Regionally specific disturbance of dorsolateral prefrontal-hippocampal functional connectivity in schizophrenia.
BACKGROUND
Two brain regions often implicated in schizophrenia are the dorsolateral prefrontal cortex (DLPFC) and the hippocampal formation (HF). It has been hypothesized that the pathophysiology of the disorder might involve an alteration of functional interactions between medial temporal and prefrontal areas.


METHODS
We used neuroimaging data acquired during a working memory challenge and a sensorimotor control task in 22 medication-free schizophrenic patients and 22 performance-, age-, and sex-matched healthy subjects to investigate "functional connectivity" between HF and DLPFC in schizophrenia. The HF blood flow, measured with positron emission tomography, was assessed within a probabilistic template. Brain areas whose activity was positively or negatively coupled to HF were identified using voxelwise analysis of covariance throughout the entire brain and analyzed using a random effects model.


RESULTS
During working memory, patients showed reduced activation of the right DLPFC and left cerebellum. In both groups, inverse correlations were observed between the HF and the contralateral DLPFC and inferior parietal lobule. While these did not differ between diagnostic groups during the control task, the working memory challenge revealed a specific abnormality in DLPFC-HF functional connectivity-while the right DLPFC was significantly coupled to the left HF in both groups during the control task, this correlation was not seen in healthy subjects during working memory but persisted undiminished in patients, resulting in a significant task-by-group interaction.


CONCLUSIONS
Our results suggest a regionally specific alteration of HF-DLPFC functional connectivity in schizophrenia that manifests as an unmodulated persistence of an HF-DLPFC linkage during working memory activation. Thus, a mechanism by which HF dysfunction may manifest in schizophrenia is by inappropriate reciprocal modulatory interaction with the DLPFC.
Meyer-Lindenberg
Andreas S
AS
Unit on Integrative Neuroimaging, National Institute of Mental Health, 9000 Rockville Pike, Bethesda, MD 20892, USA. andreasml@nih.gov
Olsen
Rosanna K
RK
Kohn
Philip D
PD
Brown
Timothy
T
Egan
Michael F
MF
Weinberger
Daniel R
DR
Berman
Karen Faith
KF
D000328:Adult; D001931:Brain Mapping; D005260:Female; D007839:Functional Laterality / Q000502:physiology; D006624:Hippocampus / Q000098:blood supply / Q000000981:diagnostic imaging / Q000503:physiopathology*; D006801:Humans; D008297:Male; D009434:Neural Pathways / Q000098:blood supply / Q000000981:diagnostic imaging / Q000503:physiopathology; D010104:Oxygen Radioisotopes; D049268:Positron-Emission Tomography; D017397:Prefrontal Cortex / Q000098:blood supply / Q000000981:diagnostic imaging / Q000503:physiopathology*; D011597:Psychomotor Performance / Q000502:physiology; D012039:Regional Blood Flow / Q000502:physiology; D012559:Schizophrenia / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000503:physiopathology*; D014867:Water
D010104:Oxygen Radioisotopes; D014867:Water