There is a special place in our memory system for events that “stick-out”. What are the human subcortical and cortical circuits that are involved in upregulating memory for exceptional events? What are the circuit dynamics that mechanistically underlie encoding and remembering the exceptional? The European Research Council (ERC) Consolidator Grant awarded to Bryan Strange will combine innovative experiments in cohorts of rare patients. as well as healthy human participants, and advanced analytical techniques to address these questions.

The summary of the project is provided here:

RememberEx – Human Subcortical-Cortical Circuit Dynamics for Remembering the Exceptional

Our memory system is optimised for remembering the exceptional over the mundane. We remember better those events that violate predictions generated by the prevailing context, particularly because of surprise or emotional impact. Understanding how we form and retrieve long-term memories for important or salient events is critical for combating the rapidly growing incidence of pathologies associated with memory dysfunction with huge socio-econonomic burden. Human lesion and non-invasive functional imaging data, motivated by findings from animal models, have identified subcortical structures that are critical for upregulating hippocampal function during salient event memory. However, mechanistic understanding of these processes in humans remains scarce, and requires better experimental approaches such as direct intracranial recordings from, and focal electrical stimulation of, these subcortical structures. This project will characterise human subcortico-cortical neuronal circuit dynamics associated with enhanced episodic memory for salient stimuli by studying direct recordings from human hippocampus, amygdala, nucleus accumbens, ventral midbrain and cortex. Within this framework, I will elucidate the electrophysiological mechanisms underlying amygdala-hippocampal-cortical coupling that lead to better memory for emotional stimuli, extend the hippocampal role in detecting unpredicted stimuli to define its role in orchestrating cortical dynamics in unpredictable contexts, and discover the neuronal response profile of the human mesolimbic dopamine system during salient stimulus encoding. The predicted results, based on my own preliminary data, will offer several conceptual breakthroughs, particularly regarding hippocampal function and the role of dopaminergic ventral midbrain in memory. The knowledge gained from this project is a fundamental requirement for designing therapeutic interventions for patients with memory deficits and other neuropsychiatric disorders.

Publications

Manuela Costa, Diego Lozano-Soldevilla, Antonio Gil-Nagel Rein, Rafael Toledano, Carina Oehrn, Lukas Kunz, Mar Yebra, Constantino Mendez-Bertolo, Lennart Stieglitz, Johannes Sarnthein, Nikolai Axmacher, Stephan Moratti, Bryan A Strange (2022) Aversive memory formation in humans involves an amygdala-hippocampus phase code. Nature Communications 13:6403. LINK.

Mar Yebra, Ana Galarza Vallejo, Vanesa Soto-Leon, Javier J  Gonzalez-Rosa, Archy O de Berker, Sven Bestmann, Antonio Oliviero, Marijn CW Kroes, Bryan A Strange (2019) Action boosts episodic memory encoding in humans via engagement of a noradrenergic system. Nature Communications 10(1):3534. LINK

M Yebra, O Jensen, L Kunz, S Moratti, N Axmacher, BA Strange (2021) A gradient of electrophysiological novelty responses along the human hippocampal long axis. [bioRXiv]

Svenja Treu, Javier J. Gonzalez-Rosa, Vanesa Soto-Leon, Diego Lozano-Soldevilla, Antonio Oliviero, Fernando Lopez-Sosa, Blanca Reneses-Prieto, Juan A Barcia, Bryan A Strange (2021) A ventromedial prefrontal dysrhythmia in obsessive-compulsive disorder is attenuated by nucleus accumbens deep brain stimulation. Brain Stimulation.  14(4):761-770. LINK

Alba Peris-Yague, Darya Frank, Bryan A Strange (2021) Emotional salience modulates the forward flow of memory. [psyarxiv]

Press commentaries

Investigación para comprender cómo consigue el cerebro recordar mejor los sucesos excepcionales [Research to understand how the brain better remembers exceptional event]. InnovaSpain. 21 May 2019

For any enquiries related to this project, please write to bryan.strange@upm.es