How to Build Better Digital Twins of the Human Brain

The potential to create personalized digital twins of your brain and body is a hot topic in neuroscience and medicine today. These computer models are designed to simulate how parts of your brain interact and how the brain may respond to stimulation, disease, or medication.

The extraordinary complexity of the brain's billions of neurons makes this a very difficult task, of course, even in the era of AI and big data. Until now, whole-brain models have struggled to capture what makes each brain unique.

People’s brains are all wired slightly differently, so everyone has a unique network of neural connections that represents a kind of “brain fingerprint.”

However, most so-called brain twins are currently more like distant cousins. Their performance is barely any closer to the real thing than if the model were using the wiring diagram of a random stranger.

This matters because digital twins are increasingly proposed as tools for testing treatments by computer simulation, before applying them to real people. If these models fail to capture fundamental principles of each patient’s unique brain organization, their predictions won’t be personalized—and in worst cases could be misleading.

In our latest study, published in Nature Neuroscience, we show that realistic digital brain twins require something that many existing models overlook: competition between the brain’s different systems.

Our findings suggest that without competition, digital twins risk being overly generic, missing out on what makes you “you.”

Excess of Cooperation

The human brain is never static. The ebb and flow of its activity can be mapped non-invasively using neuroimaging methods such as functional MRI. A computer model can be built from this, specific to that person and simulating how the regions of their brain interact. This is the idea of the digital twin.

The brain is often described as a highly cooperative system. Yet everyday experiences such as focusing attention or switching between tasks tells us intuitively that brain systems compete for limited resources. Our brains cannot do everything at once, and not all regions can be active together all the time.

Despite this, the vast majority of brain simulations over the past 20 years have not taken these competitive interactions between regions into account. Rather, they have “forced” neighboring regions to cooperate. This can push the simulated brain into overly synchronized states that are rarely seen in real brains.

In a large comparative study of humans, macaque monkeys, and mice, our international team of researchers used non-invasive brain activity recordings to show that the most realistic whole-brain models not only require cooperative interactions within specialized brain circuits, but long-range competitive interactions between different circuits.

To achieve this, we compared two types of brain model: one in which all interactions between brain regions were cooperative, and another in which regions could either excite or suppress each other’s activity. In humans, monkeys, and mice, the models that included competitive interactions consistently outperformed cooperative-only models.

Using a large-scale analysis of over 14,000 neuroimaging studies, we found that spontaneous activity in the competitive models more faithfully reflected known cognitive circuits, such as those involved in attention or memory. This suggests competition is crucial for enabling the brain to flexibly activate appropriate combinations of regions—a hallmark of intelligent behavior.

Visual summary of our study: