# Neuronal Substrates of Hemodynamic Signals in the Prefrontal Cortex

> **NIH NIH R01** · CALIFORNIA INSTITUTE OF TECHNOLOGY · 2020 · $647,591

## Abstract

Neuronal Substrates of Hemodynamic Signals in the Prefrontal Cortex 
 
PIs: Dr. John P. O'Doherty and Dr. Doris Tsao 
Institution: California Institute of Technology
PROJECT SUMMARY
fMRI is the dominant technique for probing human prefrontal cortex functions in cognition, learning and
decision-making. This work is predicated on the assumption that fMRI activation relates in a principled manner
to the underlying neuronal activity in a given area of prefrontal cortex. Yet, virtually nothing is known about how
fMRI activations relate to the underlying neural computations within the prefrontal cortex. The absence of
knowledge in this domain is in contrast to burgeoning work on the relationship between measured fMRI signals
and neural responses in visual areas of the brain, illuminating for instance how neuronal responses in face
responsive areas give rise to fMRI activations in the temporal lobes. Compared to visual cortical areas,
neurons in prefrontal cortex have more sparse, heterogeneous, and functionally distributed response
characteristics, thereby rendering the relationship between neuronal and fMRI responses more enigmatic.
The overarching goal of this proposal is to elucidate the relationship between neuronal computations and fMRI
responses in the same areas of the prefrontal cortex. To achieve this goal we will measure fMRI activity to
identify the locus of activations in prefrontal cortex while separately recording neuronal activity using a multi-
electrode recording system whose placement is guided by those fMRI activations. We will also probe the
neurophysiological basis of functional connectivity typically found between regions of prefrontal cortex in
human fMRI studies, by recording simultaneously from multiple regions identified as being functionally
connected through our fMRI measurements.
 We will first address these questions in macaque monkeys, and then extend our findings directly to
humans, scanning healthy human participants with fMRI, and making use of a rare opportunity to obtain both
intracranial electrophysiological signals and fMRI scans from the prefrontal cortex in a group of human patients
undergoing evaluation for surgical treatment of epilepsy. For behavioral tasks we will draw from the domain of
value-based decision-making, because (a) such tasks involve multiple regions of prefrontal cortex in both
monkey electrophysiology and human fMRI studies, (b) we can use virtually identical tasks with well
constrained behavior in both species, and (c) most importantly, stark discrepancies exist between what is
currently known about the response properties of single neurons in the prefrontal cortex of monkeys and
activations measured with fMRI during decision-making tasks in humans, which are ripe for resolving with our
proposed approach.
 By combining across these different techniques and methodologies in both humans and monkeys, we
will be able to address the question of which aspects of underlying neuronal responses gives r...

## Key facts

- **NIH application ID:** 9988502
- **Project number:** 5R01MH111425-05
- **Recipient organization:** CALIFORNIA INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Matthew A. Howard
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $647,591
- **Award type:** 5
- **Project period:** 2016-09-14 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9988502

## Citation

> US National Institutes of Health, RePORTER application 9988502, Neuronal Substrates of Hemodynamic Signals in the Prefrontal Cortex (5R01MH111425-05). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/9988502. Licensed CC0.

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