A cholinergic explanation of dense amnesia

Abstract

Traditionally, dense amnesia in humans has been thought to be caused by damage to memory structures within the medial temporal lobe, either the hippocampus, the perirhinal cortex or a combination of the two. Recent work in animals has indicated that damage to the hippocampus results in memory impairments that are specific to memories for events. In contrast, damage to the perirhinal cortex impairs object memories in primates, which are likely to be analogous to human semantic memory. Discrete damage to either of these structures does not appear to result in severe and global memory impairments. We propose an alternative to this medial temporal lobe explanation of dense amnesia, based on our recent work. We have shown that the cholinergic cells of the basal forebrain are essential for new learning of both object and event-like memories in the monkey. Our model of learning in the primate brain rests on the proposal that there is a route of communication between the frontal cortex and inferior temporal cortex and hippocampus via the basal forebrain, which is critical for memory encoding. Interruption to this circuit at any stage will result in a severe and global anterograde amnesia.