Regulating Memory Persistence: Peripheral Nerve Stimulation Across the Forgetting Continuum

Abstract

This thesis investigates how memory persistence is regulated across a proposed "forgetting continuum", reframing remembering and forgetting as outcomes of dynamic, adaptive control processes rather than opposing states. Drawing on contemporary evidence, it conceptualises forgetting as an active mechanism that governs the accessibility, stability, and updating of memory representations. Dysregulation within this system can manifest as either excessive forgetting, as observed in conditions such as preclinical Alzheimer's disease and epilepsy, or insufficient forgetting, which contributes to maladaptive memory persistence in disorders including post-traumatic stress disorder and addiction.

To account for these patterns, the thesis advances a unifying framework integrating active forgetting theory with predictive processing accounts. Within this model, memory persistence is regulated by precision-weighted prediction error signals that determine whether memory traces are stabilised or weakened. Central to this process is the locus coeruleus-noradrenergic (LC-NA) system, proposed as a neuromodulatory gatekeeper that modulates arousal, attention, and synaptic plasticity in response to uncertainty.

Empirically, the research examines whether greater occipital nerve transcranial direct current stimulation (GON-tDCS), which engages LC-NA pathways, can differentially influence memory and forgetting outcomes. Across multiple experimental paradigms, findings demonstrate that GON-tDCS does not produce uniform memory enhancement. Instead, its effects are selective and depend on memory stage, type, and baseline neural state.

Stimulation enhances reconsolidation but does not reduce retrieval-induced forgetting, indicating dissociable mechanisms underlying memory stabilisation and suppression. In aversive learning contexts, it attenuates fear responses and reduces physiological markers of noradrenergic activity. In preclinical Alzheimer's disease, GON-tDCS does not mitigate accelerated long-term forgetting, with memory outcomes shaped by individual neural dynamics. Moreover, beta dynamics predict responsiveness to stimulation, demonstrating that neuromodulatory interventions interact with intrinsic brain states to shape memory outcomes.

These findings challenge the assumption that neuromodulation universally enhances memory. Taken together, this thesis advances a novel account of memory control architecture as a dynamically regulated system, in which persistence emerges from the interaction of synaptic plasticity mechanisms, neuromodulatory gating, and predictive processing dynamics across the forgetting continuum.