Reduced intrinsic visual cortical connectivity is associated with impaired perceptual closure in schizophrenia

Sensory perceptual processing deficits, such as impaired visual object identification and perceptual closure, have been reported in schizophrenia. These perceptual impairments may be associated with neural deficits in visual association areas, including lateral occipital cortex and inferior temporal areas. However, it remains unknown if such deficits can be found in the intrinsic architecture of the visual system. In the current study, we measured perceptual closure performance and resting-state functional connectivity using functional magnetic resonance imaging (FMRI) in 16 schizophrenia patients and 16 matched healthy controls. We estimated intrinsic functional connectivity using self-organized grouping spatial ICA, which clusters component maps in the subject space according to spatial similarity. Patients performed worse than controls in the perceptual closure task. This impaired closure performance of patients was correlated with increased severity of psychotic symptoms. We also found that intrinsic connectivity of the visual processing system was diminished in patients compared to controls. Lower perceptual closure performance was correlated to lower visual cortical intrinsic connectivity overall. We suggest that schizophrenia is associated with impaired intrinsic connectivity of the visual system, and that it is a potential mechanism leading to impaired visual object perception. These findings contribute to increasing evidence for impairments of higher visual functions in schizophrenia

Abnormal connectional fingerprint in schizophrenia: a novel network analysis of diffusion tensor imaging data

The graph theoretical analysis of structural magnetic resonance imaging (MRI) data has received a great deal of interest in recent years to characterize the organizational principles of brain networks and their alterations in psychiatric disorders, such as schizophrenia. However, the characterization of networks in clinical populations can be challenging, since the comparison of connectivity between groups is influenced by several factors, such as the overall number of connections and the structural abnormalities of the seed regions. To overcome these limitations, the current study employed the whole-brain analysis of connectional fingerprints in diffusion tensor imaging data obtained at 3 T of chronic schizophrenia patients (n = 16) and healthy, age-matched control participants (n = 17). Probabilistic tractography was performed to quantify the connectivity of 110 brain areas. The connectional fingerprint of a brain area represents the set of relative connection probabilities to all its target areas and is, hence, less affected by overall white and gray matter changes than absolute connectivity measures. After detecting brain regions with abnormal connectional fingerprints through similarity measures, we tested each of its relative connection probability between groups. We found altered connectional fingerprints in schizophrenia patients consistent with a dysconnectivity syndrome. While the medial frontal gyrus showed only reduced connectivity, the connectional fingerprints of the inferior frontal gyrus and the putamen mainly contained relatively increased connection probabilities to areas in the frontal, limbic, and subcortical areas. These findings are in line with previous studies that reported abnormalities in striatal–frontal circuits in the pathophysiology of schizophrenia, highlighting the potential utility of connectional fingerprints for the analysis of anatomical networks in the disorder

Adolescent brain maturation and cortical folding: evidence for reductions in gyrification

Evidence from anatomical and functional imaging studies have highlighted major modifications of cortical circuits during adolescence. These include reductions of gray matter (GM), increases in the myelination of cortico-cortical connections and changes in the architecture of large-scale cortical networks. It is currently unclear, however, how the ongoing developmental processes impact upon the folding of the cerebral cortex and how changes in gyrification relate to maturation of GM/WM-volume, thickness and surface area. In the current study, we acquired high-resolution (3 Tesla) magnetic resonance imaging (MRI) data from 79 healthy subjects (34 males and 45 females) between the ages of 12 and 23 years and performed whole brain analysis of cortical folding patterns with the gyrification index (GI). In addition to GI-values, we obtained estimates of cortical thickness, surface area, GM and white matter (WM) volume which permitted correlations with changes in gyrification. Our data show pronounced and widespread reductions in GI-values during adolescence in several cortical regions which include precentral, temporal and frontal areas. Decreases in gyrification overlap only partially with changes in the thickness, volume and surface of GM and were characterized overall by a linear developmental trajectory. Our data suggest that the observed reductions in GI-values represent an additional, important modification of the cerebral cortex during late brain maturation which may be related to cognitive development

Connectivity disturbances in schizophrenia : evidence from anatomical and functional Magnetic Resonance Imaging

In 1911 Eugen Bleuler (Bleuler, 1911) postulated that schizophrenia was a disorder resulting from inability to properly integrate mental processes. Around the same time, Carl Wernicke (Wernicke, 1894) proposed that psychosis might result from disruption of white matter tracts. Both of these statements can be considered early cornerstones of modern connectivity hypotheses developed towards the end of the twentieth century by such researchers as Karl Friston (1998) and Nancy Andreansen (1998). In the current work, the hypothesis that schizophrenia, rather than being a disorder or either anatomical or functional connectivity, is a disorder where both of these processes interact and influence the clinical presentation of patients, is examined. This is achieved through a detailed examination of a sample of chronic schizophrenia patients using a combination of functional and anatomical Magnetic Resonance Imaging techniques. The relationship of these measures to clinical symptoms is also explored. In the first study, anatomical connectivity at the whole-brain level is examined using Diffusion Tensor Imaging. The results of the study contribute to the previous literature on auditory hallucinations in schizophrenia and provide the first direct correlation between increased anatomical connectivity and increased severity of psychotic symptoms. The second study provides a thorough examination of the interhemispheric connectivity. This is achieved through a detailed examination of the corpus callosum using a combination of diffusivity and volumetric values. This is the first study to date where several anatomical methods are used in one sample. The results illustrate the importance of using different techniques to accurately characterize anatomical abnormalities observed in schizophrenia. In addition, contrary to previous research reports, the results of the current study imply that only specific sub-sections of the corpus callosum are affected by anatomical abnormalities. The pattern of these changes may influence clinical presentation of patients. Finally, functional connectivity at the whole-brain level is examined during resting-state using Independent Component Analysis. Similarly to the results of the anatomical examinations, it provides further supporting evidence that the pattern of disturbances observed in the current sample of schizophrenia patients examined herein reflects a combination of hypo- and hyperconnectivity. Moreover, the study further validates resting-state functional Magnetic Resonance Imaging as a reliable tool for examining functional abnormalities in schizophrenia.Zu Beginn des 20. Jahrhunderts postulierte Eugen Bleuler (Bleuler, 1911), dass die Symptome der Schizophrenie aus einer Desintegration mentaler Prozesse resultieren. Etwa zur selben Zeit vermutete Carl Wernicke (1894), dass die Ursache psychotischer Störungen in einer Beeinträchtigung der Faserverbindungen der weißen Substanz liegen könnte. Beide Ideen können heute als Vorläufer moderner Diskonnektivitätshypothesen betrachtet werden, die gegen Ende des letzten Jahrhunderts von Karl Friston (1998) und Nancy Andreasen (1998) als Modelle zur Pathogenese der Schizophrenie weiterentwickelt worden sind. In der vorliegenden Arbeit wurde die Hypothese untersucht, dass schizophrene Psychosen auf einer Störung sowohl der strukturellen als auch der funktionellen Konnektivität beruhen und die klinische Symptomatik insbesondere durch die Interaktion dieser beiden Aspekte entscheidend beeinflusst wird. Zu diesem Zweck wurde eine Gruppe schizophrener Patienten mittels funktioneller und anatomischer kernspintopographischer Messungen des Gehirns untersucht. Ein Schwerpunkt der Arbeit lag dabei auf der Untersuchung des Einflusses struktureller und funktioneller Veränderungen des Gehirns auf die klinische Symptomatik. In der ersten Studie wurde die anatomische Konnektivität des Gehirns mittels Diffusion Tensor Imaging (DTI) gemessen. Die Ergebnisse erweitern die bisherigen Erkenntnisse über die Pathogenese akustische Halluzinationen in der Schizophrenie, indem sie zum ersten Mal eine direkte Korrelation zwischen der Stärke struktureller Faserverbindungen und der Ausprägung psychotischer Symptome im Sinne einer Hyperkonnektivität belegen. Die zweite Studie befasst sich mit der genaueren Untersuchung interhemisphärischer Konnektivität. Hierzu wurde eine detaillierte Auswertung volumetrischer und anatomischer DTI-Daten des Corpus callosum vorgenommen. Es handelt sich hierbei um die erste Studie, in der eine Kombination verschiedener Methoden aus dem Bereich der anatomischen Bildgebung des Gehirns innerhalb einer Stichprobe angewandt wurde. Die Ergebnisse veranschaulichen die Notwendigkeit, unterschiedliche bildgebende Methoden gezielt zu kombinieren, um die anatomischen Veränderungen bei der Schizophrenie exakt charakterisieren zu können. Im Gegensatz zu früheren Untersuchungen weisen die Ergebnisse der aktuellen Studie zudem darauf hin, dass nur bestimmte Subregionen des Corpus callosum von anatomischen Veränderungen betroffen sind. Darüber hinaus ließ sich zeigen, dass ein Zusammenhang zwischen dem Muster dieser Veränderungen und der klinischen Symptomkonstellation besteht. In der dritten Studie wurde die funktionelle Konnektivität des Gehirns im Ruhezustand mittels Independent Component Analysis (ICA) untersucht. Ähnlich wie die beiden anatomischen Studien liefert auch diese Untersuchung Hinweise darauf, dass unterschiedliche syndromale Erscheinungsformen der Schizophrenie durch unterschiedliche Ausprägungen regionaler Hypoand Hyperkonnektivität charakterisiert sind

Automated segmentation of lateral ventricles from human and primate magnetic resonance images using cognition network technology

Automatic segmentation of different types of tissue from magnetic resonance images is of great importance for clinical and research applications, particularly large-scale and longitudinal studies of brain pathology. We developed a fully automated algorithm for the segmentation of lateral ventricles from cranial magnetic resonance images. This problem is of interest in the study of schizophrenia, dementia and other neuropsychiatric disorders. Our algorithm achieves comparable results to expert human raters. The theoretical approach, which is based on an emerging object-oriented technology that has been adapted and evaluated to process 3D data for the first time, may, in the future, be transferred to other important problems of magnetic resonance image analysis like gray/white matter segmentation

The corpus callosum in schizophrenia-volume and connectivity changes affect specific regions

The corpuscallosum (CC) is of great interest for pathophysiological models of schizophrenia. Volume and structural integrity of the CC have been examined by volumetric and diffusion tensor imaging (DTI) studies, but results were not consistent across methods or studies. A possible explanation may be varying methodologies and accuracy of measurements based on a single slice or small regions of interest. In addition, none of the studies examined volume and diffusion values in the same group of patients, and thus the relationship between these anatomical measures is not clear. We used an automatic algorithm to segment seven midline slices of the CC from DTI images. We compared volume and the DTI measures fractional anisotropy (FA) and mean diffusivity (MD) in the CC and its subdivisions in the schizophrenia patients and matched controls. Patients had decreased volume, decreased FA and increased MD of the whole CC. The important novel finding is, however, that not all regions were equally affected by anatomical changes. The results emphasize the importance of using different methods in evaluation of white matter (WM) in schizophrenia to avoid false negative findings. In addition, the measures were highly correlated with each other, implying a common pathological process influencing FA, MD and volume of the CC. Although we cannot rule out other mechanisms affecting volume, FA and MD, converging evidence from cytoarchitectonic and genetic studies suggests that WM changes observed in schizophrenia may involve disintegration of healthy, functional axons and strengthening of aberrant connections resulting in increased severity of clinical symptoms

Resting-state functional network correlates of psychotic symptoms in schizophrenia

Schizophrenia has been associated with aberrant intrinsic functional organization of the brain but the relationship of such deficits to psychopathology is unclear. In this study, we investigated associations between resting-state networks and individual psychopathology in sixteen patients with paranoid schizophrenia and sixteen matched healthy control participants. We estimated whole-brain functional connectivity of multiple networks using a combination of spatial independent component analysis and multiple regression analysis. Five networks (default-mode, left and right fronto-parietal, left fronto-temporal and auditory networks) were selected for analysis based on their involvement in neuropsychological models of psychosis. Between-group comparisons and correlations to psychopathology ratings were performed on both spatial (connectivity distributions) and temporal features (power-spectral densities of temporal frequencies below 0.06 Hz). Schizophrenia patients showed aberrant functional connectivity in the default-mode network, which correlated with severity of hallucinations and delusions, and decreased hemispheric separation of fronto-parietal activity, which correlated with disorganization symptoms. Furthermore, the severity of positive symptoms correlated with functional connectivity of fronto-temporal and auditory networks. Finally, default-mode and auditory networks showed increased spectral power of low frequency oscillations, which correlated with positive symptom severity. These results are in line with findings from studies that investigated the neural correlates of positive symptoms and suggest that psychopathology is associated with aberrant intrinsic organization of functional brain networks in schizophrenia

Interhemispheric hypoconnectivity in schizophrenia: Fiber integrity and volume differences of the corpus callosum in patients and unaffected relatives

Changes in hemispheric asymmetry and inter-hemispheric connectivity have been reported in schizophrenia. However, the genetic contribution to these alterations is still unclear. In the current study, we applied an automatic segmentation method to structural MRI and diffusion tensor imaging (DTI) data and examined volume and fiber integrity of the corpus callosum (CC), the main interhemispheric fiber tract, in 16 chronic schizophrenia (SZ) patients, matched first degree relatives and controls. SZ patients and relatives had smaller CC volumes than controls, particularly in the posterior genu, isthmus and splenium. Fractional anisotropy (FA), an indicator of fiber integrity, was reduced in patients and relatives in the whole CC, the inferior genu, the superior genu and the isthmus. Correspondingly, the mean diffusivity (MD) values of the whole CC and the isthmus were higher in patients and their unaffected relatives, indicating decreased compactness and increased intercellular space. Relatives had intermediate values in the volumetric and fiber integrity measurements between patients and controls. Lower CC volume and fiber integrity in SZ patients were associated with more severe auditory hallucinations. These results support the connectivity hypothesis of SZ (Friston, 1998) and particularly highlight the altered interhemispheric connectivity, which appears to be a genetic feature of SZ risk