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.

The ability to transform newly encoded representations into stable long-term memories is crucial for learning, retaining knowledge, and adapting to life's challenges. The processes by which memories are transformed over time is termed memory consolidation and involves interactions between distributed brain areas, notably the cortex and hippocampus. During sleep, limited intake of new information and specific brain wave patterns favour long-term storage and organisation of memories across hippocampal-cortical networks. Indeed, electrophysiological markers of effective cortical-hippocampal communication and their association with sleep-dependent memory consolation have been identified through intracranial recordings. However, our ability to investigate these processes in humans is hindered by the invasive procedures required to access the hippocampus.
The overarching aim of this project is to propel us into a new frontier, in which we will deploy a causal, non-invasive approach to modulate hippocampal activity to probe the interplay between spatial and temporal dynamics of the cortical-hippocampal dialogue during sleep.
To achieve this, we will pair electroencephalography (EEG), to record brain activity on the millisecond timescale at which cortical-hippocampal interactions operate, with temporal interference stimulation (TIS). TIS is a form of non-invasive electrical stimulation that takes advantage of the interference pattern generated by overlapping electric fields to selectively influence neural activity in deep brain regions. We have recently demonstrated that TIS can selectively target the human hippocampus, modulate its activity, and impact memory. Using this approach, we will investigate outstanding questions on how the cortical-hippocampal dialogue operates to support memory consolidation in humans. Our findings can lead to the development of interventions to shape the consolidation of memories to treat memory disorders.