Neuromodulation of episodic memory - how stress influences Time In MEmory and perception

Project Information

TIME

Grant agreement ID: 101064781

DOI

10.3030/101064781

EC signature date 23 May 2022

Start date 1 August 2023

End date 31 July 2026

Funded under

• Marie Skłodowska-Curie Actions (MSCA)

Total cost

No data

EU contribution

€ 319 516,16

Coordinated by

SCUOLA INTERNAZIONALE SUPERIORE DI STUDI AVANZATI DI TRIESTE
Italy

Periodic Reporting for period 1 - TIME (Neuromodulation of episodic memory - how stress influences Time In MEmory and perception)

Reporting period: 2023-08-01 to 2025-07-31

Summary of the context and overall objectives of the project

Recent European data shows that stress shortens life expectancy by 2.8 years. Critically, it also affects the way we sense and remember everyday life. TIME presents a novel approach to a fundamental question in neuroscience: how does stress affect our memory and perception of experience over time? Previous research disregarded the role of specific neuromodulators, studied stress effects selectively on a particular memory stage, and used isolated stimuli rather than complex events in naturalistic contexts. Moreover, the impact of stress on memory has never been linked to time perception during a stressful experience.

TIME addresses these critical gaps with an innovative combination of cutting-edge tools: brain imaging (functional magnetic resonance, fMRI), a controlled increase of stress hormones (with pharmacological manipulations), precise measurements of sensing time (with psychophysics), and immersive virtual reality (VR) experiments. The project aims at building the first comprehensive model of stress effects on temporal memory and perception of time.

The project aims to verify two hypotheses. First, we hypothesized that a stress hormone, cortisol, released in our bodies across all memory stages (encoding, consolidation, retrieval), makes it harder to separate overlapping episodes and to break our experience into coherent events (WP1, WP2). Second, we hypothesized that stress may speed up how the brain samples incoming information, which could distort our sense of time and influence how we later recall events over time (WP3).

Involved mechanisms will be measured and verified at the behavioral (WP1, WP2, WP3), physiological (WP1, WP2, WP3), and neural (WP2) level. I will carry out this research at CISA, Geneva (outgoing phase) and SISSA, Trieste (return phase). Together, these world-leading centers offer a unique environment to make the project realistically achievable by bridging the gaps between neuropharmacology, neuroscience, psychophysics, and psychophysiology. TIME will move basic and applied science forward, boost my academic or non-academic career prospects.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

The realization of WP1 was achieved in three independent studies. Study 1 looked at how emotions influence memory for complex events in space and time. We started with a well-established task for studying how people break continuous experience into separate events and added emotional sounds to see their impact. We then adapted this task into a virtual reality setting, where participants experienced sequences of objects evoked by the wall color changes (marking event boundaries) while hearing neutral or negative sounds. Later, we tested how well they remembered the order of events and the link between objects and their contexts.

Study 2 examined how the stress hormone cortisol affects episodic memory at different stages. Using a within-subject, double-blind, placebo-controlled design, we administered cortisol either before learning, after learning, or before retrieval. Participants encoded pairs of words and emotional or neutral images, and after 24 hours, their memory was tested both for individual items and for associations between them.

Study 3 built on these findings to test how cortisol administered after learning affects two key memory processes: pattern separation (distinguishing similar items) and event segmentation. In a between-subjects, double-blind, placebo-controlled design, participants first learned sequences of objects in VR. Afterward, they received either hydrocortisone or a placebo. A day later, they performed tasks that required discriminating old objects from similar lures (pattern separation) and recalling contextual details like wall color and spatial location (event segmentation).

WP2 builds on WP1 to test how cortisol affects memory for time. We designed a computer-based task combined with pharmacological manipulation. Study 4 validated this behavioral paradigm, followed by a pilot fMRI study to establish the scanning parameters. Full fMRI data collection and analysis will be completed in the return phase.

WP3 focuses on how cortisol influences time perception and basic visual processing. Study 5 used a mixed, double-blind, placebo-controlled design where participants received hydrocortisone or a placebo. We tracked stress markers (salivary cortisol and pupil size) while testing two aspects: (i) whether cortisol altered how long visual stimuli felt, and (ii) whether it affected contrast sensitivity, a fundamental process in visual perception.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

WP1 included three studies, two of which are already summarized in scientific publications. WP2 and WP3 are in good progress, with manuscripts in preparation.

WP1, Study 1 examined how emotion and event segmentation shape episodic memory. We found that event segmentation enhanced memory for the object-colour associations, while emotion impaired it. On the contrary, event segmentation impaired temporal order memory, but emotion enhanced it. These findings, published in Cognition and Emotion, show how perceptual changes and emotional fluctuations jointly shape episodic memory in naturalistic settings.

WP1, Study 2 investigated how cortisol affects memory across different stages and stimulus types. We found that post-encoding cortisol enhanced item memory, whereas pre-encoding and pre-retrieval cortisol impaired it. Pre-encoding cortisol also impaired associative memory, but only for neutral stimuli. Moreover, both salivary cortisol levels and stimulus emotionality modulated performance. These results, published in Psychoneuroendocrinology, highlight the complex ways cortisol influences item and associative memory for neutral and emotional events across memory stages.

Overall, this project advances our understanding of how episodic memory is organized in naturalistic settings, where perceptual changes and emotional fluctuations constantly interact. Building the first comprehensive model of stress effects on memory and time perception, it contributes to scientific progress across disciplines, as reflected in publications in leading international journals. The project also opens new research directions with strong potential for future studies and has established lasting collaboration between SISSA and CISA through a three-way exchange of expertise.

The findings have important societal implications in Europe and beyond. Since the COVID-19 pandemic, the number of people experiencing severe stress symptoms has risen sharply—from 11% to 20% (coronastress.ch). Stress-related mental disorders, such as PTSD, not only impair memory but also increase the risk of neurodegenerative disease. Recent European data show that stress can reduce life expectancy by 2.8 years and impose an economic burden of at least €600 billion per year. Insights from this project can inform therapeutic interventions to address such challenges.

The results are also valuable for education, where stressors such as exams, deadlines, and interpersonal conflicts strongly affect learning. By integrating insights from psychology and neuroscience, the project highlights ways to improve educational systems. Finally, on a technological level, the project aligns with the EU’s H2020 FET proactive theme Future Technologies for Social Experience, demonstrating the potential of virtual reality and related tools for understanding and improving social and cognitive functioning.

Fig. 1 Schematic of experimental procedure and results of WP1, Study 1