# Machine learning-based brain aging morphological signatures of chronic musculoskeletal pain

> **NIH NIH K01** · UNIVERSITY OF FLORIDA · 2024 · $126,333

## Abstract

Project Summary/Abstract.
Chronic musculoskeletal (MSK) pain is experienced by millions in the United States (US), with highest
prevalence in older adults, leading to disability. An approach to attain improvement in diagnosis and treatment
that has gained momentum over the last decade is to increase understanding of the neural underpinnings of
chronic pain by looking at the associated brain changes. Biomarkers of healthy brain aging, derived from machine
learning (ML) models that map MRI patterns to chronological age, offer a look at these pathological changes
since deviations from healthy brain aging indicate potential underlying pathologies. The Predicted brain Age
Difference (PAD; predicted brain age minus chronological age), proposed as a biomarker of disease, was found
to be higher with the presence, and positively correlated with the severity, of MSK pain. However, because it is
based on a ‘global’ brain age measure, the PAD is limited to signal a ‘poorer health’ state without specifying the
type of underlying pathology. This project proposes to develop novel spatially distributed brain age measures
(brain age maps) able to capture the brain atrophy signature of different MSK conditions like chronic back pain,
osteoarthritis and neck or shoulder pain. These brain age maps will be obtained from T1-weighted MRIs via very
innovative convolutional neural network (CNN) architectures that fuse local and global mechanisms of contextual
information in the image using the so-called “transformers”. The project then proposes to develop biomarkers
specific to these MSK types informed by the brain age maps via CNNs and the so-called “vision transformers”,
a cutting-edge methodology ideal for image classification. By accomplishing these goals, this project will reveal
useful information about distinct neurobiological mechanisms of different MSK types and their determinants (e.g.,
aberrant sensory testing or resting functional networks), and how brain age is associated to the multidimensional
experience of pain. This could be particularly useful to understand the causes of the high MSK prevalence in
older adults. For example, the highest MSK prevalence in older adults might be the consequence of a more
‘natural’ accelerated brain aging, in contrast to more ‘insult-like’ causes in younger adults. Thus, the project also
aims to investigate possible age-related differences in PAD maps of MSK. Finally, we evaluate the brain age
maps’ ability prognosticate chronic pain chronification and pain-related functional decline. This proposal is
powered by the tens of thousands of participants with MRI and pain data in the UK Biobank and leverages the
University of Florida’s Artificial Intelligence (AI) Initiative, endowed with one of the most powerful high
performance computing infrastructures across universities in the US. With this significant study, the applicant
pursues an independent career as an expert in ML/AI methodologies to be used to identify novel pain and...

## Key facts

- **NIH application ID:** 10886872
- **Project number:** 1K01AG083228-01A1
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Pedro Antonio Valdes Hernandez
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $126,333
- **Award type:** 1
- **Project period:** 2024-06-15 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10886872

## Citation

> US National Institutes of Health, RePORTER application 10886872, Machine learning-based brain aging morphological signatures of chronic musculoskeletal pain (1K01AG083228-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10886872. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*
