# Characterizing the Sensory and Affective Neural Components of Persistent Dyspnea

> **NIH NIH R01** · FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH · 2022 · $414,727

## Abstract

Abstract:
The neuronal circuitry underlying respiration has been investigated thoroughly within the brainstem. In recent
years, mounting evidence in animals and humans has revealed that ‘higher-level’ brain structures above the
brainstem modulate key aspects of respiration, a finding that has important implications to design effective
treatments for patients suffering from certain types of respiratory disease. This is especially relevant for cases
where lung disease is not reversible and where neural or psychogenic influences are suspected, as in some
forms of COPD, asthma, interstitial lung disease, cardiac and neuromuscular diseases, as well as palliative care
and COVID-19. The overall aim of this proposal is to determine how higher-level brain regions interfere
with automatic brainstem respiratory circuits to give rise to the complex pathology underlying
respiratory disease in humans. To answer this question, we use a model of dyspnea (breathing discomfort)
which is one of the leading symptoms (rivaling chronic pain) that cause approximately 10% of the general
population to seek medical care. Patients suffering from persistent dyspnea choose descriptors such as “feeling
suffocated” and “feeling like air is more precious than water”. Dyspnea is the result of an imbalance between the
neural drive to breathe and the corresponding respiratory-related afferents. Current treatments that target the
brain (rather than the lungs) to alleviate dyspnea are limited to opioids and/or benzodiazepines, but these drugs
can suppress ventilatory drive, produce dependence and contribute to hypercapnic respiratory failure. We work
towards meeting the clinical need of finding a treatment that reduces dyspnea without reducing
ventilatory drive, by providing a better understanding of the cortical mechanisms that modulate
respiratory-related afferents and ultimately shape the subjective sensations of dyspnea.
 Available evidence on the neural substrates of dyspnea in humans comes from noninvasive EEG and
fMRI studies which do not afford the level of resolution required to access the deep sources involved in dyspnea
nor disentangle the temporal dynamics of its different components (sensory and affective). We will utilize
intracranial recordings (iEEG) from multiple cortical and subcortical regions in patients with chronically
implanted electrodes for reasons unrelated to the present study (undergoing epilepsy treatment) and leverage
on our recent finding that neural oscillations in these regions, recorded using iEEG, track the respiratory cycle,
the so called Respiratory-Related Brain Oscillations (RRBO). The proposed experiments aim to:
Aim 1: Further characterize RRBO: Determining causality between brain oscillations and the breathing cycle.
Aim 2: Validate RRBO as neural marker of dyspnea: Detecting neural features of dyspnea in RRBO recorded
in the primary (sensory dyspnea dimension) and secondary (affective dyspnea dimension) interoceptive cortex.
Aim 3: Using di...

## Key facts

- **NIH application ID:** 10419096
- **Project number:** 1R01HL163578-01
- **Recipient organization:** FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH
- **Principal Investigator:** Jose Luis Herrero Rubio
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $414,727
- **Award type:** 1
- **Project period:** 2022-08-05 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10419096

## Citation

> US National Institutes of Health, RePORTER application 10419096, Characterizing the Sensory and Affective Neural Components of Persistent Dyspnea (1R01HL163578-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10419096. Licensed CC0.

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