extensions of this framework including nonlinear SBM, biclustered independent component analysis (B-ICA) and conclude with the possible directions of work for future.

10.
Schizophr Bull ; 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31595302

RESUMO

Negative symptoms are core contributors to vocational and social deficits in schizophrenia (SZ). Available antipsychotic medications typically fail to reduce these symptoms. The neurohormone oxytocin (OT) is a promising treatment for negative symptoms, given its role in complex social behaviors mediated by the amygdala. In sample 1, we used a double-blind, placebo-controlled, crossover design to test the effects of a single dose of intranasal OT on amygdala resting-state functional connectivity (rsFC) in SZ (n = 22) and healthy controls (HC, n = 24) using a whole-brain corrected approach: we identified regions for which OT modulated SZ amygdala rsFC, assessed whether OT-modulated circuits were abnormal in SZ relative to HC on placebo, and evaluated whether connectivity on placebo and OT-induced connectivity changes correlated with baseline negative symptoms in SZ. Given our modest sample size, we used a second SZ (n = 183) and HC (n = 178) sample to replicate any symptom correlations. In sample 1, OT increased rsFC between the amygdala and left middle temporal gyrus, superior temporal sulcus, and angular gyrus (MTG/STS/AngG) in SZ compared to HC. Further, SZ had hypo-connectivity in this circuit compared to HC on placebo. More severe negative symptoms correlated with less amygdala-to-left-MTG/STS/AngG connectivity on placebo and with greater OT-induced connectivity increases. In sample 2, we replicated the correlation between amygdala-left-MTG/STS/AngG hypo-connectivity and negative symptoms, finding a specific association with expressive negative symptoms. These data suggest intranasal OT can normalize functional connectivity in an amygdala-to-left-MTG/STS/AngG circuit that contributes to negative symptoms in SZ.

11.
Front Psychiatry ; 10: 499, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31396111

RESUMO

Functional connectivity is one of the most widely used tools for investigating brain changes due to schizophrenia. Previous studies have identified abnormal functional connectivity in schizophrenia patients at the resting state brain network level. This study tests the existence of functional connectivity effects at whole brain and domain levels. Domain level refers to the integration of data from several brain networks grouped by their functional relationship. Data integration provides more consistent and accurate information compared to an individual brain network. This work considers two domain level measures: functional connectivity strength and randomness. The first measure is simply an average of connectivities within the domain. The second measure assesses the unpredictability and lack of pattern of functional connectivity within the domain. Domains with less random connectivity have higher chance of exhibiting a biologically meaningful connectivity pattern. Consistent with prior observations, individuals with schizophrenia showed aberrant domain connectivity strength between subcortical, cerebellar, and sensorial brain areas. Compared to healthy volunteers, functional connectivity between cognitive and default mode domains showed less randomness, while connectivity between default mode-sensorial areas showed more randomness in schizophrenia patients. These differences in connectivity patterns suggest deleterious rewiring trade-offs among important brain networks.

12.
Neuroimage Clin ; : 101989, 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31451406

RESUMO

Bipolar disorder (BD) is a severe manic-depressive illness. Patients with BD have been shown to have gray matter (GM) deficits in prefrontal, frontal, parietal, and temporal regions; however, the relationship between structural effects and clinical profiles has proved elusive when considered on a region by region or voxel by voxel basis. In this study, we applied parallel independent component analysis (pICA) to structural neuroimaging measures and the positive and negative syndrome scale (PANSS) in 110 patients (mean age 34.9 ±â€¯11.65) with bipolar disorder, to examine networks of brain regions that relate to symptom profiles. The pICA revealed two distinct symptom profiles and associated GM concentration alteration circuits. The first PANSS pICA profile mainly involved anxiety, depression and guilty feelings, reflecting mood symptoms. Reduced GM concentration in right temporal regions predicted worse mood symptoms in this profile. The second PANSS pICA profile generally covered blunted affect, emotional withdrawal, passive/apathetic social withdrawal, depression and active social avoidance, exhibiting a withdrawal or apathy dominating component. Lower GM concentration in bilateral parietal and frontal regions showed worse symptom severity in this profile. In summary, a pICA decomposition suggested BD patients showed distinct mood and apathy profiles differing from the original PANSS subscales, relating to distinct brain structural networks.

13.
Artigo em Inglês | MEDLINE | ID: mdl-31328176

RESUMO

Background: Social anxiety is characterized by a tendency to overestimate the likelihood of negative outcomes and consequences before, during, and after interpersonal interactions with social partners. Recent evidence suggests that a network of brain regions critical for perspective-taking, threat appraisal, and uncertainty resolution may function atypically in those prone to social anxiety. In this study, we used functional magnetic resonance imaging to examine neural activity in specific regions of interest in a sample of young adults who endorsed high or low levels of social anxiety. Methods: We recruited 31 college student volunteers (age: 18-28 years), categorized as having high or low anxiety based on their Liebowitz Social Anxiety Scale-Self Report scores. These participants were each scanned while playing the iterated Prisoner's Dilemma game with three computerized confederates, two of whom they were deceived to believe were human co-players. This study focuses on data collected during play with the presumed humans. Regions of interest were defined for the temporoparietal junction, anterior midcingulate, and dorsomedial prefrontal cortex. Average weighted mean blood-oxygen-level-dependent signals for each subject were extracted and analyzed using mixed design analyses of variance to detect group differences in activation during decision-making, anticipation, and appraisal of round outcomes during the game. Results: Behavior analysis revealed that the high-anxiety group was more likely to defect than the low-anxiety group. Neuroimaging analysis showed that the high-anxiety group exhibited elevated blood-oxygen-level-dependent activity relative to the low-anxiety group in all three regions during the social feedback appraisal phase but not during decision-making or the anticipation of interaction outcomes. Conclusions: These findings provide evidence that some behaviors linked to cognitive biases associated with social anxiety may be mediated by a network of regions involved in recognizing and processing directed social information. Future investigation of the neural basis of cognition and bias in social anxiety using the prisoner's dilemma and other economic-exchange tasks is warranted. These tasks appear to be highly effective, functional magnetic resonance imaging-compatible methods of probing altered cognition and behavior associated with anxiety and related conditions.

14.
Front Psychiatry ; 10: 494, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31354550

RESUMO

Current diagnoses of schizophrenia and related psychiatric disorders are classified by phenomenological principles and clinical descriptions while ruling out other symptoms and conditions. Specific biomarkers are needed to assist the current diagnostic system. However, complicated gene and environment interactions induce great disease heterogeneity. This unclear etiology and heterogeneity raise difficulties in distinguishing schizophrenia-related effects. Simultaneously, the overlap in symptoms, genetic variations, and brain alterations in schizophrenia and related psychiatric disorders raises similar difficulties in determining disease-specific effects. Imaging genetics is a unique methodology to assess the impact of genetic factors on both brain structure and function. More importantly, imaging genetics builds a bridge to understand the behavioral and clinical implications of genetics and neuroimaging. By characterizing and quantifying the brain measures affected in psychiatric disorders, imaging genetics is contributing to identifying potential biomarkers for schizophrenia and related disorders. To date, candidate gene analysis, genome-wide association studies, polygenetic risk score analysis, and large-scale collaborative studies have made contributions to the understanding of schizophrenia with the potential to serve as biomarkers. Despite limitations, imaging genetics remains promising as more aggregative, clustering methods and imaging genetics-compatible clinical assessments are employed in future studies. We review imaging genetics' contribution to our understanding of the heterogeneity within schizophrenia and the commonalities across schizophrenia and other diagnostic borders, and we will discuss whether imaging genetics is ready to form its own diagnostic system.

15.
Front Neurosci ; 13: 634, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31316333

RESUMO

Brain functional connectivity has been shown to change over time during resting state fMRI experiments. Close examination of temporal changes have revealed a small set of whole-brain connectivity patterns called dynamic states. Dynamic functional network connectivity (dFNC) studies have demonstrated that it is possible to replicate the dynamic states across several resting state experiments. However, estimation of states and their temporal dynamicity still suffers from noisy and imperfect estimations. In regular dFNC implementations, states are estimated by comparing connectivity patterns through the data without considering time, in other words only zero order changes are examined. In this work we propose a method that includes first order variations of dFNC in the searching scheme of dynamic connectivity patterns. Our approach, referred to as temporal variation of functional network connectivity (tvFNC), estimates the derivative of dFNC, and then searches for reoccurring patterns of concurrent dFNC states and their derivatives. The tvFNC method is first validated using a simulated dataset and then applied to a resting-state fMRI sample including healthy controls (HC) and schizophrenia (SZ) patients and compared to the standard dFNC approach. Our dynamic approach reveals extra patterns in the connectivity derivatives complementing the already reported state patterns. State derivatives consist of additional information about increment and decrement of connectivity among brain networks not observed by the original dFNC method. The tvFNC shows more sensitivity than regular dFNC by uncovering additional FNC differences between the HC and SZ groups in each state. In summary, the tvFNC method provides a new and enhanced approach to examine time-varying functional connectivity.

16.
Neuroimage Clin ; 23: 101887, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31176952

RESUMO

The progress of schizophrenia at various stages is an intriguing question, which has been explored to some degree using single-modality brain imaging data, e.g. gray matter (GM) or functional connectivity (FC). However it remains unclear how those changes from different modalities are correlated with each other and if the sensitivity to duration of illness and disease stages across modalities is different. In this work, we jointly analyzed FC, GM volume and single nucleotide polymorphisms (SNPs) data of 159 individuals including healthy controls (HC), drug-naïve first-episode schizophrenia (FESZ) and chronic schizophrenia patients (CSZ), aiming to evaluate the links among SNP, FC and GM patterns, and their sensitivity to duration of illness and disease stages in schizophrenia. Our results suggested: 1) both GM and FC highlighted impairments in hippocampal, temporal gyrus and cerebellum in schizophrenia, which were significantly correlated with genes like SATB2, GABBR2, PDE4B, CACNA1C etc. 2) GM and FC presented gradually decrease trend (HC > FESZ>CSZ), while SNP indicated a non-gradual variation trend with un-significant group difference observed between FESZ and CSZ; 3) Group difference between HC and FESZ of FC was more remarkable than GM, and FC presented a stronger negative correlation with duration of illness than GM (p = 0.0006). Collectively, these results highlight the benefit of leveraging multimodal data and provide additional clues regarding the impact of mental illness at various disease stages.

17.
Psychol Med ; : 1-11, 2019 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-31155012

RESUMO

BACKGROUND: Schizophrenia is associated with robust hippocampal volume deficits but subregion volume deficits, their associations with cognition, and contributing genes remain to be determined. METHODS: Hippocampal formation (HF) subregion volumes were obtained using FreeSurfer 6.0 from individuals with schizophrenia (n = 176, mean age ± s.d. = 39.0 ± 11.5, 132 males) and healthy volunteers (n = 173, mean age ± s.d. = 37.6 ± 11.3, 123 males) with similar mean age, gender, handedness, and race distributions. Relationships between the HF subregion volume with the largest between group difference, neuropsychological performance, and single-nucleotide polymorphisms were assessed. RESULTS: This study found a significant group by region interaction on hippocampal subregion volumes. Compared to healthy volunteers, individuals with schizophrenia had significantly smaller dentate gyrus (DG) (Cohen's d = -0.57), Cornu Ammonis (CA) 4, molecular layer of the hippocampus, hippocampal tail, and CA 1 volumes, when statistically controlling for intracranial volume; DG (d = -0.43) and CA 4 volumes remained significantly smaller when statistically controlling for mean hippocampal volume. DG volume showed the largest between group difference and significant positive associations with visual memory and speed of processing in the overall sample. Genome-wide association analysis with DG volume as the quantitative phenotype identified rs56055643 (ß = 10.8, p < 5 × 10-8, 95% CI 7.0-14.5) on chromosome 3 in high linkage disequilibrium with MOBP. Gene-based analyses identified associations between SLC25A38 and RPSA and DG volume. CONCLUSIONS: This study suggests that DG dysfunction is fundamentally involved in schizophrenia pathophysiology, that it may contribute to cognitive abnormalities in schizophrenia, and that underlying biological mechanisms may involve contributions from MOBP, SLC25A38, and RPSA.

18.
Front Neurosci ; 13: 494, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31156374

RESUMO

Neuroimaging research is growing rapidly, providing expansive resources for synthesizing data. However, navigating these dense resources is complicated by the volume of research articles and variety of experimental designs implemented across studies. The advent of machine learning algorithms and text-mining techniques has advanced automated labeling of published articles in biomedical research to alleviate such obstacles. As of yet, a comprehensive examination of document features and classifier techniques for annotating neuroimaging articles has yet to be undertaken. Here, we evaluated which combination of corpus (abstract-only or full-article text), features (bag-of-words or Cognitive Atlas terms), and classifier (Bernoulli naïve Bayes, k-nearest neighbors, logistic regression, or support vector classifier) resulted in the highest predictive performance in annotating a selection of 2,633 manually annotated neuroimaging articles. We found that, when utilizing full article text, data-driven features derived from the text performed the best, whereas if article abstracts were used for annotation, features derived from the Cognitive Atlas performed better. Additionally, we observed that when features were derived from article text, anatomical terms appeared to be the most frequently utilized for classification purposes and that cognitive concepts can be identified based on similar representations of these anatomical terms. Optimizing parameters for the automated classification of neuroimaging articles may result in a larger proportion of the neuroimaging literature being annotated with labels supporting the meta-analysis of psychological constructs.

19.
Hum Brain Mapp ; 40(13): 3795-3809, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31099151

RESUMO

There is growing evidence that rather than using a single brain imaging modality to study its association with physiological or symptomatic features, the field is paying more attention to fusion of multimodal information. However, most current multimodal fusion approaches that incorporate functional magnetic resonance imaging (fMRI) are restricted to second-level 3D features, rather than the original 4D fMRI data. This trade-off is that the valuable temporal information is not utilized during the fusion step. Here we are motivated to propose a novel approach called "parallel group ICA+ICA" that incorporates temporal fMRI information from group independent component analysis (GICA) into a parallel independent component analysis (ICA) framework, aiming to enable direct fusion of first-level fMRI features with other modalities (e.g., structural MRI), which thus can detect linked functional network variability and structural covariations. Simulation results show that the proposed method yields accurate intermodality linkage detection regardless of whether it is strong or weak. When applied to real data, we identified one pair of significantly associated fMRI-sMRI components that show group difference between schizophrenia and controls in both modalities, and this linkage can be replicated in an independent cohort. Finally, multiple cognitive domain scores can be predicted by the features identified in the linked component pair by our proposed method. We also show these multimodal brain features can predict multiple cognitive scores in an independent cohort. Overall, results demonstrate the ability of parallel GICA+ICA to estimate joint information from 4D and 3D data without discarding much of the available information up front, and the potential for using this approach to identify imaging biomarkers to study brain disorders.

20.
J Neurosci Methods ; 323: 68-76, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31005575

RESUMO

BACKGROUND: Autocorrelation (AC) in fMRI time-series is a well-known phenomenon, typically attributed to colored noise and therefore removed from the data. We hypothesize that AC reflects systematic and meaningful signal fluctuations that may be tied to neural activity and provide evidence to support this hypothesis. NEW METHOD: Each fMRI time-series is modeled as an autoregressive process from which the autocorrelation is quantified. Then, autocorrelation during resting-state fMRI and auditory oddball (AOD) task in schizophrenia and healthy volunteers is examined. RESULTS: During resting-state, AC was higher in the visual cortex while during AOD task, frontal part of the brain exhibited higher AC in both groups. AC values were significantly lower in specific brain regions in schizophrenia patients (such as thalamus during resting-state) compared to healthy controls in two independent datasets. Moreover, AC values had significant negative correlation with patients' symptoms. AC differences discriminated patients from healthy controls with high accuracy (resting-state). COMPARISON WITH EXISTING METHODS: Contrary to most prior works, the results suggest AC shows meaningful patterns that are discriminative between patients and controls. Our results are in line with recent works attributing autocorrelation to feedback loop of brain's regulatory circuit. CONCLUSIONS: Autoconnectivity is cognitive state dependent (resting-state vs. task) and mental state dependent (healthy vs. schizophrenia). The concept of autoconnectivity resembles a recurrent neural network and provides a new perspective of functional integration in the brain. These findings may have important implications for understanding of brain function in health and disease as well as for analysis of fMRI time-series.

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