Disturbed functional connectivity within brain networks subserving domain-specific subcomponents of working memory in schizophrenia: relation to performance and clinical symptoms.
BACKGROUND
Disturbed interregional functional connectivity has been hypothesized to be a promising marker of schizophrenia. The relationship between working memory (WM) impairment, disturbed functional connectivity, and the characteristic symptoms of schizophrenia, however, remains elusive.


METHODS
We used functional MRI (fMRI) to investigate in patients with schizophrenia and matched controls the patterns of functional connectivity during the performance of different tasks selectively engaging subcomponent processes of working memory.


RESULTS
Compared with controls, patients showed reduced connectivity of the prefrontal cortex with the intraparietal cortex and the hippocampus and abnormal negative interactions between the ventrolateral and dorsolateral prefrontal cortex during the non-articulatory maintenance of phonological information. During the maintenance of visuospatial information, patients presented reduced connectivity between regions in the superior parietal and occipital cortex, as well as enhanced positive connectivity of the frontal eye field with visual processing areas.


CONCLUSIONS
Our findings suggest complex dysregulations within the networks supporting working memory functions in schizophrenia, which manifest as decreased positive and abnormal negative interactions. Correlations between the connection strength and WM performance suggest that these dysregulations may be neurofunctional correlates of the WM deficits seen in schizophrenia. Altered prefronto-hippocampal and parieto-occipital connectivity was further found to be associated with higher positive symptoms, providing a possible explanation for the development of delusions and disorganization symptoms.


CONCLUSIONS
The present findings can help to better understand the relationship between altered patterns of synchronized brain activity and the cognitive and clinical symptoms of schizophrenia.
Henseler
Ilona
I
Centre for Translational Research in Systems Neuroscience and Clinical Psychiatry, Department of Psychiatry and Psychotherapy, Georg August University, D-37075 Goettingen, Germany. ihensel@gwdg.de
Falkai
Peter
P
Gruber
Oliver
O
D000328:Adult; D001921:Brain / Q000503:physiopathology*; D016022:Case-Control Studies; D039721:Diagnostic and Statistical Manual of Mental Disorders; D005260:Female; D007839:Functional Laterality; D006624:Hippocampus / Q000503:physiopathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008570:Memory, Short-Term; D009415:Nerve Net / Q000503:physiopathology; D009434:Neural Pathways / Q000503:physiopathology*; D009483:Neuropsychological Tests; D009778:Occipital Lobe / Q000503:physiopathology; D010296:Parietal Lobe / Q000503:physiopathology; D010364:Pattern Recognition, Visual; D017397:Prefrontal Cortex / Q000503:physiopathology; D011597:Psychomotor Performance; D012559:Schizophrenia / Q000175:diagnosis / Q000503:physiopathology*; D012565:Schizophrenic Psychology; D013037:Spatial Behavior; D014705:Verbal Behavior