'Online' integration of sensory and fear memories in the rat medial temporal lobe

Wong, Francesca S.; Westbrook, R. Frederick; Holmes, Nathan M.

doi:10.7554/elife.47085

Cited by 48 publications

(69 citation statements)

References 52 publications

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“…This is surely not the case. Indeed even when preconditioning is the readout, we know that interfering with several cortical areas including hippocampus ( Port et al, 1987 ), retrosplenial cortex ( Robinson et al, 2011 ; Robinson et al, 2014 ; Fournier et al, 2020 ), and perirhinal cortex ( Holmes et al, 2013 ; Wong et al, 2019 ) seems to impair the acquisition of sensory-sensory associations. While most cortical and subcortical areas encode variables relevant to predicting biologically-relevant outcomes ( Milad and Quirk, 2002 ; Burgos-Robles et al, 2009 ; Kennerley et al, 2011 ; Cai and Padoa-Schioppa, 2012 ; Burgos-Robles et al, 2013 ; Giustino et al, 2016 ; Giustino et al, 2019 ; Halladay et al, 2020 ), few studies look at whether the same areas track incidental sensory-sensory associations.…”

Section: Discussionmentioning

confidence: 99%

Responding to preconditioned cues is devaluation sensitive and requires orbitofrontal cortex during cue-cue learning

Hart

Sharpe

Gardner

et al. 2020

eLife

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The orbitofrontal cortex (OFC) is necessary for inferring value in tests of model-based reasoning, including in sensory preconditioning. This involvement could be accounted for by representation of value or by representation of broader associative structure. We recently reported neural correlates of such broader associative structure in OFC during the initial phase of sensory preconditioning (Sadacca et al., 2018). Here, we used optogenetic inhibition of OFC to test whether these correlates might be necessary for value inference during later probe testing. We found that inhibition of OFC during cue-cue learning abolished value inference during the probe test, inference subsequently shown in control rats to be sensitive to devaluation of the expected reward. These results demonstrate that OFC must be online during cue-cue learning, consistent with the argument that the correlates previously observed are not simply downstream readouts of sensory processing and instead contribute to building the associative model supporting later behavior.

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Section: Discussionmentioning

confidence: 99%

Responding to preconditioned cues is devaluation sensitive and requires orbitofrontal cortex during cue-cue learning

Hart

Sharpe

Gardner

et al. 2020

eLife

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“…However, it is important to keep in mind that behavior can be driven by several independent mechanisms and that inference-based behavior supported by mechanisms in OFC may occur in parallel with support from additional mechanisms such as mediated learning ( Schlichting and Preston, 2015 ), which may recruit hippocampus ( Shohamy and Wagner, 2008 ; Wimmer and Shohamy, 2012 ; Kurth-Nelson et al, 2015 ) and perirhinal cortex ( Wong et al, 2019 ). Nevertheless, the susceptibility of inference-based responding to OFC-targeted cTBS indicates that at least some amount of behavior in our task is based on real-time model-based computations.…”

Section: Discussionmentioning

confidence: 99%

Targeted Stimulation of an Orbitofrontal Network Disrupts Decisions Based on Inferred, Not Experienced Outcomes

et al. 2020

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When direct experience is unavailable, animals and humans can imagine or infer the future to guide decisions. Behavior based on direct experience versus inference may recruit partially distinct brain circuits. In rodents, the orbitofrontal cortex (OFC) contains neural signatures of inferred outcomes, and OFC is necessary for behavior that requires inference but not for responding driven by direct experience. In humans, OFC activity is also correlated with inferred outcomes, but it is unclear whether OFC activity is required for inference-based behavior. To test this, we used noninvasive network-based continuous theta burst stimulation (cTBS) in human subjects (male and female) to target lateral OFC networks in the context of a sensory preconditioning task that was designed to isolate inference-based behavior from responding that can be based on direct experience alone. We show that, relative to sham, cTBS targeting this network impairs reward-related behavior in conditions in which outcome expectations have to be mentally inferred. In contrast, OFC-targeted stimulation does not impair behavior that can be based on previously experienced stimulus–outcome associations. These findings suggest that activity in the targeted OFC network supports decision-making when outcomes have to be mentally simulated, providing converging cross-species evidence for a critical role of OFC in model-based but not model-free control of behavior. SIGNIFICANCE STATEMENT It is widely accepted that the orbitofrontal cortex (OFC) is important for decision-making. However, it is less clear how exactly this region contributes to behavior. Here we test the hypothesis that the human OFC is only required for decision-making when future outcomes have to be mentally simulated, but not when direct experience with stimulus–outcome associations is available. We show that targeting OFC network activity in humans using network-based continuous theta burst stimulation selectively impairs behavior that requires inference but does not affect responding that can be based solely on direct experience. These results are in line with previous findings in animals and suggest a critical role for human OFC in model-based but not model-free behavior.

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“…However, it is important to keep in mind that behavior can be driven by several independent mechanisms and that inference-based behavior may occur in parallel with support from additional mechanisms such as mediated learning , which may recruit hippocampus (Shohamy and Wagner, 2008;Wimmer and Shohamy, 2012;Kurth-Nelson et al, 2015) and perirhinal cortex (Wong et al, 2019). Nevertheless, the susceptibility of inferencebased responding to OFC-targeted cTBS indicates that at least some amount of behavior in our task is based on real-time model-based computations.…”

Section: Discussionmentioning

confidence: 99%

Targeted stimulation of an orbitofrontal network disrupts decisions based on inferred, not experienced outcomes

Wang

Howard

Voss

et al. 2020

Preprint

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ABSTRACTWhen direct experience is unavailable, animals and humans can imagine or infer the future to guide decisions. Behavior based on direct experience versus inference may recruit distinct but overlapping brain circuits. In rodents, the orbitofrontal cortex (OFC) contains neural signatures of inferred outcomes, and OFC is necessary for behavior that requires inference but not for responding driven by direct experience. In humans, OFC activity is also correlated with inferred outcomes, but it is unclear whether OFC activity is required for inference-based behavior. To test this, we used non-invasive network-based continuous theta burst stimulation (cTBS) to target lateral OFC networks in the context of a sensory preconditioning task that was designed to isolate inference-based behavior from responding that can be based on direct experience alone. We show that relative to sham, cTBS targeting this network impairs reward-related behavior in conditions in which outcome expectations have to be mentally inferred. In contrast, OFC-targeted stimulation does not impair behavior that can be based on previously experienced stimulus-outcome associations. These findings suggest that activity in the targeted OFC network supports decision making when outcomes have to be mentally simulated, providing converging cross-species evidence for a critical role of OFC in model-based but not model-free control of behavior.

show abstract

'Online' integration of sensory and fear memories in the rat medial temporal lobe

Cited by 48 publications

References 52 publications

Responding to preconditioned cues is devaluation sensitive and requires orbitofrontal cortex during cue-cue learning

Responding to preconditioned cues is devaluation sensitive and requires orbitofrontal cortex during cue-cue learning

Targeted Stimulation of an Orbitofrontal Network Disrupts Decisions Based on Inferred, Not Experienced Outcomes

Targeted stimulation of an orbitofrontal network disrupts decisions based on inferred, not experienced outcomes

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