Epilepsy Laboratory

Dr Marita Broberg and Dr Maayke Hunfeld in the Laboratory, 2010

Epilepsy is a disorder of humans and animals that may occur spontaneously or may be triggered by brain disease. It is characterised by an abrupt change in behaviour, which corresponds to a sudden change in the electrical and chemical activity of brain cells. Many different kinds of epileptic attacks occur. They generally last a few minutes and may consist of jerking of arms and legs with unconsciousness (major epilepsy), or simple loss of awareness without any movement (minor epilepsy). Our research addresses processes that occur during the change from normal brain function to occurrence of the epileptic attack (also known as the ‘seizure’). We are focussing on three aspects of seizure initiation: the brain’s electrical activity (in particular high frequency brain rhythms - gamma EEG), the role of the support cells of the brain (astrocytes) and on changes in the size of brain cells at the time of seizure initiation.

Investigators

John O Willoughby, MBBS, PhD, FRACP
Kenneth J Pope, AMusA, BSc(Ma), BEd(Hons), PhD (Cantab)
Marita Broberg, MSc, PhD (Gothenburg)
Sean P Fitzgibbon, BSc(Hons), PhD
Trent W Lewis, BSc(Hons), PhD

Visiting Research Fellows / Scholars

Dr Maayke Hunfeld, MMed, MD(Den Haag), Holland

Contacts

Emeritus Prof John O. Willoughby
Ph: (08) 8204 6125 Int Ph: +61 8 8204 6125 Fax: (08) 8204 5931 Int Fax: +61 8 8204 5931 Email: john.willoughby@flinders.edu.au University Profile Page

Research Projects

We examine epilepsies in humans and seizures in animals treated with specific convulsant drugs. The drugs cause diminished inhibitory activity, induced by the GABAa receptor-chloride channel blocker picrotoxin, or excessive excitability, induced by the glutamate-kainate/AMPA receptor agonist kainic acid. Focal seizures are also induced with an astrocytic metabolic inhibitor (fluorocitrate). Progressive EEG changes occur prior to seizures induced by these agents and they are analysed using comprehensive mathematical analysis of EEG wave-forms. We also measure cell volume by specialised techniques.

• Human EEG analysis
• Cell swelling participating in epileptogenesis in rat models of epilepsy

Collaborative Research

• Prof Andrea Yoole, Department of Physiology, University of Adelaide: We have undertaken preliminary studies of agents altering water transport (aquaporin agonists and antagonists) provided by Prof Yoole. The agents have altered the rates of water movement out of the brain after systemic water infusion, but do not prevent water accumulation in cells. We have yet to test the effect of these agents on seizure induction.

Selected Recent Publications

Mackenzie L, Pope KJ, Willoughby JO (2010) EEG spindles in the rat: Evidence for a synchronous network phenomenon. Epilepsy Res. 89(2-3):194-206

Pope KJ, Fitzgibbon SP, Lewis TW, Whitham EM, Willoughby JO (2009) Relation of gamma oscillations in scalp recordings to muscular activity. Brain Topogr. 22(1):13-7

Bach LA, Berkovic SF, Willoughby JO, Scheffer IE, Reutens DC (2008) Association of a nicotinic receptor mutation with reduced height and blunted physostigmine-stimulated growth hormone release. Journal of Clinical Endocrinology and Metabolism, 93:634-7

Broberg M, Pope KJ, Lewis T, Olsson T, Nilsson M, Willoughby JO (2008) Cell swelling precedes seizures induced by inhibition of astrocytic metabolism. Epilepsy Research, 80:132-41

Whitham EM, Lewis T, Pope KJ, Fitzgibbon SP, Clark CR, Loveless S, DeLosAngeles D, Wallace A, Broberg M, Willoughby JO (2008) Thinking activates EMG in scalp electrical recordings. Clinical Neurophysiology, 119:1166–1175

DeLosAngeles D , Williams G, Burston J, Pope KJ, Clark CR, Loveless S, Lewis T, Whitham E, Fitzgibbon S, Wallace A and Willoughby JO: Electroencephalographic changes during states of Buddhist concentrative meditation. Proceedings of the Scientific Meeting of the International Brain Research Organisation, Melbourne, July 2007

Broberg M, van de Riet S, Pope KJ, Lewis T, Olsson T, Nilsson M, Willoughby JO: Pre-ictal cell-swelling – the first sign of seizure onset. Proceedings of the Scientific Meeting of the International Brain Research Organisation, Melbourne, July 2007

Broberg M, Pope KJ, Nilsson M, Wallace A, Wilson J, Willoughby JO. (2007) Preseizure increased gamma electroencephalographic activity has no effect on extracellular potassium or calcium. J Neurosci Res. 85(4):906-18

Whitham EM, Pope KJ, Fitzgibbon SP, Lewis T, Clark RC, Loveless S, Willoughby JO: Scalp EEG during paralysis: augmented gamma activity can be detected during cognitive processing. Proceedings of the Scientific Meeting of the International Brain Research Organisation, Melbourne, July 2007

Whitham EM, Pope KJ, Fitzgibbon SP, Lewis T, Clark CR, Loveless S, Broberg M, Wallace A, DeLosAngeles D, Lillie P, Hardy A, Fronsko R, Pulbrook A, Willoughby JO. (2007) Scalp electrical recording during paralysis: quantitative evidence that EEG frequencies above 20 Hz are contaminated by EMG. Clin Neurophysiol. 118(8):1877-88

 

Updated July 2, 2011