Tim Bussey, Scientist and Western Research Chair in Cognitive Neuroscience
My father was a biochemist and my mother worked in a pathology lab, so I played with hand-me-down test tubes and used lab coats. At age nine, I gained two new musical brothers. Perhaps because of this environment, for me it has always been a choice between a career in science or music.
I was inspired by my high school chemistry teacher and did my undergrad in chemistry/biochemistry while also playing in bands.
After I graduated, music won out and I worked as a musician for a number of years. I did a lot of reading during this time and decided to go back to school. I was accepted into medical school, but once I discovered behavioural neuroscience, I made the switch to research.
I had the good fortune to work with Tony Phillips and Emma Wood at UBC during this time, and they encouraged me to pursue my PhD at Cambridge with Trevor Robbins. I received a Commonwealth Scholarship and moved to England where I completed my PhD and returned to sharing my time between research and music. I did a post-doc with John Aggleton in Cardiff, Wales, and Betsy Murray at NIMH, then ran my own lab with Lisa Saksida in Cambridge for 16 years. Now, I am back in Canada – 25 years after leaving!
I aim to understand cognition – learning, memory, attention etc. – and how the brain does it, what goes wrong in conditions like Alzheimer’s disease or schizophrenia, and possible targets for therapy, using several different converging methods of enquiry.
Our theoretical work has challenged prevailing views regarding the organization of brain function, and has recently been substantiated by a number of studies carried out in our own and several independent laboratories. In another stream of research, we have elucidated the neural mechanisms underpinning object recognition memory and related cognitive functions. We are currently using the methods developed in these studies to investigate psychiatric and neurodegenerative diseases, and testing potential therapeutic agents.
A contribution of mine is the co-invention of the touchscreen testing method for rodents, which allows computer-automated cognitive testing of rodent models on the same types of tests currently used to diagnose and study human patients. This device went to market in 2009, and is now being used in over 120 institutions and featured in well over 100 publications. We have developed many cognitive tests for mouse and rat models of neuropsychiatric and neurodegenerative disease, and continue to develop novel batteries for the assessment of precise aspects of cognition.
I co-direct the Translational Cognitive Neuroscience Lab (TCNLab) with Lisa Saksida, PhD. I'm interested in cognition in the healthy brain, what goes wrong in neurodegenerative and neuropsychiatric disease such as Alzheimer’s and Schizophrenia, and identifying targets for therapy.
Because the loss of memory is the most common symptom lamented by affected patients, the disease is often regarded simply as a memory disorder. In the majority of individuals with Alzheimer's disease, however, multiple cognitive domains are compromised including attention and response control; indeed such impairments can occur early in the disease and precede language and spatial impairments. Our work in this area mainly involves developing and validating assays for phenotyping murine models of this disease across all of these domains of cognition.
Current anti-psychotics do quite a good job suppressing these psychotic symptoms. However, they do not do very much to address the cognitive symptoms, and so the cognitive symptoms – impairments in learning, memory, perception, reasoning, etc. – persist. We work on the development of assays for understanding cognition in models of schizophrenia. Our work focuses on developing new animal models and the use of brain recording and behavioural tests to identify innovative and effective drugs for schizophrenia.
Cognitive Task Development
A major difficulty in moving research from the bench to the clinic is the translational gap between animal studies and clinical trials. For example, although many medications for Alzheimer’s disease have been successful in animal tests, they have failed to lead to functional improvement in human clinical trials (Gravitz, 2011, Cummings, 2010, Bezprozvanny, 2010). One of the factors that may have contributed to these failures is differences between how efficacy of compounds is assessed in animals and humans, which in diseases affecting cognition usually means cognitive and behavioural tests.
A major thrust of the TCNLab is to improve translation to the clinic, mainly through scientific and technological innovation. Most people in the lab are working in one way or another on the development of a touchscreen-based cognitive assessment system for rodents. The system enables us to utilize very similar, and in many cases identical, cognitive assays in mice and humans. This method has the tremendous advantage of eliminating numerous confounds, in addition to maximizing the likelihood that the same underlying cognitive processes are being probed in both mice and humans. Thus, the effects of manipulations at multiple levels on cognition can be evaluated in mouse and rat models of neurodegenerative and neuropsychiatric disease, and then directly compared to the cognitive profiles of human patients.
Modularity of Function in the Medial Temporal Lobe
The work that has formed the backbone of our research over the past 10 years has involved the development of a novel theory of the organization of cognition in the medial temporal lobe and ventral visual stream. The main idea behind this 'representational-hierarchical' view is that, rather than confining ourselves to the prevailing paradigm of assuming modularity of cognitive processes within anatomically-defined cognitive boxes in the brain, we would do better to consider the representations maintained in differing brain circuits, which can subserve a variety of cognitive functions.
These organizational principles have been instantiated in computational models, which have in turn been used to drive empirical work. Initial experiments tested the implications of this framework for memory in the healthy brain; however, over the past five years we have been applying it to the understanding of cognitive function in the dysfunctional brain, in conditions such as amnesia and dementia. Recent work, for example, has explored the prediction of this model that memory impairment in cases of medial temporal lobe amnesia and Alzheimer’s Disease may be due in large part to abnormal susceptibility to perceptual interference.
We believe that novel thinking can lead to novel therapies and indeed, in these experiments treatments suggested by the predictions of the model were found to ameliorate memory impairments resulting from brain damage and Alzheimer’s pathology.
For most people, memory is about time. It is easier to remember a set of items in a memory test if they are presented a few seconds before memory retrieval, than if they are presented several hours before. When memory fails, as it does normally in old age, or under pathological conditions such as Alzheimer’s disease, this failure is reflected in the inability to remember over an extended period of time – although the ability to remember over a few seconds may remain intact. Increasingly, however, memory researchers are becoming interested in the ability not to remember over time, but to keep memories distinct and resistant to confusion. If asked to remember where you parked your car this morning, yesterday morning and the day before, the task is difficult not because you need to remember over a long period – you can easily remember many things that happened three days ago – but because the similar memories of your car in that same parking lot are so easily confused.
The ability to separate the components of memories into distinct complex memory representations that are unique and less easily confused has been simulated by computational models of memory and has been referred to as ‘pattern separation’.
The psychological and neurobiological mechanisms underlying pattern separation are a particular interest of this lab.
Ph.D. Experimental Psychology, University of Cambridge
H.BSc. (First Class) Psychology, University of British Columbia
H.Bsc. Chemistry, University of Victoria
Postdoctoral Fellowship, University of Cardiff (John Aggleton)
Fogarty International Research Fellow – Elisabeth Murray, National Institute of Mental Health
Western Research Chair, Cognitive Neuroscience, 2015
Elected Fellow of the Association for Psychological Science, 2010
Highly Commended Prize, National Centre for the Replacement, Refinement & Reduction of Animals in Research (NC3Rs), 2008
Association of Commonwealth Universities Scholarship, 1992-1995
My work to date has resulted in over 140 publications which have been highly cited and published in high impact journals including Science, PNAS, Nature Neuroscience, Nature Protocols, Neuron, Brain, Trends in Cognitive Sciences, Nature Reviews Neuroscience, Current Opinion in Biology, Annual Reviews in Neuroscience and Journal of Neuroscience. Several of these articles have been recommended by the Faculty of 1000 and/or have been featured in Nature ‘News and Views’ or similar.
The touchscreen operant platform for testing learning and memory in rats and mice.
Horner, A.E., Heath, C.J., Hvoslef-Eide, M., Kent, B.A., Kim, C.H., Nilsson, S., Alsiö, J., Oomen, C.A., Holmes, A., Saksida, L.M., & Bussey, T.J. (2013)
Nature Protocols, 8(10):1961-1984.
Synaptic scaffold evolution generated components of vertebrate cognitive complexity
Nithianantharajah, J, Komiyama N.H., McKechanie, A., Johnstone, M., Blackwood D.H., St Clair, D., Emes R.D., van de Lagemaat L.N., Saksida L.M., Bussey T.J. * & Grant, S.G.N. * (2013)
Nature Neuroscience, 16(1):16-24.
Running enhances spatial pattern separation in mice
Creer, D., Romberg C., Saksida L.M., van Praag, H., Bussey T.J. (2010)
Proc Natl Acad Sci U S A ;107(5):2367-2372. PMC2836679
Functional dissociations within the ventral object processing pathway: cognitive modules or a hierarchical continuum?
Cowell, R., Bussey, T.J. & Saksida, L.M. (2010).
Journal of Cognitive Neuroscience, 22(11):2460-2479.
A functional role for adult hippocampal neurogenesis in spatial pattern separation.
Clelland C.D., Choi M., Romberg C., Clemenson G.D. Jr., Tyers P., Jessberger S., Saksida L.M., Barker R.A., Gage F.H., Bussey T.J. (2009)
Double dissociation between the effects of peri-postrhinal cortex and hippocampal lesions on tests of object recognition and spatial memory: Heterogeneity of function within the temporal lobe.
Winters, B. D., Forwood, S. E., Cowell, R. A., Saksida, L. M., & Bussey, T. J. (2004).
Journal of Neuroscience, 24:5901-5908