This study aims to  externally validate the detection of intrinsci innate lumbosacral spinal cord activity in humans within regions involved in lower urinary tract (LUT) control, building on prior pilot work  from Dr. Khavari’s team[1,2]. While prior work has demonstrated the feasibility of capturing such activity, and despite significant advancements in functional magnetic resonance imaging (fMRI) that have improved our understanding of supraspinal control of bladder function, a substantial gap remains in characterizing real-time spinal cord involvement. The aim of this study was therefore to validate and reproduce an imaging protocol capable of reliably capturing lumbosacral spinal activation in healthy adults during both task-based and resting-state fMRI, using a natural bladder filling paradigm.

Healthy adult men and women (≥18 years old) with no history of urinary symptoms or genitourinary abnormalities were recruited as part of the EDEN research protocol (ClinicalTrials.gov: NCT05218460). Eligibility required a post-void residual (PVR) <100 mL Before scanning, participants ingested 500 mL of water within 5 minutes prior to entering a 3-Tesla Siemens Prisma scanner. The protocol included anatomical imaging followed by alternating resting-state and task-based fMRI under both full and empty bladder conditions. The task-based stimulation used a device designed to trigger a simulated bulbocavernosus reflex (sBCR). Spinal fMRI data were processed with a dedicated pipeline that included the Spinal Cord Toolbox (SCT), FSL (FEAT), and Python scripting for preprocessing. First-level analyses employed FMRIB’s Improved Linear Model (FILM), with Z-statistic images thresholded at Z>3.1 and cluster correction set at p=0.05.

Twelve healthy participants (men and women) were included in the analysis. Detectable lumbosacral spinal cord activation was observed in all participants. Four participants demonstrated activation in the empty-bladder condition, three of whom did not exhibit activation in the full bladder condition. Conversely, seven participants showed activation during the full bladder condition, four of whom did not exhibit activation during the empty bladder condition. Overall, these findings highlight condition-specific activation patterns with limited within-subject overlap between bladder states.

Consistent with prior pilot findings, the detected activation patterns support the reproducibility of capturing lumbosacral spinal cord activity in regions implicated in LUT control. The differences between full and empty bladder conditions suggests state-dependent modulation of spinal networks involved in urinary function. The limited within-subject overlap across conditions  may reflect distinct neural mechanisms underlying storage and voiding phases; however, given the small sample size these findings should be interpreted cautiously and require confirmation in larger cohorts.

This study externally validates a previously developed spinal fMRI protocol and confirms its ability to detect real-time  the lumbosacral spinal cord activation in humans. The identification of condition-specific activation patterns further supports the sensitivity of this approach to physiological bladder states. This validated framework provides a basis  for future studies exploring disease-related alterations in spinal cord activity and, ultimately, for informing the development and evaluation of targeted therapeutic strategies.

Salazar BH, Mazeaud CM, Hoffman KA, Stampas A, Khavari R. Spinal Cord Lower Urinary Tract Control in Humans. Neurourol Urodyn. 2025 Apr 30;nau.70059. doi:10.1002/nau.70059
Hoffman KA, Mazeaud C, Salazar BH, Thompson LN, Stampas A, Karmonik C, et al. Conception and implementation of an MRI-compatible device to elicit the bulbocavernosus reflex for an open spinal cord study. Neurourol Urodyn. 2024 Jun;43(5):1230–7. doi:10.1002/nau.25461