Based on prior animal and computational models, we propose a double dissociation between the associative learning deficits observed in patients with medial temporal (hippocampal) damage versus patients with Parkinson's disease (basal ganglia dysfunction). Specifically, we expect that basal ganglia dysfunction may result in slowed learning, while individuals with hippocampal damage may learn at normal speed. However, when challenged with a transfer task where previously learned information is presented in novel recombinations, we expect that hippocampal damage will impair generalization but basal ganglia dysfunction will not. We tested this prediction in a group of healthy elderly with mild-to-moderate hippocampal atrophy, a group of patients with mild Parkinson's disease, and healthy controls, using an “acquired equivalence” associative learning task. As predicted, Parkinson's patients were slower on the initial learning but then transferred well, while the hippocampal atrophy group showed the opposite pattern: good initial learning with impaired transfer. To our knowledge, this is the first time that a single task has been used to demonstrate a double dissociation between the associative learning impairments caused by hippocampal versus basal ganglia damage/dysfunction. This finding has implications for understanding the distinct contributions of the medial temporal lobe and basal ganglia to learning and memory.

Older people with declining cognitive function typically display deficits in declarative memory processes, often most evident on tests of associative learning (AL). The hippocampal formation (HF) is thought to be critically involved in the encoding and retrieval of such associations, consistent with neuroimaging findings that the HF is damaged in early stages of neurodegenerative disease and in older people with AL impairments. In the clinic, older people with cognitive decline commonly report difficulties associating names with faces. However, we have observed that such people are particularly impaired on tests requiring the association of novel stimuli. In Experiment 1, a series of AL tasks were administered to older people with cognitive decline to determine whether they were impaired at simply making associations, or at making associations between novel stimuli. In Experiment 2, we measured HF function in these subjects by administering an AL task designed to differentiate between HF-damaged and HF-intact individuals. Our experimental protocols were guided by a computational model of HF function in AL described by Gluck and Myers (1997). Older people with cognitive decline displayed impaired performance on tasks designed to be highly dependent upon intact HF function, including a task in which novel patterns and spatial locations were to be associated. These results suggest that the AL impairments observed in older people with cognitive decline may be due to HF dysfunction.