Functional neuromodulation and novel therapeutics

About

A large proportion of patients suffering from psychiatric disease have symptoms that do not respond to current treatments. The Functional Neuromodulation and Novel Therapeutics Laboratory, led by Dr Susannah Tye, has as its overarching goal to understand why some individuals fail to improve in response to such therapies and to advance progress towards the discovery and development of novel treatments to help this vulnerable patient population. Our research is interdisciplinary, drawing on approaches and techniques from neuroscience, molecular biology, biochemistry, and neuroengineering. We are particularly interested in the potential to use key biomarkers of refractory illness to diagnose and inform treatment decisions, and the possibility that real-time feedback may be used to customise neuromodulatory treatments. Ongoing projects in the lab address both basic and translational neuroscience questions.

Basic Neuroscience

Through these projects we use preclinical rodent models to investigate the pathophysiological basis of psychiatric and neurologic illness. Specifically, we are interested in the relationship between genetic and environmental risk factors for depression, bipolar disorder, stress disorders, and Parkinson’s Disease. The lab has extensive experience with cutting edge experimental technologies, such as fast scan cyclic voltammetry (FSCV) and in vivo neuromodulation (electrical/ optogenetic).

Translational Neuroscience

Translational projects build on findings from basic neuroscience research to work towards making neuromodulation and brain stimulation technology viable as treatment options for human patients. Our long-term research strategy is to develop a system that customises neuromodulation parameters based on integrated feedback to optimise patient outcomes.

 

 

 

Contact

  +61 7 344 32493

  s.tye@uq.edu.au


Group Publications

Research Areas

  • Deep Brain Stimulation
  • Neuromodulation
  • Depression
  • Bipolar disorder
  • Stress disorders
  • Parkinson’s Disease
  • Biomarkers
  • Refractory psychiatric illness

Group Leader


Students

 


Research Members

Bioenergetics and synaptic plasticity as potential targets for individualizing treatment for depression

Price, J. Blair, Bronars, Carrie, Erhardt, Sophie, Cullen, Kathyrn R., Schwieler, Lilly, Berk, Michael, Walder, Ken, McGee, Sean L., Frye, Mark A. and Tye, Susannah J. (2018) Bioenergetics and synaptic plasticity as potential targets for individualizing treatment for depression. Neuroscience and Biobehavioral Reviews90 212-220. doi:10.1016/j.neubiorev.2018.04.002

A Review of Brain Insulin Signaling in Mood Disorders: From Biomarker to Clinical Target

Nguyen, Thanh Thanh L, Chan, Lily C, Borreginne, Kristin, Kale, Rajas P, Hu, Chunling and Tye, Susannah J (2018) A Review of Brain Insulin Signaling in Mood Disorders: From Biomarker to Clinical Target. Neuroscience and biobehavioral reviews, . doi:10.1016/j.neubiorev.2018.05.014

Refereed journal articles

  1. Tye SJ, Miller AD, Blaha CD. Differential corticosteroid receptor regulation of mesoaccumbens dopamine efflux during the peak and nadir of the circadian rhythm: a molecular equilibrium in the midbrain? Synapse. 2009 Nov;63(11):982-90. doi: 10.1002/syn.20682.
  2. Agnesi F, Tye SJ, Bledsoe JM, Griessenauer CJ, Kimble CJ, Sieck GC, Bennet KE, Garris PA, Blaha CD, Lee KH. Wireless Instantaneous Neurotransmitter Concentration System-based amperometric detection of dopamine, adenosine, and glutamate for intraoperative neurochemical monitoring. J Neurosurg. 2009 Oct;111(4):701-11. doi: 10.3171/2009.3.JNS0990.
  3. Shon YM, Chang SY, Tye SJ, Kimble CJ, Bennet KE, Blaha CD, Lee KH. Comonitoring of adenosine and dopamine using the Wireless Instantaneous Neurotransmitter Concentration System: proof of principle. J Neurosurg. 2010 Mar;112(3):539-48. doi: 10.3171/2009.7.JNS09787.
  4. Griessenauer CJ, Chang SY, Tye SJ, Kimble CJ, Bennet KE, Garris PA, Lee KH. Wireless Instantaneous Neurotransmitter Concentration System: electrochemical monitoring of serotonin using fast-scan cyclic voltammetry--a proof-of-principle study. J Neurosurg. 2010 Sep;113(3):656-65. doi: 10.3171/2010.3.JNS091627.
  5. Chopra A, Tye SJ, Lee KH, Matsumoto J, Klassen B, Adams AC, Stead M, Sampson S, Kall BA, Frye MA. Voltage-dependent mania after subthalamic nucleus deep brain stimulation in Parkinson's disease: a case report. Biol Psychiatry. 2011 Jul 15;70(2):e5-7. doi: 10.1016/j.biopsych.2010.12.035. Epub 2011 Mar 16.
  6. Walker AJ, Burnett SA, Hasebe K, McGillivray JA, Gray LJ, McGee SL, Walder K, Berk M, Tye SJ. Chronic adrenocorticotrophic hormone treatment alters tricyclic antidepressant efficacy and prefrontal monoamine tissue levels. Behav Brain Res.  2013 Apr 1;242:76-83. doi: 10.1016/j.bbr.2012.12.033. Epub 2012 Dec 28.
  7. Tye SJ, Miller AD, Blaha CD. Ventral tegmental ionotropic glutamate receptor stimulation of nucleus accumbens tonic dopamine efflux blunts hindbrain-evoked phasic neurotransmission: implications for dopamine dysregulation disorders. Neuroscience. 2013 Nov 12;252:337-45. doi: 10.1016/j.neuroscience.2013.08.010. Epub 2013 Aug 17. 
  8. Tye SJ, van Rooy W, Pollard I. Drug and Alcohol Use, Sexual Intimacy and Associated Health Status of Senior High School Students. EJAIB 2013; 23(1): 23-30.
  9. Kouzani AZ, Abulseoud OA, Tye SJ, Hosain MD, Berk M. A Low Power Micro Deep Brain Stimulation Device for Murine Preclinical Research. IEEE J Transl Eng Health Med. 2013 Jun 4;2:1500109. doi: 10.1109/JTEHM.2013.2264093. eCollection 2013.
  10. Hosain MK, Kouzani AZ, Tye SJ, Abulseoud OA, Berk M. Design and analysis of an antenna for wireless energy harvesting in a head-mountable DBS device. Conf Proc IEEE Eng Med Biol Soc. 2013;2013:3078-81. doi: 10.1109/EMBC.2013.6610191.
  11. Holland BJ, Conlan XA, Stevenson PG, Tye S, Reker A, Barnett NW, Adcock JL, Francis PS. Determination of neurotransmitters and their metabolites using one-and two-dimensional liquid chromatography with acidic potassium permanganate chemiluminescence detection. Anal Bioanal Chem. 2014 Sep;406(23):5669-76. doi: 10.1007/s00216-013-7514-9. Epub 2013 Dec 7.
  12. Broadbent J, Sitka N, Macfarlane S, McGillivray J, Tye S. Informing Brain Health Behaviour Choices: The efficacy of a High-School Brain Awareness pilot study. British Journal of Education, Society & Behavioural Science. 06/2014; 4(6):755-767. Doi: 10.9734/BJESBS/2014/6694
  13. Hosain MD, Kouzani AZ, Tye SJ, Abulseoud OA, Amiet A, Galehdar A, Kaynak A, Berk M. Development of a Compact Rectenna for Wireless Powering of a Head-Mountable Deep Brain Stimulation Device. IEEE J Transl Eng Health Med. 2014 Mar 26;2:1500113. doi: 10.1109/JTEHM.2014.2313856. eCollection 2014.
  14. Hosain MK, Kouzani AZ, Tye S, Kaynak A, Berk M. RF rectifiers for EM power harvesting in a Deep Brain Stimulating device. Australas Phys Eng Sci Med. 2015 Mar;38(1):157-72. doi: 10.1007/s13246-015-0328-7. Epub 2015 Jan 20.
  15. Frye MA, Blier P, Tye SJ. Concomitant benzodiazepine use attenuates ketamine response: implications for large scale study design and clinical development. J Clin Psychophramacol. 2015 Jun;35(3):334-6. doi: 10.1097/JCP.0000000000000316.
  16. Walker AJ, Foley BM, Sutor SL, McGillivray JA, Frye MA, Tye SJ. Peripheral proinflammatory markers associated with ketamine response in a preclinical model of antidepressant-resistance. Behav Brain Res. 2015 Oct 15;293:198-202. doi: 10.1016/j.bbr.2015.07.026. Epub 2015 Jul 21.
  17. Hosain MK, Kouzani AZ, Tye SJ, Samad MF, Kale RP, Bennet KE, Manciu FS, Berk  M. Radio frequency energy harvesting from a feeding source in a passive deep brain stimulation device for murine preclinical research. Med Eng Phys. 2015 Oct;37(10):1020-6. doi: 10.1016/j.medengphy.2015.07.003. Epub 2015 Aug 28.
  18. Frye MA, Nassan MM, Jenkins GD, Kung S, Veldic M, Palmer BA, Feeder SE, Tye SJ, Choi DS, Biernacka JM. Feasibility of Investigating Differential Proteomic Expression in Depression: Implications for Biomarker Development in Mood Disorders. Transl Psychiatry 2015 Dec 8;5:e689. doi: 10.1038/tp.2015.185
  19. Kim Y, McGee S, Czeczor JK, Walker AJ, Kale RP, Kouzani AZ, Walder K, Berk M,  Tye SJ. Nucleus accumbens deep-brain stimulation efficacy in ACTH-pretreated rats: alterations in mitochondrial function relate to antidepressant-like effects. Transl Psychiatry. 2016 Jun 21;6(6):e842. doi: 10.1038/tp.2016.84
  20. Kim Y, Morath B, Hu C, Byrne LK, Sutor SL, Frye MA, Tye SJ. Antidepressant actions of lateral habenula deep brain stimulation differentially correlate with  CaMKII/GSK3/AMPK signaling locally and in the infralimbic cortex. Behav Brain Res. 2016 Jun 1;306:170-7. doi: 10.1016/j.bbr.2016.02.039. Epub 2016 Mar 5.
  21. Abulseoud OA, Kasasbeh A, Min HK, Fields JA, Tye SJ, Goerss S, Knight EJ, Sampson SM, Klassen BT, Matsumoto JY, Stoppel C, Lee KH, Frye MA. Stimulation-Induced Transient Nonmotor Psychiatric Symptoms following Subthalamic Deep Brain Stimulation in Patients with Parkinson's Disease: Association with Clinical Outcomes and Neuroanatomical Correlates. Stereotact Funct Neurosurg. 2016;94(2):93-101. doi: 10.1159/000445076. Epub 2016 Apr 20.
  22. Kale RP, Kouzani AZ, Berk J, Walder K, Berk M, Tye SJ. Electrical resistance increases at the tissue-electrode interface as an early response to nucleus accumbens deep brain stimulation. Conf Proc IEEE Eng Med Biol Soc. 2016 Aug;2016:1814-1817. doi: 10.1109/EMBC.2016.7591071.
  23. Patten CA, Bronars CA, Vickers Douglas KS, Ussher MH, Levine JA, Tye SJ, Hughes CA, Brockman TA, Decker PA, DeJesus RS, Williams MD, Olson TP, Clark MM, Dieterich AM. Supervised, Vigorous Intensity Exercise Intervention for Depressed Female Smokers: A Pilot Study. Nicotine Tob Res. 2017 Jan;19(1):77-86. Epub 2016 Sep 9.
  24. Vande Voort JL, Morgan RJ, Kung S, Rasmussen KG, Rico J, Palmer BA, Schak KM, Tye SJ, Ritter MJ, Frye MA, Bobo WV. Continuation phase intravenous ketamine in adults with treatment-resistant depression. J Affect Disord. 2016 Dec;206:300-304. doi: 10.1016/j.jad.2016.09.008. Epub 2016 Sep 12.
  25. Veerabhadrappa R, Lim CP, Nguyen TT, Berk M, Tye SJ, Monaghan P, Nahavandi S, Bhatti A. Unified selective sorting approach to analyse multi-electrode extracellular data. Sci Rep. 2016 Jun 24;6:28533. doi: 10.1038/srep28533.
  26. Kouzani AZ, Kale RP, Zarate-Garza PP, Berk M, Walder K, Tye SJ. Validation of a Portable Low-Power Deep Brain Stimulation Device Through Anxiolytic Effects in a Laboratory Rat Model. IEEE Trans Neural Syst Rehabil Eng. 2017 Sep;25(9):1365-1374. doi: 10.1109/TNSRE.2016.2628760. Epub 2016 Nov 15.
  27. Parastarfeizabadi M, Kouzani AZ, Gibson I, Tye SJ. A miniature closed-loop deep brain stimulation device. Conf Proc IEEE Eng Med Biol Soc. 2016 Aug;2016:1786-1789. doi: 10.1109/EMBC.2016.7591064.
  28. Edward ES, Kouzani AZ, Kale RP, Tye SJ. Portable closed-loop optogenetic stimulation device. Conf Proc IEEE Eng Med Biol Soc. 2016 Aug;2016:5250-5253.doi: 10.1109/EMBC.2016.7591911.
  29. Luthar SS, Curlee A, Tye SJ, Engelman JC, Stonnington CM. Fostering Resilience among Mothers under Stress: "Authentic Connections Groups" for Medical Professionals. Womens Health Issues. 2017 May - Jun;27(3):382-390. doi:10.1016/j.whi.2017.02.007. Epub 2017 Apr 14.
  30. Albott CS, Lim KO, Forbes MK, Erbes C, Tye SJ, Grabowski JG, Thuras P, Batres-Y-Carr TM, Wels J, Shiroma PR. Efficacy, Safety, and Durability of Repeated Ketamine Infusions for Comorbid Posttraumatic Stress Disorder and Treatment-Resistant Depression. J Clin Psychiatry. 2018 May 1;79(3). pii:17m11634. doi: 10.4088/JCP.17m11634. [Epub ahead of print]
  31. Edward ES, Kouzani AZ, Tye SJ. Towards miniaturized closed-loop optogenetic stimulation devices. J Neural Eng. 2018 Apr;15(2):021002. doi:10.1088/1741-2552/aa7d62.
  32. Yang J, Lopez Cervera R, Tye SJ, Ekker SC, Pierret C. Adolescent mental health education InSciEd Out: a case study of an alternative middle school population. J Transl Med. 2018 Apr 3;16(1):84. doi: 10.1186/s12967-018-1459-x.
  33. Ahmed AT, Frye MA, Rush AJ, Biernacka JM, Craighead WE, McDonald WM, Bobo WV, Riva-Posse P, Tye SJ, Mayberg HS, Flavin DH, Skime MK, Jenkins GD, Wang L, Krishnan RR, Weinshilboum RM, Kaddurah-Daouk R, Dunlop BW; Mood Disorders Precision Medicine Consortium (MDPMC). Mapping depression rating scale phenotypes onto research domain criteria (RDoC) to inform biological research in mood disorders. J Affect Disord. 2018 May 25;238:1-7. doi: 10.1016/j.jad.2018.05.005. [Epub ahead of print]

Reviews

  1. Tye SJ, Frye MA, Lee KH. Disrupting disordered neurocircuitry: treating refractory psychiatric illness with neuromodulation. Mayo Clin Proc. 2009 Jun;84(6):522-32. doi: 10.1016/S0025-6196(11)60584-3. Review.
  2. Tye SJ, Covey DP, Griessenauer CJ. A balancing act: D4 receptor activation and the neurobiological basis of emotional learning. J Neurosci. 2009 Sep2;29(35):10785-7. doi: 10.1523/JNEUROSCI.2822-09.2009. Review.
  3. Chopra A, Tye SJ, Lee KH, Sampson S, Matsumoto J, Adams A, Klassen B, Stead M, Fields JA, Frye MA. Underlying neurobiology and clinical correlates of mania status after subthalamic nucleus deep brain stimulation in Parkinson's disease: a review of the literature. J Neuropsychiatry Clin Neurosci. 2012 Winter;24(1):102-10. doi: 10.1176/appi.neuropsych.10070109. Review.
  4. Anderson RJ, Frye MA, Abulseoud OA, Lee KH, McGillivray JA, Berk M, Tye SJ. Deep brain stimulation for treatment-resistant depression: efficacy, safety and mechanisms of action. Neurosci Biobehav Rev. 2012 Sep;36(8):1920-33. doi:10.1016/j.neubiorev.2012.06.001. Epub 2012 Jun 18. Review.
  5. Walker AJ, Kim Y, Price JB, Kale RP, McGillivray JA, Berk M, Tye SJ. Stress, Inflammation, and Cellular Vulnerability during Early Stages of Affective Disorders: Biomarker Strategies and Opportunities for Prevention and Intervention. Front Psychiatry. 2014 Apr 9;5:34. doi: 10.3389/fpsyt.2014.00034.eCollection 2014. Review.
  6. Hosain MK, Kouzani A, Tye S. Closed loop deep brain stimulation: an evolving technology. Australas Phys Eng Sci Med. 2014 Dec;37(4):619-34. doi:10.1007/s13246-014-0297-2. Epub 2014 Sep 7. Review.
  7. Frye MA, Prieto ML, Bobo WV, Kung S, Veldic M, Alarcon RD, Moore KM, Choi DS, Biernacka JM, Tye SJ. Current landscape, unmet needs, and future directions for treatment of bipolar depression. J Affect Disord. 2014 Dec;169 Suppl 1:S17-23. doi: 10.1016/S0165-0327(14)70005-9. Review.
  8. Tye S, Van Voorhees E, Hu C, Lineberry T. Preclinical perspectives on posttraumatic stress disorder criteria in DSM-5. Harv Rev Psychiatry. 2015 Jan-Feb;23(1):51-8. doi: 10.1097/HRP.0000000000000035. 
  9. Davis J, Maes M, Andreazza A, McGrath JJ, Tye SJ, Berk M. Towards a classification of biomarkers of neuropsychiatric disease: from encompass to compass. Mol Psychiatry. 2015 Feb;20(2):152-3. doi: 10.1038/mp.2014.139. Epub 2014 Oct 28. Review.
  10. Kale RP, Kouzani AZ, Walder K, Berk M, Tye SJ. Evolution of optogenetic microdevices. Neurophotonics. 2015 Jul;2(3):031206. doi: 10.1117/1.NPh.2.3.031206. Epub 2015 Jun 25. Review.
  11. Bobo WV, Vande Voort JL, Croarkin PE, Leung JG, Tye SJ, Frye MA. Ketamine for Treatment-resistant Unipolar and Bipolar Major Depression: Critical Review and Implications for Clinical Practice.  Depress Anxiety. 2016 Aug;33(8):698-710. doi: 10.1002/da.22505. Epub 2016 Apr 6. Review.
  12. Berk M, Tye S, Walder K, McGee S. Hyperthermia for Major Depressive Disorder? JAMA Psychiatry. 2016 Oct 1;73(10):1095-1096. doi:10.1001/jamapsychiatry.2016.1532.
  13. Adams S, Kouzani AZ, Mohammed M, Usma C, Tye SJ. Fabrication of Biocompatible Enclosures for an Electronic Implant Using 3D Printing. Int. J. of Raid Manufacturing. 2016; vol. 6, no. 1, pp. 17-32, doi: 10.1504/IJRAPIDM.2016.078742. 
  14. Morris G, Walder K, McGee SL, Dean OM, Tye SJ, Maes M, Berk M. A model of the mitochondrial basis of bipolar disorder. Neurosci Biobehav Rev. 2017 Mar;74(PtA):1-20. doi: 10.1016/j.neubiorev.2017.01.014. Epub 2017 Jan 14. Review.
  15. Zarate-Garza PP, Biggs BK, Croarkin P, Morath B, Leffler J, Cuellar-Barboza A, Tye SJ. How Well Do We Understand the Long-Term Health Implications of Childhood Bullying? Harv Rev Psychiatry. 2017 Mar/Apr;25(2):89-95. doi: 10.1097/HRP.0000000000000137. Review.
  16. Brimijoin S, Tye S. Favorable Impact on Stress-Related Behaviors by Modulating Plasma Butyrylcholinesterase. Cell Mol Neurobiol. 2018 Jan;38(1):7-12. doi:10.1007/s10571-017-0523-z. Epub 2017 Jul 15. Review.
  17. Morris G, Walder K, Carvalho AF, Tye SJ, Lucas K, Berk M, Maes M. The role of hypernitrosylation in the pathogenesis and pathophysiology of neuroprogressive diseases. Neurosci Biobehav Rev. 2018 Jan;84:453-469. doi:10.1016/j.neubiorev.2017.07.017. Epub 2017 Aug 5. Review.
  18. Adams SD, Kouzani AZ, Tye SJ, Bennet KE, Berk M. An investigation into closed-loop treatment of neurological disorders based on sensing mitochondrial dysfunction. J Neuroeng Rehabil. 2018 Feb 13;15(1):8. doi:10.1186/s12984-018-0349-z. Review.

Chapters

  1. Tye SJ (2006) Learning to Remember: The biological basis of memory. In: A Cross Cultural Introduction to Bioethics; Macer DRJ ed. Eubios Ethics Institute, Bangkok, Thailand; pp. 229-234.
  2. Tye SJ, Pollard I (2006) The neuroscience of pleasure, reward and addiction. In: A Cross Cultural Introduction to Bioethics; Macer DRJ ed. Eubios Ethics Institute, Bangkok, Thailand; pp. 235-240.
  3. Kouzani AZ, Tye SJ, Walder K, Kong L (2011) A head mountable deep brain stimulation device for laboratory animals. In: Advances in Computer, Communication, Control and Automation; Wu, Y ed. Springer-Verlag, Berlin, Germany; pp. 275-280.
  4. Kale RP, Kouzani AZ, Berk M, Walder K, Tye SJ (2014) Wireless Optogenetics: An Exploration of Portable Microdevices for Small Animal Photostimulation. In Electrical and Electronics Engineering. Springer-Verlag, Berlin, Germany.
  5. Veerabhadrappa R , Bhatti A , Lim CP , Nguyen TT , Tye SJ , Monaghan P , Nahavandi S. Statistical modelling of artificial neural network for sorting temporally synchronous spikes. Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics) 2015; Springer-Verlag, Berlin, Germany; 9491:261-72
  6. Kim YS, Wininger K, Tye SJ (2017). Deep Brain Stimulation for Treatment Resistant Depression. In: Brain Stimulation: Methods and Interventions. Eds Lee KH and Duffy P. Elsevier, USA.
  7. Frye MA, Croarkin PE, Veldic M, Nassan MM, Moore KM, Kung S, Tye SJ, Bobo WV, Vande Voort JL (2017). Evidence-based treatment of bipolar depression. In: The Treatment of Bipolar Disorder. Eds Carvalho & Vieta. Oxford University Press, UK.
  8. Andreazza AC, Kale RP, Duong A. Molina F, Tye SJ. (2017) Mitochondrial function and inflammation pathways in the neuroprogression of mental disorders. In: Neuroprogression in Psychiatry. Eds Kapczinski F, Magalhaes PVS, Berk M. Oxford University Press, UK.
  9. Kale RP, Paek S., Tye SJ, Kouzani AZ (2017) Revolutionizing Causal Circuitry Neurostimulation Utilizing the Optogenetic Technique Through Advanced Microsystems Development. Emerging Trends in Neuro Engineering and Neural Computation. Bhatti A, Lee KH, Garmestani H, Lim CP eds. Springer, Singapore. pp. 61-80

National

International 

  • Professor Helen Mayberg - Center for Advanced Circuit Therapeutics for the Icahn School of Medicine at Mount Sinai
  • Professors Kendall Lee and Kevin Bennett - Mayo Clinic Neural Engineering Laboratories
  • Professor Mark Frye and Dr Kate Schak - Mayo Clinic Depression Center
  • Professor Sophie Erhardt and Dr Lilly Schwieler- Karolinska Institutet Neuropsychoimmunology Group
  • Associate Professor Katie Cullen - University of Minnesota
  • Professor Andrew Miller - Emory University
     

  1. Understanding the pathophysiological mechanisms of treatment resistance, particularly the role of stress, inflammation, and metabolic dysfunction;
  2. Defining the therapeutic mechanisms of novel pharmaceutical agents and brain stimulation technologies with the ultimately goal of identifying specific biomarkers of treatment response;
  3. Establishing translational behavioural paradigms that can be effectively used across species (rodent to human) to quantify specific neural correlates of disease pathophysiology and treatment response;
  4. Developing novel technologies for brain stimulation;
  5. Translating novel treatment approaches and neuromodulation technologies to the clinic.