# Understanding the Distributed Control of Flexible Behavior

> **NIH NIH F32** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2024 · $76,756

## Abstract

ABSTRACT
Our brains have the remarkable ability to both produce precise, consistent movements in an invariant
environment and dynamically adjust behavior to a changing environment. Almost all our everyday actions, such
as driving a car or riding a bike, necessitate such flexible multi-tasking. Losing the ability to flexibly adjust
behavior is dramatic and debilitating, as evidenced by disorders such as obsessive-compulsive disorder (OCD)
or profound forms of autism spectrum disorder (ASD). While considerable work has examined how the brain’s
distributed motor network controls consistent movements in an invariant environment, the mechanisms that allow
for flexibility in movement control remain unknown. In this project, I develop a behavioral model to study the
flexible production of multiple distinct reaching movements in mice. The extensive previous work that has
characterized the neural control of reaching movements provides a powerful framework to precisely understand
the neural control of flexibility. I use this model to investigate the distributed control of flexible movements across
the primary motor cortex (M1), basal ganglia (BG), and cerebellum (CB). While the M1-BG and M1-CB networks
have been previously investigated in isolation, how all three regions interact is largely unexplored. I leverage (1)
large-scale multi-site neurophysiology in M1, BG, and CB, (2) genetically controlled thalamic manipulations of
M1-BG and M1-CB networks, (3) multi-region recurrent neural network models, and (4) mouse models of OCD
and ASD that display behavioral inflexibility to uncover fundamental principles by which the brain’s distributed
motor network governs flexibility in movement control and shed light on how these mechanisms dysfunction in
brain disorders.

## Key facts

- **NIH application ID:** 10889952
- **Project number:** 5F32NS131217-02
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Stefan Lemke
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $76,756
- **Award type:** 5
- **Project period:** 2023-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10889952

## Citation

> US National Institutes of Health, RePORTER application 10889952, Understanding the Distributed Control of Flexible Behavior (5F32NS131217-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10889952. Licensed CC0.

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