# Direct sub-second measurement of neuromodulator signaling during risky decision-making

> **NIH NIH R01** · VIRGINIA POLYTECHNIC INST AND ST UNIV · 2021 · $654,439

## Abstract

PROJECT SUMMARY
Much work in decision neuroscience has been predicated on the hypothesis that dopaminergic signaling plays
a critical role in value representations and their updating, and recent work has linked abnormalities in such
value representations to specific features of psychiatric illness (e.g., anhedonia in major depression). However,
despite the fundamental role that risk plays in evaluating choice options as well as the role sensitivity to risk
plays in psychiatric illness, including anxiety disorders at one extreme and health risk behaviors like substance
use at another other, an understanding of the neurobiology of risk remains elusive. Indirect evidence from
pharmacological studies have suggested both serotoninergic and noradrengergic signaling may play roles in
representations of risk; however, direct measurement of serotonin or norepinephrine signaling during risky
choice has yet to be examined in humans.
Recent advances by MPI Montague’s group allow the unprecedented ability to track neuromodulator
responses with high temporal resolution and chemical specificity. Specifically, MPI Montague’s team is able to
directly and simultaneously measure dopamine and serotonin responses in awake humans with the temporal
resolution (~ 1 ms) required to examine the relationship of neuromodulator release with decision-making
processes. For signal identification and extraction, the recording method uses machine-learning algorithms
(elastic net regression) combined with electrochemistry using only off-the shelf hardware and software. The
product of this ‘elastic net electrochemistry’ is recordings of in vivo neuromodulator fluctuations at sub-second
resolution. This application merges the decision neuroscience expertise of MPI King-Casas with these
advances of MPI Montague to directly examine serotonergic, noradrenergic, and dopaminergic functioning
during risky choice.
To achieve this goal, we will record neuromodulator responses in participants with medication-resistant
epilepsy who already have intracranial depth electrodes in place for phase-II monitoring. Depth electrodes will
be implanted by our neurosurgery colleagues at Virginia Tech’s medical affiliate Carilion Clinic (Carilion Clinic
PI: Witcher). During recording, participants will perform i) a risk elicitation task (Holt & Laury type task) and ii) a
reward learning task (multi-arm bandit task) that have been shown by our group and others both to reliably
evoke neural responses associated with risk and representations as they are monitored in a standard (i.e.,
non-surgical) hospital suite. Depth recordings will be made using a standard montage that includes multiple
contacts along the dorsal-rostral axis of the medial prefrontal cortex.

## Key facts

- **NIH application ID:** 10141302
- **Project number:** 5R01MH122948-02
- **Recipient organization:** VIRGINIA POLYTECHNIC INST AND ST UNIV
- **Principal Investigator:** Brooks Casas
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $654,439
- **Award type:** 5
- **Project period:** 2020-04-08 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10141302

## Citation

> US National Institutes of Health, RePORTER application 10141302, Direct sub-second measurement of neuromodulator signaling during risky decision-making (5R01MH122948-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10141302. Licensed CC0.

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