Deep brain stimulation of brainstem arousal circuits: manipulating sleep and wakefulness

Thesis

Arousal is modulated through the projections of brainstem areas, such as the Pedunculopontine Nucleus (PPN) and the Locus Coeruleus (LC), to a wider network of brain areas. These nuclei deliver activating afferents to cortical regions, while associated pathology and particularly neurodegenerative changes lead to disrupted sleep and diurnal patterns.

We sought to develop a method for surgical neuromodulation of arousal circuits in order to manipulate sleep states in the human, utilising overlaps between current therapeutic indications of deep brain stimulation (DBS) targeting and these crucial sleep-modulating networks for our pilot experiments. We additionally sought to explore the mechanisms that underpin transitions to quiet wakefulness both prior to and after brainstem stimulation, in order to further understand relevant circuit dynamics. Finally, we applied some of the insights from this combined process in an effort to ameliorate sleep and wake regulation pathologies in two patients who had been implanted with a novel device.

This work could help optimise stimulation protocols in disorders of sleep and consciousness, advancing device development and broadening the indications for DBS therapies.

Authors: Stavropoulou-Deli, A

• DOI: 10.5287/ora-rvy6gk4qd
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English
• Keywords: brainstem; sleep modulation; deep brain stimulation; implantable devices; neurotechnology
• Subjects: Sleep; Deep brain stimulation; Functional neurosurgery; Neurotechnology (bioengineering); Circadian rhythms; Sleep disorders; Neurophysiology; Neuromodulation