Memory Engrams in the Neocortex.

While in the past much of our knowledge about memory representations in the brain has relied on loss-of-function studies in which whole brain regions were temporarily inactivated or permanently lesioned, the recent development of new methods has ushered in a new era of downright "engram excitement." Animal research is now able to specifically label, track, and manipulate engram cells in the brain. While early studies have mostly focused on single brain regions like the hippocampus, recently more and more evidence for brain-wide distributed engram networks is emerging. Memory research in humans has also picked up pace, fueled by promising magnetic resonance imaging (MRI)-based methods like diffusion-weighted MRI (DW-MRI) and brain decoding. In this review, we will outline recent advancements in engram research, with a focus on human data and neocortical representations. We will illustrate the available noninvasive methods for the detection of engrams in different neocortical regions like the medial prefrontal cortex and the posterior parietal cortex and discuss evidence for systems consolidation and parallel memory encoding. Finally, we will explore how reactivation and prior knowledge can lead to and enhance engram formation in the neocortex.