Journal Club

Editor’s Note: These short, critical reviews of recent papers in the Journal, written exclusively by graduate students or postdoctoralfellows, are intended to summarize the important findings of the paper and provide additional insight and commentary. For moreinformation on the format and purpose of the Journal Club, please see http://www.jneurosci.org/misc/ifa_features.shtml.

The Medial Prefrontal Cortex and the Deceptiveness ofMemory

Marlieke T.R. van Kesteren and Thackery I. BrownDepartment of Psychology, Stanford University, Stanford, California 94305

Review of Warren et al.

Imagine you have read an interesting arti-cle that strongly reminded you of one ofyour former colleagues’ research. You no-tice that is written by a different researchgroup, but you do not pay too much at-tention to this and read the article withmuch pleasure. A few months later youmeet your former colleague at a confer-ence and remember the paper you read.You tell him/her that you really enjoyedreading their article. Relating the new ar-ticle to your colleagues’ research hasclearly helped you remember its contents,but you have also falsely remembered thearticle to be theirs. How did that happen?

This situation is one example of howan important process that allows us to in-tegrate and generalize across memories indaily life can also open opportunities formnemonic errors. The medial prefrontalcortex (mPFC) is thought to be one struc-ture underlying these abilities. In recentyears, mPFC function has emerged as akey area of study for understanding higher-order memory and decision-making pro-cesses. It is a large, functionally andcytoarchitectonically diverse region, whoseintimate connectivity with the medialtemporal lobes (MTL) may underlie itsinvolvement in a multitude of memory-

related tasks. Lesions to the mPFC lead toa range of differences in decision-making,judging emotional and moral states, andtask switching. Additionally, patients withmPFC damage often confabulate and lackmemory-enhancing effects related to per-sonal social and mnemonic reasoning.

Recent interest in the role that priorknowledge (or a schema) plays in learningand memory has provided a new frame-work for understanding how componentsof the mPFC contribute to cognition.Theories of mPFC function centered onschemas propose that this region plays acritical role in guiding decision makingand mnemonic processes that interact withpreviously stored knowledge (van Kesterenet al., 2012; Preston and Eichenbaum,2013). Consequently, patients with lesionsto the mPFC are assumed to lack guidanceof prior knowledge in mnemonic reasoning,memory formation, and decision-making.Indeed, mPFC damage has frequentlybeen associated with cognitive and mem-ory impairments. For example, mPFC le-sions abolish memory-enhancing effectssuch as the self-referencing effect in whichself-related memories are better remem-bered (Philippi et al., 2012) and improvedtransitive inference of relationships betweenseparately learned associations (Koscik andTranel, 2012). Moreover, in a navigationsetting, mPFC damage has been found toimpair the ability to overcome interferencefrom alternative, incorrect navigationalmemories (Ciaramelli, 2008).

Despite the importance of the mPFCfor memory and decision making, mPFC

functions may also lead to overgeneraliza-tion and overreliance on prior knowledge,which can underlie false memories or falseconfidence about details of a memory. Con-sequently, damage to this region could ac-tually improve memory performance insome circumstances. In a recently pub-lished paper, Warren et al. (2014) rea-soned that if the mPFC is indeed involvedin relating current experience and behav-ior to prior knowledge, then mnemonicconsequences of this mechanism shouldbe absent in lesion patients. If mPFC le-sion patients cannot draw on semantic orcontextual similarities to make judgmentsabout a memory, they are expected tohave fewer false memories that arise be-cause of erroneous attribution to previ-ously learned information, such as in theexample where an article is misattributedto a colleague. Paradoxically, this will leadthem to benefit from their lesion by en-coding a memory trace that is less biasedtoward previously learned informationthan their healthy peers.

In psychology, a common way to testfalse memory is through the Deese-Roediger-McDermott (DRM) paradigm,in which participants learn a set of wordswith a common theme (such as “cold,”“blizzard,” “winter”). When subsequentlytested, participants often falsely assign arelated word (e.g., “snow”) to the learnedlist. Because the mPFC has been suggestedto link information to a mnemonic schema,Warren and colleagues (2014) hypothesizedthat patients with lesions in this regionwould show less of these misattributed

Received July 25, 2014; revised Aug. 21, 2014; accepted Aug. 25, 2014.M.T.R.v.K. is supported by a Rubicon Fellowship from the Netherlands

Organization for Scientific Research. We thank Rik Henson for proofreading.Correspondence should be addressed to Dr. Marlieke T. R. van Kesteren,

Department of Psychology, Jordan Hall, Building 420, Mail Code 2130,Stanford, CA 94305. E-mail: m.vankesteren@stanford.edu.

DOI:10.1523/JNEUROSCI.3091-14.2014Copyright © 2014 the authors 0270-6474/14/3413569-02$15.00/0

The Journal of Neuroscience, October 8, 2014 • 34(41):13569 –13570 • 13569

false memories in the DRM paradigm.They thus tested memory on the DRMparadigm in a group of mPFC-lesionedpatients and compared performance tohealthy controls. For free recall of wordson the list, they found that the patientgroup showed a significantly lower amountof false memories, indicating that mPFC le-sions indeed keep patients from misat-tributing related words to the learned list.This decrease in false memories likely re-lates to a shared mechanistic account thatalso underlies the diminished memory-enhancing effects described above. Addi-tionally, these findings support directpredictions from the schema literaturethat hypothesize that mPFC lesions lowerenhancing effects of prior knowledge onlearning and consolidating new infor-mation. This could then lead to a weakerbias toward knowledge structures and aconsequent decrease in false memoriesat retrieval.

Moving forward, a challenge for re-searchers seeking to understand the com-plex functions of the mPFC is to identifythe links between empirical data and ex-tant theoretical accounts. In rodents, mPFClesions have been shown to abolish thetask/context selectivity of some neuronsrepresenting objects at locations (Nava-wongse and Eichenbaum, 2013), poten-tially impairing the ability to leveragecontextual information to retrieve specificmemories. Based on these findings andthe findings of Warren and colleagues(2014), mPFC functioning might serve asa mechanism for flexibly accessing mem-ories based on contextual information in-cluding task rules and goals (Kroes andFernandez, 2012; Brown et al., 2014). Thedecrease in false alarms found by Warrenand colleagues (2014) could then repre-sent a deficit in the natural ability of hu-mans to leverage contextual information(such as the “theme” of the words beingtested or your knowledge about your col-leagues’ research when reading a new pa-per) to make mnemonic judgments whenmemory traces are weak. Such a mecha-nism is typically beneficial when filteringincoming information for relevance orbasing decisions on prior outcomes.

The findings of Warren and colleagues(2014) might motivate researchers to takea different view on memory systems andthe characterization of memory success.In an experimental setting, whether amemory is remembered or forgottenmight not only result from brain states(e.g., attention and motivation) at themoment of encoding, but may also be in-fluenced by complex interactions withprior knowledge. Activation of relevantprior knowledge can help boost newmemories and store them more schemat-ically, because they can be directly relatedto a network of previously learned associ-ations (van Kesteren et al., 2012). Whenmemories lack such a connection to priorknowledge, they may be forgotten moreeasily or may require stronger retrievalcues to be activated. A critical question inmemory research is therefore whether therelationship between newly learned infor-mation and prior knowledge can also leadmemories to be stored differently: eithermore episodically detailed or assimilatedwithin previously stored semantic traces.

In addition to encoding processes,offline consolidation processes are alsosuggested to be affected by interactionswith prior knowledge (Tse et al., 2007).Therefore, the role of the mPFC in consol-idating knowledge should be further ex-amined in future research. For example,do mPFC lesion patients show retrogradeamnesia that is specific to the prior knowl-edge effects mentioned above? Conse-quently, will they also show less of thedescribed false memory effects for knowl-edge that was acquired before their lesionor are the mPFC influences specific to en-coding processes? Furthermore, are thedecreased false memory effects that Warrenand colleagues (2014) describe preservedover a future period of consolidation or dothey fade away? And finally, regardless of theanswers to the previous questions, whatwould the findings mean for the interpreta-tion of previously reported retrograde am-nesia effects following MTL lesions?

In the real-world example where youfalsely remember the authors of a greatpaper, the fact that you forgot that the pa-per was actually written by other research-

ers might be a consequence of your braintrying to make the complex world moreconsistent and predictable. Consequently,less significance is given to the fact that thedata actually originate from a differentand unknown research group, which leadsto misattribution errors. The findings ofWarren and colleagues (2014) suggestthat the mPFC may play a role in sucherrors, and provide important insightsinto the conditions under which mPFCfunction may impair, rather than facili-tate, certain types of memory.

ReferencesBrown TI, Whiteman AS, Aselcioglu I, Stern CE

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Ciaramelli E (2008) The role of ventromedialprefrontal cortex in navigation: a case of im-paired wayfinding and rehabilitation. Neuro-psychologia 46:2099 –2105. CrossRef Medline

Koscik TR, Tranel D (2012) The human ventro-medial prefrontal cortex is critical for transitiveinference. J Cogn Neurosci 24:1191–1204.CrossRef Medline

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Philippi CL, Duff MC, Denburg NL, Tranel D,Rudrauf D (2012) Medial PFC damage abol-ishes the self-reference effect. J Cogn Neurosci24:475– 481. CrossRef Medline

Preston AR, Eichenbaum H (2013) Interplay ofhippocampus and prefrontal cortex in memory.Curr Biol 23:R764–R773. CrossRef Medline

Tse D, Langston RF, Kakeyama M, Bethus I,Spooner PA, Wood ER, Witter MP, MorrisRG (2007) Schemas and memory consolida-tion. Science 316:76 – 82. CrossRef Medline

van Kesteren MT, Ruiter DJ, Fernandez G, Hen-son RN (2012) How schema and noveltyaugment memory formation. Trends Neuro-sci 35:211–219. CrossRef Medline

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13570 • J. Neurosci., October 8, 2014 • 34(41):13569 –13570 van Kesteren and Brown • Journal Club