| The laboratory tools available for clinically monitoring changes to neuromuscular function are based on electroneurography and electromyography, which measure the electrical events associated with nerve conduction, neuromuscular transmission, and muscle fiber electrical activation. Alternatively, near-infrared spectroscopy (NIRS) is a non-invasive optical tool with promising diagnostic potential. Using NIRS, an optical signal was recently discovered following brief electrical stimulation of the peripheral nerve in human subjects. The focus of the work presented here is to understand the biological origin of this signal. The central hypothesis was that it describes changes in light absorption, caused by tissue translation induced by muscle contraction. To test this hypothesis, experiments were conducted using both human subjects and a newly developed animal model of the signal. Using the animal model, signals were obtained after pharmacologically and surgically disconnecting the nerve from its muscle, thereby eliminating muscle motion as a possibility. These manipulations had the effect of eliminating the optical signal. In an experiment in human subjects, stimulation of mixed sensory/motor nerves was found to induce large amplitude optical responses, while pure sensory nerve stimulation did not. When measurements were made directly from exposed muscles of the animal model, their waveform features were found to precisely follow the time course and amplitude of isometric muscle contraction. In particular, the signals could distinguish the soleus muscle from the gastrocnemius, on the basis of their time course. Finally, in a study of human subjects at risk for neuromuscular disease associated with diabetes, the NIRS optical response and the force generated from single twitches of abductor pollicis brevis, induced by median nerve stimulation, were shown to be lower in amplitude than those obtained from age and gender-matched control subjects.;The results of these experiments indicate that this signal reflects the mechanical events associated with muscle contraction. Moreover, their time course and amplitude are highly correlated to that of muscle contraction. Finally, these signals have different morphologies in a population of subjects diagnosed with diabetes. Together, these data indicate that these signals have great potential as a noninvasive tool for monitoring the contractile health of muscle. |
