Causal evidence for lateral prefrontal cortex dynamics supporting cognitive control

  1. Derek Evan Nee  Is a corresponding author
  2. Mark D'Esposito
  1. Florida State University, United States
  2. Helen Wills Neuroscience Institute, University of California, United States

Abstract

The lateral prefrontal cortex (LPFC) is essential for higher-level cognition, but how its interactions support cognitive control remains elusive. Previously (Nee and D'Esposito, 2016), dynamic causal modeling (DCM) indicated that mid LPFC integrates abstract, rostral and concrete, caudal influences to inform context-appropriate action. Here, we use continuous theta-burst transcranial magnetic stimulation (cTBS) to causally test this model. cTBS was applied to three LPFC sites and a control site in counterbalanced sessions. Behavioral modulations resulting from cTBS were largely predicted by information flow within the previously estimated DCM. However, cTBS to caudal LPFC unexpectedly impaired processes presumed to involve rostral LPFC. Adding a pathway from caudal to mid-rostral LPFC significantly improved the model fit and accounted for the observed behavioral findings. These data provide causal evidence for LPFC dynamics supporting cognitive control and demonstrate the utility of combining DCM with causal manipulations to test and refine models of cognition.

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Article and author information

Author details

  1. Derek Evan Nee

    Department of Psychology, Florida State University, Tallahassee, United States
    For correspondence
    derek.evan.nee@gmail.com
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7858-6871
  2. Mark D'Esposito

    Department of Psychology, Helen Wills Neuroscience Institute, University of California, Berkeley, United States
    Competing interests
    The authors declare that no competing interests exist.

Funding

National Institute of Neurological Disorders and Stroke (F32 NS0802069)

  • Derek Evan Nee

National Institute of Neurological Disorders and Stroke (P01 NS040813)

  • Mark D'Esposito

National Institute of Mental Health (R01 MH063901)

  • Mark D'Esposito

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Human subjects: Informed consent was obtained in accordance with the Committee for Protection of Human Subjects at the University of California, Berkeley under protocol number 2010-02-781.

Copyright

© 2017, Nee & D'Esposito

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Derek Evan Nee
  2. Mark D'Esposito
(2017)
Causal evidence for lateral prefrontal cortex dynamics supporting cognitive control
eLife 6:e28040.
https://doi.org/10.7554/eLife.28040

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https://doi.org/10.7554/eLife.28040

Further reading

    1. Neuroscience
    Derek Evan Nee, Mark D'Esposito
    Research Article

    Higher-level cognition depends on the lateral prefrontal cortex (LPFC), but its functional organization has remained elusive. An influential proposal is that the LPFC is organized hierarchically whereby progressively rostral areas of the LPFC process/represent increasingly abstract information facilitating efficient and flexible cognition. However, support for this theory has been limited. Here, human fMRI data revealed rostral/caudal gradients of abstraction in the LPFC. Dynamic causal modeling revealed asymmetrical LPFC interactions indicative of hierarchical processing. Contrary to dominant assumptions, the relative strength of efferent versus afferent connections positioned mid LPFC as the apex of the hierarchy. Furthermore, cognitive demands induced connectivity modulations towards mid LPFC consistent with a role in integrating information for control operations. Moreover, the strengths of these dynamics were related to trait-measured higher-level cognitive ability. Collectively, these results suggest that the LPFC is hierarchically organized with the mid LPFC positioned to synthesize abstract and concrete information to control behavior.

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    When retrieved, seemingly stable memories can become sensitive to significant events, such as acute stress. The mechanisms underlying these memory dynamics remain poorly understood. Here, we show that noradrenergic stimulation after memory retrieval impairs subsequent remembering, depending on hippocampal and cortical signals emerging during retrieval. In a three-day study, we measured brain activity using fMRI during initial encoding, 24 hr-delayed memory cueing followed by pharmacological elevations of glucocorticoid or noradrenergic activity, and final recall. While post-retrieval glucocorticoids did not affect subsequent memory, the impairing effect of noradrenergic arousal on final recall depended on hippocampal reactivation and category-level reinstatement in the ventral temporal cortex during memory cueing. These effects did not require a reactivation of the original memory trace and did not interact with offline reinstatement during rest. Our findings demonstrate that, depending on the retrieval-related neural reactivation of memories, noradrenergic arousal after retrieval can alter the future accessibility of consolidated memories.