Structural abnormalities in language circuits in genetic high-risk subjects and schizophrenia patients.

Schizophrenia is a severe psychiatric disorder with a strong genetic predisposition. Structural and functional brain deficits throughout the cerebral cortex, particularly in the language-processing associated brain regions, are consistently reported. Recently, increasing evidence from magnetic resonance imaging (MRI) studies suggests that healthy relatives of schizophrenia patients also show structural brain abnormalities in cortical gray matter (GM) volume and thickness, suggesting that this may be associated with an unexpressed genetic liability for the disorder. Unfortunately, the findings are not consistent, which may be caused by different age ranges of the cohorts studied. In the present study, we examined the voxel-based whole brain cortical thickness, area, GM volume densities, and regional cortical thickness-related laterality indices in 14 bilateral regions of interest (ROIs) from known language-processing circuits in 20 schizophrenia patients, 21 young non-psychotic subjects with heightened genetic risk for schizophrenia at the peak ages for development of the disorder, and 48 matched controls. The results showed widespread significant reductions in cortical thickness, cortical GM volume density, and scattered decreases in cortical surface area in the schizophrenia patients compared with those in the high-risk subjects and normal controls. Moreover, the genetic high-risk subjects showed significantly increased regional cortical thickness in 7 of the 14 ROIs in the language-processing pathway when compared with controls. They also had increased GM volume density in scattered regions associated with language-processing when compared with the normal controls. Laterality analyses showed that the spatial distribution of abnormal cortical thickness in the schizophrenia patients, as well as in the high-risk subjects, contributes to a decrease of the normal left-greater-than-right anatomical asymmetry in the inferior orbital frontal area, and a increased left-greater-than-right pattern in the inferior parietal and occipital regions. Together with the existing findings in the literature, the results of the present study suggest that developmental disruption of the anatomical differentiation of the hemispheres provides a basis for understanding the language impairment and symptoms of psychosis, and that these may arise because of abnormal left-right hemispherical communications that interrupt the normal flow of information processing. The early structural deficits in language-processing circuits may precede the appearance of psychotic symptoms and may be an indicator of an increased risk of developing schizophrenia.

Subcortical structure alterations impact language processing in individuals with schizophrenia and those at high genetic risk.

OBJECTIVE: Cortical structural and functional anomalies have been found to associate with language impairments in both schizophrenia patients and genetic high risk individuals for developing schizophrenia. However, subcortical structures that contribute to language processing haven't been well studied in this population, and thus became the main objective of this study. METHOD: We examined structural MRI data from 20 patients with schizophrenia, 21 individuals at genetic high risk, and 48 controls. Surface shape and volume differences of 6 subcortical structures that are involved in language processing, including nuclei pallidum, putamen, caudate, amygdala, thalamus, and hippocampus from both hemispheres, were compared between groups. Performance scores of language-associated cognitive tests were obtained to identify relationships of subcortical structures to language-related behaviors. RESULTS: Significantly reduced volumes of both the left and right side caudate nuclei, thalami and right side amygdala were shown in patients when compared with controls. Very interestingly, the high risk group demonstrated significantly increased correlations between volumes of left side pallidum nucleus and bilateral thalami and language-related cognitive test scores when compared to controls. CONCLUSIONS: This study furthers our understanding of subcortical structural alterations in schizophrenia and high risk individuals, and suggests the contribution of subcortical structures to the language impairments that may serve as an early sign for impending development of schizophrenia.

Topological organization of the "small-world" visual attention network in children with attention deficit/hyperactivity disorder (ADHD).

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is the most commonly diagnosed childhood psychiatric disorder. Disrupted sustained attention is one of the most significant behavioral impairments in this disorder. We mapped systems-level topological properties of the neural network responsible for sustained attention during a visual sustained task, on the premise that strong associations between anomalies in network features and clinical measures of ADHD would emerge. METHODS: Graph theoretic techniques (GTT) and bivariate network-based statistics (NBS) were applied to fMRI data from 22 children with ADHD combined-type and 22 age-matched neurotypicals, to evaluate the topological and nodal-pairing features in the functional brain networks. Correlation testing for relationships between network properties and clinical measures were then performed. RESULTS: The visual attention network showed significantly reduced local-efficiency and nodal-efficiency in frontal and occipital regions in ADHD. Measures of degree and between-centrality pointed to hyper-functioning in anterior cingulate cortex and hypo-functioning in orbito-frontal, middle-occipital, superior-temporal, supra-central, and supra-marginal gyri in ADHD. NBS demonstrated significantly reduced pair-wise connectivity in an inner-network, encompassing right parietal and temporal lobes and left occipital lobe, in the ADHD group. CONCLUSIONS: These data suggest that atypical topological features of the visual attention network contribute to classic ADHD symptomatology, and may underlie the inattentiveness and hyperactivity/impulsivity that are characteristics of this syndrome.

A review of attention-deficit/hyperactivity disorder from the perspective of brain networks.

Attention-deficit/hyperactivity disorder (ADHD) is the most commonly diagnosed neurodevelopmental disorder in childhood, which affects more than 5% of the population worldwide. ADHD is characterized by developmentally inappropriate behaviors of inattention, and/or impulsivity and hyperactivity. These behavioral manifestations contribute to diminished academic, occupational and social functioning, and have neurobiological bases. Neuronal deficits, especially in the attention and executive function processing networks, have been implicated in both children and adults with ADHD by using sophisticated structural and functional neuroimaging approaches. These structural and functional abnormalities in the brain networks have been associated with the impaired cognitive, affective, and motor behaviors seen in the disorder. The goal of this review is to summarize and integrate emerging themes from the existing neuroimaging connectivity studies based on advanced imaging techniques, applied in data of structural magnetic resonance imaging (MRI), functional MRI (fMRI), diffusion tensor imaging, electroencephalography and event related potential; and to discuss the results of these studies when considering future directions for understanding pathophysiological mechanisms and developmental trajectories of the behavioral manifestations in ADHD. We conclude this review by suggesting that future research should put more effort on understanding the roles of the subcortical structures and their structural/functional pathways in ADHD.

White matter changes in patients with amnestic mild cognitive impairment detected by diffusion tensor imaging.

Compared to normal aging adults, individuals with amnestic mild cognitive impairment (aMCI) have significantly increased risk for progressing into Alzheimer's disease (AD). Autopsy studies found that most of the brains of aMCI cases showed anatomical features associated with AD pathology. The recent development of non-invasive neuroimaging technique, such as diffusion tensor imaging (DTI), makes it possible to investigate the microstructures of the cerebral white matter in vivo. We hypothesized that disrupted white matter (WM) integrity existed in aMCI. So we used DTI technique, by measuring fractional anisotropy (FA) and mean diffusivity (MD), to test the brain structures involved in patients with aMCI. DTI scans were collected from 40 patients with aMCI, and 28 normal controls (NC). Tract-based spatial statistics (TBSS) analyses of whole-brain FA and MD images in each individual and group comparisons were carried out. Compared to NC, aMCI patients showed significant FA reduction bilaterally, in the association and projection fibers of frontal, parietal, and temporal lobes, corpus callosum, bilateral corona radiation, right posterior thalamic radiation and right sagittal stratum. aMCI patients also showed significantly increased MD widespreadly in the association and projection fibers of frontal, parietal and temporal lobes, and corpus callosum. Assessment of the WM integrity of the frontal, parietal, temporal lobes, and corpus callosum by using DTI measures may aid early diagnosis of aMCI.

Thalamic shape and connectivity abnormalities in children with attention-deficit/hyperactivity disorder.

Attention-deficit/hyperactivity disorder (ADHD) is characterized by widespread structural and functional abnormalities in the cortico-striato-thalmo-cortical (CSTC) loops that subserve attention and executive functions. In this study, we analyzed thalamic shape and its white matter connections using structural magnetic resonance imaging and diffusion (DTI) data acquired from children with ADHD (n=19) and controls (n=19). Shape morphology of the thalamus was assessed using shape-based analysis, while connectivity between the thalamus and other brain regions was determined using probabilistic diffusion tractography. Shape-based analysis indicated significant regional atrophy in the left thalamus in children with ADHD compared to controls. Group analyses of white matter connectivity measures showed significantly decreased mean fractional anisotropy (FA) and volume of the tracts between thalamus and striatum, hippocampus, and prefrontal lobe in children with ADHD compared to controls. The structural abnormalities within the thalamus and the reduced integrity of the white matter tracks between the thalamus and other brain regions, as shown from the results of this study, may be the anatomical bases of the impaired cognitive performances in the attention and executive function domains in ADHD.

Unique topology of language processing brain network: a systems-level biomarker of schizophrenia.

OBJECTIVE: Schizophrenia is a severe and heritable brain disorder. Language impairment has been hypothesized to spur its onset and underlie the characteristic symptoms. In this study, we investigate whether altered topological pattern of the language processing brain network exists and could be a potential biomarker of schizophrenia. We hypothesized that both patients with schizophrenia and the genetic high risk population would show significantly weakened efficiencies of the network hubs for normal language processing, especially at left inferior frontal and bilateral temporal lobes. METHOD: Language task-based fMRI data from 21 patients with schizophrenia, 22 genetic high risk subjects and 36 controls were analyzed. Graph theoretic and post hoc analyses of the fMRI data, and correlations between the functional network features and scores of language tests were carried out. RESULTS: Compared to controls, patients with schizophrenia and the high risk subjects showed significantly weakened network hubs in left inferior frontal and right fusiform gyri. A unique topology of super active and intercommunicating network hubs at left fusiform gyrus and right inferior/middle frontal gyri, which were associated with the behavioral language impairment was found in the patient group, compared to the high risk and control groups. CONCLUSIONS: Aberrant systems-level topology of language processing network, especially significantly weakened network hubs in left inferior frontal and right fusiform gyri, may serve as a candidate biomarker of schizophrenia. Supported by existing findings, the hyperactive left fusiform gyrus communicating with right frontal lobe might be the key neurophysiological component causing hallucinations in schizophrenia. These findings provided a new systems-level diagnostic target for the disorder.