Dimension reduction for systems with slow relaxation

We develop reduced, stochastic models for high dimensional, dissipative dynamical systems that relax very slowly to equilibrium and can encode long term memory. We present a variety of empirical and first principles approaches for model reduction, and build a mathematical framework for analyzing the reduced models. We introduce the notions of universal and asymptotic filters to characterize `optimal' model reductions for sloppy linear models. We illustrate our methods by applying them to the practically important problem of modeling evaporation in oil spills.Comment: 48 Pages, 13 figures. Paper dedicated to the memory of Leo Kadanof

Dopaminergic D1 receptor signalling is necessary, but not sufficient for cued fear memory destabilisation

Rationale. Pharmacological targeting of memory reconsolidation is a promising therapeutic strategy for the treatment of fear memory-related disorders. However, the success of reconsolidation-based approaches depends upon the effective destabilisation of the fear memory by memory reactivation. Objectives. Here, we aimed to determine the functional involvement of dopamine D1 receptors in cued fear memory destabilisation, using systemic drug administration. Results. We observed that direct D1 receptor agonism was not sufficient to stimulate tone fear memory destabilisation to facilitate reconsolidation disruption by the glucocorticoid receptor antagonist mifepristone. Instead, administration of the nootropic nefiracetam did facilitate mifepristone-induced amnesia, in a manner that was dependent upon dopamine D1 receptor activation, although. Finally, while the combined treatment with nefiracetam and mifepristone did not confer fear-reducing effects under conditions of extinction learning, there was some evidence that mifepristone reduces fear expression irrespective of memory reactivation parameters. Conclusions. The use of combination pharmacological treatment to stimulate memory destabilisation and impair reconsolidation has potential therapeutic benefits, without risking a maladaptive increase of fear

Reminder duration determines threat memory modification in humans

Abstract Memory reminders can return a memory into an unstable state such that it will decay unless actively restabilized into long-term memory through reconsolidation. Exposure to a memory reminder, however, does not always lead to destabilization. The ‘trace dominance’ principle posits that the extent of exposure to memory reminders governs memory susceptibility to disruption. Here, we provide a first systematic investigation of reminder duration effects on threat memory modification in humans. Reminder duration was parametrically varied across 155 participants in a three-day protocol. We found that short reminders (1 s and 4 s) made the memory prone to interference from post-retrieval extinction, suggesting that the memory had been updated. In contrast, no reminder or long reminders (30 s and 3 min) made the memory resistant to such interference, and robustly return. Reminder duration therefore influences memory stability and may be a critical determinant of therapeutic efficacy