Prefrontal broadband noise, working memory, and genetic risk for schizophrenia.
OBJECTIVE
It has been suggested that increased variability of prefrontal physiological responses may represent a fundamental mechanism underlying frontal lobe deficits in schizophrenia. Increased response variability ("noise") is thought to result from impaired phase resetting of stimulus-induced dynamic changes of ongoing rhythmic oscillations (field potentials) generated in the apical dendrites of pyramidal neurons. In the present study, the authors explored whether this particular physiological abnormality predicts working memory performance and is related to the genetic risk for schizophrenia.


METHODS
Prefrontal response variability of discrete frequency components was investigated across a broad frequency range (0.5-45.0 Hz) during processing of an oddball paradigm in patients with schizophrenia (N=66), their clinically unaffected siblings (N=115), and healthy comparison subjects (N=89).


RESULTS
As hypothesized, prefrontal noise was negatively correlated with working memory performance across all subjects. In addition, it was observed that prefrontal noise possesses trait characteristics and is strongly associated with genetic risk for schizophrenia.


CONCLUSIONS
Frontal lobe-related cognitive function depends on the ability to synchronize cortical pyramidal neurons, which is in part genetically controlled. Increased prefrontal "noise" is an intermediate phenotype related to genetic susceptibility for schizophrenia.
Winterer
Georg
G
Clinical Brain Disorders Branch, National Institute of Mental Health, Bethesda, MD 20892, USA. wintereg@intra.nimh.nih.gov
Coppola
Richard
R
Goldberg
Terry E
TE
Egan
Michael F
MF
Jones
Douglas W
DW
Sanchez
Carmen E
CE
Weinberger
Daniel R
DR
D000328:Adult; D001143:Arousal / Q000502:physiology*; D001288:Attention / Q000502:physiology*; D001931:Brain Mapping; D002540:Cerebral Cortex / Q000503:physiopathology; D004569:Electroencephalography; D005071:Evoked Potentials / Q000235:genetics / Q000502:physiology; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D008297:Male; D008570:Memory, Short-Term / Q000502:physiology*; D008875:Middle Aged; D008957:Models, Genetic; D009483:Neuropsychological Tests; D010897:Pitch Discrimination / Q000502:physiology; D017397:Prefrontal Cortex / Q000503:physiopathology*; D011594:Psychometrics; D017966:Pyramidal Cells / Q000502:physiology; D012016:Reference Values; D018570:Risk Assessment; D012559:Schizophrenia / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D012565:Schizophrenic Psychology; D012569:Schizotypal Personality Disorder / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology / Q000523:psychology; D035781:Siblings / Q000523:psychology; D012815:Signal Processing, Computer-Assisted