Exploratory Study of Melatonin Induced Sleep Regularization in Severe Brain Injury

Patients with severe brain injuries often have slow accumulating recoveries of function. In ongoing studies, we have discovered that elements of electrical activity during sleep may correlate with the level of behavioral recovery observed in patients. It is unknown whether such changes are causally linked to behavioral recovery. Sleep processes are, however, associated with several critical processes supporting the cellular integrity of neurons and neuronal mechanisms associated with learning and synaptic modifications. These known associations suggest the possibility that targeting the normalization of brain electrical activity during sleep may aid the recovery process. A well-studied mechanism organizing the pattern of electrical activity that characterizes sleep is the body's release of the substance melatonin. Melatonin is produced in the brain and released at a precise time during the day (normally around 8-10PM) to signal the brain to initiate aspects of the sleep process each day. Ongoing research by other scientists has demonstrated that providing a small dose of melatonin can improve the regular pattern of sleep and help aid sleep induction. Melatonin use has been shown to be effective in the treatment of time change effects on sleep ("jet lag") and mood disturbances associated with changes in daily light cues such as seasonal affective disorder. We propose to study the effects of melatonin administration in patients with severe structural brain injuries and disorders of consciousness. We will measure the patient's own timing of release of melatonin and provide a dose of melatonin at night to test the effects on the electrical activity of sleep over a three month period. In addition to brain electrical activity we will record sleep behavioral data and physical activity using activity monitors worn by the patients. Patient subjects in this study will be studied twice during the three month period in three day inpatient visits where they will undergo video monitoring and sampling of brain electrical activity using pasted electrodes ("EEG"), hourly saliva sampling for one day, and participation in behavioral testing.