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Resting-state thalamic dysconnectivity in schizophrenia and relationships with symptoms

Published online by Cambridge University Press:  15 February 2018

J. Ferri ,
J. M. Ford ,
B. J. Roach ,
J. A. Turner ,
T. G. van Erp ,
J. Voyvodic ,
A. Preda ,
A. Belger ,
J. Bustillo  and
D. O'Leary
...Show all authors
J. Ferri
Affiliation:
Department of Psychiatry, University of California, San Francisco, San Francisco, CA, USA San Francisco VA Health Care System, San Francisco, CA, USA
J. M. Ford
Affiliation:
Department of Psychiatry, University of California, San Francisco, San Francisco, CA, USA San Francisco VA Health Care System, San Francisco, CA, USA
B. J. Roach
Affiliation:
San Francisco VA Health Care System, San Francisco, CA, USA
J. A. Turner
Affiliation:
The Mind Research Network, Albuquerque, NM, USA
T. G. van Erp
Affiliation:
Department of Psychiatry and Human Behavior, University of California, Irvine, Irvine, CA, USA
J. Voyvodic
Affiliation:
Department of Psychiatry, Duke University, Raleigh-Durham, NC, USA
A. Preda
Affiliation:
Department of Psychiatry and Human Behavior, University of California, Irvine, Irvine, CA, USA
A. Belger
Affiliation:
Department of Psychiatry, University of North Carolina, Chapel Hill, NC, USA
J. Bustillo
Affiliation:
Department of Psychiatry, University of New Mexico, Albuquerque, NM, USA
D. O'Leary
Affiliation:
Department of Psychiatry, University of Iowa, Iowa City, IA, USA
B. A. Mueller
Affiliation:
Department of Psychiatry, University of Minnesota, Minneapolis, MN, USA
K. O. Lim
Affiliation:
Department of Psychiatry, University of Minnesota, Minneapolis, MN, USA
S. C. McEwen
Affiliation:
Department of Psychiatry, University of California, Los Angeles, Los Angeles, CA, USA
V. D. Calhoun
Affiliation:
The Mind Research Network, Albuquerque, NM, USA Department of Psychiatry, University of New Mexico, Albuquerque, NM, USA Department of Electrical and Computer Engineering, University of New Mexico, Albuquerque, NM, USA
M. Diaz
Affiliation:
Department of Psychiatry, Duke University, Raleigh-Durham, NC, USA
G. Glover
Affiliation:
Department of Radiology, Stanford University, Stanford, CA, USA
D. Greve
Affiliation:
Department of Radiology, Massachusetts General Hospital, Boston, MA, USA
C. G. Wible
Affiliation:
Department of Psychiatry, Harvard University, Boston, MA, USA VA Boston Healthcare System, Brockton, MA, USA
J. G. Vaidya
Affiliation:
Department of Psychiatry, University of Iowa, Iowa City, IA, USA
S. G. Potkin
Affiliation:
Department of Psychiatry and Human Behavior, University of California, Irvine, Irvine, CA, USA
D. H. Mathalon*
Affiliation:
Department of Psychiatry, University of California, San Francisco, San Francisco, CA, USA San Francisco VA Health Care System, San Francisco, CA, USA
*
Author for correspondence: D. H. Mathalon, E-mail: [email protected]
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Abstract

Background

Schizophrenia (SZ) is a severe neuropsychiatric disorder associated with disrupted connectivity within the thalamic-cortico-cerebellar network. Resting-state functional connectivity studies have reported thalamic hypoconnectivity with the cerebellum and prefrontal cortex as well as thalamic hyperconnectivity with sensory cortical regions in SZ patients compared with healthy comparison participants (HCs). However, fundamental questions remain regarding the clinical significance of these connectivity abnormalities.

Method

Resting state seed-based functional connectivity was used to investigate thalamus to whole brain connectivity using multi-site data including 183 SZ patients and 178 matched HCs. Statistical significance was based on a voxel-level FWE-corrected height threshold of p < 0.001. The relationships between positive and negative symptoms of SZ and regions of the brain demonstrating group differences in thalamic connectivity were examined.

Results

HC and SZ participants both demonstrated widespread positive connectivity between the thalamus and cortical regions. Compared with HCs, SZ patients had reduced thalamic connectivity with bilateral cerebellum and anterior cingulate cortex. In contrast, SZ patients had greater thalamic connectivity with multiple sensory-motor regions, including bilateral pre- and post-central gyrus, middle/inferior occipital gyrus, and middle/superior temporal gyrus. Thalamus to middle temporal gyrus connectivity was positively correlated with hallucinations and delusions, while thalamus to cerebellar connectivity was negatively correlated with delusions and bizarre behavior.

Conclusions

Thalamic hyperconnectivity with sensory regions and hypoconnectivity with cerebellar regions in combination with their relationship to clinical features of SZ suggest that thalamic dysconnectivity may be a core neurobiological feature of SZ that underpins positive symptoms.

Keywords

Thalamusresting-state fMRIschizophreniaconnectivity
Type
Original Articles
Information
Psychological Medicine , Volume 48 , Issue 15 , November 2018 , pp. 2492 - 2499
Copyright
Copyright © Cambridge University Press 2018 

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