No abstract

Loss of organized sleep electrophysiology is a characteristic finding following severe brain injury. The return of structured elements of sleep architecture has been associated with positive prognosis across injury etiologies, suggesting a role for sleep dynamics as biomarkers of wakeful neuronal circuit function. In a continuing study of one minimally conscious state patient studied over the course of ~8½ years, we sought to investigate whether changes in daytime brain activation induced by central thalamic deep brain stimulation (CT-DBS) influenced sleep electrophysiology. In this patient subject, we previously reported significant improvements in sleep electrophysiology during 5½ years of CT-DBS treatment, including increased sleep spindle frequency and SWS delta power. We now present novel findings that many of these improvements in sleep electrophysiology regress following CT-DBS discontinuation; these regressions in sleep features correlate with a significant decrease in behavioral responsiveness. We also observe the re-emergence of alpha-delta sleep, which had been previously suppressed by daytime CT-DBS in this patient subject. Importantly, CT-DBS was only active during the daytime and has been proposed to mediate recovery of consciousness by driving synaptic activity across frontostriatal systems through the enhancement of thalamocortical output. Accordingly, the improvement of sleep dynamics during daytime CT-DBS and their subsequent regression following CT-DBS discontinuation implicates wakeful synaptic activity as a robust modulator of sleep electrophysiology. We interpret these findings in the context of the “synaptic homeostasis hypothesis,” whereby we propose that daytime upregulation of thalamocortical output in the severely injured brain may facilitate organized frontocortical circuit activation and yield net synaptic potentiation during wakefulness, providing a homeostatic drive that reconstitutes sleep dynamics over time. Furthermore, we consider common large-scale network dynamics across several neuropsychiatric disorders in which alpha-delta sleep has been documented, allowing us to formulate a novel mechanistic framework for alpha-delta sleep generation. We conclude that the bi-directional modulation of sleep electrophysiology by daytime thalamocortical activity in the severely injured brain: (1) emphasizes the cyclical carry-over effects of state-dependent circuit activation on large-scale brain dynamics, and (2) further implicates sleep electrophysiology as a sensitive indicator of wakeful brain activation and covert functional recovery in the severely injured brain.

The persistent vegetative state (PVS) is one of the most iconic and misunderstood phrases in clinical neuroscience. Coined as a diagnostic category by Scottish neurosurgeon Bryan Jennett and American neurologist Fred Plum in 1972, the phrase "vegetative" first appeared in Aristotle's treatise On the Soul (circa mid-fourth century BCE). Aristotle influenced neuroscientists of the nineteenth and early-twentieth centuries, Xavier Bichat and Walter Timme, and informed their conceptions of the vegetative nervous system. Plum credits Bichat and Timme in his use of the phrase, thus putting the ancient and modern in dialogue. In addition to exploring Aristotle's definition of the "vegetative" in the original Greek, we put Aristotle in conversation with his contemporaries-Plato and the Hippocratics-to better apprehend theories of mind and consciousness in antiquity. Utilizing the discipline of reception studies in classics scholarship, we demonstrate the importance of etymology and historical origin when considering modern medical nosology.