Nocturnal sleep features in narcolepsy: a model-based approach

The internal structure of night sleep in subjects with narcolepsy significantly differs as compared to the controls. The differences consist in the presence of sleep onset REM periods (SOREMPs) and in a longer duration (120 minutes versus 90 minutes) of the NREM-REM cycles. Another difference consists in the lack of increase in REM sleep duration during the night, cycle after cycle. These characteristics, taken as a whole, suggest that the sleep structure of narcoleptic patients is due to an imbalance between the homeostatic process and the enhanced pressure of REM inducing mechanisms. With regard to the intrasleep dynamics the current extension of the Two-process model cannot give a satisfactory explanation because REM sleep is included as an external trigger with no intrinsic rhythmic property. Neurobiologic studies lead to consider the REM cyclic occurrence as the result of reciprocal interaction between two populations of REM-ON and REM-OFF cells. The introduction in the Two-process-model extended to the intra-night dynamics of an ultradian oscillator, based on a REM-ON--REM-OFF reciprocal interaction, allows the theoretical possibility to simulate a SOREMP. This revised model accounts for the progressive extension of REM sleep-periods duration in the course of the night. The sleep structure of narcoleptic patients can be simulated leaving unaltered the pressure of the homeostatic process and enhancing the REM inducing pressure. Such an enhanced REM pressure can be achieved by increasing the value of the numerical coefficient, which represents the strength of connection between the two types of REM-ON and REM-OFF cells. This modification allows not only to obtain a stronger ultradian oscillator but also a longer periodicity of REM sleep occurrence. By coupling the homeostatic process, considered as normal, to such a modified ultradian oscillator, our model can explain the intra-night sleep dynamics of narcoleptic subjects. A REM-ON REM-OFF dysregulation can be hypothesized to explain the pathophysiological basis of nocturnal sleep features in narcolepsy.