Evidence of altered prefrontal-thalamic circuitry in schizophrenia: An optimized diffusion MRI study

Centre for Magnetic Resonance, University of Queensland, Brisbane 4072, Australia.
NeuroImage (Impact Factor: 6.36). 09/2006; 32(1):16-22. DOI: 10.1016/j.neuroimage.2006.03.003
Source: PubMed


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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    • "On the other hand, patients with a lesion in the MD of the thalamus can exhibit clinical manifestations similar to those associated with a PFC injury, possibly because of thalamocortical connections between the MD of the thalamus and the PFC.7,8,9 Furthermore, frontal network syndrome has also been referred to patients with a lesion within the thalamocortical connections between the MD of the thalamus and the PFC.1 Furthermore, these connections are also known to be involved in many psychiatric diseases, such as, schizophrenia, addiction, depression, and bipolar disorder.2,10 Therefore, the elucidation of these thalamocortical connections would undoubtedly be useful in the clinical field in terms of neurorehabilitation and psychiatry. "
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    ABSTRACT: The elucidation of thalamocortical connections between the mediodorsal nucleus (MD) of thalamus and the prefrontal cortex (PFC) is important in the clinical fields of neurorehabilitation and psychiatry. However, little is known about these connections in human brain. We attempted to identify and investigate the anatomical characteristics of the thalamocortical connection between MD and PFC in human brain using diffusion tensor tractography (DTT). Thirty-two healthy volunteers were recruited for this study. Diffusion tensor images were scanned using a 1.5-T. A seed region of interest was placed at the MD of the thalamus on coronal images, and target regions of interest were placed on the dorsolateral prefrontal cortex (DLPFC), the ventrolateral prefrontal cortex (VLPFC), and the orbitofrontal cortex (OFC), respectively. The three thalamocortical connections found were reconstructed using Functional Magnetic Resonance Imaging of the Brain (FMRIB) software. The three thalamocortical connections were arranged in subcortical white matter in the following order from upper to lower levels: the DLPFC, the VLPFC, and the OFC. In terms of fractional anisotropy and mean diffusivity values, no significant differences were observed between the DLPFC, VLPFC and OFC (p>0.05). In contrast, the OFC tract volume was higher than those of the DLPFC and the VLPFC (p<0.05). Three thalamocortical connections were reconstructed between MD and PFCs in human brain using DTT. We believe that the results of this study would be helpful to clinicians in treating frontal network syndrome and psychiatric diseases.
    Full-text · Article · May 2014 · Yonsei medical journal
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    • "Our results were also in agreement with two recent meta-analyses that employed voxel-based analyses of FA to reveal a WM microstructural alteration in both the frontal and temporal regions; however, the alteration was more prevalent in the latter region (Ellison-Wright and Bullmore, 2009; Bora et al., 2011). Likewise, increased RD or MD was reported in the same regions in other studies (Rose et al., 2006; Scheel et al., 2013). Interestingly, WM abnormalities in schizophrenia have also been observed in fiber bundles related to the language network, such as the uncinate (Seal et al., 2008; de Weijer et al., 2011; Kitis et al., 2012; Kunimatsu et al., 2012; Mandl et al., 2012; Scheel et al., 2013) and (arcuate) superior longitudinal fasciculi (Shergill et al., 2007; Seal et al., 2008; Catani et al., 2011; de Weijer et al., 2011; Mandl et al., 2012) connecting the frontal and temporal regions, in agreement with our results. "
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    ABSTRACT: Schizophrenia is a mental disorder characterized by functional abnormalities in the language network. Anatomical white matter (WM) abnormalities (volume and integrity) have also been reported for this pathology. Nevertheless, few studies have investigated anatomo-functional relationships in schizophrenia, and none has focused on the language comprehension network in relation to various diffusion parameters. We hypothesized that the WM abnormalities that are reflected by several diffusion parameters underlie functional deficits in the language network. Eighteen DSM-IV patients with schizophrenia and 18 healthy controls without any significant differences in sex, age, or level of education were included. First, functional brain activation within the language network was estimated. Then, using diffusion tensor imaging, fractional anisotropy (FA), radial diffusivity (RD), and mean diffusivity (MD) values were extracted within WM regions adjacent to this network and their anatomo-functional relationships were investigated. Compared with healthy participants, both functional and diffusion deficits were observed in patients with schizophrenia. Primarily, an altered diffusion-functional relationship was observed in patients in the left middle temporal region: functional activations were positively correlated with FA, but were negatively correlated with RD. Our findings indicate a close relationship between diffusion and functional deficits in patients with schizophrenia, suggesting that WM integrity disturbance might be one cause of functional alterations in the language network in patients with schizophrenia. Thus, the present multimodal study improves our understanding of the pathophysiology of schizophrenia.
    Full-text · Article · Aug 2013 · Schizophrenia Research
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    • "The thalamus features prominently in major hypotheses about the neural circuitry implicated in schizophrenia (Andreasen et al, 1996), and evidence for its involvement derives from multiple fields of investigation but remains controversial (reviewed in Byne et al, 2009). Abnormalities in the medio-dorsal, pulvinar, and centromedian nuclei of the thalamus, all connected to the lateral prefrontal cortex (LPFC), a site of well-documented abnormalities in schizophrenia (Weinberger et al, 2001), have been reported with several methods (eg, Andrews et al, 2006; Byne et al, 2002; Byne et al, 2007; Harms et al, 2007; Hazlett et al, 1999; Kemether et al, 2003; Kessler et al, 2009; Kumari et al, 2010; Lehrer et al, 2005; Popken et al, 2000; Rose et al, 2006, but see, for example, Danos et al, 2005; Dorph-Petersen et al, 2004; Kreczmanski et al, 2007 for negative findings). Some functional MRI (fMRI) studies found abnormalities in the correlation between the activity in the thalamus and the PFC in schizophrenia (eg, Meda et al, 2010; Schlosser et al, 2003; Welsh et al, 2010; Zhou et al, 2007), which may reflect alterations in anatomical connectivity. "
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    ABSTRACT: The purpose of this study was to examine measures of anatomical connectivity between the thalamus and lateral prefrontal cortex (LPFC) in schizophrenia and to assess their functional implications. We measured thalamocortical connectivity with diffusion tensor imaging (DTI) and probabilistic tractography in 15 patients with schizophrenia and 22 age- and sex-matched controls. The relationship between thalamocortical connectivity and prefrontal cortical blood-oxygenation-level-dependent (BOLD) functional activity as well as behavioral performance during working memory was examined in a subsample of 9 patients and 18 controls. Compared with controls, schizophrenia patients showed reduced total connectivity of the thalamus to only one of six cortical regions, the LPFC. The size of the thalamic region with at least 25% of model fibers reaching the LPFC was also reduced in patients compared with controls. The total thalamocortical connectivity to the LPFC predicted working memory task performance and also correlated with LPFC BOLD activation. Notably, the correlation with BOLD activation was accentuated in patients as compared with controls in the ventral LPFC. These results suggest that thalamocortical connectivity to the LPFC is altered in schizophrenia with functional consequences on working memory processing in LPFC.
    Full-text · Article · Sep 2011 · Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology
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