Epilepsy and Neuropharmacology

  • Group Leader

    Professor Terence O'Brien
    T: + 61 3 8344 5490
    E: obrientj@unimelb.edu.au
    Location: The Department of Medicine, The Royal Melbourne Hospital, 4th Floor, Clinical Sciences Building, Royal Parade, Parkville, 3050
    W: Personal web page

Research Overview

The Research of the Epilepsy and Neuropharmacology Research Group is broad based, covering both basic and clinical studies relevant to epilepsy and related areas, including traumatic brain injury and dementing disorders.

The Group's Research has had two primary goals: First to better understand the determinants of treatment response by identify biomarkers for treatment outcomes – imaging, electrophysiological, genomic and clinical, and to develop new treatment approaches. Second to investigate the fundamental neurobiological basis of the neuropsychiatric co-morbidities present in many patients with epilepsy and related conditions.

The group has an extensive network of collaboratiors, locally, nationally and internationally. We are highly active in research training, with more than 25 PhD students compled over the past 15 years, as well as multiple Masters, Honours, and Medical Students in research. We are always welcoming of new students who are bright and enthusiastic about udertaking basic or clinical research that aims to ultimately made a difference to patients lives. Our research is funded by multiple NHMRC, ARC and international grants, as well as Philanthropic support, in particular from the RMH Neuroscience Foundation, and industry partnerships.

Staff

Funding

  • National Health & Medical Research Council, Australia
  • Australian Research Council
  • National Institutes of Health, US
  • RMH Neuroscience Foundation
  • Industry Partnerships

Competitive, peer-reviewed, research-grant funding obtained totals >$39M, including 14 NHMRC Project grants (CIA on 6), 3 NHMRC Development Grants, a NHMRC Centre for Research Excellence Grant, a NHMRC Program Grant, two Victorian Neurotrauma Initiative Grants and three US competitive grant (NARSAD, Epilepsy Research Foundation & James S. McDonnell Foundation), and industry funding >$5M.

Research Opportunities

This research project is available to PhD students to join as part of their thesis.
Please contact the Research Group Leader to discuss your options.

Research Publications

The group has published >320 peer-reviewed original papers in leading neurological, pharmacological and imaging journals, 6 other papers, 12 book chapters and >2000 abstracts. The work is highly cited (>9300 times, H-index 52, Google Scholar). A brief selection below:

  • Carne R, O’Brien TJ, Kilpatrick C, MacGregor L, Hicks R, Murphy M, Bowden SC, Kaye A, Cook MJ. MRI-negative PET-positive temporal lobe epilepsy: a distinct surgically remediable syndrome. Brain 127:2276-2285 (2004).
  • Vajda F, O’Brien TJ, Hitchcock A, Graham J, Cook M, Lander C, Eadie M. Critical relationship between sodium valproate dose and human teratogenicity results of the Australian register of anti-epileptic drugs in pregnancy. J Clin Neurosci 11(8):854-8 (2004).
  • Petty SJ, Paton LM, O'Brien TJ, Makovey J, Erbas B, Sambrook P, Berkovic SF, Wark JD. Effect of antiepileptic medication on bone mineral measures. Neurology 65:1358-1363 (2005).  
  • Liu L, Zheng T, Morris MJ, Wallengren C, Clarke A, Reid C, Petrou S, O’Brien TJ. The mechanism of carbamazepine aggravation of absence seizures. J Pharmacol Exp Ther 319: 790-798 (2006).  
  • Salzberg M, Kumar G, Supit L, Jones NC, Morris MJ, Rees S, O’Brien TJ. Early postnatal stress confers enduring vulnerability to limbic epileptogenesis. Epilepsia 2007;48:2079-2085.  
  • Jones NC, Salzberg MR, Kumar G, Couper A, Morris MJ, O'Brien TJ. Elevated anxiety and depressive-like behavior in a rat model of genetic generalized epilepsy suggesting common causation. Experimental Neurology 2008;209:254-60.
  • Vinton AB, Carne R, Hicks RJ, Desmond PM, Kilpatrick C, Kaye AH, O’Brien TJ. The extent of resection of FDG-PET hypometabolism relates to outcome of temporal lobectomy. Brain 130(Pt 2):548-60 (2007).  
  • Powell KL, Cain SM, Ng C, Sirdesai S, David LS, Kyi M, Garcia E, Tyson JR, Reid CA, Bahlo M, Foote SJ, Snutch TP, O’Brien TJ. A Cav3.2 T-type calcium channel point mutation has splice variant-specific effects on function and segregates with seizure expression in a polygenic rat model of absence epilepsy. J Neuroscience 2009;29:371-380.  
  • Petrovski S, Szoeke CEI, Jones NC, Salzberg MR, Sheffield LJ, Huggins RM, O’Brien TJ. Neuropsychiatric Symptomatology Predicts Seizure Recurrence in Newly Treated Patients. Neurology 2010;75:1015–1021.
  • Liu YR., Cardamone L, Hogan RE, Gregoire M-C, Williams JP, Hicks RJ, Binns D, Koe A, Jones NC, Myers DE, O'Brien TJ, Bouilleret V. Progressive metabolic and structural cerebral perturbations after traumatic brain injury: an in vivo imaging study in the rat. Journal of Nuclear Medicine 2010; 51:1788–1795.  
  • Tringham E, Powell KL,  Cain S, Kuplast K, Mezeyova J, Weerapura M, Eduljee C, Jiang X, Smith P, Morrison1 J, Jones NC, Braine E, Rind G, Parker D, Pajouhesh H, O’Brien TJ, Snutch TP. T-type calcium channel blockers that attenuate thalamic burst firing and suppress absence seizures. Science Translational Medicine 2012;4:121ra19. [I.F. 14.414].  
  • Yuen TI, Morokoff A, Bjorksten A, AbacoGD, Paradiso L, Finch S,Wong D, Reid CA, Powell KL, Drummond K, Rosenthal MA, Kaye AH, O’Brien TJ. Glutamate is associated with a higher risk of seizures in patients with gliomas. Neurology 2012;79:883-9.  
  • Cook MJ, O’Brien TJ, Berkovic SF, Murphy M, Morokoff A, Fabinyi G, D’Souza W, Yerra R, Archer J, Litewka L, Hoskings S, Lightfoot P, Himes D, Ruedebusch V, Sheffield D, Leyde K. Prediction of Seizure likelihood with a long-term ambulatory, implanted seizure advisory system in patients with drug-resistent epilepsy: A first-in-man study. Lancet Neurology 2013;12:563-71.  
  • Ahmad BS, Hill KD, O’Brien TJ, Gorelik A, Habib N, Wark JD. Falls and fractures in patients chronically treated with antiepileptic drugs. Neurology 2012 79:145-51.  
  • Speed D, Hoggart C, Petrovski S, Tachmazidou I, Jorgensen A, De Iorio M, Todaro M, Coffey A, Tisham D, Smith D, Smith PE, Jackson M, Cooper P, Kellett M, Howell S, Newton M, Yerra R, Tan M, French C, Reuber M, Sills GE, Chadwick D, Pirmohamed M, Bentley D, Scheffer I, Berkovic S, Balding D, Marson A, Palotie A, O’Brien TJ*, Johnson MR. Genome-wide association study and biological pathway analysis of epilepsy progrnosis in a prospective cohort of newly treated epilepsy. Human Molecular Genetics 2014;23:247-58.  *TJ O’Brien joint senior author.
  • Shultz SR, Wright DK, Zheng P, Stuchbery R, Liu S-J, Sashindranath M, Medcalf RL, Johnston L, Hovens CM, Jones NC, O’Brien TJ. Sodium selenate reduces hyperphosphorylated tau and improves outcomes after traumatic brain injury. Brain 2015 May;138(Pt 5):1297-313. [I.F. 10.226].
  • Oxley TJ, Opie NI, John SE, Rind GS, Ronayne SM, Wheeler TL, Judy JW, McDonald AJ, Dornom A, Lovell TJH, Steward C, Garrett DJ, Moffatt BA, Lui EH, Yassi N, Campbell BCV, Wong YT, Fox KE, Nurse ES, Bennett IE, Bauquier SH, Liyanage KA, van der Nagel NR, Perucca P, Ahnood A, Gill KP, Yan B, Churilov L, French CR, Desmond PM, Horne MK, Kiers L, Prawer S, Davis SM, Burkitt AN, Mitchell PJ, Grayden DB, May CN, O'Brien TJ. Endovascular stent-electrode array for minimally invasive high-fidelity chronic recordings of cortical neural activity. Nature Biotechnology 2016 Mar;34(3):320-7. doi: 10.1038/nbt.3428. Epub 2016 Feb 8. PMID: 26854476.
  • Liu S, Zheng P, Wright DK, Dezsi G, Braine E, Nguyen T, Corcoran B, Johnston LA, Hovens CM, Mayo JN, Hudson M, Shultz SR, Jones NC, O’Brien TJ. Sodium selenate retards epileptogenesis in acquired epilepsy models reversing changes in protein phosphatase 2A and hyperphosphorylated tau. Brain 2016 139(Pt 7):1919-38. PMID: 27289302.
  • Chen Z, Lusicic A, O’Brien TJ, Velakoulis D, Adams SJ, Kwan P. Psychotic disorders induced by antiepleptic drugs in people with epilepsy. Brain 2016 Aug 8. pii: aww196. [Epub ahead of print] PMID: 27503872.

Research Projects

This Research Group doesn't currently have any projects



Faculty Research Themes

Neuroscience

School Research Themes

Neuroscience & Psychiatry



Key Contact

For further information about this research, please contact Professor Terence O'Brien

Department / Centre

Medicine and Radiology