A medical device system and method for monitoring cardiac signal activity in patients with nervous system disorders. In some embodiments, a brain signal and a cardiac signal are received by a processor, brain events are identified in the brain signal, and the brain events are used to identify portions of the cardiac signal. In some embodiments, Event portions of the cardiac signal are identified corresponding to brain event time periods, and Inter-event portions are identified corresponding to time periods between brain events. An Inter-event heart-rate variability (HRV) calculation is performed using Inter-event portions of the cardiac signal, and an output of the medical device system is modified based upon the calculated Inter-event HRV according to certain embodiments of the invention. An Event HRV may also be calculated according to certain embodiments, and an output modified based on comparisons of the Event HRV to the Inter-event HRV, for example.