title: Restoring Conscious Arousal During Focal Limbic Seizures with Deep Brain Stimulation.
abstract: Impaired consciousness occurs suddenly and unpredictably in people with epilepsy, markedly worsening quality of life and increasing risk of mortality. Focal seizures with impaired consciousness are the most common form of epilepsy and are refractory to all current medical and surgical therapies in about one-sixth of cases. Restoring consciousness during and following seizures would be potentially transformative for these individuals. Here, we investigate deep brain stimulation to improve level of conscious arousal in a rat model of focal limbic seizures. We found that dual-site stimulation of the central lateral nucleus of the intralaminar thalamus (CL) and the pontine nucleus oralis (PnO) bilaterally during focal limbic seizures restored normal-appearing cortical electrophysiology and markedly improved behavioral arousal. In contrast, single-site bilateral stimulation of CL or PnO alone was insufficient to achieve the same result. These findings support the "network inhibition hypothesis" that focal limbic seizures impair consciousness through widespread inhibition of subcortical arousal. Driving subcortical arousal function would be a novel therapeutic approach to some forms of refractory epilepsy and may be compatible with devices already in use for responsive neurostimulation. Multisite deep brain stimulation of subcortical arousal structures may benefit not only patients with epilepsy but also those with other disorders of consciousness.
authors.affiliation: Department of Neurology.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Kundishora
authors.affiliation: Department of Neurosurgery, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Abhijeet
authors.initials: A
authors.lastname: Gummadavelli
authors.affiliation: Department of Neurology.
authors.forename: Chanthia
authors.initials: C
authors.lastname: Ma
authors.affiliation: Department of Neurology.
authors.forename: Mengran
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Neurology.
authors.forename: Cian
authors.initials: C
authors.lastname: McCafferty
authors.affiliation: Department of Neurology, Weill-Cornell Medical College, New York, NY 10021, USA.
authors.forename: Nicholas D
authors.initials: ND
authors.lastname: Schiff
authors.affiliation: Department of Neurological Surgery.
authors.forename: Jon T
authors.initials: JT
authors.lastname: Willie
authors.affiliation: Department of Neurological Surgery.|Department of Neurology, Emory School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Gross
authors.affiliation: Department of Neurosurgery, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Gerrard
authors.affiliation: Department of Neurology.|Department of Neuroscience.|Department of Neurosurgery, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Hal
authors.initials: H
authors.lastname: Blumenfeld
mesh_terms: D000818:Animals; D001143:Arousal / Q000502:physiology; D003243:Consciousness / Q000502:physiology; D003244:Consciousness Disorders / Q000209:etiology / Q000503:physiopathology / Q000628:therapy*; D046690:Deep Brain Stimulation / Q000379:methods*; D004195:Disease Models, Animal; D004828:Epilepsies, Partial / Q000150:complications / Q000503:physiopathology / Q000628:therapy*; D005106:Exploratory Behavior / Q000502:physiology; D005260:Female; D020646:Intralaminar Thalamic Nuclei / Q000503:physiopathology; D009433:Neural Inhibition / Q000502:physiology; D011149:Pons / Q000503:physiopathology; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000150:complications / Q000503:physiopathology / Q000628:therapy*
keywords: consciousness; epilepsy; intralaminar thalamus; neurostimulation; pontine reticular formation