Novelty detection and encoding for memory within the human hippocampal system

Intracranial recordings of cognitive potentials within the human hippocampal system have identified N400 potentials in the anterior mesial temporal lobe (AMTL-N400) that correlate with verbal memory performance and are associated with novelty detection. Moreover their amplitudes to "new" but not "old" words in a verbal recognition task correlate with the neuronal density of the hippocampal CA1-region and can be reduced selectively by the NMDA-receptor blocker ketamine. Recently, we found that NMDA-receptor dependent long-term potentiation (LTP), a form of synaptic plasticity with Hebbian characteristics can be readily induced in human hippocampal slices but not in patients with hippocampal sclerosis. In the latter patient group, we also found a reduction of AMTL-N400 amplitudes that was similar to the one induced by ketamine. In addition, we could show that hippocampal novelty detection is associated with successful encoding for declarative memory. Together, our findings suggest, successful encoding for declarative memory is at least in part mediated by NMDA-receptor dependent novelty detection within the human hippocampal system.