The neurophysiological substrates underlying motor imagery are now well established. However, the neural processes of motor inhibition while mentally rehearsing an action are poorly understood. This concern has received limited experimental investigations leading to divergent conclusions. Whether motor command suppression is mediated by specific brain structures or by intracortical facilitation/inhibition is a matter of debate. Interestingly, although motor commands are inhibited during motor imagery (MI) in healthy participants, spinal cord injury may result in weakened motor inhibition. Using magnetoencephalography, we observed that mental and actual execution of a goal-directed pointing task elicited similar primary motor cortex activation in a C6-C7 quadriplegic patient, thus confirming the hypothesis of weakened motor inhibition during MI. In an age-matched healthy control participant, however, primary motor area activation during MI was significantly reduced compared to physical practice. Brain activation during actual movement resulted in enhanced recruitment of premotor areas in the patient. In the healthy participant, we found functional relationships between the primary motor area and peri-rolandic sites including the primary sensory area and the supplementary motor area during MI. This neural network was not activated when the quadriplegic patient performed MI. We assume that the primary sensory area and the supplementary motor area may be part of a functional network underlying motor inhibition during MI. These data provide insights into brain function changes due to neuroplasticity after spinal cord injury and evidence cortical substrates underlying weakened motor inhibition during MI after deafferentation and deefferentation.