Direct Cortical Stimulation to Manipulate Human Memory Function (MEMSTIM)

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Our memories of past events define who we are and allow us to imagine and plan for the future. Gaining insight into the fundamental mechanisms of human memory function therefore has implications ranging from education, eye witness testimony, and the design of intelligent machines, to the treatment of memory dysfunction associated with stress, trauma, and dementia. Damage to the hippocampus can have profound effects on memory which, in severe cases, results in a complete inability to remember new events. Within the hippocampus, the activity of single 'place cells' and 'concept cells' code for specific locations, people, animals, and objects. It is believed that ongoing experience is rapidly captured by the strengthening of synaptic connections between these neurons before memory traces are 'consolidated' within a wider network of brain areas to support memory guided behaviour. Crucially, the neural mechanisms supporting these functions remain elusive. Electrophysiology data from rodents suggest that both consolidation and planning may be supported by the 'replay' of activity sequences in hippocampal neurons, but causal evidence from humans is missing. To bridge this explanatory gap, I will record hippocampal single cell activity in pre-surgical epilepsy patients performing cognitive tasks that probe the encoding, storage, and recall of event memories. In addition, I will use an innovative cortical stimulation paradigm to detect and disrupt memory for specific events in real time, looking for a causal role in memory guided behaviour; and state of the art MEG decoding techniques to extend these findings to the whole brain level. I will synthesise these results with existing knowledge from computational modelling, rodent electrophysiology and neuroimaging to provide direct empirical support for a neural level model of human memory function that links the dynamics of single cells in the human brain to behaviour, illuminating novel treatment pathways for memory disorders.