# Modulating spinal interoceptive pathways to evaluate their role and therapeutic potential in MDD symptomatic domains

> **NIH NIH R61** · UNIVERSITY OF CINCINNATI · 2024 · $898,025

## Abstract

Project summary
Spinal interoceptive pathways (SIPs) convey bodily signals to an interoceptive system in the brain and their
dysregulation is linked to major depressive disorder (MDD). Current treatments are partially effective and the
role of SIPs in MDD is vastly unexplored. Preliminary data suggests that SIPs are feasible therapeutic targets
in MDD. The central hypothesis is that non-invasive spinal cord stimulation will modulate SIPs to elucidate their
role and therapeutic potential in MDD using an R61/33 phased innovation approach.
R61 phase specific aims (SA). The specific goal will be to evaluate spinal and brain-based SIPs target
engagement markers of transcutaneous spinal direct current stimulation (tsDCS) in MDD with two SAs:
SA1) To determine tsDCS SIPs modulation using laser-evoked potentials (LEPs) as
electroencephalography (EEG)- based neural measures of target engagement.
SA2) To evaluate optimal tsDCS dose based upon tolerability and SIPs target engagement markers.
Anodal tsDCS will be evaluated as a tool to modulate SIPs in MDD. SIPs (Aδ and C fibers) can be evaluated
via LEPs as neural measures (EEG) elicited in MDD-relevant brain regions within an interoceptive system.
Prior data shows anodal tsDCS inhibits SIPs and LEPs N2 component will be assessed as tsDCS engagement
markers. Adults with MDD (n=67) will participate in a double-blind, crossover, sham-controlled study to
evaluate tsDCS at 0,2.5,3, and 3.5 mA. The working hypothesis is that tsDCS will induce a change in LEPs
(SA1) in a dose-dependent and tolerable manner (SA2), supporting their use as SIPs engagement markers.
Go/No-Go milestones: Compared to sham, the active tsDCS dose that induces a change in LEPs at a pre-
established threshold will be evidence of SIPs engagement and “Go” criteria for the R33 phase.
R33 phase SAs. The most robust LEPs-based SIPs engagement markers at a well-tolerated dose from the
R61 phase will be replicated and used to evaluate tsDCS effects on MDD symptoms with three SAs:
SA3) To replicate R61 phase tsDCS LEPs-based SIPs engagement markers (as required by RFA).
SA4) To determine tsDCS effects on MDD symptomatic domains, safety, and tolerability.
SA5) To evaluate SIPs engagement markers as predictors of change in MDD symptomatic domains.
Adults with MDD (n=80) will participate in an 8-week, double-blind, parallel-group, sham-controlled study.
Based on pilot data, we will evaluate tsDCS (3/week) SIPs modulation effects on symptom severity score
(primary outcome), safety, tolerability, and secondary/exploratory domains. The working hypothesis is that
tsDCS will improve symptom severity (primary) in a safe and tolerable manner, and that SIPs engagement
markers will be replicated (SA3 & 4). LEPs-based markers will also predict change in symptoms (SA5).
Results from this study will support the development of tsDCS as an innovative and feasible SIPs
neuromodulation tool with therapeutic potential and will inform on SIPs role in MDD symptomatic do...

## Key facts

- **NIH application ID:** 10869491
- **Project number:** 1R61MH133770-01A1
- **Recipient organization:** UNIVERSITY OF CINCINNATI
- **Principal Investigator:** Francisco Romo-Nava
- **Activity code:** R61 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $898,025
- **Award type:** 1
- **Project period:** 2024-08-15 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10869491

## Citation

> US National Institutes of Health, RePORTER application 10869491, Modulating spinal interoceptive pathways to evaluate their role and therapeutic potential in MDD symptomatic domains (1R61MH133770-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10869491. Licensed CC0.

---

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