Clinical symptoms and alpha band resting-state functional connectivity imaging in patients with schizophrenia: Implications for novel approaches to treatment

Leighton B N Hinkley, Sophia Vinogradov, Adrian G. Guggisberg, Melissa Fisher, Anne M. Findlay, Srikantan S. Nagarajan

Research output: Contribution to journalArticlepeer-review

81 Scopus citations


Background: Schizophrenia (SZ) is associated with functional decoupling between cortical regions, but we do not know whether and where this occurs in low-frequency electromagnetic oscillations. The goal of this study was to use magnetoencephalography (MEG) to identify brain regions that exhibit abnormal resting-state connectivity in the alpha frequency range in patients with schizophrenia and investigate associations between functional connectivity and clinical symptoms in stable outpatient participants. Methods: Thirty patients with SZ and 15 healthy comparison participants were scanned in resting-state MEG (eyes closed). Functional connectivity MEG source data were reconstructed globally in the alpha range, quantified by the mean imaginary coherence between a voxel and the rest of the brain. Results: In patients, decreased connectivity was observed in left prefrontal cortex (PFC) and right superior temporal cortex, whereas increased connectivity was observed in left extrastriate cortex and the right inferior PFC. Functional connectivity of left inferior parietal cortex was negatively related to positive symptoms. Low left PFC connectivity was associated with negative symptoms. Functional connectivity of midline PFC was negatively correlated with depressed symptoms. Functional connectivity of right PFC was associated with other (cognitive) symptoms. Conclusions: This study demonstrates direct functional disconnection in SZ between specific cortical fields within low-frequency resting-state oscillations. Impaired alpha coupling in frontal, parietal, and temporal regions is associated with clinical symptoms in these stable outpatients. Our findings indicate that this level of functional disconnection between cortical regions is an important treatment target in SZ.

Original languageEnglish (US)
Pages (from-to)1134-1142
Number of pages9
JournalBiological psychiatry
Issue number12
StatePublished - Dec 15 2011

Bibliographical note

Funding Information:
This work was supported by the San Francisco VA Medical Center, the National Institutes of Health (NIH) ( R01 MH068725-01A1 to SV, R01 Grants DC004855 , DC006435 , DC10145 , and NS67962 and National Science Foundation Grant BCS 926196 to SSN), the NIH/National Center for Research Resources (UCSF-CTSI UL1 RR024131 to SSN), the Dystonia Medical Research Foundation (to LBNH), and UCSF/REAC Grants (to SSN). The contents of this study are solely the responsibility of the authors and do not necessarily represent the official views of the NIH.


  • Functional connectivity
  • magnetoencephalography
  • neuroimaging
  • resting-state
  • schizophrenia
  • symptoms

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