ASSOCIATIVE LEARNING IN BASAL FOREBRAIN AMNESIA

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Patients with anterior communicating artery (ACoA) aneurysm often show an anterograde amnesia syndrome: relatively poor ability to form new memories but relative sparing of older memories (e.g., DeLuca and Diamond, 1995). ACoA amnesia is thus superficially similar to the amnesia which may follow damage to the hippocampus and associated medial temporal (MT) structure (e.g., Squire, 1987), although the ACoA amnesics have no direct MT damage. Animal models, pharmacological data, and computational models suggest that basal forebrain structures modulate hippocampal processing, leading to disrupted hippocampal processing in ACoA amnesia (e.g., Myers et al., 1996). However, these models also predict subtle differences in residual memory abilities following basal forebrain versus MT damage (e.g., Myers et al., 1996). This work proposes testing a population of ACoA amnesic (and appropriate matched controls) on a series of associative learning tasks of the kind known to be impaired or spared in MT amnesia and hippocampal-lesioned animals. These include motor-reflex conditioning of the eye-blink responses and computer-based operant conditioning tasks. Whereas simple conditioning is spared in MT amnesia, but more complex conditioning involving contextual or configural information is impaired, we expect the opposite pattern of results to obtain in the ACoA amnesics. If this prediction hods, these results will represent evidence differentiating the memory deficit in these two populations. This will inform current understanding of how hippocampus and basal forebrain interact in normal memory. Additionally, a battery of tasks which are sensitive to basal forebrain damage would be useful in a assessing lesion extent in ACoA amnesics, for whom neuroimaging is typically inconclusive. Finally, this study represents an opportunity for the PI, trained in computational modeling of memory systems, to gain new experience and training in clinical behavioral studies through collaboration with Drs. DeLuca and Diamond, who have extensive experience working with ACoA aneurysm survivors and ACoA amnesia.