title: Thalamic stimulation to improve level of consciousness after seizures: evaluation of electrophysiology and behavior.
abstract: OBJECTIVE
  Understanding the neural mechanisms that support human consciousness is an important frontier in neuroscience and medicine. We previously developed a rodent model of temporal lobe seizures that recapitulates the human electroencephalography (EEG) signature of ictal and postictal neocortical slow waves associated with behavioral impairments in level of consciousness. The mechanism of slow-wave production in epilepsy may involve suppression of the subcortical arousal systems including the brainstem and intralaminar thalamic nuclei. We hypothesized that intralaminar thalamic stimulation may lead to electrophysiologic and functional rescue from postictal slow waves and behavioral arrest.
  
  
  METHODS
  We electrically stimulated the central lateral thalamic nucleus (a member of the intralaminar nuclei) under anesthesia and after electrically induced hippocampal seizures in anesthetized and in awake-behaving animal model preparations.
  
  
  RESULTS
  We demonstrated a proof-of-principle restoration of electrophysiologic and behavioral measures of consciousness by stimulating the intralaminar thalamic nuclei after seizures. We measured decreased cortical slow waves and increased desynchronization and multiunit activity in the cortex with thalamic stimulation following seizures. Functionally, thalamic stimulation produced resumption of exploratory behaviors in the postictal state.
  
  
  CONCLUSIONS
  Targeting of nodes in the neural circuitry of consciousness has important medical implications. Impaired consciousness with epilepsy has dangerous consequences including decreased school/work performance, social stigmatization, and impaired airway protection. These data suggest a novel therapeutic approach for restoring consciousness after seizures. If paired with responsive neurostimulation, this may allow rapid implementation to improve level of consciousness in patients with epilepsy.
authors.affiliation: Department of Neurology, Yale University School of Medicine, New Haven, Connecticut, U.S.A.
authors.forename: Abhijeet
authors.initials: A
authors.lastname: Gummadavelli
authors.forename: Joshua E
authors.initials: JE
authors.lastname: Motelow
authors.forename: Nicholas
authors.initials: N
authors.lastname: Smith
authors.forename: Qiong
authors.initials: Q
authors.lastname: Zhan
authors.forename: Nicholas D
authors.initials: ND
authors.lastname: Schiff
authors.forename: Hal
authors.initials: H
authors.lastname: Blumenfeld
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000503:physiopathology*; D003243:Consciousness / Q000502:physiology*; D003244:Consciousness Disorders / Q000209:etiology / Q000503:physiopathology*; D004558:Electric Stimulation / Q000379:methods*; D004569:Electroencephalography; D055724:Electrophysiological Phenomena; D020646:Intralaminar Thalamic Nuclei; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000150:complications / Q000503:physiopathology*
keywords: Consciousness; Cortical slow waves; Deep brain stimulation; Epilepsy; Postictal; Thalamus