Myoclonus appears to be generated by a brief transient activation of a focal region of motor cortex. Activation of a focal region of motor cortex can also give rise to a transient depression of function. If a subject, or patient, is trying to produce movement, this depression would lead to a brief lapse in muscle activation that would be interpreted as either asterixis or negative myoclonus. Both positive events and negative events can occur either individually or together. The physiological substrate in the cortex appears to be different for the two phenomena, and the pharmacology may differ as well.