Our memory system is optimised for remembering the exceptional over the mundane. We remember better those events that violate predictions generated by the prevailing context, particularly because of surprise or emotional impact. Understanding how we form and retrieve long-term memories for important or salient events is critical for combating the rapidly growing incidence of pathologies associated with memory dysfunction with huge socio-econonomic burden. Human lesion and non-invasive functional imaging data, motivated by findings from animal models, have identified subcortical structures that are critical for upregulating hippocampal function during salient event memory. However, mechanistic understanding of these processes in humans remains scarce, and requires better experimental approaches such as direct intracranial recordings from, and focal electrical stimulation of, these subcortical structures.
This project will characterise human subcortico-cortical neuronal circuit dynamics associated with enhanced episodic memory for salient stimuli by studying direct recordings from human hippocampus, amygdala, nucleus accumbens, ventral midbrain and cortex. Within this framework, I will elucidate the electrophysiological mechanisms underlying amygdala-hippocampal-cortical coupling that lead to better memory for emotional stimuli, extend the hippocampal role in detecting unpredicted stimuli to define its role in orchestrating cortical dynamics in unpredictable contexts, and discover the neuronal response profile of the human mesolimbic dopamine system during salient stimulus encoding. The predicted results, based on my own preliminary data, will offer several conceptual breakthroughs, particularly regarding hippocampal function and the role of dopaminergic ventral midbrain in memory. The knowledge gained from this project is a fundamental requirement for designing therapeutic interventions for patients with memory deficits and other neuropsychiatric disorders.