Cerebrum Winter 2022

“For the first time, we’re really starting to get a handle on the networks that humans use to

How about memory versus stimulus from the outside world? Does that play into studying default mode? BUCKNER: Absolutely. I think that is a potentially critical bit that we need to understand. It seems that there are predominant constraints on what drives networks, such as sensory stimulation from the retina that drives the activity in the visual system. There are other networks that may be built not off of external stimulation but of things that are generated internally from mnemonic associations, which are the bits and snippets we’ve captured and stored in our brains to help us with memory. This mnemonic information, in part, may be providing the driving information that these other networks elaborate on. I find that to be potentially critical to this distinction. The brain networks that are expanded and able to utilize internally generated information from mnemonic systems, at their essence, may be different from some of the other networks that we think of as being driven by external events in the world around us, or that we think of in terms of sensory motor function that are primarily driven by taking in sensory stimulation from the outside world and acting upon it. Instead, these networks that utilize internally generated information are about taking information from internal mnemonic systems and elaborating it. Could further understanding of the default mode help treat autism, Alzheimer’s, or psychiatric problems? What’s the goal? BUCKNER: Many forms of illnesses affect high-order cognition, whether it be neurodegenerative illness or psychiatric illness. Differences in high-order faculties seems to be a common outcome of many routes to atypical brain development and degeneration. Sometimes I wonder—from a clinical perspective—if we focus too much on the default network and problems with high- order mental functions, at least insomuch as we think the origins of the illness result from selective dysfunction in these networks. It’s true that we notice dysfunction of the default network in illnesses like psychosis associated with schizophrenia. I don’t know if that necessarily means that the illness is due to a specific dysfunction in these networks, as much as it is that you notice the difficulties

mentally explore.”

the typical trajectory. That said, being able to measure how someone’s brain works when it’s working well, and knowing how the networks are interacting and competing, might be a window into whether therapies are working. That’s important, because as we try to mitigate brain dysfunction, we need ways of measuring and seeing the working brain and restoring the working brain. That’s one kind of path I think this work has taken. There are ways of potentially measuring typical interactions between networks and having that knowledge and being able to make those measurements that are part of the translational research effort. The fact that, in Alzheimer’s disease, we can see the amyloid pathology building up in these networks makes one wonder what it is about these networks—and about their metabolic levels—that is conducive to the pathology and sets up the vulnerability. That’s much more of a direct insight, measuring pathology, which can be now be made with molecular PET scans and eventually, potentially blood biomarkers. In thinking about the mechanisms there, I’ve started to wonder why the metabolic activity sets up risk for Alzheimer’s in your eighth and ninth decades. But when you ask the question, ‘What should we be prioritizing for clinical translation, I think that our ability to see these networks may lead to ways of looking and seeing if therapies, or behavioral interventions, are having positive effects—even if they’re not intimate and mechanistically linked to the origins of the illness. l

in the higher order functions first when network coordination or development hasn’t gone in

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