Causal Manipulations of the Cortical-Hippocampal Dialogue in Humans

In the absence of sleep memories remain unstable. Sleep provides an ideal environment for the formation and stabilisation of memories through a process called memory consolidation. This process is what enables new information acquired during wakefulness to be stored into representations that can later be accessed to guide behaviour and influence our actions. Memory consolidation requires coordinated interactions between neuronal activity in cortical regions in the brain's surface and the hippocampus, a structure that lies deeper in the brain. Until now, our ability to investigate the dialogue between the cortex and the hippocampus has been limited because the only tools available to influence neuronal activity in the human hippocampus required the invasive placement of intracranial electrodes. However, in a recent study we demonstrated that, using a technique called Temporal Interference Stimulation (TIS), we can now selectively influence brain activity in the human hippocampus without surgery. TIS is a form of non-invasive electrical brain stimulation that uses an ingenious combination of high frequency (kHz) oscillating currents at slightly different frequencies that by themselves are too fast to influence the activity of neurons but can travel and meet at a target location deep in the brain. Where they meet, they generate an interference pattern that changes the activity of neurons at this location. Using TIS, we can now influence activity in the hippocampus and thereby investigate how the hippocampus influences the cortex during sleep and how it contributes to the interactions required to the formation of stable memories. In this project, we will combine TIS with electroencephalography (EEG) to measure brain activity while we sleep. EEG uses electrodes placed on the scalp to record the activity of neurons, and like TIS, is non-invasive. Using EEG, we can detect brain wave patterns associated with memory consolidation. These patterns have been associated with a stage of sleep called non-rapid eye movement (NREM) sleep. We will use these NREM sleep patterns and measures of memory performance to assess the effects of TIS on memory consolidation. Our project is comprised of a series of studies, each investigating one question pertinent to understanding the cortical-hippocampal dialogue during sleep. We will begin by investigating whether influencing hippocampal activity before or after playing sound cues during sleep to artificially enhance which memories are consolidated affects the brain wave patterns related to memory consolidation and memory performance. We will then use TIS protocols designed to synchronise activity between the cortex and the hippocampus to enhance the naturally occurring brain-wave patterns associated with memory consolidation during NREM sleep and improve memory performance. Finally, we will direct our attention to our other sleep stage, rapid eye movement (REM) sleep. REM has fascinated scientists for almost a century because of its possible association with dreams, but we know less about its role in memory consolidation. By influencing the activity of the hippocampus during REM sleep, we hope to understand more about the role of REM sleep in human memory consolidation. By the end of the project, we will know more about how the cortex and hippocampus can be influenced non-invasively to shape how memories are consolidated during sleep. This knowledge can then be applied to boost sleep's memory functions in those suffering from memory disorders.