Hippocampus

may then bind reactivated content to current experience, resulting in an integrated trace. Following integration in hippocampus, memory models may be updated with new content as needed through direct hippocampal inputs CHIR-99021 clinical trial to mPFC [18]. Through this process, mPFC may come to represent integrated memories that have been abstracted away from individual episodes (i.e., schema) over time 18 and 25. A number of studies suggest that memory integration persists into post-encoding rest [26] and sleep [27], with offline consolidation processes facilitating generalization across episodes. Specifically, hippocampus-driven reactivation during slow-wave sleep is thought to transform memories, allowing connections to be formed among representations co-activated in neocortex [28]. This

process is thought to promote both the integration of new information into existing memories and abstraction across episodes in neocortical regions, particularly mPFC [28]. Memory integration has largely positive effects on behavior (though see Box 2 for examples of negative behavioral consequences). Below, we review recent work highlighting these benefits across a number see more of cognitive domains. While the effects of integration on behavior are largely beneficial, a few studies have uncovered negative consequences of integration. For example, integration may lead to false memories (i.e., through overgeneralization) [59•], and memory misattributions 5, 22•, 55 and 56. Interestingly, patients with ventral mPFC lesions show reduced false memories relative to healthy control participants for words that were never seen but are thematically related to a studied word list

[59•], consistent with the notion that ventral mPFC constructs generalized memory representations. Integration may also explain the phenomenon of memory misattribution, in which an episodic experience is incorrectly attributed to a different encoding Thalidomide context than the one in which it occurred (e.g., as measured by intrusions; Box 1). Misattributions may occur when prior knowledge is reactivated and updated with the current experience to the detriment of memory accuracy. One fMRI study [5] used neural decoding to quantify the neural reinstatement of the context associated with prior memories (List 1) during new learning (List 2). Results showed that greater evidence for reactivation of the List 1 context was associated with more misattributions of List 2 words to List 1. Another study [22•] showed that when participants reactivated a prior experience during new encoding, ventral mPFC and hippocampal engagement was associated with later memory misattributions, consistent with a role for these regions in linking experiences across time. Perhaps the most familiar and widely studied form of memory integration stems from Tolman’s seminal work on cognitive maps [7].