PMID- 30012697
OWN - NLM
STAT- MEDLINE
DCOM- 20191010
LR  - 20231004
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 38
IP  - 48
DP  - 2018 Nov 28
TI  - Differentiation of Human Medial Prefrontal Cortex Activity Underlies Long-Term 
      Resistance to Forgetting in Memory.
PG  - 10244-10254
LID - 10.1523/JNEUROSCI.2290-17.2018 [doi]
AB  - It is well known that distributing study events over time leads to better memory 
      over long time scales, compared with massing study events together. One 
      explanation for such long-term resistance to forgetting is that distributed study 
      leads to neural differentiation in memory, which supports retrieval of past 
      experiences by disambiguating highly similar memory representations. 
      Neuroanatomical models of episodic memory retrieval propose that the hippocampus 
      and medial prefrontal cortex (MPFC) work together to enable retrieval of 
      behaviorally appropriate memories. However, it is not known how representations 
      in these regions jointly support resistance to forgetting long after initial 
      learning. Using fMRI, we measured differentiation in retrieved memory 
      representations following an extended delay in male and female human 
      participants. After 1 week, word-object associations were better remembered if 
      studied across 2 d (overnight), allowing associations to be learned in distinct 
      temporal contexts, compared with learning within a single day (same day). MPFC 
      retrieval patterns showed differentiation for overnight relative to same day 
      memories, whereas hippocampal patterns reflected associative retrieval success. 
      Overnight memory differentiation in MPFC was higher for associative than item 
      memories and higher than differentiation assessed over a brain-wide set of 
      retrieval-active voxels. The memory-related difference in MPFC pattern 
      differentiation correlated with memory success for overnight learning and with 
      hippocampal-MPFC functional connectivity. These results show that learning 
      information across days leads to differentiated MPFC memory representations, 
      reducing forgetting after 1 week, and suggest this arises from persistent 
      interactions between MPFC and hippocampus.SIGNIFICANCE STATEMENT Neural activity 
      in both the hippocampus and medial prefrontal cortex (MPFC) has been linked to 
      memory-related representations, but prior work has not examined how these 
      representations support episodic memory retrieval over extended time scales that 
      are characteristic of everyday retrieval. We show that differentiation in MPFC 
      activity 1 week after encoding is higher for retrieved information learned across 
      2 d compared with within a single day. In hippocampus, differentiation was 
      greater for detailed memory retrieval but was not influenced by whether 
      information had been learned over 1 or 2 d. Differentiation in MPFC predicted 
      behavioral robustness to forgetting and was correlated with hippocampal-MPFC 
      connectivity. The results suggest that context-based differentiation supports 
      robust long-term memory via persistent MPFC-hippocampal interactions.
CI  - Copyright (c) 2018 the authors 0270-6474/18/3810244-11$15.00/0.
FAU - Ezzyat, Youssef
AU  - Ezzyat Y
AD  - Department of Psychology, University of Pennsylvania, Philadelphia, Pennsylvania 
      19104.
FAU - Inhoff, Marika C
AU  - Inhoff MC
AD  - Department of Psychology, University of California, Davis, California 95616, and.
FAU - Davachi, Lila
AU  - Davachi L
AD  - Department of Psychology, Columbia University, New York, New York 10027 
      ld24@columbia.edu.
LA  - eng
GR  - R01 MH074692/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20180716
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
SB  - IM
MH  - Adult
MH  - Association Learning/*physiology
MH  - Female
MH  - Hippocampus/*diagnostic imaging/*physiology
MH  - Humans
MH  - Magnetic Resonance Imaging/trends
MH  - Male
MH  - Memory, Long-Term/*physiology
MH  - Mental Recall/physiology
MH  - Prefrontal Cortex/*diagnostic imaging/*physiology
MH  - Time Factors
MH  - Young Adult
PMC - PMC6262147
OTO - NOTNLM
OT  - consolidation
OT  - episodic memory retrieval
OT  - hippocampus
OT  - medial prefrontal cortex
OT  - pattern separation
OT  - temporal context
EDAT- 2018/07/18 06:00
MHDA- 2019/10/11 06:00
PMCR- 2019/05/28
CRDT- 2018/07/18 06:00
PHST- 2017/08/13 00:00 [received]
PHST- 2018/06/12 00:00 [revised]
PHST- 2018/06/12 00:00 [accepted]
PHST- 2018/07/18 06:00 [pubmed]
PHST- 2019/10/11 06:00 [medline]
PHST- 2018/07/18 06:00 [entrez]
PHST- 2019/05/28 00:00 [pmc-release]
AID - JNEUROSCI.2290-17.2018 [pii]
AID - 2290-17 [pii]
AID - 10.1523/JNEUROSCI.2290-17.2018 [doi]
PST - ppublish
SO  - J Neurosci. 2018 Nov 28;38(48):10244-10254. doi: 10.1523/JNEUROSCI.2290-17.2018. 
      Epub 2018 Jul 16.