HMN 2026: How the brain’s physical shape guides its internal wiring

A new study led by Monash University researchers has shed light on the factors shaping the intricate wiring of our brains. The research, published in the journal Cell, reveals that the brain’s complex wiring diagram, known as the cortical connectome, does not form at random. Instead, a new mathematical model shows that connections preferentially form between locations that support natural, shape-driven “resonant patterns.”

Lead author Francis Normand, from the Turner Institute for Brain and Mental Health at Monash University, likened the brain to a musical instrument, such as a bell or a drum. “Just as the physical shape of a bell or a drum determines its vibrations and the music that it produces, the physical geometry of the brain constrains the patterns of neural activity it can support,” he said.

Normand conducted the research alongside Professor Alex Fornito and Dr. James Pang, both from the Turner Institute for Brain and Mental Health at Monash University. By testing their mathematical formula against publicly available datasets, the research team showed that this geometric rule holds true across various species, from mice to humans.

This demonstrates that the physical shape of the brain has served as a blueprint in guiding its internal wiring for at least 90 million years of mammalian evolution.

A formula for brain wiring

The researchers also showed that the formula successfully predicts both how the brain is wired—its “topology”—and where the wires physically go—its “topography”—important properties that previous theories have failed to predict.

Normand said that while the general idea of physical space constraining the brain has long been recognized, this study is the first to formalize and mathematically quantify the rule using a framework called neural field theory.

“Traditional models treat the brain as a collection of distinct regions sending signals through their connections. Our model suggests that the cortex can be treated like a continuous physical medium through which waves of activity propagate,” Normand said.

Low-frequency patterns take priority

“The model assumes that connections are strengthened between locations that show coordinated activity fluctuations when the brain expresses certain resonant patterns that it prefers due to its shape, much like the ripples formed by a raindrop will be influenced by the shape of a pond.

“Crucially, our model suggests the brain wires itself in an energy-efficient way to support these resonant patterns, strongly favoring low-frequency patterns, resembling a deep, low hum rather than a high-pitched chirp. These broad, brain-wide patterns require far less energy to sustain,” he said.

Clues for disordered brain structure

The research opens new doors for brain modeling and could help researchers understand how structural changes or malformations alter the brain’s wiring in psychiatric or neurological disorders.

“The fact that a single mathematical formula can accurately predict brain networks in both a tiny mouse and a human reveals just how powerful physical geometry is in shaping brain connectivity,” Normand said.

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