Relationship of Prefrontal and Temporal Lobe MRI Measures to Neuropsychological Performance in Chronic Schizophrenia Larry J. Seidman, Deborah Yurgelun-Todd, William S. Kremen, Bryan T. Woods, Jill M. Goldstein, Stephen V. Faraone, and Ming T. Tsuang i iii This preliminary study focused on the relationship between prefrontal and temporal lobe MR! measures and neuropsychological performance in chronic schizophrenia• Seventeen schizo- phrenic inpatients received an MR! and a neuropsychological test battery after clinical stabiliza- tion, on average 2 months after admission. The central finding was a significant inverse correla- tion between neurocognitive measures of prefrontal function and dorsolateral prefrontal cortex (DLPFC) area, strongest in the left hemisphere. Neurocognitive performance did not correlate significantly with orbital frontal area or total temporal lobe volume. The correlations of neurop- sychological performance with total frontal volume and whole brain volume were generally not significant, although the pattern was similar to that associated with the DLPFC. Because a number of executive-attention and abstraction measures were significantly associated with the DLPFC, dysfunctions of this region may underlie a syndrome of cognitive dysfunctions. Long- term memory functions were also significantly correlated with the DLPFC, raising the possibility that recall memory defects in schizophrenia are, in part, associated with prefrontal contributions of attention, abstract reasoning, and executive function. This study needs replication with a larger sample of patients and more comprehensive volumetric morphometric analyses. Key Words: Dorsolateral, orbital prefrontal, MRI. neuropsychology, schizophrenia From the Neuropsychology Laboratory, Clinical Psychology Service, Department of Psychiatry, Harvard Medical School, Massachusetts Mental Health Center. Bos- ton, MA (US, JMG); Department of Psychiatry, Harvard Medical School at the Brockton-West Roxbury VA Medical Center, Brockton, MA, and the Massachu- setts Mental Health Center, Boston, MA (US, WSK, JMG. SVF. MTi'), Depart. meat of Epidemiology, Harvard School of Public Health, Boston. MA (MTr): Department of Psychiatry, Harvard Medical School, McLean Hospital. Belmont. MA (DY-T). Department of Neurology. Harvard Medical School. Brain Imaging Center and Mailman Research Center, McLean Hospital. Belmont. MA (DY-T); Department of Medicine• VA Medical Center. Temple. TX (BTW). Address reprint requests to Larry J. Seidman. PhD. Neuropsychology Laboratory. Massachusetts Mental Health Center. 74 Fenwood Road. Boston. MA 02 ! 15. Preparation of this article was supported in part by National Instituteof Mental Health Grants MH44277 and MH435i 8-01 (MERIT Award). MH46318 and a Veterans Administration Medical Research Merit Review Grant to Dr. Tsuang. This manuscript was partially prepared while Dr. Tsuang was a Fellow at the Center for Advanced Study in the Behavioral Sciences. We are grateful for financial support provided by the John D. and Catherine T. MacArthur Foundation and the Foundations Fund for Research in Psychiatry Endowment. Received February 18,1992: revised June 23.1993. © 1994 Society of Biological Psychiatry One of the central brain-behavior relationships in schizo- phrenia is the positive association between neuropsycholo- gical impairment and brain abnormalities of structure and function (Seidman 1983; Zec and Weinberger 1986; Wein- berger and Berman 1988). This association has provided some confirmation that neuropsychological impairment has a neurologic basis, at least in chronic patients. Moreover. these findings reciprocally support the clinical significance of anatomical and metabolic neuroimaging measures and neuropsychological performance in schizophrenia. Perhaps the most prominent of these observed associations is the link between impaired, in vivo Wisconsin Card Sorting Test (WCST) performance and lowered dorsolateral prefrontal cortical (DLPFC) blood flow in chronically ill schizog, hren- 0006.3223194/$07.00