The Story

In May 2022, four years ago, Iosif and Nikola, fellows in the Biotechnology and Health Extension branch of the Foresight Institute, attended a workshop in San Francisco. Nikola presented his research on the heterogeneous aging of functional brain networks to a rapt audience of (at least) one. Iosif had spent the prior seven years seeking a way to test a hypothesis he had started developing in 2016 on a purely theoretical basis: that as people age, loss of myelin should cause timing discrepancies, undermining the coherent communication within brain networks that healthy cognition relies on. By 2019, having dubbed it the Decoherence via Demyelination Hypothesis - DDH - he was writing to neuroscientist after neuroscientist looking for someone whose research could help substantiate the idea.

The two stayed behind afterward and talked for hours about the brain and the mechanisms driving its aging. Together they were looking at a figure of myelin measures in the participants of the UCSF healthy aging cohort - a figure depicting the continuous changes of myelin across the lifespan. Iosif saw the connection he had been convinced of all those years: change of that magnitude in myelin should produce a loss of synchronization across the network. Nikola, looking at the same figure, saw the path forward - the patterns of functional network aging he had been documenting offered exactly what was needed to test the prediction. For the first time, the hypothesis had landed in front of the researcher whose empirical foundation was a precise match: someone who could not only engage with it, but make it real.

That moment reframed the problem. Rather than understanding brain aging primarily through the lens of neurons losing synapses, it pointed toward network dynamics - and toward myelination strength as the variable governing them. The two believed it mattered, and over the next four years Nikola and Iosif did the work of turning DDH into science. Nikola led the empirical investigations, developed the analytical framework, sharpened the theoretical claims against the data, and carried the weight of moving the project from a conjecture between two people into a research program with experimental footing. Together they convinced the rest of the team to join, and built DDH from a hypothesis into the integrated theory it is today.

DDH unifies observations from fields that had remained largely isolated from one another. From a mechanism for information transmission between pairs of areas, it extends the “communication through coherence” theory to the multi-region level. From the literature on compositionality, it adopts the view that brain function is widely distributed - that subsets of neurons across different regions coordinate their activity to produce cognition. From cognitive development, it incorporates the understanding that myelin is tuned through experience to establish the functional networks that support cognition.

What emerged is a framework in which tracking structural loss with age becomes a window into both processes at once - the mechanisms producing the aging brain, and the principles by which the healthy young brain computes in the first place.