Functional MRI determination of a dose-response relationship to lower extremity neuromuscular electrical stimulation in healthy subjects

Although empirical evidence supports the use of neuromuscular electrical stimulation (NMES) to treat physical impairments associated with stroke, the mechanisms underlying the efficacy of this modality are poorly understood. Recent studies have employed functional imagine, to investigations of brain responses to median nerve stimulation. These studies suggest a dose-response relationship may exist between selected stimulation parameters and hemodynamic responses in sensorimotor regions. However, substantial gaps exist in this literature. The present study was designed to address these deficiencies. Ten healthy subjects participated. In phase one, four stimulus intensity levels were established: (1) sensory threshold [Th], (2) (MM-Th)x0.333+Th [low-intermediate level, LI], (3) (MM-Th)x0.666+Th [high-intermediate level, HI], and (4) maximal motor (MM). In phase two, subjects were scanned using a spiral-echoplanar imagine, technique at each stimulus level. Image sets were analyzed to determine hemodynamic responses at the highest Pearson correlation level (r) ascertained for each of five areas of interest (AOI): (1) primary sensory, (2) primary motor, (3) cingulate gyrus, (4) thalamus, and (5) cerebellum. ANOVA demonstrated significant main effects for BOLD signal amplitude (p<0.05) changes in all AOI. Similarly, ANOVA showed significant differences in the volume of activation (p<0.05) with increasing stimulus intensity in four AOI. Secondary analyses of pooled data showed increasing probabilities of activation at higher stimulus intensities within each AOI. Collectively, these data indicate a dose-response relationship exists between lower extremity NMES and brain activation in specific neural regions. The current results, while limited in their generalizability, are foundational for future studies of interventions using NMES.