The neural correlates of performance in adolescents at risk for schizophrenia: inefficiently increased cortico-striatal responses measured with fMRI.
BACKGROUND
fMRI studies indicate that schizophrenia patients and their adult relatives require greater prefrontal activation to maintain performance at levels equal to controls, but studies have not established if this pattern of inefficiency is observed in child and adolescent offspring of schizophrenia patients (SCZ-Off).


METHODS
Using a task with visual working memory demands, we investigated activation in cortico-striatal networks and dorsal prefrontal modulation of regions underlying visual working memory in a group of SCZ-Off (n = 19) and controls with no family history of psychosis (n = 25 subjects) using an event-related design. Trials were divided based on memory performance (correct vs. incorrect) to specifically identify the neural correlates of correct working memory performance.


RESULTS
Whereas groups did not differ in terms of behavioral accuracy, SCZ-Off demonstrated significantly increased fMRI-measured activation in dorsal prefrontal cortex and the caudate nucleus during correct, relative to incorrect memory performance. Whereas activation in SCZ-Off was high and independent of performance in each region, in controls the fMRI response was related to behavioral proficiency in the caudate. Further, exploratory analyses indicated that this inefficiency in the dorsal prefrontal cortex response increased with age in SCZ-Off (but in no other regions or group). Finally, these differences were not based in differences in dorsal prefrontal modulation of other regions during successful performance.


CONCLUSIONS
These results are consistent with observed patterns in adult patients and first-degree relatives. Inefficient fronto-striatal responses during working memory may characterize the schizophrenia diathesis and may reflect the effects of the illness and vulnerability for the illness.
Department of Psychiatry & Behavioral Neuroscience, Wayne State University SOM, MI 48201, USA. vdiwadka@med.wayne.edu
Vaibhav A
VA
Diwadkar
Patrick
P
Pruitt
Allison
A
Zhang
Jacqueline
J
Radwan
Matcheri S
MS
Keshavan
Eric
E
Murphy
Usha
U
Rajan
Caroline
C
Zajac-Benitez
D000293:Adolescent; D001931:Brain Mapping; D016022:Case-Control Studies; D002540:Cerebral Cortex / Q000098:blood supply* / Q000473:pathology; D002648:Child; D016241:Child of Impaired Parents / Q000523:psychology; D003342:Corpus Striatum / Q000098:blood supply* / Q000473:pathology; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008569:Memory Disorders / Q000209:etiology*; D009483:Neuropsychological Tests; D010100:Oxygen; D010364:Pattern Recognition, Visual / Q000502:physiology; D010775:Photic Stimulation; D011930:Reaction Time / Q000502:physiology; D012559:Schizophrenia / Q000150:complications / Q000235:genetics / Q000473:pathology
D010100:Oxygen