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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The following data sets were generated

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.

Reviewing Editor

  1. Lila Davachi, New York University, United States

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.

Version history

  1. Received: April 25, 2017
  2. Accepted: August 30, 2017
  3. Accepted Manuscript published: September 13, 2017 (version 1)
  4. Version of Record published: October 13, 2017 (version 2)

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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    Mechanosensory neurons located across the body surface respond to tactile stimuli and elicit diverse behavioral responses, from relatively simple stimulus location-aimed movements to complex movement sequences. How mechanosensory neurons and their postsynaptic circuits influence such diverse behaviors remains unclear. We previously discovered that Drosophila perform a body location-prioritized grooming sequence when mechanosensory neurons at different locations on the head and body are simultaneously stimulated by dust (Hampel et al., 2017; Seeds et al., 2014). Here, we identify nearly all mechanosensory neurons on the Drosophila head that individually elicit aimed grooming of specific head locations, while collectively eliciting a whole head grooming sequence. Different tracing methods were used to reconstruct the projections of these neurons from different locations on the head to their distinct arborizations in the brain. This provides the first synaptic resolution somatotopic map of a head, and defines the parallel-projecting mechanosensory pathways that elicit head grooming.