Exploring the sensitivity limits of neuronal current imaging with MRI and MEG in the human brain

Introduction Conventional BOLD-fMRI relies on hemodynamic responses that are temporally and spatially indirect markers of neural activity. Developing alternative contrasts, sensitive to neuroelectrical phenomena, is a critical challenge in brain imaging. Spin-lock (SL) fMRI has shown promise in phantom studies for detecting magnetic field changes associated with neuronal activity, but its in-vivo sensitivity and practicality remain unclear. This study evaluated whether SL contrast can effectively detect and localize human neuronal activation, benchmarked against complementary functional modalities, magnetoencephalography (MEG) and 3T BOLD-fMRI, to assess the sensitivity of MR-based neuronal current imaging. Methods Thirteen healthy young volunteers underwent SL-based imaging during 8 Hz visual stimulation, along with BOLD and MEG acquisitions. Subjects viewed quadrant-checkerboard stimuli to elicit localized cortical responses. Two balanced SL contrast mechanisms, rotary excitation (REX) and stimulus-induced rotary saturation (SIRS), were employed. Postprocessing targeted stimulus-locked signal fluctuations using a regression-filtering-rectification strategy. Phantom experiments tested sensitivity and analysis pipeline performance. Results MEG revealed robust stimulus-locked responses in occipital cortex, with estimated local magnetic field amplitudes of ∼0.07 nT. Conventional BOLD-fMRI confirmed reliable hemodynamic activation. In contrast, neither balanced REX nor balanced SIRS produced consistent stimulus-related activation in vivo. Phantom experiments subsequently yielded detection thresholds of 0.2 nT for REX and 0.6 nT for SIRS, exceeding the MEG-estimated physiological field amplitudes. Conclusions Under the present experimental conditions, the tested spin-lock fMRI implementations did not achieve sufficient sensitivity for reliable in-vivo detection of neuronal magnetic fields at 3T. Phantom and MEG-based estimates indicate that physiological field amplitudes in the visual cortex lie below current detection limits. These findings establish quantitative constraints on direct neuronal current imaging with MRI and provide a benchmark for future methodological developments aimed at bridging electrophysiology and functional MRI. Key points We assessed spin-lock fMRI sensitivity using combined SL-fMRI, BOLD-fMRI, MEG, and phantom measurements during visual stimulation. MEG and BOLD-fMRI confirmed robust neuronal and hemodynamic activation in the visual cortex. SL-fMRI did not achieve reliable in-vivo detection of neuronal magnetic fields; phantom sensitivity limits exceeded MEG-estimated physiological field amplitudes.