Neuromodulation of sleep rhythms in schizophrenia: Towards the rational design of non-invasive brain stimulation.

Brain function critically depends on oscillatory synchronization of neuronal populations both during wake and sleep. Originally, neural oscillations have been discounted as an epiphenomenon. More recently, specific deficits in the structure of brain oscillations have been linked to psychiatric diseases. For example, schizophrenia is hallmarked by abnormalities in different brain oscillations. Key sleep rhythms during NEM sleep such as sleep spindles, which are implicated in memory consolidation and are related to cognitive functions, are strongly diminished in these patients compared to healthy controls. To date, it remains unclear whether these reductions in sleep oscillations are causal for the functional impairments observed in schizophrenia. The application of non-invasive brain stimulation permits the causal examination of brain network dynamics and will help to establish the causal association of sleep oscillations and symptoms of schizophrenia. To accomplish this, stimulation paradigms that selectively engage specific network targets such as sleep spindles or slow waves are needed. We propose that the successful development and application of these non-invasive brain stimulation approaches will require rational design that takes network dynamics and neuroanatomical information into account. The purpose of this article is to prepare the grounds for the next steps towards such rational design of non-invasive stimulation, with a special focus on electrical and auditory stimulation. First, we briefly summarize the deficits in network dynamics during sleep in schizophrenia. Then, we discuss today's and tomorrow's non-invasive brain stimulation modalities to engage these network targets.