Altered effective connectivity in drug free schizophrenic patients

Schlößer, R.; Gesierich, Thomas; Kaufmann, Bettina; Vučurević, Goran; Stoeter, P.

doi:10.1097/00001756-200312020-00020

Cited by 65 publications

(26 citation statements)

References 23 publications

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“…The measures derived with this method were highly reproducible in two repeated scans of a subset of the control subjects (ICC40.82); the effect size of the differences between diagnostic groups appeared robust (Cohen's dB0.8), and unlikely to be due to several possible confounding factors (eg, age and chlorpromazine equivalents). Our data offer a possible anatomical substrate for differences in functional connectivity between patients with schizophrenia and controls previously described with fMRI (Meda et al, 2010;Schlosser et al, 2003;Welsh et al, 2010;Zhou et al, 2007) and are consistent with a reduction in connectivity from multiple sources in the thalamus to the LPFC. Besides three studies showing that neurons specifically projecting to LPFC in the medio-dorsal nucleus of the thalamus may be reduced in schizophrenia (Byne et al, 2002;Popken et al, 2000;Young et al, 2000), reduced sizes of the pulvinar, of the centromedian nuclei (both projecting in part to the LPFC: Byne et al, 2007;Kemether et al, 2003) and reductions in oligodendrocyte number in the anterior principal nucleus (Byne et al, 2006(Byne et al, , 2008 were found in schizophrenia.…”

Section: Discussionsupporting

confidence: 87%

“…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. Thus, the changes in the coordinated functioning of the PFC and the thalamus might be relevant to the pathophysiology of schizophrenia.…”

Section: Introductionmentioning

confidence: 99%

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Investigation of Anatomical Thalamo-Cortical Connectivity and fMRI Activation in Schizophrenia

Marenco

Stein

Savostyanova

et al. 2011

Neuropsychopharmacol

143

101

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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.

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Section: Discussionsupporting

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Investigation of Anatomical Thalamo-Cortical Connectivity and fMRI Activation in Schizophrenia

Marenco

Stein

Savostyanova

et al. 2011

Neuropsychopharmacol

143

101

View full text Add to dashboard Cite

show abstract

“…The DLPFC, on the other hand, is responsible for higher order processing such as monitoring, comparison, and manipulation of information that is maintained in the IFG (Rowe et al, 2000;Wagner et al, 2001). Decreased FC between the IFG and DLPFC has been found in SCZ patients (Schlosser et al, 2003;Spence et al, 2000), which suggests a failure of functional integration between the IFG and DLPFC for SCZ patients. It needs to be mentioned that the risk allele carriers always showed negative FCs between the IFG and DLPFC during cognitive performance in this study, which may be because that the DLPFC was recruited when the IFG's activation was low (Egner, 2011;Petrides, 2000).…”

Section: Discussionmentioning

confidence: 99%

Evidence for the Contribution of NOS1 Gene Polymorphism (rs3782206) to Prefrontal Function in Schizophrenia Patients and Healthy Controls

Zhang¹,

Chen

et al. 2014

Neuropsychopharmacol

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Nitric oxide (NO), a gaseous neurotransmitter, has been implicated in the pathogenesis of schizophrenia. Accordingly, several polymorphisms of the gene that codes for the main NO-producing enzyme, the nitric oxide synthase 1 (NOS1), have been found to convey a risk for schizophrenia. This study examined the role of NOS1 gene polymorphisms in cognitive functions and related neural mechanism. First, with a sample of 580 schizophrenia patients and 720 healthy controls, we found that rs3782206 genotype had main effects on the 1-back task (P ¼ 0.005), the 2-back task (P ¼ 0.049), the AY condition of the dot-pattern expectancy (DPX) task (P ¼ 0.001), and the conflict effect of the attention network (ANT) test (Po0.001 for RT differences and P ¼ 0.002 for RT ratio) and interaction effects with diagnosis on the BX condition of the DPX (P ¼ 0.009), the AY condition of the DPX (Po0.001), and the Stroop conflict effect (P ¼ 0.003 for RT differences and P ¼ 0.038 for RT ratio). Simple effect analyses further showed that the schizophrenia risk allele (T) of rs3782206 was associated with poorer performance in five measures for the patients (1-back, P ¼ 0.025; BX, P ¼ 0.017; AY, Po0.001; ANT conflict effect (RT differences), P ¼ 0.005; Stroop conflict effect (RT differences), P ¼ 0.019) and three measures for the controls ( for the 2-back task, P ¼ 0.042; for the ANT conlict effect (RT differences), P ¼ 0.013; for the ANT conflict effect (RT ratios), P ¼ 0.028). Then, with a separate sample of 78 healthy controls, we examined the association between rs3782206 and brain activation patterns during the N-back task and the Stroop task. Whole brain analyses found that the risk allele carriers showed reduced activation at the right inferior frontal gyrus (IFG) during both tasks. Finally, we examined functional connectivity seeded from the right IFG to the dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex under three conditions (the N-back task, the Stroop task, and the resting state). Results showed reduced connectivity with the DLPFC for the risk allele carriers mainly in the Stroop task and the resting state. Taken together, results of this study strongly suggested a link between NOS1 gene polymorphism at rs3782206 and cognitive functions and their neural underpinnings at the IFG. These results have important implications for our understanding of the neural mechanism underlying the association between NOS1 gene polymorphism and schizophrenia.

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“…These methods provide a means of testing for interregional correlations in functional activity that show the largest changes across diagnostic groups or task conditions; strongly positive or negative correlations between regions imply that these regions are connected functionally [McKeown et al, 1998]. This approach has been applied with some success to studies of schizophrenia [Jacobsen et al, 2004;Jennings et al, 1998;Lawrie et al, 2002;Meyer-Lindenberg et al, 2001;Schlosser et al, 2003]. These studies provide increasing evidence that cognitive dysfunction in schizophrenia may involve not only impaired function of specific neuroanatomical regions, but also impairment in the ability to engage functional networks subserving specific cognitive challenges [e.g., Friston and Frith, 1995].…”

Section: Discussionmentioning

confidence: 99%

Beyond hypofrontality: A quantitative meta‐analysis of functional neuroimaging studies of working memory in schizophrenia

Glahn

Ragland

Abramoff

et al. 2005

Human Brain Mapping

557

393

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Abstract:Although there is considerable evidence that patients with schizophrenia fail to activate the dorsolateral prefrontal cortex (DLPFC) to the degree seen in normal comparison subjects when performing working memory or executive tasks, hypofrontality may be coupled with relatively increased activity in other brain regions. However, most imaging studies of working memory in schizophrenia have focused on DLPFC activity. The goal of this work is to review functional neuroimaging studies that contrasted patients with schizophrenia and healthy comparison subjects during a prototypical working memory task, the n-back paradigm, to highlight areas of hyper-and hypoactivation in schizophrenia. We utilize a quantitative metaanalysis method to review 12 imaging studies where patients with schizophrenia were contrasted with healthy comparison subjects while performing the n-back paradigm. Although we find clear support for hypofrontality, we also document consistently increased activation in anterior cingulate and left frontal pole regions in patients with schizophrenia compared to that in controls. These data suggest that whereas reduced DLPFC activation is reported consistently in patients with schizophrenia relative to healthy subjects, abnormal activation patterns are not restricted to this region, raising questions as to whether the pathophysiological dysfunction in schizophrenia is specific to the DLPFC and about the relationship between impaired performance and aberrant activation patterns. The complex pattern of hyper-and hypoactivation consistently found across studies implies that rather than focusing on DLPFC dysregulation, researchers should consider the entire network of regions involved in a given task when making inferences about the biological mechanisms of schizophrenia. Hum Brain Mapp 25:60 -69, 2005.

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Altered effective connectivity in drug free schizophrenic patients

Cited by 65 publications

References 23 publications

Investigation of Anatomical Thalamo-Cortical Connectivity and fMRI Activation in Schizophrenia

Investigation of Anatomical Thalamo-Cortical Connectivity and fMRI Activation in Schizophrenia

Evidence for the Contribution of NOS1 Gene Polymorphism (rs3782206) to Prefrontal Function in Schizophrenia Patients and Healthy Controls

Beyond hypofrontality: A quantitative meta‐analysis of functional neuroimaging studies of working memory in schizophrenia

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