Prefrontal cortex: Role in acquisition of overlapping associations and transitive inference

DeVito, Loren M.; Lykken, Christine; Kanter, Benjamin R.; Eichenbaum, Howard

doi:10.1101/lm.1685710

Cited by 66 publications

(70 citation statements)

References 47 publications

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“…No other regions showed significant retrieval success effects in either ANOVA or simple effects analysis. These findings highlight the unique role of the PFC in predicting trial-by-trial transfer success at test, but not at encoding, and are consistent with the notion of inferential processing during retrieval (DeVito et al, 2010b;Wendelken and Bunge, 2010).…”

Section: Encoding: Mtl Supports Flexibility Through Integration Acrossupporting

confidence: 68%

“…IFG has been implicated in non-mnemonic relational reasoning where multiple relationships must be considered to infer an unknown relationship (Christoff et al, 2001;Wendelken and Bunge, 2010), suggesting that PFC contributions to flexible AC transfer may be through inferential judgments from premise associations (AB and BC, therefore AC). Animal lesion studies have demonstrated that PFC is essential for transitive inference in rats (DeVito et al, 2010b). However, because lesions to PFC were performed before learning, the exact mechanism by which PFC contributes to flexibility could not be determined.…”

Section: Discussionmentioning

confidence: 99%

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Flexible Memories: Differential Roles for Medial Temporal Lobe and Prefrontal Cortex in Cross-Episode Binding

Zeithamová

Preston²

2010

J. Neurosci.

207

283

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Episodic memory is characterized by rapid formation of new associations that bind information within individual episodes. A powerful aspect of episodic memory is the ability to flexibly apply and recombine information from past experience to guide new behavior. A critical question for memory research is how medial temporal lobe (MTL) and prefrontal cortex (PFC), regions implicated in rapid within-episode binding, further support cross-episode binding in service of mnemonic flexibility. We set to answer this question using an associative inference task in humans that required rapid binding of information across overlapping experiences (AB, BC) to enable successful transfer to novel test probes (AC). Within regions predicting subsequent associative memory for directly learned associations, encoding activation in MTL, including hippocampus and parahippocampal cortex, uniquely predicted success on novel transfer trials both within and across participants, consistent with an integrative encoding mechanism where overlapping experiences are linked into a combined representation during learning. In contrast, during retrieval, PFC activation predicted trial-by-trial transfer success while MTL predicted transfer performance across participants. Moreover, increased MTL-PFC coupling was observed during novel transfer trials compared with retrieval of directly learned associations. These findings suggest that inferential processes support transfer of rapidly acquired experiences to novel events during retrieval where multiple memories are recalled and flexibly recombined in service of successful behavior. Together, these results demonstrate distinct encoding and retrieval mechanisms that support mnemonic flexibility, revealing a unique role for MTL regions in cross-episode binding during encoding and engagement of interactive MTL-PFC processes during flexible transfer at test.

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Section: Encoding: Mtl Supports Flexibility Through Integration Acrossupporting

confidence: 68%

Section: Discussionmentioning

confidence: 99%

Flexible Memories: Differential Roles for Medial Temporal Lobe and Prefrontal Cortex in Cross-Episode Binding

Zeithamová

Preston²

2010

J. Neurosci.

207

283

View full text Add to dashboard Cite

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“…Increasing evidence from human (Kesner and Rogers 2004;Blumenfeld and Ranganath 2007) and animal (Hirsch and Crepel 1992;Morris et al 1999;Takita et al 1999; There is converging evidence that links fear memory specificity and generality with information processing in the hippocampus-thalamus-PFC-amygdala circuit (Marr 1971;O'Reilly and McClelland 1994;Leutgeb et al 2007;McHugh et al 2007;Kumaran and McClelland 2012;Nakashiba et al 2012;Xu et al 2012;Navawongse and Eichenbaum 2013;Xu and Sudhof 2013). Involvement of the PFC in context or odor discrimination during information acquisition has been previously studied (DeVito et al 2010;Xu et al 2012;Xu and Sudhof 2013); however, the contribution of the PFC in the discrimination of auditory patterns, such as FM-sweep direction, has not been previously explored. FM-sweep direction discrimination is important in speech recognition (Zeng et al 2005) but its underlying neural mechanism is unknown.…”

Section: Discussionmentioning

confidence: 99%

“…Studies of neural substrates and mechanisms underlying memory resolution are focused on the hippocampal circuit (Leutgeb et al 2007;Sahay et al 2011). Recent studies also implicate prefrontal circuitry in the contextual fear memory specificity and generalization (Xu et al 2012;Xu and Sudhof 2013) or discrimination of more discrete multiple odor stimuli (DeVito et al 2010).…”

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confidence: 99%

Prefrontal consolidation supports the attainment of fear memory accuracy

et al. 2014

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The neural mechanisms underlying the attainment of fear memory accuracy for appropriate discriminative responses to aversive and nonaversive stimuli are unclear. Considerable evidence indicates that coactivator of transcription and histone acetyltransferase cAMP response element binding protein (CREB) binding protein (CBP) is critically required for normal neural function. CBP hypofunction leads to severe psychopathological symptoms in human and cognitive abnormalities in genetic mutant mice with severity dependent on the neural locus and developmental time of the gene inactivation. Here, we showed that an acute hypofunction of CBP in the medial prefrontal cortex (mPFC) results in a disruption of fear memory accuracy in mice. In addition, interruption of CREB function in the mPFC also leads to a deficit in auditory discrimination of fearful stimuli. While mice with deficient CBP/CREB signaling in the mPFC maintain normal responses to aversive stimuli, they exhibit abnormal responses to similar but nonrelevant stimuli when compared to control animals. These data indicate that improvement of fear memory accuracy involves mPFC-dependent suppression of fear responses to nonrelevant stimuli. Evidence from a context discriminatory task and a newly developed task that depends on the ability to distinguish discrete auditory cues indicated that CBP-dependent neural signaling within the mPFC circuitry is an important component of the mechanism for disambiguating the meaning of fear signals with two opposing values: aversive and nonaversive.

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“…In rodents, mPFC lesions impair various forms of spatial memory (Lee and Kesner 2003;Jo et al 2007; Lee and Solivan 2008;Churchwell et al 2010). The mPFC has also been shown to be involved in a number of nonspatial memory tasks, including fear conditioning and extinction (Sotres-Bayon and Quirk 2010), transitive inference (DeVito et al 2010), and memory for sequential order (DeVito and Eichenbaum 2011). Although these studies clearly suggest that the mPFC is involved in typical rodent memory tasks, there is currently no consensus about the precise contribution of the PFC to memory encoding and retrieval processes.…”

mentioning

confidence: 99%

The medial prefrontal cortex is critical for memory retrieval and resolving interference

et al. 2013

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The prefrontal cortex (PFC) is known to be critically involved in strategy switching, attentional set shifting, and inhibition of prepotent responses. A central feature of this kind of behavioral flexibility is the ability to resolve conflicting response tendencies, suggesting a general role of the PFC in resolving interference. If so, the PFC should also be involved in memory retrieval, which involves competition between potential retrieval targets. Moreover, the PFC should be needed whenever interference is high, regardless of the strategic or attentional requirements of the task. To test this hypothesis, we temporarily inactivated the mPFC with muscimol and tested rats on several olfactory learning tasks. Rats given muscimol were able to learn a few discrimination problems when they were learned one at a time. However, they were severely impaired when they had to learn and remember many odors concurrently. Rats given muscimol also suffered greater interference when learning two lists of conflicting odor discrimination problems. Additionally, temporary mPFC inactivation during the acquisition of one set of odor memories actually improved the ability to learn a new set of conflicting odor memories. This paradoxical release from interference suggests that the mPFC plays an important role in acquiring and promoting the long term retrieval of memories. These results suggest that the mPFC plays a general role in resolving interference and that this is a key aspect of behavioral flexibility.

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Prefrontal cortex: Role in acquisition of overlapping associations and transitive inference

Cited by 66 publications

References 47 publications

Flexible Memories: Differential Roles for Medial Temporal Lobe and Prefrontal Cortex in Cross-Episode Binding

Flexible Memories: Differential Roles for Medial Temporal Lobe and Prefrontal Cortex in Cross-Episode Binding

Prefrontal consolidation supports the attainment of fear memory accuracy

The medial prefrontal cortex is critical for memory retrieval and resolving interference

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