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Cereb Cortex. 2014 Dec;24(12):3116-30. doi: 10.1093/cercor/bht165. Epub 2013 Jul 3.

Characterizing thalamo-cortical disturbances in schizophrenia and bipolar illness.

Author information

1
Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06511, USA NIAAA Center for the Translational Neuroscience of Alcoholism, New Haven, CT 06519, USA Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, New Haven, CT 06519, USA.
2
Department of Psychology, Washington University in St. Louis, St. Louis, MO 63130, USA.
3
Department of Psychology, University of Ljubljana, Ljubljana, Slovenia.
4
Department of Neurobiology, Department of Physics, Yale University, New Haven, CT 06510, USA.
5
Olin Neuropsychiatry Research Center, Institute of Living, Hartford Hospital, CT 06106, USA.
6
Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06511, USA Olin Neuropsychiatry Research Center, Institute of Living, Hartford Hospital, CT 06106, USA Oxford University, John Radcliffe Hospital, Headington, Oxford OX3 9DU, UK and.
7
Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06511, USA Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, New Haven, CT 06519, USA University Psychiatric Hospital Vrapce, University of Zagreb, Zagreb 10000, Croatia.
8
Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06511, USA Department of Neurobiology, Olin Neuropsychiatry Research Center, Institute of Living, Hartford Hospital, CT 06106, USA.
9
Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06511, USA Olin Neuropsychiatry Research Center, Institute of Living, Hartford Hospital, CT 06106, USA.

Abstract

Schizophrenia is a devastating neuropsychiatric syndrome associated with distributed brain dysconnectivity that may involve large-scale thalamo-cortical systems. Incomplete characterization of thalamic connectivity in schizophrenia limits our understanding of its relationship to symptoms and to diagnoses with shared clinical presentation, such as bipolar illness, which may exist on a spectrum. Using resting-state functional magnetic resonance imaging, we characterized thalamic connectivity in 90 schizophrenia patients versus 90 matched controls via: (1) Subject-specific anatomically defined thalamic seeds; (2) anatomical and data-driven clustering to assay within-thalamus dysconnectivity; and (3) machine learning to classify diagnostic membership via thalamic connectivity for schizophrenia and for 47 bipolar patients and 47 matched controls. Schizophrenia analyses revealed functionally related disturbances: Thalamic over-connectivity with bilateral sensory-motor cortices, which predicted symptoms, but thalamic under-connectivity with prefrontal-striatal-cerebellar regions relative to controls, possibly reflective of sensory gating and top-down control disturbances. Clustering revealed that this dysconnectivity was prominent for thalamic nuclei densely connected with the prefrontal cortex. Classification and cross-diagnostic results suggest that thalamic dysconnectivity may be a neural marker for disturbances across diagnoses. Present findings, using one of the largest schizophrenia and bipolar neuroimaging samples to date, inform basic understanding of large-scale thalamo-cortical systems and provide vital clues about the complex nature of its disturbances in severe mental illness.

KEYWORDS:

bipolar illness; connectivity; resting state; schizophrenia; thalamus

PMID:
23825317
PMCID:
PMC4224238
DOI:
10.1093/cercor/bht165
[Indexed for MEDLINE]
Free PMC Article
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