Resting-state functional connectivity changes in the human brain from electrically-stimulated (2 Hz), rhythmic muscle...

Sensory nerves from contracting skeletal muscles can alter autonomic functions mediated by connections in the medulla and hypothalamus. We hypothesized that low-frequency, non-voluntary, rhythmical electrical stimulation of small muscles of the hand, in contrast to continuous sensory stimulation of the overlying skin, will change functional connectivity in the brain revealing specific regions of the muscle afferent-pituitary axis. Using a 2x2 design, eight healthy young participants underwent resting-state functional magnetic resonance imaging (rsfMRI) immediately before and after a 45-min electrical stimulation session with 2 Hz to the left hand muscles and a counterbalanced session with continuous 100 Hz skin stimulation to the same region. Using standardized CONN toolbox software, functional connectivity data were analyzed. Rhythmic muscle stimulation led to significant differences in connectivity associated with the autonomic and limbic systems such as the hypothalamus, amygdala, periaqueductal gray, thalamus, basal ganglia, plus insulae and cingulate cortices. In addition, the muscle stimulation led to changes in several resting state networks. Importantly, using a tightly controlled 2x2 rsfMRI design, the different stimulation protocols were applied to each subject (within-subject design), which led to significant differences in patterns of functional connectivity changes after the muscle versus skin stimulation conditions with only a small number of participants. In conclusion, significant differences in brain networks involving autonomic and limbic systems were activated by using low-frequency, rhythmical stimulation of small hand muscles. In contrast to skin electrical stimulation, which primarily entailed exteroceptive input, muscle electrical stimulation significantly engaged neural networks implicated in interoception, including the insula and hypothalamus.