# Neural Mechanisms of Cognitive Meta-Flexibility

> **NIH NIH R01** · DUKE UNIVERSITY · 2021 · $395,841

## Abstract

Project Summary/Abstract
Adaptive behavior requires the ability to keep a current task set in mind and shield it from distraction (cognitive
stability), as well as to update task sets in response to changing requirements (cognitive flexibility). Cognitive
stability and flexibility are complementary but opponent processing modes, as greater stability comes at the cost of
lower flexibility, and vice versa. Importantly, neither a stable nor a flexible mental state is inherently beneficial;
rather, it is the adaptation of one’s flexibility level to varying environmental demands – or meta-flexibility - that
produces optimal cognition. Accordingly, adopting a contextually optimal set point in the stability/flexibility trade-off is considered a challenging (and poorly understood) “cognitive control dilemma”, and this ability is severely
impaired in many psychiatric disorders. Therefore, understanding the neural mechanisms that mediate meta-flexibility is of great significance to both basic and clinical brain science. However, whereas individual differences
and externally (e.g., drug-) induced changes in flexibility set points have been studied with some success, it is not
presently known how the brain produces strategic meta-flexibility, i.e., learning to adapt one’s flexibility level to
changing contexts. While a budding behavioral literature shows that people strategically adapt their readiness to
switch tasks in line with changes in contextual switch-likelihood, no study to date has examined the neural
mechanisms underlying these dynamic, learned changes in cognitive flexibility. Therefore, the overall goal of this
proposal is to foster a new understanding of strategic meta-flexibility. We triangulate this goal via 3 strategic aims:
in aim 1 we delineate the neural loci and mechanisms of meta-flexibility by combining proactive (Study 1) and
reactive (Study 2) cognitive flexibility learning protocols with functional magnetic resonance imaging (fMRI) and a
suite of cutting-edge analysis approaches, including brain state “pinging” and representational similarity (RSA),
multivoxel pattern (MVPA), and dynamic functional connectivity (dFC) analyses. In aim 2, we then move on to
determine the learning processes that guide the above mechanisms of strategic shifts in switch-readiness. Here, we
use model-based fMRI, multivariate measures of neural memory reinstatement, and fMRI-guided model-based
transcranial magnetic stimulation (TMS) to test how both “incremental” reinforcement learning (RL) (Studies 3 and
4) and episodic reinstatement (Study 5) may contribute to guiding strategic meta-flexibility. Having established the
basic brain mechanisms of strategic meta-flexibility, in aim 3 we then examine its potential clinical significance as
a transdiagnostic cognitive endophenotype, by leveraging large-scale online data collection to relate individual
differences in strategic meta-flexibility to variance in clinically relevant self-report measures (Study 6). We ...

## Key facts

- **NIH application ID:** 10105368
- **Project number:** 5R01MH116967-03
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Tobias Egner
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $395,841
- **Award type:** 5
- **Project period:** 2019-04-04 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10105368

## Citation

> US National Institutes of Health, RePORTER application 10105368, Neural Mechanisms of Cognitive Meta-Flexibility (5R01MH116967-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10105368. Licensed CC0.

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