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MBPhD Programme

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Cavanagh, Sean

Entered:

Sept 2015

Current Position (2019/20):

Post PhD: MBBS Year 4 - Integrated Clinical Care

PhD title:

Neural computations for working memory and decision making

Principal Supervisor:

Dr Steve Kennerley, Department of Clinical and Movement Neurosciences, Queen Square Institute of Neurology

Funding Source:

Middlesex Hospital Medical School General Charitable Trust

Description of Project:

It has long been known that neurons can possess spatial receptive fields, but whether they exhibit temporal receptive fields is relatively unexplored. Higher cognition relies upon processing across long timescales, such as: the holding of information in working memory, or the accumulation of evidence to form decisions. The temporal dynamics of individual neurons during these processes, and how they facilitate circuit-level computations, are pressing questions. My thesis presents four studies that try to address these questions using a variety of techniques: behavioural analyses, single neuron electrophysiology, pharmacology, and computational modelling. It first presents a method to index the temporal receptive field of single neurons, which highlights heterogeneity within prefrontal cortical regions. This heterogeneity is functionally significant, as neurons with longer timescales exhibit stronger and more sustained value correlates during choice. This may provide a neural mechanism for maintaining predictions and updating stored values during learning. A second study shows that the concept of temporal receptive fields can be used to reconcile competing accounts of neuronal activity during working memory tasks. A neuron’s temporal receptive field is predictive of both its degree of task involvement, and its working memory coding dynamics. Next, a further behavioural study probed the role of visual attention in evidence accumulation – revealing fixations are drawn towards valuable and novel stimuli. Finally, data from a complex decision-making task is presented, where monkeys had to accumulate evidence across time. The function of N-methyl-D-aspartate (NMDA) receptors during this extended cognitive process was investigated using pharmacological manipulations. The induced behavioural changes were consistent with those predicted by a lowering of the excitation-inhibition (E/I) ratio in a spiking cortical circuit model. Together these results provide important insights into the role of neuronal timescales in high-level cognition, and have implications for cognitive deficits in neuropsychiatric disorders associated with cortical E/I dysfunction.

 

Publications:

Cavanagh, S. E., Lam, N. H., Murray, J. D., Hunt, L. T., & Kennerley, S. W. (2019). A circuit mechanism for irrationalities in decision-making and NMDA receptor hypofunction: behaviour, computational modelling, and pharmacology. BioRxiv, 826214. 

Cavanagh, S. E., Malalasekera, W. M. N., Miranda, B., Hunt, L. T., & Kennerley, S. W. (2019). Visual fixation patterns during economic choice reflect covert valuation processes that emerge with learning. Proceedings of the National Academy of Sciences, 201906662. 

Cavanagh, S. E., Towers, J. P., Wallis, J. D., Hunt, L. T., & Kennerley, S. W. (2018). Reconciling persistent and dynamic hypotheses of working memory coding in prefrontal cortex. Nature Communications, 9(1). 

Hannah, R., Cavanagh, S. E., Tremblay, S., Simeoni, S., & Rothwell, J. C. (2018). Selective suppression of local interneuron circuits in human motor cortex contributes to movement preparation. Journal of Neuroscience, 38(5), 1264–1276. 

Hannah, R., Sommer, M., Cavanagh, S., Jerjian, S., & Rothwell, J. C. (2017). Motor outcomes of repetitive transcranial magnetic stimulation are dependent on the specific interneuron circuit targeted. In Biosystems and Biorobotics (Vol. 15, pp. 3–7). 

Cavanagh, S. E., Wallis, J. D., Kennerley, S. W., & Hunt, L. T. (2016). Autocorrelation structure at rest predicts value correlates of single neurons during reward-guided choice. ELife. 

Cavanagh, S., Malalasekera, N., & Kennerley, S. (2015). In the blink of an eye: Value and novelty drive saccades. Annals of Medicine and Surgery, 4(3), 319–320. 
 

Awards & Prizes:

2019: Jon Driver Prize (£500). 
2017: Art of Neuroscience Competition Winner (€1000). Media coverage in Scientific American and Atlas Obscura
2016: Brain travel award to attend Society for Neuroscience meeting, USA (£800)
2015: PhD studentship funding from Middlesex Hospital Medical School General Charitable Trust (£77,076)
2015: Dean's List, Faculty of Life Sciences
2014: Wolfson Foundation Intercalated Degree Fellowship (£5000)
2013: The Kaye, Carter, Cayley and Keene Prize (fourth prize for overall performance)