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      Thalamocortical Anatomical Connectivity in Schizophrenia and Psychotic Bipolar Disorder

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          Abstract

          Background

          Anatomical connectivity between the thalamus and cortex, including the prefrontal cortex (PFC), is abnormal in schizophrenia. Overlapping phenotypes, including deficits in executive cognitive abilities dependent on PFC-thalamic circuitry, suggest dysrupted thalamocortical anatomical connectivity may extend to psychotic bipolar disorder. We tested this hypothesis and examined the impact of illness stage to inform when in the illness course thalamocortical dysconnectivity emerges.

          Methods

          Diffusion-weighted imaging data were collected on 70 healthy individuals and 124 people with a psychotic disorder (schizophrenia spectrum = 75; psychotic bipolar disorder = 49), including 62 individuals in the early stage of psychosis. Anatomical connectivity between major divisions of the cortex and thalamus was quantified using probabilistic tractography and compared between groups. Associations between PFC-thalamic anatomical connectivity and executive cognitive abilities were examined using regression analysis.

          Results

          Psychosis was associated with lower PFC-thalamic and elevated somatosensory-thalamic anatomical connectivity. Follow-up analyses established that lower PFC-thalamic and elevated somatosensory-thalamic anatomical connectivity were present in both schizophrenia and psychotic bipolar disorder. Lower PFC-thalamic anatomical connectivity was also present in early-stage and chronic psychosis. Contrary to expectations, lower PFC-thalamic anatomical connectivity was not associated with impaired executive cognitive abilities.

          Conclusions

          Altered thalamocortical anatomical connectivity, especially reduced PFC-thalamic connectivity, is a transdiagnostic feature of psychosis detectable in the early stage of illness. Further work is required to elucidate the functional consequences of the full spectrum of thalamocortical connectivity abnormalities in psychosis.

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          Most cited references63

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          The unity and diversity of executive functions and their contributions to complex "Frontal Lobe" tasks: a latent variable analysis.

          This individual differences study examined the separability of three often postulated executive functions-mental set shifting ("Shifting"), information updating and monitoring ("Updating"), and inhibition of prepotent responses ("Inhibition")-and their roles in complex "frontal lobe" or "executive" tasks. One hundred thirty-seven college students performed a set of relatively simple experimental tasks that are considered to predominantly tap each target executive function as well as a set of frequently used executive tasks: the Wisconsin Card Sorting Test (WCST), Tower of Hanoi (TOH), random number generation (RNG), operation span, and dual tasking. Confirmatory factor analysis indicated that the three target executive functions are moderately correlated with one another, but are clearly separable. Moreover, structural equation modeling suggested that the three functions contribute differentially to performance on complex executive tasks. Specifically, WCST performance was related most strongly to Shifting, TOH to Inhibition, RNG to Inhibition and Updating, and operation span to Updating. Dual task performance was not related to any of the three target functions. These results suggest that it is important to recognize both the unity and diversity of executive functions and that latent variable analysis is a useful approach to studying the organization and roles of executive functions. Copyright 2000 Academic Press.
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            Probabilistic diffusion tractography with multiple fibre orientations: What can we gain?

            We present a direct extension of probabilistic diffusion tractography to the case of multiple fibre orientations. Using automatic relevance determination, we are able to perform online selection of the number of fibre orientations supported by the data at each voxel, simplifying the problem of tracking in a multi-orientation field. We then apply the identical probabilistic algorithm to tractography in the multi- and single-fibre cases in a number of example systems which have previously been tracked successfully or unsuccessfully with single-fibre tractography. We show that multi-fibre tractography offers significant advantages in sensitivity when tracking non-dominant fibre populations, but does not dramatically change tractography results for the dominant pathways.
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              Subcortical brain volume abnormalities in 2028 individuals with schizophrenia and 2540 healthy controls via the ENIGMA consortium

              The profile of brain structural abnormalities in schizophrenia is still not fully understood, despite decades of research using brain scans. To validate a prospective meta-analysis approach to analyzing multicenter neuroimaging data, we analyzed brain MRI scans from 2028 schizophrenia patients and 2540 healthy controls, assessed with standardized methods at 15 centers worldwide. We identified subcortical brain volumes that differentiated patients from controls, and ranked them according to their effect sizes. Compared with healthy controls, patients with schizophrenia had smaller hippocampus (Cohen's d=−0.46), amygdala (d=−0.31), thalamus (d=−0.31), accumbens (d=−0.25) and intracranial volumes (d=−0.12), as well as larger pallidum (d=0.21) and lateral ventricle volumes (d=0.37). Putamen and pallidum volume augmentations were positively associated with duration of illness and hippocampal deficits scaled with the proportion of unmedicated patients. Worldwide cooperative analyses of brain imaging data support a profile of subcortical abnormalities in schizophrenia, which is consistent with that based on traditional meta-analytic approaches. This first ENIGMA Schizophrenia Working Group study validates that collaborative data analyses can readily be used across brain phenotypes and disorders and encourages analysis and data sharing efforts to further our understanding of severe mental illness.
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                Author and article information

                Journal
                Schizophrenia Bulletin
                Oxford University Press (OUP)
                0586-7614
                1745-1701
                September 2020
                September 21 2020
                March 27 2020
                September 2020
                September 21 2020
                March 27 2020
                : 46
                : 5
                : 1062-1071
                Affiliations
                [1 ]Department of Psychiatry and Behavioral Sciences, Vanderbilt University School of Medicine, Nashville, TN
                [2 ]Vanderbilt University Institute of Imaging Science, Nashville, TN
                [3 ]Medical College of Wisconsin, Wauwatosa, WI
                [4 ]Vanderbilt University School of Engineering, Nashville, TN
                [5 ]Research and Development, Department of Veterans Affairs Medical Center, Nashville, TN
                Article
                10.1093/schbul/sbaa022
                7505173
                32219397
                5cd379e5-fdea-4c8b-bb5d-f8faf71198df
                © 2020

                https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model

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