title: Characterisation and imaging of cortical impedance changes during interictal and ictal activity in the anaesthetised rat.
abstract: Epilepsy affects approximately 50 million people worldwide, and 20-30% of these cases are refractory to antiepileptic drugs. Many patients with intractable epilepsy can benefit from surgical resection of the tissue generating the seizures; however, difficulty in precisely localising seizure foci has limited the number of patients undergoing surgery as well as potentially lowered its effectiveness. Here we demonstrate a novel imaging method for monitoring rapid changes in cerebral tissue impedance occurring during interictal and ictal activity, and show that it can reveal the propagation of pathological activity in the cortex. Cortical impedance was recorded simultaneously to ECoG using a 30-contact electrode mat placed on the exposed cortex of anaesthetised rats, in which interictal spikes (IISs) and seizures were induced by cortical injection of 4-aminopyridine (4-AP), picrotoxin or penicillin. We characterised the tissue impedance responses during IISs and seizures, and imaged these responses in the cortex using Electrical Impedance Tomography (EIT). We found a fast, transient drop in impedance occurring as early as 12ms prior to the IISs, followed by a steep rise in impedance within ~120ms of the IIS. EIT images of these impedance changes showed that they were co-localised and centred at a depth of 1mm in the cortex, and that they closely followed the activity propagation observed in the surface ECoG signals. The fast, pre-IIS impedance drop most likely reflects synchronised depolarisation in a localised network of neurons, and the post-IIS impedance increase reflects the subsequent shrinkage of extracellular space caused by the intense activity. EIT could also be used to picture a steady rise in tissue impedance during seizure activity, which has been previously described. Thus, our results demonstrate that EIT can detect and localise different physiological changes during interictal and ictal activity and, in conjunction with ECoG, may in future improve the localisation of seizure foci in the clinical setting.
authors.affiliation: Dept. of Medical Physics and Biomedical Engineering, University College London, UK. Electronic address: anna.vongerichten@uniklinik-freiburg.de.
authors.forename: Anna N
authors.initials: AN
authors.lastname: Vongerichten
authors.affiliation: Dept. of Medical Physics and Biomedical Engineering, University College London, UK.
authors.forename: Gustavo Sato Dos
authors.initials: GSD
authors.lastname: Santos
authors.affiliation: Dept. of Medical Physics and Biomedical Engineering, University College London, UK.
authors.forename: Kirill
authors.initials: K
authors.lastname: Aristovich
authors.affiliation: Dept. of Medical Physics and Biomedical Engineering, University College London, UK.
authors.forename: James
authors.initials: J
authors.lastname: Avery
authors.affiliation: Institute of Neurology, University College London, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: McEvoy
authors.affiliation: Institute of Neurology, University College London, UK.
authors.forename: Matthew
authors.initials: M
authors.lastname: Walker
authors.affiliation: Dept. of Medical Physics and Biomedical Engineering, University College London, UK.
authors.forename: David S
authors.initials: DS
authors.lastname: Holder
mesh_terms: D000758:Anesthesia; D000818:Animals; D002540:Cerebral Cortex / Q000473:pathology* / Q000503:physiopathology*; D003292:Convulsants; D017097:Electric Impedance; D004569:Electroencephalography / Q000379:methods / Q000706:statistics & numerical data; D005260:Female; D007091:Image Processing, Computer-Assisted / Q000379:methods; D009415:Nerve Net / Q000473:pathology; D009474:Neurons / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012640:Seizures / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology*; D014054:Tomography / Q000379:methods*
chemical_list: D003292:Convulsants
keywords: EIT; Epilepsy; Imaging; Interictal spike; Seizure; Tissue impedance