PMID- 19164577
OWN - NLM
STAT- MEDLINE
DCOM- 20090213
LR  - 20240322
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 106
IP  - 4
DP  - 2009 Jan 27
TI  - Hyperactivity and hyperconnectivity of the default network in schizophrenia and 
      in first-degree relatives of persons with schizophrenia.
PG  - 1279-84
LID - 10.1073/pnas.0809141106 [doi]
AB  - We examined the status of the neural network mediating the default mode of brain 
      function, which typically exhibits greater activation during rest than during 
      task, in patients in the early phase of schizophrenia and in young first-degree 
      relatives of persons with schizophrenia. During functional MRI, patients, 
      relatives, and controls alternated between rest and performance of working memory 
      (WM) tasks. As expected, controls exhibited task-related suppression of 
      activation in the default network, including medial prefrontal cortex (MPFC) and 
      posterior cingulate cortex/precuneus. Patients and relatives exhibited 
      significantly reduced task-related suppression in MPFC, and these reductions 
      remained after controlling for performance. Increased task-related MPFC 
      suppression correlated with better WM performance in patients and relatives and 
      with less psychopathology in all 3 groups. For WM task performance, patients and 
      relatives had greater activation in right dorsolateral prefrontal cortex (DLPFC) 
      than controls. During rest and task, patients and relatives exhibited abnormally 
      high functional connectivity within the default network. The magnitudes of 
      default network connectivity during rest and task correlated with psychopathology 
      in the patients. Further, during both rest and task, patients exhibited reduced 
      anticorrelations between MPFC and DLPFC, a region that was hyperactivated by 
      patients and relatives during WM performance. Among patients, the magnitude of 
      MPFC task suppression negatively correlated with default connectivity, suggesting 
      an association between the hyperactivation and hyperconnectivity in 
      schizophrenia. Hyperactivation (reduced task-related suppression) of default 
      regions and hyperconnectivity of the default network may contribute to 
      disturbances of thought in schizophrenia and risk for the illness.
FAU - Whitfield-Gabrieli, Susan
AU  - Whitfield-Gabrieli S
AD  - Department of Brain and Cognitive Sciences, Massachusetts Institute of 
      Technology, Cambridge, MA 02139, USA. swg@mit.edu
FAU - Thermenos, Heidi W
AU  - Thermenos HW
FAU - Milanovic, Snezana
AU  - Milanovic S
FAU - Tsuang, Ming T
AU  - Tsuang MT
FAU - Faraone, Stephen V
AU  - Faraone SV
FAU - McCarley, Robert W
AU  - McCarley RW
FAU - Shenton, Martha E
AU  - Shenton ME
FAU - Green, Alan I
AU  - Green AI
FAU - Nieto-Castanon, Alfonso
AU  - Nieto-Castanon A
FAU - LaViolette, Peter
AU  - LaViolette P
FAU - Wojcik, Joanne
AU  - Wojcik J
FAU - Gabrieli, John D E
AU  - Gabrieli JD
FAU - Seidman, Larry J
AU  - Seidman LJ
LA  - eng
GR  - R01 MH040799/MH/NIMH NIH HHS/United States
GR  - R01 MH043518/MH/NIMH NIH HHS/United States
GR  - R01 MH063951/MH/NIMH NIH HHS/United States
GR  - R01 MH050740/MH/NIMH NIH HHS/United States
GR  - R21 MH062157/MH/NIMH NIH HHS/United States
GR  - MH 50740/MH/NIMH NIH HHS/United States
GR  - P41 RR014075/RR/NCRR NIH HHS/United States
GR  - P41RR14075/RR/NCRR NIH HHS/United States
GR  - R37 MH043518/MH/NIMH NIH HHS/United States
GR  - MH 65562/MH/NIMH NIH HHS/United States
GR  - MH 40799/MH/NIMH NIH HHS/United States
GR  - R01 MH065562/MH/NIMH NIH HHS/United States
GR  - R25 MH 60485/MH/NIMH NIH HHS/United States
GR  - MH 62157/MH/NIMH NIH HHS/United States
GR  - MH 43518/MH/NIMH NIH HHS/United States
GR  - MH 63951/MH/NIMH NIH HHS/United States
GR  - R25 MH060485/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20090121
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
SB  - IM
EIN - Proc Natl Acad Sci U S A. 2009 Mar 17;106(11):4572
MH  - *Brain Mapping
MH  - Family/*psychology
MH  - Humans
MH  - Memory
MH  - Nerve Net/*physiopathology
MH  - Rest
MH  - Schizophrenia/*physiopathology
MH  - Schizophrenic Psychology
MH  - Task Performance and Analysis
PMC - PMC2633557
COIS- The authors declare no conflict of interest.
EDAT- 2009/01/24 09:00
MHDA- 2009/02/14 09:00
PMCR- 2009/07/27
CRDT- 2009/01/24 09:00
PHST- 2009/01/24 09:00 [entrez]
PHST- 2009/01/24 09:00 [pubmed]
PHST- 2009/02/14 09:00 [medline]
PHST- 2009/07/27 00:00 [pmc-release]
AID - 0809141106 [pii]
AID - 6431 [pii]
AID - 10.1073/pnas.0809141106 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2009 Jan 27;106(4):1279-84. doi: 
      10.1073/pnas.0809141106. Epub 2009 Jan 21.