Until recently, many brain scientists thought that working memory, the ability to retain information briefly, worked through sustained activity of brain cells. But during his postdoc at Oxford, Spaak began to doubt that. "I then used advanced analytical methods to see if that idea held up. That turned out not to be the case," he says.
So what then? Inspired by research on long-term memory, the idea arose that working memory might work through rapid changes in connectivity between brain cells. "For long-term memory, we know that new connections emerge or existing ones get stronger. For working memory, that is still a hypothesis and I now want to test it."
Two tracks
The project focuses on two major tracks. The first is technological: Spaak is developing new analysis methods that allow him to estimate how cells are connected to each other based on “spike data”, the electrical activity of brain cells, and how that connectivity might change during memory tasks. ‘The idea is that if you need to memorise a six, for example, a different connectivity pattern will form in a split second than if you need to memorise an eight.’
The second track is experimental. Spaak is working with existing datasets from two collaborations: one with researchers in Harvard and Berlin, who measured brain activity in rats, and one with a hospital in Bielefeld, Germany, where patients played memory tasks with implanted electrodes. "We designed those tasks as a video game, so that patients enjoy it. As a result, we have a particularly large amount of data per person."
The duration of the project is 3.5 years. In that time, Spaak expects several milestones: first the development of the analysis tool, then its application to datasets, and finally a symposium with international experts. "If we find evidence of rapid connectivity changes, this could unlock new avenues for research: how do those connections change so fast? We don't know that mechanism yet."
Relevant for memory disorders
While the research is fundamental, it may also be clinically relevant over time. Working memory disorders play a role in diseases such as Parkinson's, Alzheimer's and ADHD. ‘I am not a clinical researcher myself,’ stresses Spaak, ‘but if we know how working memory does work in healthy brains, that is an important basis for future treatments.’