Epilepsy Laboratory

Dr Marita Broberg: demonstrating cell swelling prior to seizures

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). We are defining processes that occur during the change from normal brain function to the electrical discharge of the epileptic attack. We are focusing on the brain’s electrical activity, in particular high frequency brain rhythms (gamma EEG), on the role of the support cells of the brain (astrocytes) and on changes in the size of brain cells at the time the attack is developing.

Investigators

John O Willoughby, MBBS, PhD, FRACP
Kenneth J Pope, AMusA, BSc(Ma), BE (Hons), PhD (Cantab)
Emma M Whitham, BSc, PhD, MBBCh (Oxon)
Marita Broberg, MSc, PhD (Gothenburg)
Sean P Fitzgibbon, BSc (Hons) PhD
Trent W Lewis, BSc (Hons), PhD
C Richard Clark, BSc (Hons), PhD

Support Staff

Stephen Loveless, BSc, BCSc

Students

Angus Wallace, BSc, BEng, PhD Student
Dylan DeLosAngeles, BSc (Hons), PhD Student

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

Research Projects

Examining the results from the paralysis study
(l to r): Drs Emma Whitham, Kenneth Pope, Mr Steve Loveless, Dr Sean Fitzgibbon

We examine generalised convulsive epilepsy in humans and in animal models of seizure using specific convulsant drugs. The animal models are: 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, infused intravenously. We examine focal epilepsy using intracerebral injections of an astrocytic metabolic inhibitor (fluorocitrate) or focal injection of bicuculline or kainic acid. The characteristics of EEG disturbances and chemical nature of the brain involved in single seizures induced by these agents are determined by comprehensive mathematical analysis of epileptic discharge wave-forms and by measurement of ion-concentration or cell volume by specialised techniques.

• Non-linear analysis of EEG
• Human EEG analysis
• Cell swelling participating in epileptogenesis
• Ions participating in epileptogenesis

Collaborative Research

Physiology of Meditation: Studies of the physiological correlates of meditation have now commenced in the form of a PhD project for D DeLosAngeles. The studies examine the extent to which awareness of external stimuli is altered as a result of the meditative states, and the extent to which meditative states are associated with altered ability to maintain concentration on mental tasks. Our collaborators and co-investigators in this project are Dr Graham Williams (B.Mus (Hons), PhD, Grad. Dip.Ed. and Dip.T, Licence de Concert Ecole Normale de Musique, Paris) and Mr John Burston (BSc) from the Lifeflow Meditation Centre, Fullarton Rd, Beulah Park.

Media Appearances

• Channel 10 News in Adelaide, Sydney and Brisbane: Dr Marita Broberg and Dr Emma Whitham, on migraine and epilepsy and their likely common relationship in neuronal excitability and astrocytic swelling (14 July 2006).
• ABC Radio: Migraine (2003)
• Channel 10 TV: Epilepsy Unit Opening (2003)

Publications

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

Olsson T, Broberg M, Pope KJ, Wallace A, Mackenzie L, F Blomstrand, Nilsson M, Willoughby JO: (2006) Cell swelling, seizures and spreading depression: an impedance study. Neuroscience 140: 505-515

Mackenzie L, Pope KJ, Willoughby JO. (2005) Gamma rhythms are not integral to EEG spindle phenomena. Clin Neurophysiol. 116(4):861-70

Willoughby JO, Mackenzie L, Pope KJ, Broberg M, Nilsson M. (2005) Localised astroglial dysfunction disrupts high-frequency EEG rhythms. J Neural Transm. 112(2):205-13

Fitzgibbon SP, Pope KJ, Mackenzie L, Clark CR, Willoughby JO. (2004) Cognitive tasks augment gamma EEG power. Clinical Neurophysiology 115: 1802-9

Mackenzie L, Pope KJ, Willoughby JO. (2004) Regional distribution of the power of EEG rhythms associated with physiological and pathological spindling phenomena. Brain Research 1008: 92–106

Wallace AK, Pope KJ, Mackenzie L, Willoughby JO. (2003) Epilepsy examined using non-linear analysis of EEG. Proceedings of World Congress on Medical Physics and Biomedical Engineering [CD rom], ISSN 1727-1983

Willoughby JO, Mackenzie L, Broberg M, Thoren AE, Medvedev A, Sims NR, Nilsson M: (2003) Fluorocitrate-mediated astroglial dysfunction causes seizures. J Neurosci Res 74(1): 160-6

Willoughby JO, Fitzgibbon SP, Pope KJ, Mackenzie L, Davey M, Wilcox RA, Clark CR: (2003) Mental tasks induce gamma EEG with reduced responsiveness in primary generalized epilepsies. Epilepsia 44(11):1406-12

Willoughby JO, Pope KJ, Eaton V: (2003) Nicotine as an antiepileptic agent in ADNFLE: an N-of-one study. Epilepsia 44(9):1238-40

Willoughby JO, Fitzgibbon SP, Pope KJ, Mackenzie L, Medvedev AV, Clark CR, Davey MP, Wilcox RA. (2003) Persistent abnormality detected in the non-ictal electroencephalogram in primary generalised epilepsy. J Neurol Neurosurg Psychiatry. 74(1):51-5

Medvedev AV. (2002) Epileptiform spikes desynchronize and diminish fast (gamma) activity of the brain. An "anti-binding" mechanism? Brain Res Bull. 58(1):115-28

Mackenzie L, Medvedev A, Hiscock JJ, Pope KJ, Willoughby JO. (2002) Picrotoxin-induced generalised convulsive seizure in rat: changes in regional distribution and frequency of the power of electroencephalogram rhythms. Clin Neurophysiol. 113(4):586-96

Tran HB, Ohlsson M, Beroukas D, Hiscock J, Bradley J, Buyon JP, Gordon TP. (2002) Subcellular redistribution of la/SSB autoantigen during physiologic apoptosis in the fetal mouse heart and conduction system: a clue to the pathogenesis of congenital heart block. Arthritis Rheum. 46(1):202-8

Hiscock JJ, Mackenzie L, Medvedev A, Willoughby JO. (2001) Kainic acid and seizure-induced Fos in subtypes of cerebrocortical neurons. J Neurosci Res. 66:1094-1100

Medvedev AV. (2001) Temporal binding at gamma frequencies in the brain: paving the way to epilepsy? Australas Phys Eng Sci Med. 24:37-48

Hiscock JJ, Murphy S and Willoughby JO: (2000) Confocal microscopic estimation of GABAergic nerve terminals in the central nervous system. Journal of Neuroscience Methods 95:1-11

Medvedev A, Mackenzie L, Hiscock JJ and Willoughby JO: (2000) Kainic acid induces distinct types of epileptiform discharge with differential involvement of hippocampus and neocortex. Brain Research Bulletin 52:89-98

Willoughby JO: (2000) Mechanisms underlying partial (focal, or lesional) epilepsy (review). Journal of Clinical Neuroscience 7:291-4

Updated March 31, 2008