A quantitative comparison of BOLD fMRI responses to noxious and innocuous stimuli in the human spinal cord

Recent studies have shown that functional magnetic resonance imaging (fMRI) can non-invasively assess spinal cord activity. Yet, a quantitative description of nociceptive and non-nociceptive responses in the human spinal cord, compared with random signal fluctuations in resting state data, is still lacking. Here we have investigated the intensity and spatial extent of blood oxygenation level dependent (BOLD) fMRI responses in the cervical spinal cord of healthy volunteers, elicited by stimulation of the hand dorsum (C6-C7 dermatomes). In a block design fMRI paradigm, periods (20 s each) of repetitive noxious (laser heat) or innocuous (brushing) stimulation were alternated with rest. To estimate the level of false positive responses, functional images were acquired during a separate run while subjects were at rest. In a first analysis of averaged peri-stimulus signals from all voxels within each half of the spinal cord, we found bilateral fMRI responses to both stimuli. These responses were significantly larger during noxious than during innocuous stimulation. No significant fMRI signal change was evident over corresponding time periods during the Rest run. In a second, general linear model analysis, we identified a voxel population preferentially responding to noxious stimulation, which extended rostro-caudally over the length (4 cm) of the explored spinal cord region. By contrast, we found no evidence of voxel populations responding uniquely to innocuous stimuli, or showing decreased activity following either kind of somatosensory stimulus. These results provide the first false-positive-controlled comparison of spinal BOLD fMRI responses to noxious and innocuous stimuli in humans, confirming and extending physiological information obtained in other species.