title: Dynamic neurovascular coupling and uncoupling during ictal onset, propagation, and termination revealed by simultaneous in vivo optical imaging of neural activity and local blood volume.
abstract: Traditional models of ictal propagation involve the concept of an initiation site and a progressive outward march of activation. The process of neurovascular coupling, whereby the brain supplies oxygenated blood to metabolically active neurons presumably results in a similar outward cascade of hyperemia. However, ictal neurovascular coupling has never been assessed in vivo using simultaneous measurements of membrane potential change and hyperemia with wide spatial sampling. In an acute rat ictal model, using simultaneous intrinsic optical signal (IOS) and voltage-sensitive dye (VSD) imaging of cerebral blood volume and membrane potential changes, we demonstrate that seizures consist of multiple dynamic multidirectional waves of membrane potential change with variable onset sites that spread through a widespread network. Local blood volume evolves on a much slower spatiotemporal scale. At seizure onset, the VSD waves extend beyond the IOS signal. During evolution, spatial correlation with hemodynamic signal only exists briefly at the maximal spread of the VSD signal. At termination, the IOS signal extends spatially and temporally beyond the VSD waves. Hence, vascular reactivity evolves in a separate but parallel fashion to membrane potential changes resulting in a mechanism of neurovascular coupling and uncoupling, which is as dynamic as the seizure itself.
authors.affiliation: Department of Neurological Surgery, Weill Cornell Medical College, New York, NY 10065, USA. Hom2001@med.cornell.edu
authors.forename: Hongtao
authors.initials: H
authors.lastname: Ma
authors.forename: Mingrui
authors.initials: M
authors.lastname: Zhao
authors.forename: Theodore H
authors.initials: TH
authors.lastname: Schwartz
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008959:Models, Neurological; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D061848:Optical Imaging; D026902:Potassium Channel Blockers / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology; D013003:Somatosensory Cortex / Q000098:blood supply* / Q000166:cytology*; D013997:Time Factors; D056969:Voltage-Sensitive Dye Imaging
chemical_list: D026902:Potassium Channel Blockers; D015761:4-Aminopyridine