Awakening after a sleeping pill: Restoring functional brain networks after severe brain injury

Hisse Arnts,Willemijn S Van Erp,Lennard I Boon,Conrado A Bosman,Marjolein M Admiraal,Anouk Schrantee,Cyriel M.A Pennartz,Rick Schuurman,Cornelis J Stam,Anne-Fleur Van Rootselaar,Arjan Hillebrand,Pepijn Van Den Munckhof

doi:10.1016/j.cortex.2020.08.011

Abstract

Some patients with severe brain injury show short-term neurological improvements, such as recovery of consciousness, motor function, or speech after administering zolpidem, a GABA receptor agonist. The working mechanism of this paradoxical phenomenon remains unknown. In this study, we used electroencephalography and magnetoencephalography to investigate a spectacular zolpidem-induced awakening, including the recovery of functional communication and the ability to walk in a patient with severe hypoxic-ischemic brain injury. We show that cognitive deficits, speech loss, and motor impairments after severe brain injury are associated with stronger beta band connectivity throughout the brain and suggest that neurological recovery after zolpidem occurs with the restoration of beta band connectivity. This exploratory work proposes an essential role for beta rhythms in goal-directed behavior and cognition. It advocates further fundamental and clinical research on the role of increased beta band connectivity in the development of neurological deficits after severe brain injury.

Highlights

Paradoxical signs of temporary neurological recovery have previously been described in a subgroup of patients with severe brain injury after administering zolpidem, a GABA receptor agonist (Bomalaski, Claflin, Townsend, & Peterson, 2017)
We suggest that the widespread hypoxic-ischemic injury in our patient might have resulted in a similar pathological enhancement of beta band functional connectivity throughout the brain, causing abnormally strong inhibition of behavioral and cognitive functions
We present the neurophysiological results of a single patient, similar effects were seen in both the EEG as MEG recordings, which were made on two different occasions under similar conditions

Summary

Introduction

Paradoxical signs of temporary neurological recovery have previously been described in a subgroup of patients with severe brain injury after administering zolpidem, a GABA receptor agonist (Bomalaski, Claflin, Townsend, & Peterson, 2017). Zolpidem has gained considerable research interest in recent years, as its action mechanism may represent a new treatment for patients with a variety of neurological disorders. This action mechanism and the reason for zolpidem’s selective activity remain largely unknown

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