# Project 2 The neural basis of sequence monitoring in human and nonhuman primates

> **NIH NIH P20** · BROWN UNIVERSITY · 2020 · $300,627

## Abstract

PROJECT SUMMARY / ABSTRACT 
 We perform sequences of tasks every day, such as making a cup of coffee. These `abstract' sequences 
can be distinguished from motor sequences along a variety of dimensions. In contrast to a specific order of 
muscle activations (e.g. playing piano) found in typical motor sequences, abstract sequences consist of sub- 
goals that might be achieved by any of a number of actions. Patients with frontal lobe damage have deficits in 
completing every day task sequences, even when they perform normally on non-sequential tests of executive 
function. Despite the importance of abstract sequences for understanding human behavior in health and for 
treating disease, relatively little is known about their neural mechanisms. Systematically answering this 
question is the defining goal of our research program. 
 Our previous work using a sequential decision making task revealed a novel and necessary dynamic 
where activity in the rostrolateral prefrontal cortex (RLPFC) increased from the beginning to the end of each 
abstract sequence (“ramped”) using fMRI and TMS in humans. We hypothesized this ramp represented the 
resolution of accumulating positional uncertainty through the sequence. However, also inherent to all of these 
tasks requiring complex decision making is monitoring, and placing in order, multiple variables. The goal of this 
project is to test the prediction that RLPFC and its associated network support sequence monitoring modulated 
by uncertainty; and, simultaneously, develop an animal model of this human cognitive process that can be 
used for future cross-species hypothesis testing. 
 The experiments in Aim 1 with utilize human fMRI in two separate but complimentary experiments to 
investigate how the dynamics in the rostral frontal previously found to be necessary for sequential task 
performance are modulated during sequence monitoring and uncertainty. Aim 2 will utilize nonhuman primate 
fMRI and the same behavioral paradigm as in humans to establish an animal model of abstract sequence 
monitoring and directly test functional homology with humans. This study will be the first comparison of 
performance of a sequential task of this kind across both species. In Aim 3 we will determine the necessity of 
the signals revealed in Aims 1 and 2, with direct manipulation of the circuits using TMS in humans and 
neurotransmitter agonists in monkeys. 
 Together, the proposed experiments will compose a unique, cross-species investigation of the neural 
basis of abstract sequence performance. Such investigation is necessary to understand the complex yet 
ubiquitous sequences of tasks that make up daily life, and that patients with frontal lobe damage and 
Parkinson's Disease often struggle with. This understanding could contribute to novel treatments and therapies 
for such disorders.

## Key facts

- **NIH application ID:** 9994935
- **Project number:** 5P20GM103645-08
- **Recipient organization:** BROWN UNIVERSITY
- **Principal Investigator:** Theresa Marie Desrochers
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $300,627
- **Award type:** 5
- **Project period:** 2013-08-15 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9994935

## Citation

> US National Institutes of Health, RePORTER application 9994935, Project 2 The neural basis of sequence monitoring in human and nonhuman primates (5P20GM103645-08). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9994935. Licensed CC0.

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