Auditory verbal working memory load and thalamic activation in nonpsychotic relatives of persons with schizophrenia: an fMRI replication.

First-degree relatives of persons with schizophrenia are at genetic risk for the illness and show deficits on high-load information-processing tasks. In a prior study of auditory working memory (WM) using functional MRI (fMRI), the authors demonstrated that adult relatives had significantly increased activation in the dorsomedial (DM) thalamus, anterior cingulate, and prefrontal cortex (H. W. Thermenos et al., 2004). In this study, the authors extended this work using a parametric WM task designed for fMRI in an independent, unmedicated sample. Twelve nonpsychotic relatives of persons with schizophrenia and 13 healthy controls were administered multiple versions of an auditory continuous performance test during fMRI. Data were analyzed using Statistical Parametric Mapping software. Compared with controls, relatives showed significantly greater task-elicited activation in the DM thalamus. When fMRI signal change was modeled as a function of increasing WM load, there was a significant Group x Load interaction, with relatives showing significantly greater task-elicited activation in the right DM thalamus compared with controls. Greater DM thalamic activation in the relatives remained significant when WM performance, vocabulary score, and education were controlled. This replication suggests that altered thalamic activation is a feature of neurobiological risk for schizophrenia.

Sex differences in prefrontal cortical brain activity during fMRI of auditory verbal working memory.

Functional imaging studies of sex effects in working memory (WMEM) are few, despite significant normal sex differences in brain regions implicated in WMEM. This functional MRI (fMRI) study tested for sex effects in an auditory verbal WMEM task in prefrontal, parietal, cingulate, and insula regions. Fourteen healthy, right-handed community subjects were comparable between the sexes, including on WMEM performance. Per statistical parametric mapping, women exhibited greater signal intensity changes in middle, inferior, and orbital prefrontal cortices than men (corrected for multiple comparisons). A test of mixed-sex groups, comparable on performance, showed no significant differences in the hypothesized regions, providing evidence for discriminant validity for significant sex differences. The findings suggest that combining men and women in fMRI studies of cognition may obscure or bias results.

Functional magnetic resonance imaging during auditory verbal working memory in nonpsychotic relatives of persons with schizophrenia: a pilot study.

BACKGROUND: First-degree relatives of persons with schizophrenia carry elevated genetic risk for the illness and show deficits on high-load information processing tasks. We used functional magnetic resonance imaging (fMRI) to test whether nonpsychotic relatives show altered functional activation in the prefrontal cortex (PFC), thalamus, hippocampus, and anterior cingulate during a working memory task requiring interference resolution. METHODS: Twelve nonpsychotic relatives of persons with schizophrenia and 12 healthy control subjects were administered an auditory, verbal working memory version of the Continuous Performance Test during fMRI. An asymmetric, spin-echo, T2*-weighted sequence (15 contiguous, 7-mm axial slices) was acquired on a full-body MR scanner. Data were analyzed by Statistical Parametric Mapping (SPM). RESULTS: Compared with control subjects, relatives showed greater task-elicited activation in the PFC and the anterior and dorsomedial thalamus. When task performance was controlled, relatives showed significantly greater activation in the anterior cingulate. When effects of other potentially confounding variables were controlled, relatives generally showed significantly greater activation in the dorsomedial thalamus and anterior cingulate. CONCLUSIONS: This pilot study suggests that relatives of persons with schizophrenia have subtle differences in brain function in the absence of psychosis. These differences add to the growing literature identifying neurobiological vulnerabilities to schizophrenia.