Individuals with Down syndrome have well known cognitive and sensorimotor impairments, however, the underlying neural processes are poorly understood. The objective of this study was to investigate the underlying spatial localization and functional connectivity during voluntary movements of the right index finger. Adults with Down syndrome and healthy control adults participated in this study. Cortical responses were recorded with a 151-channel magnetoencephalographic system. In the Down syndrome group, we observed two distinct patterns of brain activation, an ipsilateral pattern and a contralateral pattern in the low-frequency band. The two distinct patterns of neural activation and the altered underlying network dynamics have not been reported previously, and may reflect differences in sensorimotor organization.