THE PREFRONTAL cortex is complex and heterogenous, with subregions varying in cytoarchitecture and connectivity to primary, multimodal association areas and subcortical nuclei.^1-4 It modulates cognition, executive functions—abstraction, attention, inhibition, planning, and working memory—motivation, and emotion.^1-3 These neurobehavioral domains are aberrant in schizophrenia, leading to examination with structural^5-9 and functional neuroimaging.^9-12 Human in vivo and postmortem research has converged with primate findings to elucidate intercellular processes modulating cortical circuitry.^1,13-17 Magnetic resonance imaging can parcellate gray matter (GM) and white matter (WM) volumes, addressing feature variability of gyri and sulci.

TEMPORAL LOBE structures and circuitry modulate cognition and emotion, prompting their neuroanatomic examination in schizophrenia. Investigations with magnetic resonance imaging (MRI) have evaluated lobar volumes^1-5 and specific subregions^6-15 implicated in neurobehavioral domains aberrant in schizophrenia, such as memory. Regional volumes have also been linked to clinical features, including thought disorder and auditory hallucinations.^7,8 This research complements neuropathological findings documenting abnormal morphometry, cytoarchitecture, and neuroreceptors in temporolimbic structures.^16-18

Background: Quantitative magnetic resonance imaging (MRI) studies demonstrate reduced brain volumes in schizophrenics, but specific structural abnormalities have not been clearly delineated. The structural abnormalities of this disorder are likely to be heterogeneous, consistent with its diverse clinical presentation. To investigate the relationship between structural abnormality and clinical symptoms, we examined regional brain and cerebral spinal fluid (CSF) volumes in a large sample of schizophrenic patients and controls, with patients aggregated into clinical subtypes. Methods: Right and left hemisphere frontal and temporal lobe brain and CSF volumes were quantified from 5-mm axial spin-echo MRIs for 71 schizophrenic patients and 77 age- and sex-matched controls. The following four standardized rating scales were used to assess symptom severity: Negative Symptoms, Disorganization, Schneiderian Delusions and Hallucinations, and Suspicion-Hostility. Patients were also subtyped as either deficit or nondeficit on the basis of enduring negative symptoms. Results: Schizophrenic patients overall exhibited ab-a normal brain asymmetry, with selective decrease in brain volume in the left temporal and right frontal regions. Left temporal lobe parenchymal volume reduction and CSF volume increase were correlated with the severity of negative symptoms. Consistent with this, the subtype analysis revealed abnormal temporal lobe asymmetry for the deficit subgroup only. Right frontal lobe volume reduction correlated with the duration of illness, independent of symptom severity or schizophrenic subtype. Conclusions: Abnormal lateral asymmetry suggests selective structural deficits in schizophrenia, rather than diffusely undifferentiated CNS abnormalities. The pattern of regional abnormalities is related to clinical symptoms, with negative symptoms being associated with left temporal lobe rather than frontal lobe abnormality. This is consistent with suggestions of a temporolimbic prefrontal network abnormality in schizophrenia. Further longitudinal studies are warranted, using higherresolution MRI technology and gray matter—white matter segmentation to confirm and extend these findings.