Two distinct functional networks for successful resolution of proactive interference.

In proactive interference (PI) paradigms, previous learning impairs the acquisition of new, related information. In rats, efficient resolution of PI relies on cholinergic modulation from the basal forebrain (BF). To test whether humans resolve PI using a functional network dependent on the medial septum/diagonal band of Broca (MS/DB) nuclei of the BF, we analyzed functional magnetic resonance imaging signal recorded while human participants learned to respond to baseline color paired associates and then additional pairs that interfered with the baseline pairs. Multivariate, partial least-squares analysis supported a MS/DB-dependent functional network: MS/DB activity covaried with activity in areas important to selective attention, including intraparietal sulcus, and memory that are direct cholinergic efferents of the MS/DB, including the hippocampus, as well as the ventrolateral prefrontal cortex, implicated in PI resolution. This network was associated with effective PI-resolution behavior. A second network also correlated with PI resolution but appearing not to be driven by the MS/DB, included the lateral orbitofrontal cortex. Patients with compromised BF function did not engage the MS/DB-dependent network reliably; instead their PI-resolution behavior was well explained by the second network. Thus, 2 functional networks may underly a single cognitive function; when the MS/DB-dependent attention/memory integration network is compromised, an alternate network is available to maintain normal levels of performance.