Fronto-parietal hypo-activation during working memory independent of structural abnormalities: conjoint fMRI and sMRI analyses in adolescent offspring of schizophrenia patients.

ABSTRACT

Adolescent offspring of schizophrenia patients (HR-S) are an important group in whom to study impaired brain function and structure, particularly of the frontal cortices. Studies of working memory have suggested behavioral deficits and fMRI-measured hypoactivity in fronto-parietal regions in these subjects. Independent structural MRI (sMRI) studies have suggested exaggerated frontal gray matter decline. Therefore the emergent view is that fronto-parietal deficits in function and structure characterize HR-S. However, it is unknown if fronto-parietal sub-regions in which fMRI-measured hypo-activity might be observed are precisely those regions of the cortex in which gray matter deficits are also observed. To investigate this question we conducted conjoint analyses of fronto-parietal function and structure in HR-S (n=19) and controls (n=24) with no family history of psychoses using fMRI data during a continuous working memory task (2 back), and sMRI collected in the same session. HR-S demonstrated significantly reduced BOLD activation in left dorso-lateral prefrontal cortex (BA 9/46) and bilateral parietal cortex (BA 7/40). Sub-regions of interest were created from the significant fronto-parietal functional clusters. Analyses of gray matter volume from volume-modulated gray matter segments in these clusters did not reveal significant gray matter differences between groups. The results suggest that functional impairments in adolescent HR-S can be independent of impairments in structure, suggesting that the relationship between impaired function and structure is complex. Further studies will be needed to more closely assess whether impairments in function and structure provide independent or interacting pathways of vulnerability in this population.