COMMEMORATIVE LECTURE Neural mechanisms of cognitive memory

It is my great honor to be here for the award of the 2003 Keio Medical Science Prize. I express my gratitude to Keio University and Dr. Mitsunada Sakaguchi. Knowledge or experiences are voluntarily recalled from memory by reactivation of their neural representations in the cerebral association cortex. Four questions are central in understanding this process: (1) Where in the brain is the mnemonic representation of objects localized? And how is it organized? (2) How is the representation created and what is the morphological and molecular basis of neural circuit reorganization? (3) Which neural circuits enable the reactivation of the representation in memory retrieval? (4) What is the neural basis of cognitive control in memory retrieval and in meta-memory judgment? Clinical studies in humans have suggested that longterm declarative memory is stored in the neocortical association area that is also engaged in sensory perception (for review, see Miyashita, 1993,1 Miyashita & Hayashi, 20002). When electrical stimulation was applied via cortical surface electrodes placed on the temporal lobe during neurosurgery under local anesthesia, epileptic patients sometimes reported recollection of past perceptual experiences (Penfield & Perot, 1963),3 suggesting that artificial electrical input to the putative memory storehouse might reactivate the ‘‘brain’s record of auditory and visual experience’’. Recent experimental studies in humans and non-human primates moved beyond those classical clinical observations and revealed clearer and more solid views on the issues, particularly regarding the memory system of visual objects. In this lecture, I will first describe how memory engrams are organized in the cerebral cortex, focusing on the neural representation of semantically linked symbols/objects. I will then discuss how memory engrams are activated, highlighting two different retrieval processes, ‘active’ and ‘automatic’. Finally, I will show you our recent attempts to clarify the neural basis of a metamemory system, which supervises the retrieval process and exerts cognitive control.