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Primary Sensory Cortex In Human Memory Reconsolidation

Reference	BB/W014408/1
Principal Investigator / Supervisor	Dr Dominik Bach
Co-Investigators / Co-Supervisors	Professor Sven Bestmann, Dr Ravi Das
Institution	University College London
Department	Institute of Neurology
Funding type	Research
Value (£)	940,590
Status	Current
Type	Research Grant
Start date	01/01/2023
End date	30/06/2026
Duration	42 months

Abstract

Integrating new information into existing memories is an important mechanism to confer memory flexibility. Reconsolidation is the synapse-level biological mechanism thought to underly memory flexibility. However, memory usually involves multiple synapses, often distributed across brain areas. Such systems-level memory networks are particularly relevant for human memory. As yet, the systems-level mechanisms of memory reconsolidation are incompletely understood. In this proposal, we seek to characterise these mechanisms using transcranial magnetic stimulation, a non-invasive tool to create virtual lesions, which is safe to use in humans. We will build on our previous work showing that sensory cortices are relevant for aversive memory. In particular, we have demonstrated that primary somatosensory cortex (S1) is required for the consolidation (but not acquisition) of a somatosensory aversive memory in humans. We propose to use continuous theta-burst stimulation (cTBS) after a previously acquired somatosensory aversive memory has been reminded and supposedly became malleable. We seek to demonstrate that the combination of reminder and cTBS reduces aversive memory retention one day later, with several negative controls designed to show that only the combination of these two procedures has this effect. We will further add a positive control - a procedure previously shown to reduce aversive memory retention - to render a negative finding in the experimental group interpretable. Using a relatively large sample (N = 350), rigorous design with several control groups, and contemporary technology, will maximise the interpretability of positive and negative findings. Because we use a non-invasive procedure in healthy humans, rather than animals, a positive finding has long-term potential to be developed into a therapeutic application for the treatment of maladaptive memory after psychological trauma.

Summary

Learning from past experience is fundamental for many animals including humans. This ability allows us to flexibly adapt to ever-changing environments. Learning requires storing completely novel information, as well as integrating new information into existing memory. The latter function demands memory flexibility. Re-consolidation has been proposed as the biological mechanism by which such flexibility is achieved. Recent research has provided us with great detail on the molecular and cellular pathways underlying memory re-consolidation in specific brain areas. However, memory often relies on an interplay of different brain regions. This is particularly the case in humans. The contribution of these different brain regions to re-consolidation remains incompletely understood. This impairs our theoretical understanding of this process in humans, and a clinical application. Memory interventions - whether experimental or therapeutic - cannot be targeted to specific brain regions without precise knowledge on their contribution. The proposed project will deliver on these shortcomings by using non-invasive brain stimulation. Our previous work has shown that interfering with one part of the brain that contributes to registering touch (somatosensory cortex) impairs remembering - but not learning - that touch predicts an aversive event. In the proposed experiments, our participants will learn that certain touch-like stimulation predicts an aversive event. We will later remind people of this association and then interfere with somatosensory cortex to create a temporary processing deficit in this region. This will allow us to investigate whether this region is crucially required for the spontaneous re-consolidation process that ensues after the memory has been recalled. If this is the case, then this will crucially inform theories of systems-level memory flexibility. It also has a potential to be further developed into a clinical application. Because we will be using a largesample (N = 350), carefully designed control groups, and state-of-the-art technology, a negative result will be equally informative and is likely to allow conclusions about systems-level differences between consolidation and re-consolidation processes, thus complementing previous research on the molecular similarities and differences between these processes.

Committee	Research Committee A (Animal disease, health and welfare)
Research Topics	X – not assigned to a current Research Topic
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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