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Cerebral Cortex Advance Access published online on September 12, 2006
Cerebral Cortex, doi:10.1093/cercor/bhl076
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© The Author 2006. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Article

Two Distinct Functional Networks for Successful Resolution of Proactive Interference

Jeremy B. Caplan 1 *, Anthony R. McIntosh 2, and Eve De Rosa 2

1 The Rotman Research Institute--Baycrest Centre, 3560 Bathurst St., Toronto, Ontario M6A 2E1, Canada; Current address: Psychology Department, Biological Sciences Building, University of Alberta, Edmonton, Alberta T6G 2E9, Canada
2 The Rotman Research Institute--Baycrest Centre, 3560 Bathurst St., Toronto, Ontario M6A 2E1, Canada; Department of Psychology, University of Toronto, 100 St. George St., Toronto, Ontario M5S 3G3, Canada

* To whom correspondence should be addressed.
Jeremy B. Caplan, E-mail: jcaplan{at}ualberta.ca


  Abstract

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.

Keywords: acetylcholine; basal forebrain; fMRI; learning and memory; proactive interference.
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