A functional MRI study of visual oddball: evidence for frontoparietal dysfunction in subjects at risk for alcoholism

Attending to rare stimuli interspersed among repetitive frequent stimuli produces a positive scalp potential at 300 to 600 ms after the target stimulus onset; this potential is known as the P300 wave. Although there is clear evidence of low visual P300 in subjects at high risk (HR) for developing alcoholism, the functional neuroanatomical correlates have not been studied. Functional and high-resolution anatomical magnetic resonance images were collected during the performance of a visual oddball task, from six control (low risk-LR) subjects with high P300s and eight HR subjects with low P300s. All the HR subjects were offspring of male alcoholics. The data were analyzed using a randomization-based statistical method that accounts for multiple comparisons, requires no assumptions about the noise structure of the data, and does not require spatial or temporal smoothing. Target counts showed that all subjects performed the task comparably. Analysis of the functional magnetic resonance imaging (fMRI) data revealed two areas with significantly lower activation in the HR group when compared to the LR group: the bilateral inferior parietal lobule (BA 40), and the bilateral inferior frontal gyrus (BA 44). Inferior parietal lobule showed significantly lower activation in the HR group in contrast to the LR group, and inferior frontal gyrus was not activated in the HR group but was only activated in the LR group. This finding indicates that a dysfunctional frontoparietal circuit may underlie the low P300 responses seen in HR subjects. This perhaps implies a deficiency in the rehearsal component of the working memory system.