Working memory and default mode network abnormalities in unaffected siblings of schizophrenia patients.
BACKGROUND
Impaired working memory (WM) is a hallmark of schizophrenia. In addition to classical WM regions such as the dorsolateral prefrontal cortex (DLPFC) and the striatum, dysfunctions in the default-mode network (DMN) contribute to these WM deficits. Unaffected siblings of patients also show WM impairments. However, the nature of the functional deficits underlying these impairments is unclear, mainly because of impaired performance confounding neuroimaging results.


METHODS
Here, we investigated WM and DMN activity in 23 unaffected siblings of schizophrenia patients and 24 healthy volunteers using fMRI and a Sternberg WM task. WM load was determined prior to scanning to ensure 90% accuracy for all subjects.


RESULTS
Siblings showed hyperactivation during the encoding phase of WM in the right medial prefrontal cortex (MPFC) which is the anterior part of the DMN. No differences were found during the maintenance phase. During the retrieval phase, siblings showed hyperactivation in WM regions: DLPFC, inferior parietal cortex and the striatum. Siblings who showed hyperactivity in the MPFC during encoding showed DLPFC and striatum hyperactivation during retrieval.


CONCLUSIONS
Our finding of hyperactivation in WM and DMN areas indicates that siblings fail to adequately inhibit DMN activity during demanding cognitive tasks and subsequently hyperactivate WM areas. This failure may reflect dopamine hyperactivity in the striatum which prevents adequate DMN suppression needed for effective WM. This study provides support for the notion that aberrant WM and DMN activation patterns may represent candidate endophenotypes for schizophrenia.
Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht, Utrecht, the Netherlands. Electronic address: mleeuw5@umcutrecht.nl.
Max
M
de Leeuw
René S
RS
Kahn
Bram B
BB
Zandbelt
Christian G
CG
Widschwendter
Matthijs
M
Vink
D000328:Adult; D001931:Brain Mapping; D003342:Corpus Striatum / Q000473:pathology*; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008569:Memory Disorders / Q000209:etiology*; D008570:Memory, Short-Term / Q000502:physiology*; D011939:Mental Recall / Q000502:physiology; D008959:Models, Neurological; D009434:Neural Pathways / Q000473:pathology; D009483:Neuropsychological Tests; D017397:Prefrontal Cortex / Q000473:pathology*; D012559:Schizophrenia / Q000150:complications*; D012565:Schizophrenic Psychology; D035781:Siblings; D055815:Young Adult
DLPFC; Default Mode Network; Schizophrenia; Siblings; Working memory