Juliette Champaud: Development of brain metastable dynamics during the equivalent of the third gestational trimester

Even in the absence of external stimuli or tasks, it remains active, continuously generating patterns of electrical and hemodynamic activity (Raichle, 2015, Shoham et al., 2006). This ongoing activity is not random but instead exhibits meaningful, structured patterns, which reflect the brain's intrinsic organization (Raichle, 2015). To uncover these patterns, we must move beyond static measurements of brain activity, which offer a limited, snapshot-like perspective. Traditional approaches, such as functional connectivity (FC), are important for understanding the brain's architecture and baseline function (Park and Friston, 2013), however, they do not capture the inherently time-varying nature of neural processes (Grosu et al., 2023) and cortico-cortical interactions (Park and Friston, 2013, Kelso, 2012). 

The brain is indeed a dynamic system that can be described as metastable (Tognoli and Kelso, 2014). Metastability is a concept originating from dynamical systems theory and refers to a system poised between stability and instability (Deco et al., 2017). It is characterized by transient occupations of equilibrium points, followed by transitions between them (Cavanna et al., 2018). In the brain, this manifests as a balance between periods of coordinated activity and flexible shifts to new configurations (Jang et al., 2024). These transient configurations of activity, i.e. equilibrium points, whether at large or small spatial or temporal scale, are denoted as metastable states. Brain metastability in adults has been already reviewed many times so we redirect the reader to other excellent reviews on the subject e.g. (Tognoli and Kelso, 2014, Brinkman et al., 2022, Kelso, 2012, Hancock et al., 2025).

Metastability represents the ability of the brain to balance brain-wide cooperation (integration), while retaining functional specificity (segregation) over time (Tognoli and Kelso, 2009, Jang et al., 2024). This balance enables flexible information routing for real-time adaptation to changing internal and external demands, which is crucial for perception, memory, decision-making, and other cognitive functions (Alderson, Thomas et al., 2020, Kelso, 2012; L. Mazzucato et al., 2019; Rabinovich et al., 2008). This adaptability ensures that the brain can allocate resources efficiently, shift between modes of processing, and maintain a coherent, task-relevant network configuration (Wang et al., 2021; Jang et al., 2024). Markers of metastability have thus been employed to explore various aspects of brain function, such as cognitive performance (higher performance associated with more flexible integration-segregation) (Alderson et al., 2020), aging (characterised by higher signal variability and more fragmented metastable transitions) (Naik et al., 2017, Davison et al., 2016), meditation and sleep (during which metastability is altered resulting in reduced flexibility) (Wiemers et al., 2023, Escrichs et al., 2019), and to characterize psychiatric conditions or neurological disorders (schizophrenia and Alzheimer for example are associated with an imbalance of functional segregation and integration) (Hancock et al., 2023, Córdova-Palomera et al., 2017, Alderson et al., 2018), advancing our understanding of neural circuits in health and disease.

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