The Human Basal Forebrain

vation of these brain regions has been proposed to reflect executive processes involved in resolving competing task demands via conflict monitoring and cognitive Summary control (D'Esposito et al., 1999; MacDonald et al., 2000; van Veen et al., 2001). To limit executive task demands Acquisition of new learning is challenged by the phe-and enable direct comparisons between human and ani-nomenon of proactive interference (PI), which occurs mal studies, we modified a simultaneous discrimination when previous learning disrupts later learning. Whereas paired-associate learning paradigm used in a rat model human neuroimaging studies have focused on the cor-of BF function (De Rosa and Hasselmo, 2000) for use in tical contributions to interference resolution, animal the fMRI environment with humans (Figure 1). Standard studies demonstrate that efficient resolution of PI de-paired-associate methods for studying PI in the human pends on cholinergic modulation from basal forebrain verbal learning tradition involve learning novel associa-(BF). Whether the BF promotes PI resolution in humans tions that compete with pre-existing associations. Simi-is unknown. Here, we adapted a PI paradigm from larly, the paired-associate PI stimuli used in the present animal studies for use in a functional MRI experiment. simultaneous discrimination task shared elements with, During PI resolution, neurologically intact subjects rebut were configurally distinct from, the initially learned cruited a BF network that included afferent anterior stimuli; therefore, the subjects were required to learn a and posterior cortical sites associated with efficient new response in a similar stimulus setting. With this memory acquisition and perceptual processing. De-paradigm, we tested the hypothesis that, independent spite normal performance, nonamnesic patients with of an executive function network, the human BF would alcoholism, which is known to disrupt BF function, did be selectively activated when resolving PI. We further not activate a BF network but instead invoked anterior hypothesized that signal from the BF nuclei would be cortical sites traditionally associated with executive modified by learning and would be associated with a function. These results provide evidence for parallel reduction of behavioral PI. neural systems, each with the potential to resolve in-The BF projection system has a complex organization terference in the face of competing information. and neurochemical composition but is customarily defined by the magnocellular cholinergic neurons (Insausti Introduction et al., 1987; Mesulam et al., 1983; Rye et al., 1984). These cholinergic neurons are colocalized with a substantial When past learning impairs the acquisition of new re-population of noncholinergic neurons that share …