Negative amplitude shifts of cortical potential are related to seizure activity in epilepsy. Regulation of the cortical potential with biofeedback has been successfully used to reduce the frequency of some patients' seizures. Although such behavioural treatments are increasingly popular as an alternative to pharmacotherapy, there has been no investigation of the mechanisms that might bridge the behavioural index of peripheral autonomic activity and the central regulation of arousal. Galvanic Skin Response (GSR) is a sensitive measurement of autonomic arousal and physiological state which reflects one's behaviour. Thus we investigated the effect of peripheral autonomic modulation on cortical arousal with the future intention of using GSR biofeedback as a therapeutic treatment for epilepsy. The cortical negative potential was induced using the paradigm called Contingent Negative Variation (CNV) and measured in different physiological states. A high skin resistance state (reflecting a state of relaxation) and a low skin resistance state (reflecting a state of arousal), were engendered by two opposing procedures of GSR biofeedback. The CNV negative potential, acting as an index of cortical excitation, was significantly greater in amplitude at high levels of skin resistance (relaxed state) than at low levels of skin resistance (aroused state). Our results suggest an inverse relationship between a peripheral measure of autonomic arousal and an index of cortical arousal, the CNV. Moreover, we demonstrate modulation of this arousal-related potential by a behavioural intervention, indicating a potential therapeutic use of arousal biofeedback using GSR in the management of treatment-resistant epilepsy.