Evidence of altered prefrontal-thalamic circuitry in schizophrenia: an optimized diffusion MRI study.
ABSTRACT MRI diffusion tensor imaging (DTI), optimized for measuring the trace of the diffusion tensor, was used to investigate microstructural changes in the brains of 12 individuals with schizophrenia compared with 12 matched control subjects. To control for the effects of anatomic variation between subject groups, all participants' diffusion images were nonlinearly registered to standard anatomical space. Significant statistical differences in mean diffusivity (MD) measures between the two groups were determined on a pixel-by-pixel basis, using Gaussian random field theory. We found significantly elevated MD measures within temporal, parietal and prefrontal cortical regions in the schizophrenia group (P > 0.001), especially within the medial frontal gyrus and anterior cingulate. The dorsal medial and anterior nucleus of the thalamus, including the caudate, also exhibited significantly increased MD in the schizophrenia group (P > 0.001). This study has shown for the first time that MD measures offer an alternative strategy for investigating altered prefrontal-thalamic circuitry in schizophrenia.
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ABSTRACT: Several lines of evidence suggest that cognitive control deficits may be regarded as a connecting link between reported impairments in different cognitive domains of schizophrenia. However, the precise interplay within the fronto-cingulo-thalamic network known to be involved in cognitive control processes and its structural correlates has only been sparsely investigated in schizophrenia. The present multimodal study was therefore designed to model cognitive control processes within the fronto-cingulo-thalamic network. A disruption in effective connectivity in patients in association with abnormal white matter (WM) structure in this network was hypothesized. 36 patients with schizophrenia and 36 healthy subjects participated in the present study. Using functional magnetic resonance imaging (fMRI) a Stroop task was applied in an event-related design. For modeling effective connectivity dynamic causal modeling (DCM) was used. Voxel-based morphometry (VBM) was employed to study WM abnormalities. In the fMRI analysis, the patients demonstrated a significantly decreased BOLD signal in the fronto-cingulo-thalamic network. In the DCM analysis, a significantly decreased bilateral endogenous connectivity between the mediodorsal thalamus (MD) and the anterior cingulate cortex (ACC) was detected in patients in comparison to healthy controls, which was negatively correlated with the Stroop interference score. Furthermore, an increased endogenous connectivity between the right DLPFC and the right MD was observed in the patients. WM volume decreases were observed in the patients in the MD and the frontal cortex. The present results provide strong evidence for the notion that an abnormal fronto-cingulo-thalamic effective connectivity may represent the basis of cognitive control deficits in schizophrenia. Moreover, the data indicate that disrupted white matter connectivity in the mediodorsal thalamus and in the fronto-cingulo-thalamic network may constitute the determining cause of fronto-cingulo-thalamic dysconnectivity.NeuroImage : clinical. 01/2013; 3:95-105.
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ABSTRACT: Die vor 30 Jahren formulierte und zunächst umstrittene Entwicklungsstörungshypothese zur Pathogenese schizophrener Störungen besagt, dass prä-/perinatal auf das Gehirn einwirkende Noxen zu pathologischen Veränderungen der Kortikogenese und der sich entwickelnden neuronalen Bahnsysteme führen, welche für den späteren Ausbruch der Erkrankung von wesentlicher ätiologischer Bedeutung sind. In den letzten Jahren konnten die zerebralen Veränderungen schizophrener Patienten mit Hilfe neuer neuropathologischer Methoden genauer als areal-, schicht- und zelltypspezifische Alterationen charakterisiert werden, durch die es zu spezifischen Abnormitäten im Bereich der intrinsischen Verschaltungen und der transregionalen Vernetzungen vor allem temporolimbischer und frontaler Hirnregionen kommt. Tiermodelle ermöglichen eine realistische Imitation dieser Strukturläsionen und damit die Aufklärung ihrer funktionellen Implikationen auf der Transmitter- und der Verhaltensebene. Mit den modernen bildgebenden Techniken können zunehmend sowohl die mikrostrukturellen Alterationen als auch zerebrale Aktivierungsänderungen exakt dargestellt und zu spezifischen psychopathologischen Merkmalen schizophrener Störungen in Beziehung gesetzt werden.Der Nervenarzt 01/2008; 79(3). · 0.86 Impact Factor
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ABSTRACT: The Disrupted-in-Schizophrenia 1 (DISC1) gene has been thought as a putative susceptibility gene for various psychiatric disorders, and DISC1 Ser704Cys is associated with variations of brain morphology and function. Moreover, our recent diffusion magnetic resonance imaging (dMRI) study reported that DISC1 Ser704Cys was associated with information transfer efficiency in the brain anatomical network. However, the effects of the DISC1 gene on functional brain connectivity and networks, especially for thalamic-prefrontal circuit, which are disrupted in various psychiatric disorders, are largely unknown. Using a functional connectivity density (FCD) mapping method based on functional magnetic resonance imaging data in a large sample of healthy Han Chinese subjects, we first investigated the association between DISC1 Ser704Cys and short- and long-range FCD hubs. Compared with Ser homozygotes, Cys-allele individuals had increased long-range FCD hubs in the bilateral thalami. The functional and anatomical connectivity of the thalamus to the prefrontal cortex was further analyzed. Significantly increased thalamic-prefrontal functional connectivity and decreased thalamic-prefrontal anatomical connectivity were found in DISC1 Cys-allele carriers. Our findings provide consistent evidence that the DISC1 Ser704Cys polymorphism influences the thalamic-prefrontal circuits in humans and may provide new insights into the neural mechanisms that link DISC1 and the risk for psychiatric disorders.Brain Structure and Function 10/2013; · 7.84 Impact Factor