Cerebral Inefficient Activation in Schizophrenia Patients and Their Unaffected Parents during the N-Back Working Memory Task: A Family fMRI Study.
BACKGROUND
It has been suggested that working memory deficits is a core feature of symptomatology of schizophrenia, which can be detected in patients and their unaffected relatives. The impairment of working memory has been found related to the abnormal activity of human brain regions in many functional magnetic resonance imaging (fMRI) studies. This study investigated how brain region activation was altered in schizophrenia and how it was inherited independently from performance deficits.


METHODS
The authors used fMRI method during N-back task to assess working memory related cortical activation in four groups (N = 20 in each group, matching task performance, age, gender and education): schizophrenic patients, their unaffected biological parents, young healthy controls for the patients and older healthy controls for their parents.


RESULTS
Compared to healthy controls, patients showed an exaggerated response in the right dorsolateral prefrontal cortex (brodmann area [BA] 46) and bilateral ventrolateral prefrontal cortex, and had reduced activation in bilateral dorsolateral prefrontal cortex (BA 9). In the conjunction analysis, the effect of genetic risk (parents versus older control) shared significantly overlapped activation with effect of disease (patients versus young control) in the right middle frontal gyrus (BA 46) and left inferior parietal gyrus (BA 40).


CONCLUSIONS
Physiological inefficiency of dorsal prefrontal cortex and compensation involvement of ventral prefrontal cortex in working memory function may one physiological characteristics of schizophrenia. And relatively inefficient activation in dorsolateral prefrontal cortex probably can be a promising intermediate phenotype for schizophrenia.
Peking University Sixth Hospital, Beijing, 100191, China; Peking University Institute of Mental Health, Beijing,100191, China; Key Laboratory of Mental Health, Ministry of Health (Peking University), Beijing, 100191, China.
Sisi
S
Jiang
Peking University Sixth Hospital, Beijing, 100191, China; Peking University Institute of Mental Health, Beijing,100191, China; Key Laboratory of Mental Health, Ministry of Health (Peking University), Beijing, 100191, China.
Hao
H
Yan
Lieber Institute for Brain Development, Baltimore, Maryland, United States of America.
Qiang
Q
Chen
Peking University Sixth Hospital, Beijing, 100191, China; Peking University Institute of Mental Health, Beijing,100191, China; Key Laboratory of Mental Health, Ministry of Health (Peking University), Beijing, 100191, China.
Lin
L
Tian
Peking University Sixth Hospital, Beijing, 100191, China; Peking University Institute of Mental Health, Beijing,100191, China; Key Laboratory of Mental Health, Ministry of Health (Peking University), Beijing, 100191, China.
Tianlan
T
Lu
Lieber Institute for Brain Development, Baltimore, Maryland, United States of America; Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
Hao-Yang
HY
Tan
Peking University Sixth Hospital, Beijing, 100191, China; Peking University Institute of Mental Health, Beijing,100191, China; Key Laboratory of Mental Health, Ministry of Health (Peking University), Beijing, 100191, China.
Jun
J
Yan
Peking University Sixth Hospital, Beijing, 100191, China; Peking University Institute of Mental Health, Beijing,100191, China; Key Laboratory of Mental Health, Ministry of Health (Peking University), Beijing, 100191, China; School of Life Sciences, Tsinghua University, Beijing, 100084, China; Peking University-Tsinghua University Joint Center for Life Sciences, Beijing, 100871, China; PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, China.
Dai
D
Zhang
D000328:Adult; D001931:Brain Mapping / Q000379:methods; D002681:China / Q000208:ethnology; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008570:Memory, Short-Term / Q000502:physiology*; D008875:Middle Aged; D010290:Parents / Q000523:psychology*; D017397:Prefrontal Cortex / Q000503:physiopathology*; D012307:Risk Factors; D012559:Schizophrenia / Q000208:ethnology / Q000503:physiopathology*; D012565:Schizophrenic Psychology; D055815:Young Adult